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Urogynecology

and
Reconstructive
Pelvic Surgery
Mark D. Walters, MD FOURTH EDITION
Professor and Vice-Chair of Gynecology
Center of Urogynecology and
Reconstructive Pelvic Surgery
Obstetrics, Gynecology, and Women’s Health Institute
Cleveland Clinic
Cleveland, Ohio

Mickey M. Karram, MD
Professor of Obstetrics and Gynecology and Urology
University of Cincinnati
Director of Urogynecology
The Christ Hospital
Cincinnati, Ohio
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

UROGYNECOLOGY AND RECONSTRUCTIVE PELVIC


SURGERY, FOURTH EDITION ISBN: 978-0-323-11377-9
Copyright © 2015 by Saunders, an imprint of Elsevier Inc.

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Dr. Geoffrey Cundiff retains copyright for his original images. Copyright © 2015 Geoffrey Cundiff.
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Library of Congress Cataloging-in-Publication Data

Urogynecology and reconstructive pelvic surgery (Walters)


Urogynecology and reconstructive pelvic surgery / [edited by] Mark D. Walters, Mickey M. Karram.
-- Fourth edition.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-323-11377-9 (hardback : alk. paper)
I. Walters, Mark D., editor. II. Karram, Mickey M., editor. III. Title.
[DNLM: 1. Female Urogenital Diseases. 2. Fecal Incontinence. 3. Urodynamics. 4. Urogenital Surgical
Procedures. WJ 190]
RG484
616.6--dc23
2014038161

Executive Content Strategist: Kate Dimock


Content Development Manager: Lucia Gunzel
Publishing Services Manager: Anne Altepeter
Project Manager: Jennifer Moore
Design Direction: Lou Forgione

Printed in China

Last digit is the print number: 9 8 7 6 5 4 3 2 1


To ginny, my best friend, with love and respect
Mark D. Walters

In memory of my parents Mike and Mary Karram,


for their love, kindness and unselfish support, as well as
for instilling in me the values of education,
discipline, and hard work
Mickey M. Karram
Contributors

MARGARITA M. APONTE, MD JANELLE EVANS, MD


Fellow in Female Pelvic Medicine and Reconstructive Urogynecology Fellow, Department of Obstetrics and
Surgery, New York University Langone Medical Center, Gynecology, University of Cincinnati College of
New York, New York Medicine, Cincinnati, Ohio

JEAN H. ASHBURN, M EVELYN L. FLEMING, MD, FACOG


Staff Surgeon, Colorectal Surgery, Department of Assistant Professor, Department of Obstetrics and
Colorectal Surgery, Digestive Diseases Institute, Gynecology, Division of Gynecologic Oncology,
Cleveland Clinic, Cleveland, Ohio Dartmouth-Hitchcock Medical Center, Lebanon,
New Hampshire
MARJAN ATTARAN, MD
Section Head, Pediatric Gynecology, Reproductive ANNA C. FRICK, MD, MPH
Endocrinology and Infertility, Obstetrics, Gynecology East Bay Physicians Medical Group, Oakland, California
and Women’s Health Institute, Cleveland Clinic,
Cleveland, Ohio JOHN B. GEBHART, MD
Associate Professor, Mayo Clinic College of Medicine;
MATTHEW D. BARBER, MD, MHS Director, Female Pelvic Medicine and, Reconstructive
Professor and Vice Chair for Clinical Research, Center Surgery Fellowship Training Program, Mayo Clinic,
of Urogynecology and Reconstructive Pelvic Surgery, Rochester, Minnesota
Obstetrics, Gynecology and Women’s Health Institute,
Cleveland Clinic, Cleveland, Ohio W. THOMAS GREGORY, MD
Assistant Professor, Division of Urogynecology and
ALFRED E. BENT, MD, FRCSC Reconstructive Pelvic Surgery, Department of Obstetrics
Professor and Head, Division of Gynaecology, Dalhousie and Gynecology, Oregon Health and Science University,
University, Department of Obstetrics and Gynaecology, Portland, Oregon
Halifax, Nova Scotia, Canada
DOUGLASS S. HALE, MD
RAYMOND A. BOLOGNA, MD Clinical Professor, Director Female Pelvic Medicine and
Assistant Professor of Urology, College of Medicine, Reconstructive Surgery Fellowship, Department of
Northeastern Ohio University, Akron, Ohio Obstetrics and Gynecology, Indiana University School of
Medicine, Indianapolis, Indiana
KATHRYN L. BURGIO, PhD
Associate Director for Research, Birmingham VA Medical B. STAR HAMPTON, MD
Center, Birmingham, Alabama Associate Professor, Department of Obstetrics
and Gynecology, Division of Urogynecology and
CHI CHIUNG GRACE CHEN, MD Reconstructive Pelvic Surgery, Warren Alpert Medical
Assistant Professor, Johns Hopkins School of Medicine; School of Brown University, Providence, Rhode Island
Female Pelvic Medicine and Reconstructive Surgery,
Department of Gynecology and Obstetrics, Johns WEN-CHEN HUANG, MD
Hopkins Bayview Medical Center, Baltimore, Associate Professor, Department of Obstetrics and
Maryland Gynecology, Taipei Medical University; Staff Physician,
Department of Obstetrics and Gynecology, Cathay
JEFFREY L. CLEMONS, MD, COL General Hospital, Taipei, Taiwan
Urogynecologist, Clinical Associate Professor, University
of Washington, MultiCare Women’s Pelvic Medicine and TRACY L. HULL, MD
Reconstructive Surgery, Tacoma, Washington Head, Section of Anal Physiology, Department of
Colorectal Surgery, Digestive Diseases Institute,
GEOFFREY W. CUNDIFF, MD, FACOG, FACS Cleveland Clinic, Cleveland, Ohio
Professor and Head, Department of Obstetrics and
Gynecology, University of British Columbia, St. Paul’s
Hospital, Vancouver, British Columbia, Canada

vi
Contributors vii

J. ERIC JELOVSEK, MD, MMEd MARIE FIDELA R. PARAISO, MD


Associate Professor of Surgery, Director of the Professor of Surgery, Lerner College of Medicine of
Multidisciplinary Simulation and Advanced Skills Case Western Reserve University; Head, Center of
Center, OB/GYN Residency Program Director, Urogynecology and Reconstructive Pelvic Surgery,
Urogynecology and Reconstructive Pelvic Surgery, Obstetrics, Gynecology and Women’s Health Institute,
Obstetrics, Gynecology and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio
Cleveland Clinic, Cleveland, Ohio
RAYMOND R. RACKLEY, MD
MICKEY M. KARRAM, MD Professor of Surgery, Lerner College of Medicine of Case
Professor of Obstetrics and Gynecology and Urology, Western Reserve University, Section of Female Urology
University of Cincinnati; Director of Urogynecology, and Voiding Dysfunction, Glickman Urological Institute,
The Christ Hospital, Cincinnati, Ohio Cleveland Clinic, Cleveland, Ohio

SHERYL A. KINGSBERG, PhD ROYA L. REZAEE, MD


Chief, Division of Behavioral Medicine, Co-Director Co-Director, Sexual and Vulvovaginal Health Program,
Sexual and Vulvovaginal Health Program, Department Medical Director, Women’s Health Center, Department
of OB/GYN, MacDonald Women’s Hospital, University of Obstetrics and Gynecology, University Hospitals
Hospitals Case Medical Center; Professor, Departments Case Medical Center, MacDonald Women’s Hospital;
of Reproductive Biology and Psychiatry, Case Western Assistant Professor, Department of Reproductive
Reserve University School of Medicine, Cleveland, Ohio Biology, Case Western Reserve University School of
Medicine, Cleveland, Ohio
AYMAN MAHDY, MD
Assistant Professor of Urology, Director Voiding HOLLY E. RICHTER, PhD, MD, FACOG, FACS
Dysfunction, Female Urology and Neurourology, Professor of Obstetrics and Gynecology, Urology and
University of Cincinnati, Cincinnati, Ohio Geriatrics; Director, Division of Urogynecology and
Pelvic Reconstructive Surgery, University of Alabama
CATHERINE A. MATTHEWS, MD at Birmingham School of Medicine, Birmingham,
Associate Professor and Division Chief, Female Pelvic Alabama
Medicine and Reconstructive Pelvic Surgery, University
of North Carolina at Chapel Hill, Chapel Hill, BERI M. RIDGEWAY, MD
North Carolina Assistant Professor of Surgery, Lerner College of
Medicine of Case Western Reserve University, Center
PAMELA A. MOALLI, MD, PhD of Urogynecology and Reconstructive Pelvic Surgery,
Associate Professor, Division of Urogynecology and Obstetrics, Gynecology and Women’s Health Institute,
Reconstructive Pelvic Surgery, Department of Cleveland Clinic, Cleveland, Ohio
Obstetrics, Gynecology, and Reproductive Sciences,
University of Pittsburgh Medical Center, Pittsburgh, REBECCA SHAFFER, MD
Pennsylvania Fellow in Female Pelvic Medicine and Reconstructive
Surgery, Department of Obstetrics, Gynecology, and
COURTENAY K. MOORE, MD Reproductive Sciences, University of Pittsburgh Medical
Asscoiate Professor of Surgery, Lerner College of Center, Pittsburgh, Pennsylvania
Medicine of Case Western Reserve University;
Section of Female Urology and Voiding Dysfunction, BAHA M. SIBAI, MD
Glickman Urological Institute, Cleveland Clinic, Professor, Department of Obstetrics, Gynecology and
Cleveland, Ohio Reproductive Sciences, University of Texas Health
Science Center at Houston, Houston, Texas
TYLER M. MUFFLY, MD
Assistant Professor, Division of Female Pelvic Medicine WILLIAM ANDRE SILVA, MD, FRCSC, FACOG
and Reconstructive Surgery, University of Colorado Urogynecologist, Franciscan Women’s Health – Federal
Anschutz Medical Campus, Aurora, Colorado Way, Federal Way, Washington

TRISTI W. MUIR, MD ELLEN R. SOLOMON, MD


Assistant Professor of Obstetrics and Gynecology, Assistant Professor, Tufts Medical School, Baystate
University of Texas Medical Branch, Galveston and Medical Center, Division Urogynecology and
League City, Texas Reconstructive Pelvic Surgery, Department of Obstetrics
and Gynecology, Springfield, Massachusetts
VICTOR W. NITTI, MD
Professor of Urology and Obstetrics and Gynecology, Vice MARY M. SOUTH, MD, FACOG
chairman Department of Urology, Director of Female Associate Professor, Summa Health System, Akron, Ohio
Pelvic Medicine and Reconstructive Surgery, New York
University Langone Medical Center, New York,
New York
viii Contributors

KEVIN J. STEPP, MD CHRISTINE M. VACCARO, DO, FACOG


Director, Advanced Surgical Specialties for Women, Chief, Urogynecology and Pelvic Reconstructive Surgery,
Urogynecology and Minimally Invasive Gynecologic Department of Obstetrics and Gynecology, Madigan
Surgery, Carolinas Medical Center, Charlotte, North Healthcare System; Clinical Assistant Professor,
Carolina Obstetrics and Gynecology, University of Washington
School of Medicine, Madigan Army Medical Center,
CARMEN J. SULTANA, MD Tacoma, Washington
Chairman and Residency Program Director, Department
of Obstetrics and Gynecology, New York Downtown SANDIP P. VASAVADA, MD
Hospital, New York, New York Urologic Director, Center for Female Pelvic Medicine and
Reconstructive Surgery, Section of Female Urology and
VIVIAN W. SUNG, MD, MPH Voiding Dysfunction, Glickman Urological Institute,
Associate Professor, Department of Obstetrics and Cleveland Clinic, Cleveland, Ohio
Gynecology; Director of Research, Division of
Urogynecology and Reconstructive Pelvic Surgery, MARK D. WALTERS, MD
Warren Alpert Medical School of Brown University, Professor and Vice-Chair of Gynecology, Center of
Providence, Rhode Island Urogynecology and Reconstructive Pelvic Surgery,
Obstetrics, Gynecology and Women’s Health Institute,
MEGAN E. TARR, MD Cleveland Clinic, Cleveland, Ohio
Center of Urogynecology and Reconstructive Pelvic
Surgery, Obstetrics, Gynecology and Women’s Health JAMES L. WHITESIDE, MD, MA, FACOG
Institute, Cleveland Clinic, Cleveland, Ohio Professor, Department of Obstetrics, Gynecology and
Surgery; Co-Director, Division of Female Pelvic
ANTHONY P. TIZZANO, MD Medicine and Reconstructive Surgery Fellowship, The
Medical Director, Cleveland Clinic, Wooster Family Health Christ Hospital, Cincinnati, Ohio
and Ambulatory Surgery Center, Cleveland, Ohio
KRISTENE E. WHITMORE, MD
ELENA TUNITSKY-BITTON, MD Pelvic and Sexual Institute, Hahnemann University
Assistant Professor, Obstetrics and Gynecology, Hospital, Philadelphia, Pennsylvania
University of Connecticut Medical School, Hartford
Hospital, Division of Urogynecology, Hartford, MASSARAT ZUTSHI, MD
Connecticut Digestive Disease Institute, Department of Colorectal
Surgery, Cleveland Clinic, Cleveland, Ohio
CECILE A. UNGER, MD, MPH
Center of Urogynecology and Reconstructive Pelvic
Surgery, Obstetrics, Gynecology and Women’s Health
Institute, Cleveland Clinic, Cleveland, Ohio
Preface

As the population lives longer and has improved health, the surgery for practicing generalists and residents in obstet-
prevalence of various pelvic floor disorders is increasing. rics and gynecology. More physicians with special exper-
The term pelvic floor disorders incorporates a broad array tise in urogynecology and vaginal and laparoscopic surgery
of inter-related clinical conditions that includes lower uri- are needed to meet the increasing patient volume and the
nary tract dysfunction, pelvic organ prolapse, defecatory additional training needs within this specialty. Over the past
dysfunction, sexual dysfunction, and a variety of pelvic pain 15 years, the specialty of Urogynecology—since renamed
disorders. More than half of women experience one or more Female Pelvic Medicine and Reconstructive Surgery—has
of these disorders for some period in their lives, and one in expanded to a fourth subspecialty approved by the American
nine will undergo surgery for pelvic floor abnormalities by Board of Obstetrics and Gynecology and a second subspe-
age 80. Economic analyses estimate that the total annual cialty approved by the American Board of Urology. Formal
direct cost of urinary incontinence in the United States 3-year fellowships (for a gynecologist) and 2-year fellow-
alone is more than $20 billion. Beyond the economic costs ships (for a urologist) are now approved by the Accredita-
and general health care burden, pelvic floor disorders result tion Council for Graduate Medical Education (ACGME),
in significant adverse psychosocial affects and can have a thus conforming with other subspecialties in medicine and
profound impact on an individual’s quality of life. Women surgery. This updated textbook is an effort to address the
desire and are able to remain active longer and are less inter- educational needs of physicians and advanced care practitio-
ested in tolerating the lower quality of life that accompanies ners interested in female pelvic floor disorders and to serve
these conditions. This leads to a greater number of other- as a core reference text in urogynecology and reconstructive
wise healthy women presenting to their physicians with var- pelvic surgery.
ious pelvic floor disorders. It is estimated that the growth The fourth edition of Urogynecology and Reconstruc-
and demand for services to care for women with pelvic floor tive Pelvic Surgery is a clinically oriented yet comprehen-
disorders will increase at twice the rate of growth of the sive textbook addressing our subspecialty. We believe that
population over the next 30 years. this subject fundamentally encompasses three main topics:
International interest in diseases of women and older female urinary incontinence and voiding dysfunction, pel-
persons in general has helped to increase awareness of the vic organ prolapse, and disorders of defecation. This book
high prevalence of urinary and fecal incontinence in women. is separated into nine sections. Chapter 1 reviews historical
Clinical care guidelines were developed by the National milestones in pelvic surgery and female urology. Chapters
Institute on Aging and the Office of Medical Applica- 2 through 8 describe in detail basic principles and subjects
tion of Research within the National Institutes of Health needed to understand and treat disorders of the lower uri-
in conjunction with other agencies. This was followed by nary tract and pelvic floor. Chapters 9 through 14 outline
expanded national research funding; the resulting data are basic and advanced concepts in the evaluation of lower uri-
now frequently being reported in high-quality manuscripts nary tract and pelvic floor disorders in women. Chapters
published in prestigious journals. The demographics of 15 through 28 present management guidelines for women
incontinence also have stimulated corporate interest, and with stress urinary incontinence and pelvic organ prolapse.
many new drugs, products, and surgical devices for the eval- Chapters 29 and 30 outline management of complications
uation and treatment of pelvic floor disorders have been or during pelvic surgery, including problems with vaginal mesh.
are being developed. Recent popularity and increased circu- Chapters 31 through 34 address disorders of defecation.
lation of journals such as International Urogynecology Jour- Chapters 35 through 38 address the subjects of overactive
nal (Springer Publishing), Neurourology and Urodynamics bladder and painful and irritative voiding disorders, as well
(Wiley Publishing), and Female Pelvic Medicine & Recon- as their expanding list of innovative treatments. Chapters
structive Surgery (Lippincott Williams & Wilkins) under- 39 through 43 discuss specific conditions and special sub-
score the heightened level of interest among clinicians and jects that are occasionally encountered by physicians treat-
researchers. Furthermore, the expanding membership and ing patients with pelvic floor disorders. Finally, Chapter 44
attendance at annual meetings of the American Urogyne- reviews important research methods regarding outcome
cology Society (AUGS); International Continence Society analysis and quality-of-life measures in pelvic floor research.
(ICS); International Urogynecology Association (IUGA); The fourth edition has been expanded to include most
and Society of Urodynamics, Female Pelvic Medicine & topics in the “Guide to Learning in Female Pelvic Medicine
Urogenital Reconstruction (SUFU) are evidence to this and Reconstructive Surgery” (2012) jointly sponsored by
specialty’s popularity. the American Board of Obstetrics and Gynecology and the
There continues to be a widespread need for education American Board of Urology. New subjects include congeni-
and training in urogynecology and reconstructive pelvic tal anomalies of the female genital and urinary tracts, pelvic
ix
x Preface

floor and vaginal physiology, sexual function and dysfunc- from previous editions are retained, but a large number of
tion, the latest information on the use of biologic and syn- new color anatomic and surgical drawings were added.
thetic prosthesis in urogynecologic and reconstructive pelvic We hope that this book will meet the training needs of
surgery, and important concepts on research methods in residents in obstetrics and gynecology, urology, and other
pelvic floor research. Because female pelvic floor disorders specialties and can be used by fellows in Female Pelvic Med-
are best managed in a multidisciplinary fashion, recognized icine and Reconstructive Surgery as an important reference
authorities in urology, reproductive endocrinology, and text. We also hope that practicing OB/GYN generalists,
colorectal surgery have contributed chapters related to their urogynecologists, and urologists will find it interesting and
particular areas of expertise. Some of the original drawings useful as they strive to take better care of their patients.
Acknowledgments

We would like to acknowledge the indispensable and exemplary work of Beth Dobish and Lara Bodart for the huge volume
of administrative support and transcribing work involved in this book, and Joe Chovin from Cincinnati and Ross Papalardo
from Cleveland Clinic for their creation of particularly clear surgical, anatomic, and urodynamic drawings.

xi
CHAPTER 1

Historical Milestones
in Female
Pelvic Surgery,
Gynecology, and
Female Urology
Anthony P. Tizzano
Tyler M. Muffly

On the Shoulders of Giants


Chapter Outline
From the earliest days of recorded medical history, physi-
cians struggled with the problems of pelvic organ prolapse On the Shoulders of Giants
(Fig. 1.1), urinary incontinence, and vesicovaginal fistula. An
inadequate understanding of pelvic anatomy plagued practi- Gynecology in Antiquity
tioners prior to the nineteenth century. Ignorance of asepsis, Medieval Medicine
the absence of anesthesia, faulty suture materials, inad-
equate instrumentation, and suboptimal exposure delayed The Renaissance
any consistent success until the mid-nineteenth century. The Seventeenth Century
The Eighteenth Century
The Nineteenth Century Prior to the
Aseptic Age
The Mid-Nineteenth Century: The Dawn of
Aseptic Surgery
The Twentieth Century: A Specialty Evolves

The evolution of pelvic surgery from the Hippocratic


age to the antiseptic period is a fascinating one in which
original theories occasionally fell from favor only to be
resurrected and popularized by subsequent generations.
Equally intriguing is the development of a wide array of
innovative instrumentation and materials that often paral-
leled many surgical advances. This chapter is an attempt
to touch upon the milestones that occurred along the
way and to pay homage to the pioneers who helped shape
a specialty and upon whose shoulders we stand. The
author’s selection of important milestones in our specialty
up to 1961 is shown in Box 1.1. Note that this chapter
emphasizes American contributions and milestones that
influenced contemporary thought, patient care, and surgi-
cal practices. We are grateful for the works of Dr. Thomas
FIGURE 1.1 Sixteenth-century woodcut showing examination of Baskett, Dr. James V. Ricci, and, particularly, to Dr. Harold
women with uterine prolapse. (From Stromayr C. Die Handschrift des Speert, whose extensive research on the subject made this
Schnitt-und Augenarzles Caspar Stromayr, Lindau Munscript, 1559.) chapter possible.
3
4 PART 1 History

Box 1.1  Timeline of Milestones Related to Pelvic Surgery and Female Urology
Second half first century CE  Soranus (De Morbis Mulierum) first good description of the human uterus.
1561 First accurate description of the human oviduct. Observationes Anatomicae by Gabriele Falloppio.
1672 First accurate account of the female reproductive organs and ovarian follicles (“Graafian follicles”) De mulierum Organis
Generationi inservientibus by Reinier de Graaf.
1677 Description of the vulvovaginal glands, “Bartholin glands.” De Ovariis Mulierum by Caspar Bartholin.
1691 Description of the female inguinal canal. Adenographia by Anton Nuck
1705 Francois Poupart describes the inguinal ligament and its function.
1727 Jacques Garengeot modifies a trivalve speculum to better differentiate “vaginal hernias” during pelvic examination.
1737 Description of the peritoneum and posterior cul-de-sac. A Description of the Peritoneum by James Douglas.
1759 Description of the embryonic mesonephros or “Wolffian body and duct.” Theoria Generationis by Caspar Friedrich Wolff.
1774 William Hunter completes his monumental work, Anatomy of the Gravid Uterus, which remains the finest work on uterine
anatomy to date.
1801 Joseph Claude Récamier popularizes the use of a tubular vaginal speculum to treat ulcers and infections of the vagina and
cervix.
1803 Pieter Camper describes the superficial layer of abdominal fascia.
1804 Astley Paston Cooper describes the ligamentous covering of the pubis and its condensation above the linea ileopectinea as it
extends from the pubis outwards.
1809 Ovariotomy performed by Ephraim McDowell.
1813 Conrad Johann Martin Langenbeck carries out the first planned and successful vaginal hysterectomy.
1825 Marie Anne Victoire Boivin devises the bivalve vaginal speculum.
1836 Charles Pierre Denonvilliers describes the rectovesical fascia.
1838 John Peter Mettauer uses lead sutures to perform the first surgical correction of vesicovaginal fistula in the United States.
1849 Anders Adolf Retzius describes prevesical space.
1852 James Marion Sims describes his knee-chest positioning of patients for vesicovaginal fistula repair.
1860 Hugh Lenox Hodge details the use of his pessary to correct for uterine displacement.
1877 Léon Le Fort describes his method of partial colpocleisis as a simple and safe means for treatment of uterine prolapse.
1877 Max Nitze introduces an electrically illuminated cystoscope.
1878 T. W. Graves designs a speculum that combines features of both bivalve and Sims specula.
1879 Alfred Hegar introduces his metal cervical dilator to replace laminaria.
1888 Archibald Donald and William Fothergill collaborate to develop the Manchester procedure for uterine prolapse.
1890 Friedrich Trendelenburg describes his technique for positioning patients to facilitate the transvesical approach in the repair of
vesicovaginal fistula.
1893 Howard Atwood Kelly devises the air cystoscope for inspection of the bladder and identification and catheterization of the
ureters.
1895 Alwin Mackenrodt provides a comprehensive and accurate description of the pelvic connective tissue and correlation with
pelvic prolapse.
1898 Ernst Wertheim performs radical hysterectomy for cervical cancer.
1899 Thomas James Watkins performs his “interposition” operation for treatment of uterine prolapse associated with cystocele. Thus,
the uterus is brought forth through an anterior colpotomy incision and sutured to the anterior vaginal wall and the cervix
secured posteriorly. The markedly anteverted uterus essentially pivots on twisted broad ligaments thus producing antagonistic
forces, because any dropping of the bladder increases the anterior displacement of the uterus and any prolapse of the uterus
elevates the cystocele.
1900 David Todd Gilliam describes his method of uterine ventrosuspension whereby he ligated the proximal round ligament and
attached it to the anterior rectus sheath lateral to the rectus muscle.
1900 Hermann Johannes Pfannenstiel introduces a transverse incision for laparotomy.
1901 Alfred Ernest Maylard advocated oblique transection of the rectus muscles to improve exposure.
1901 John Clarence Webster and John Baldy introduce their suspension technique for correction of uterine retroversion whereby the
proximal round ligament is brought under an opening made under the utero-ovarian ligament and ultimately secured at just
above the uterosacral ligament.
1909 George Reeves White notes that certain cases of cystocele are due to lateral, paravaginal defects and thus could be repaired by
reconnecting the vagina to the “white line” of the pelvic fascia.
1910 Max Montgomery Madlener introduces a popular female sterilization technique employing ligation of the tube alone.
1911 Max Brödel becomes head of the world’s first department of medical illustration at The Johns Hopkins University.
1912 Alexis Victor Moschcowitz describes the passage of silk sutures around the cul-de-sac of Douglas to prevent prolapse of the
rectum.
1913 Howard Atwood Kelly describes the Kelly plication stitch, a horizontal mattress stitch placed at the urethrovesical junction to
plicate the pubocervical fascia and “reunite the sphincter muscle.”
1914 Wilhelm Latzko describes a technique for vaginal closure of vesicovaginal fistula following hysterectomy.
1915 Arnold Sturmdorf introduces his tracheloplasty technique.
1917 W. Stoeckle is the first to successfully combine a fascial sling and sphincter plication for treatment of urinary stress
incontinence.
1929 Ralph Hayward Pomeroy devises a method of female sterilization involving ligation and resection of the tube.
CHAPTER 1  Historical Milestones in Female Pelvic Surgery, Gynecology, and Female Urology 5

Box 1.1  Timeline of Milestones Related to Pelvic Surgery and Female Urology (Continued)
1940 Noble Sproat Heaney describes his technique for vaginal hysterectomy using a clamp, needle holder, and retractor of his
own design. His method for closing the vaginal cuff that incorporates peritoneum, vessels, and ligaments is known as the
“Heaney stitch.”
1941 Leonid Sergius Cherney suggests a modified low transverse abdominal incision, whereby the rectus muscle is cut at its very
insertion into the pubis to provide better access to the space of Retzius.
1941 Raoul Palmer popularizes the use of the laparoscope in gynecology.
1942 Albert H. Aldridge reports on rectus fascia transplantation as a sling for relief of urinary stress incontinence.
1946 Richard W. Te Linde continues the Johns Hopkins legacy in gynecology with the introduction of his text Operative Gynecology.
1948 Arnold Henry Kegel describes his progressive resistance exercise to promote functional restoration of the pelvic floor and
perineal muscles.
1949 Victor Marshall, with Marchetti and Krantz, describes retropubic vesicourethral suspension for stress urinary incontinence.
1957 Milton L. McCall describes his posterior culdoplasty to prevent or treat enterocele formation at vaginal hysterectomy.
1961 John Christopher Burch introduces his method of urethrovaginal fixation for treatment of stress urinary incontinence.

Gynecology in Antiquity The Renaissance


Gynecology in antiquity finds its roots in the Ebers papy- The Renaissance period was marked by the rebirth of indi-
rus (1500 BCE) that portrayed the uterus as a wandering vidualism and the release from the ban of authority. The rise
animal, usually a tortoise, newt, or crocodile, capable of of universities, the printing press, and the subsequent emer-
movement within its host. Hippocrates perpetuated this gence of self-education elevated medicine to the next level
animalistic concept, stating that the uterus often went and provided for a clearer understanding of female anatomy.
wild when deprived of male semen. He provided the earli- Leonardo da Vinci (1452–1519), founder of iconographic
est description of a pessary employing a pomegranate to and physiologic anatomy, provided the basis for modern ana-
reduce uterine prolapse and used catheters fashioned from tomic illustration. His illustrations of female pelvic anatomy
tin and lead to irrigate and drain the uterus. The seven cells provide the earliest accurate descriptions of the fetus in
doctrine of the Common Era (CE) replaced the animalistic utero. Unfortunately, his sketches were seen by only a few
concept, depicting the uterine cavity as being divided into of his contemporaries and were not published until the end
seven compartments whereby male embryos developed on of the nineteenth century.
the right, females on the left, and hermaphrodites in the The first authenticated report of vaginal hysterectomy
center. Similar notions remained popular until the Middle was given by Giacomo Berengario da Capri (1470–1550)
Ages. Soranus of Ephesus (98–138 CE) is commonly con- in 1521. He described two cases: one that he performed in
sidered the foremost gynecologic authority of antiquity. 1507 and the other performed by his father. Ambrose Paré
He described the uterus based on human dissection and (1510–1590), a renowned military surgeon of the period,
performed hysterectomy for uterine prolapse. His writings was the first to introduce vascular ligatures for hemosta-
provided the foundation for gynecologic texts up to the sis in place of cautery. However, the use of ligatures was
seventeenth century. not popularized until Sir Joseph Lister (1827–1912) intro-
The ancients employed instruments fashioned from tin, duced a longer-lasting aseptic suture in the mid-nineteenth
iron, steel, lead, copper, bronze, wood, and horn. Those century.
made of iron and steel were likely quite popular, but very Andreas Vesalius (1514–1564) commissioned Jan Stephan
few survived the oxidation of more than two millennia. van Kalkar to produce the most famous anatomic illustra-
Gynecologic instruments including forceps, catheters, scal- tions of all time, revolutionizing the science of anatomy and
pels, as well as massive bivalve, trivalve, and quadrivalve the manner in which it was taught. Among the first to suc-
vaginal specula from the first century BCE were unearthed cessfully challenge the teachings of Galen of Pergamon, he
at Pompeii. asserted that the physician, to learn his art, must perform
cadaver dissection firsthand. Hence, Vesalius made human
dissection a viable and respectable profession. His illustra-
Medieval Medicine tions provided an accurate description of the entire female
The Dark Ages and Medieval Period (476–1453 CE), from urogenital tract and its vasculature, depicting for the first
the fall of Rome to the Goths to the fall of Constantinople time the left ovarian vein entering the left renal vein. Dis-
to the Turks, is often referred to as the “Age of Faith” or “Era tinguished pupils of Vesalius include Gabriele Falloppio
of Monastic Medicine” in which confidence in any one indi- (1523–1562) who provided the earliest accurate descrip-
vidual was replaced by divine trust. As such, Saint Benedict, tion of the human oviduct and who described the clitoris
founder of the Benedictine Order, encouraged his monks as a vasomuscular structure. Another pupil was Matthaeus
to tend to the sick but forbade any formal study of medi- Realdus Columbus (1484–1559) who is credited with the
cine. The struggle against leprosy, plagues, and prostitution earliest use of the term labia, which he considered essential
were the focus of the day, and little was added to the fund in protecting the uterus from dust, cold, and air. Lastly, his
of medical knowledge. Little surgery took place during the student Bartolomeo Eustachio (1520–1574) furnished the
period, and the majority of physicians were itinerant practi- earliest accurate delineation of the uterine cavity and cervi-
tioners, many of whom were quacks and charlatans. cal canal.
6 PART 1 History

Among the more comprehensive accounts of sixteenth numerous notable contributions were made in the fields of
century gynecologic surgery is Caspar Stromayr’s Prac- natural philosophy including microscopy, physics, and biol-
tica Copiosa that contains beautifully executed watercolors ogy. Surgery during the century began to rise above the skills
depicting diseases of women. Included are illustrations of of an individual surgeon with the founding of surgical soci-
the examination of uterine prolapse and placement of a pes- eties and the publishing of various medical journals. Phy-
sary comprising a sponge bound by twine, sealed with wax, sicians, however, remained under close public scrutiny at
and dipped in butter (Figs. 1.2 and 1.3). Despite the many the hands of popular medical caricaturists such as Thomas
advances regarding pelvic anatomy during the Renaissance, Rowlandson (1756–1827). Many outstanding contributions
the approach to most gynecologic problems changed very were made toward the understanding of pelvic anatomy dur-
little from that which was popular during the classical period. ing the period. In 1737, James Douglas (1675–1742) gave
the first adequate description of the peritoneum, which
helped pave the way to retroperitoneal surgery and the
The Seventeenth Century concomitant decrease in peritonitis that typically plagued
Throughout the seventeenth century, theories regarding
physiology, generation, and anatomy were clarified. Rei-
nier de Graaf (1641–1673) described ovarian follicles and
uterine fibroids and provided the first accurate account of
the ovary’s gross morphology, anatomic relations, and func-
tion. Pelvic surgery and instruments of the period are nicely
portrayed by the engravings of Johannes Scultetus (1595–
1645) in his Armamentarium Chururgicum. He was the
first to employ a series of illustrations to provide a stepwise
account of surgical procedures (see Fig. 1.4). Included are
examples of treatment of imperforate hymen, hematocol-
pos, clitoral hypertrophy, and the use of a T-binder following
vaginal surgery.

The Eighteenth Century


The eighteenth century is best characterized by the con-
stant conflict that occurred between old and new ideas. As
such, relatively few advances occurred in medicine while

FIGURE 1.3 Sixteenth-century woodcut showing a pessary fash-


ioned from a sponge, bound by twine, covered in wax, and dipped
in butter before placement. (From Stromayr C. Die Handschrift des
Schnitt-und Augenarzles Caspar Stromayr, Lindau Munscript, 1559.)

FIGURE 1.2 Sixteenth-century woodcut depicting placement of a FIGURE 1.4  Seventeenth-century woodcut illustrating incision and
pessary to treat uterine prolapse. (From Stromayr C. Die Handschrift drainage of a hematocolpos. (From Scultetus J. Armamentarium
des Schnitt-und Augenarzles Caspar Stromayr, Lindau Munscript, 1559.) Chirurgicum, Ulmae Suevorum, Balthasari, 1655.)
CHAPTER 1  Historical Milestones in Female Pelvic Surgery, Gynecology, and Female Urology 7

abdominal procedures of the day. Later, in 1774, William an acceptable result did not appear until a year later when
Hunter (1718–1783) completed his monumental work, George A. Hayward (1791–1863), unaware of Mettauer’s
Anatomy of the Gravid Uterus. Thanks to the artistic talent success and using silk for his repair, performed eight opera-
of Jan van Rymsdyk, many regard this work as the finest tions at the Massachusetts General Hospital, which resulted
anatomic atlas ever produced, as Choulant stated, “Anatom- in only two cures. Mettauer is also credited with the intro-
ically exact and artistically perfect.” Vaginal specula contin- duction of metallic suture and a retention catheter.
ued to evolve with a modification in 1727 by René-Jacques Surgical instruments manufactured during the presep-
Croissant de Garengeot (1688–1759) who devised blades tic era, which finally came to a close around 1890, were
with a distinctly concave surface. de Garengeot used the nothing short of extraordinary in terms of variety and
speculum for vaginal examinations and to differentiate the beauty. “Surgical instruments made before 1890 exhib-
various “vaginal hernia” (presumably pelvic organ prolapse) ited standards of workmanship, fit, finish and overall art-
as Ricci described (Fig. 1.5). istry that were later sacrificed in the production of aseptic
instruments. Moreover, instruments of the earlier period
The Nineteenth Century Prior frequently incorporated rare and beautiful materials in
their design, including ebony, tortoise shell, ivory, agate,
to the Aseptic Age gold and silver” per Edmonson (1997). Among the most
Before the nineteenth century, surgical attempts at managing notable examples was the vaginal speculum that contin-
uterine prolapse and cervical disease were, for the most part, ued to evolve with literally hundreds of modifications by
limited to amputation of the cervix. In 1813, Conrad Lan- inventors in an attempt to enhance exposure. The manu-
genbeck (1776–1851) performed the first planned and suc- facturer Charrière introduced a novel form designed for
cessful vaginal hysterectomy. Moreover, he did so alone and use as a bivalve, tri-blade, or four-blade speculum (Fig. 1.7)
without the benefit of anesthesia. As Baskett (1996) noted, in 1838. The more familiar “duckbill” design, still used by
“At one point Langenbeck was left clutching the bleeding clinicians today, was initially put forth by Edward Gabriel
area in one hand and holding one end of the ligature in his Cusco in 1870. However, the most popular speculum
teeth while tying the other end with his right hand.” currently in use was designed by T. W. Graves, a general
In America during the first half of the nineteenth cen- practitioner from Massachusetts, and was introduced more
tury, prior to the aseptic age, physicians made several than a century ago in 1878.
advances. Ephraim McDowell (1771–1830) performed In 1845, Sims began a series of surgical experiments on his
an ovariotomy in 1809; William Potts Dewees (1768– now legendary slaves, Anarcha, Betsy and Lucy, who suffered
1841) published the first American textbook on gynecol- from vesicovaginal fistulas. After nearly 40 fruitless attempts
ogy in 1826; and James Marion Sims (1813–1883; shown at fistula repair, over the course of six years Sims finally
in Fig. 1.6) described the treatment of vesicovaginal fistula in
1838. The first successful operation for vesicovaginal fistula
employed lead suture and is believed to have been performed
by a Virginia gynecologist, John Peter Mettauer (1787–1875),
in August of 1838. However, the first published report of

FIGURE 1.5  Eighteenth-century vaginal speculum used to differenti- FIGURE 1.6  James Marion Sims (1813–1883). (From Clinical Notes
ate the various “vaginal hernias.” on Uterine Surgery. London; 1866.)
8 PART 1 History

FIGURE 1.7  Four-valve vaginal speculum with detachable blades by


Charrière, c.1850, private collection.

succeeded. His triumph was due in part to his use of silver


sutures and the exposure afforded him by a speculum of his
own design employed with the patient in his knee-chest posi-
FIGURE 1.8 Sims knee-chest position. (From Bourgery JM. Traité
tion. Sims originally reported on his technique in January of
Complet de L’Anatomie de L’Homme Comprenant la Médicine
1852 and then more formally in Silver Sutures in Surgery, Opératoire. Paris: Guerin; 1866–1868.)
his 1857 discourse before the New York Academy of Medi-
cine. An immodest man, Sims declared, “silver as a suture is
the greatest surgical achievement of the century.” In a subse- entire realm of medicine. For more than two millennia,
quent narrative, Sims described the events surrounding his therapy was primarily medical, and in less than half a cen-
conception of the “Sims knee-chest position” (Fig. 1.8): tury, it became surgical and spectacular.
The rapidly increasing frequency of successful surgery
Full of thought I hurried home and the patient (with was made possible by the advent of adequate anesthesia in
the vesicovaginal fistula) was placed in the position 1846, Joseph Lister’s treatise on asepsis in 1867, and his
described, with an assistant on each side too elevate and introduction of aseptic suture (silk soaked in carbolic acid)
retract the nates. I cannot, nor is it needful to describe in 1869. The extraordinary range of pelvic surgical tech-
my emotions, when the air rushed in and dilated the niques performed before the last quarter of the nineteenth
vagina to its greatest capacity, whereby its whole surface century is beautifully illustrated in Jean-Baptiste Marc
was seen at one view, for the first time by any mortal Bourgery and Nicolas Henri Jacob’s magnificent Traité complet
man. With this sudden flash of light, with the fistulous de l’anatomie de l’homme comprenant la médicine opératoire
opening seen in its proper relations, all the principles of 1831–1854. “In the entire literature of medicine during the
the operation were presented to my mind… and thus, nineteenth century there is nothing that compares with the
in a moment, in the twinkling of an eye, new hopes and 749 hand-colored folio-sized lithographs, nearly all of which
aspirations filled my soul, for a flood of dazzling light had are in the very realistic style of Nicolas Jacob,” as stated
suddenly burst upon my enraptured vision, and I saw in in Roberts and Tomlinson’s Fabric of the Body. Figure 1.9
the distance the great and glories triumph that awaited shows an example of Bourgery’s work illustrating Sims’s
determined and persevering effort. I thought only of reliev- operation for vesicovaginal fistula.
ing the loveliest of all God’s creations of one of the most The latter half of the century is marked by many note-
loathsome maladies that can possibly befall poor human worthy contributions to pelvic surgery and an improved
nature… Full of sympathy and enthusiasm, I found myself understanding of pelvic anatomy. Anders Adolf Retzius
running headlong after the very class of sufferers that I (1796–1860) defined the boundaries of the prevesical space
had all of my professional life most studiously avoided. in 1849. In 1877, Léon Clément Le Fort (1829–1893)
described his procedure for partial colpocleisis, which con-
Although one may argue that Sims was not the first to tinues to provide a simple and safe way to manage uterine
employ silver sutures in surgical repairs, most will concede prolapse in the high-risk patient. Alwin Mackenrodt (1859–
that he was the first to combine the essentials for cure and 1925) elegantly described the cause and cure of uterine pro-
thus popularize one of the first major innovations in pelvic lapse in 1895 and put forth an accurate description of the
surgery. Within the same decade, Washington Lemuel Atlee pelvic connective tissue including the transverse cervical or
performed a myomectomy in 1844 and Walter Burnham con- cardinal ligaments (Mackenrodt’s ligaments; Fig. 1.10).
ducted the first successful abdominal hysterectomy in 1853. Soon thereafter, Archibald Donald (1840–1908) and
William Fothergill (1806–1879) developed the Manchester
The Mid-Nineteenth Century: The Dawn operation, uniting parametric and paravaginal tissues to one
another and with the cervix anteriorly to effectively counter
of Aseptic Surgery uterine prolapse. The procedure, named after their home-
During the second half of the nineteenth century, the req- town, became the first widely used procedure for uterovagi-
uisites for advancement of surgery began to fall into place. nal prolapse. Due to a high birth rate and the large workforce
These included adequate anesthesia, antisepsis, and accept- performing the manual labor of sheep shearing outside Man-
able suture materials. Throughout the latter half of the cen- chester, England, there was no shortage of young women with
tury, the evolution of pelvic surgery gained momentum, as pelvic organ prolapse. Rather than use a pessary, Donald pri-
advances in gynecologic therapy were unparalleled in the marily resuspended the uterus with a plication of the cardinal
CHAPTER 1  Historical Milestones in Female Pelvic Surgery, Gynecology, and Female Urology 9

A B

C
FIGURE 1.9  A series of watercolor lithographs depicting Sims’s operation for vesicovaginal fistula. A, Trimming the edge of vesicovaginal
fistula (note silver catheter in place). B, Placement of silver sutures. C, Completed closure of fistula. (From Bourgery JM. Traité Complet de
L’Anatomie de L’Homme Comprenant la Médicine Opératoire. Paris: Guerin; 1866–1868.)
10 PART 1 History

U.Rd.d lig.
truasp.coll lig.sa.-ut

Fasr pelv ni.


Hafd.d.lig.
lig.transadert coll.
lat.corp.

Corp.ut.

Uebg.d.sept.-i
Fasc.pl.
Symph. FIGURE 1.10 An illustration of the
Sept.rerl. cardinal ligaments in a fetus of
Sept.ves.vag. eight months. (From Mackenrodt A.
Uber die Ursachen der normalen und
Vag.wd.
Vag.wd. pathologischen Lagen des Uterus.
Arch Gynakol. 1895; 48:394.

ligaments. He performed amputation of the cervix as needed, through an anterior colpotomy incision, Watkins brought
suture plication of the cardinal ligaments in front of the cervix the uterus forward such that the bladder rests on the pos-
to elevate the cervix, anterior colporrhaphy with wide lateral terior wall of the uterus, thereby elevating the lower uter-
exposure, and posterior colporrhaphy (see Fig. 1.11A–D). ine segment and creating antagonistic forces between the
Donald emphasized that the key to restoring anatomy was prolapsing bladder and uterus. During the same year, Ernst
“that the raw surface, anterior or posterior, or in exceptional Wertheim (1864–1920) introduced and ultimately popular-
cases, both, must be high, wide, and deep, and that the deep ized radical hysterectomy to the extent that the procedure
tissues, triangular ligament, or levator ani muscles must be became known as the Wertheim operation.
brought together…” From an architectural point of view, Don- The popularity of pessaries flourished throughout the
ald believed in maintaining the uterus as the keystone of the latter half of the century, because practitioners were appar-
pelvic arch for vaginal support. This operation was also much ently concerned with uterine malposition (Fig. 1.12). Hugh
safer since the uterine arteries were not transected, decreas- Lenox Hodge (1796–1873) spoke for many gynecologists of
ing the risk of hemorrhage, and the cul-de-sac was not entered the era when in 1860 he stated:
to decrease the risk of intra-abdominal abscess or peritonitis.
In 1888, Donald and Fothergill collaborated to improve The mechanical treatment of uterine displacements by
the surgery. Fothergill felt that the severity of prolapse was intravaginal supports is essential, a “sine qua non”, for
related to failure of the parametria, which we know today their perfect relief; that by pessaries, of suitable material,
as the cardinal ligaments. He felt that vaginal surgery would size and form, the uterus may very generally be replaced
be ideal to “alter the attachment of prolapse… in such a and be maintained in situ; that the local symptoms of
way as to ‘take up the slack’ in some degree.” Fothergill was weight, pain, etc., the leucorrhea, the menorrhagia,
a proponent for trachelectomy in all patients with cervical the dysmenorrhea, and all the innumerable direct and
elongation “more than three inches in length.” The cardi- indirect symptoms of spinal and cerebral irritation,
nal ligaments were plicated using “deep buried stitches” of including neuralgia, nervous headache, nervous affec-
silver suture at first, and then chromic catgut, after Don- tions of the larynx, lungs, heart, stomach, bowels, etc., as
ald visited German physicians who preferred the handling also spasms, cramps, and convulsions, may often thus be
of the biologic suture materials. Donald made a separate dissipated; that the intellectual and spiritual being may
diamond-shaped incision for the anterior colporrhaphy with be elevated from the lowest states of depression, border-
the base of the triangle at the cervix. Fothergill joined the ing on melancholy, or delivered from the highest degree
colporrhaphy and trachelectomy incisions, extending the of maniacal excitement. Patients often are amazed at
repair posteriorly for improved exposure of the levator their own altered sensations; they can hardly realize their
myorrhaphy shelf where the uterus sits. identity–feeling as if they were either renovated, or that
Thomas J. Watkins proposed a novel approach to uter- they had been transported to a “new world.”
ine prolapse and cystocele reduction by using the uterus
as a prosthesis. He introduced his interposition operation Among the most important diagnostic and operative inno-
in 1898, contending that it was ill advised to remove the vations of the century occurred in 1877 when Maximilian
uterus in any case of prolapse unless it was diseased. Thus, Nitze (1848–1906) introduced an electrically illuminated
CHAPTER 1  Historical Milestones in Female Pelvic Surgery, Gynecology, and Female Urology 11

A B

C D
FIGURE 1.11  Manchester operation for uterine prolapse and cystocele. A, Bladder has been dissected up from cervix. Incision has been carried
through mucosa around cervix and mucosa dissected free from cervix. Bases of broad ligaments are thus exposed. The left has been clamped
and cut. Dotted line indicates where cervix is to be amputated. B, Cervix has been amputated and posterior lip covered with flap of mucosa.
The bases of the broad ligaments have been sutured to the anterior surface of the cervix. C, Pubovesicocervical fascia is being approximated
in the midline beneath the urethra, base of the bladder and the cervix. Note that the lower sutures bite into the anterior wall of cervix.
D, Operation on anterior wall has been completed. It is to be followed by a posterior colporrhaphy. (From Te Linde RW. Operative Gynecology.
1st ed. Philadelphia: Lippincott; 1946:116–117, Figure 55, with permission.)

cystoscope. This made possible great improvements in sur- The instrument apparently fell to the floor, breaking the glass
gery including excision of bladder tumors in situ, which Nitze diaphragm. Kelly reintroduced the cystoscope into the blad-
details in his important monograph on cystoscopy in 1889. der without its glass diaphragm and the bladder immediately
Shortly afterwards, in 1893, Howard Atwood Kelly (1858– distended with air, permitting visualization of its interior and
1943; Fig. 1.13) introduced his air cystoscope and published ureteric orifices. Kelly’s two-volume Operative Gynecology
a bulletin on aeroscopic examination of the female bladder (Appleton and Co., 1898), Medical Gynecology (Appleton and
and the catheterization of the ureters under direct inspection Co., 1908), and Diseases of the Kidneys, Ureters, and Bladder
(Figs. 1.14 and 1.15). His innovation occurred in part by acci- (with Burnam, 1914), the latter distinguished by the great
dent while using a water cystoscope in the knee-chest position. illustrations by the German artist Max Brödel (1870–1941),
12 PART 1 History

Retro pubic
Vertex

Right cornu
Sacral area

Base

FIGURE 1.14  Various positions that air cystoscope may take to illu-
minate all parts of the bladder. (From Kelly HA, Burnam CS. Diseases
of the Kidneys, Ureters, and Bladder. Vol. 1. New York: D. Appleton &
Co.; 1914:262, Figure 135, with permission.)

FIGURE 1.12 Various nineteenth-century pessaries. (From Bourgery


JM. Traité Complet de L’Anatomie de L’Homme Comprenant la
Médicine Opératoire. Paris: Guerin; 1866–1868.)

FIGURE 1.15 Beginning catheterization of the left ureter in knee-


chest posture through an open-air cystoscope. (From Kelly HA, Bur-
nam CS. Diseases of the Kidneys, Ureters, and Bladder. Vol. 1. New
York: D. Appleton & Co.; 1914:269, Figure 141, with permission.)

William Osler (1849–1919), addressing the Johns Hop-


kins Historical Club in January 1901, reflected on the accom-
plishments of medicine in the nineteenth century stating,

In the fullness of time, long expected, long delayed,


at last Science emptied upon him from the horn of
Amalthea blessings which cannot be enumerated, bless-
ings which have made the century forever memorable;
and which have followed each other with a rapidity so
bewildering that we know not what to expect next…
Measure as we may the progress of the world—materially,
in the advantages of steam, electricity, and other
FIGURE 1.13  Howard Atwood Kelly (1858–1943).
mechanical appliances; sociologically, in the great
improvements in the conditions of life; intellectually,
defined the specialty and laid the foundation for progress well in the diffusion of education; morally, in a possibly
into the next century. Through a thorough study of anatomy, higher standard of ethics—there is no measure which
gynecology, and surgery, Brödel revolutionized the appearance can compare with the decrease in physical suffering in
of medical literature and went on to become head of the first man, woman, and child when stricken by disease or
“Department of Art as Applied to Medicine” in the world at accident… This is the Promethean gift of the century
The Johns Hopkins University in 1911. to man.
CHAPTER 1  Historical Milestones in Female Pelvic Surgery, Gynecology, and Female Urology 13

The Twentieth Century: A Specialty The Urologic and Cutaneous Review

Evolves
The rapid evolution of technology and procedures related
to gynecology and female urology continued into the twen- P cath. G
tieth century. In 1900, David Gillman introduced round
ligament ventrosuspension of the uterus for treatment of
uterine prolapse whereby he carried the proximal round
ligament through the peritoneum just lateral to the rectus
muscle and sutured it to the posterior rectus sheath. Shortly S
thereafter, John Montgomery Baldy (1860–1934) and John
G
Clarence Webster (1863–1950) independently devised a vir- G H
tually identical operation for uterine retrodisplacement. The
Baldy-Webster uterine ventrosuspension involved plication
of redundant uterosacral ligaments to the posterior aspect
of the uterus at a point just above the uterosacral ligaments.
Hermann Johannes Pfannenstiel (1862–1909) proposed his
low transverse incision to help reduce postoperative hernias.
Frederick Foley (1891–1966) introduced a new plastic oper- G
ation for stricture at the ureteropelvic junction for treatment
of hydronephrosis. The pathogenesis of rectal prolapse as a
“H” is the head of the catheter marking the neck of
form of sliding hernia was put forth by Alexis Moschcowitz the bladder. “GGGG” are the guy sutures holding the
(1865–1933) in 1912. He devised an operation whereby silk wound open. “S” is the surface at the neck of the
sutures were passed circumferentially about the cul-de-sac bladder re-uniting the sphincter muscle.
of Douglas. Subsequently, gynecologists appropriated the FIGURE 1.16 The Kelly plication stitch for stress urinary inconti-
operation to prevent enterocele at the time of hysterectomy. nence. (From Kelly HA. Incontinence of urine in women. Urol Cutane-
Throughout the twentieth century, the evolution of uri- ous Rev. 1913; 17:291.)
nary incontinence procedures took place. In 1913, Kelly
first described his anterior plication stitch—a horizontal
mattress stitch placed at the urethrovesical junction and A New York urologist, Victor F. Marshall (1913–2001)
thereby effectively plicating the pubocervical fascia. The began to develop an operation for urinary incontinence in men
“Kelly plication stitch” as shown in Figure 1.16 resulted in during the mid-1940s. He employed a suprapubic approach
narrowing of a patulous urethra and some elevation of the to suspend the bladder and bladder neck by placement of
urethrovesical junction and was the essential component of interrupted chromic catgut sutures to the periosteum of the
anterior colporrhaphy for stress urinary incontinence. symphysis and posterior rectus sheath. Thereafter, he collab-
Although the Kelly plication was somewhat effective orated with two gynecologists, Andrew Anthony Marchetti
and popular, stress incontinence frequently recurred. Vari- (1901–1970) and Kermit Edward Krantz (1923–2007),
ous muscular and fascial sling operations were thus devised refining and modifying the procedure to treat incontinence
to treat this distressing and persistent problem. The slings in women. During the half century after its introduction, the
utilized adjacent anatomic structures with the purpose of Marshall-Marchetti-Krantz (MMK) procedure remained a
providing proper support for the urethra and of developing a standard approach to female incontinence. Necessity being
substitute muscular sphincter-like action to replace the one the mother of invention gave rise to a modification of the
that had been lost through birth injury. Muscle transposition MMK operation when John Christopher Burch (1900–1970)
procedures to create a sling under the urethra using rectus was unable to secure sutures into the retropubic periosteum
muscle, pyramidalis muscle, and levator ani were used in and ultimately found the support he required in Cooper’s
the early twentieth century. In 1917, Stoeckel, building on ligaments. His 1961 publication on the procedure remains
previous work by Goebell and Frangenheim, was the first one of the simplest, most widely accepted, and most studied
to combine sphincter plication and the use of a fascial sling methods of elevating the urethrovesical junction in cases of
with complete success. In 1942, A. H. Aldridge described stress urinary incontinence (Fig. 1.17).
a technique of making a transverse suprapubic incision and In 1934, Nobel Sproat Heaney (1880–1955) reported
developing bilateral strips of fascia attached at the midline. on 565 vaginal hysterectomies performed for benign dis-
Aldridge famously noted, “in such circumstances or when ease. Henceforth, he became one of the most influential
the sphincter muscles have undergone too much destruc- proponents of the procedure, praising its lower morbidity
tion, complete restoration of function by the usual vaginal and mortality compared to an abdominal approach. While
procedures can hardly be expected.” The fascial strips were developing the technique, he designed a needle holder,
brought down through the rectus muscle, behind the sym- retractor, and pedicle clamp to facilitate the procedure
physis, and united as a sling beneath the urethra. Aldridge and incorporated peritoneum, vessels, and ligaments in a
was one of the first to emphasize that much of stress incon- maneuver known as the “Heaney Stitch.”
tinence might be due to disruption from birth trauma. The The development of an enterocele subsequent to vaginal
Aldridge rectus fascia sling became the model for similar hysterectomy was addressed in 1957 by Milton Lawrence
fascial sling procedures used for recurrent stress inconti- McCall’s (1911–1963) posterior culdeplasty. The operation
nence and sphincter deficiency for the next 50 years. was performed from below by obliteration of redundant
14 PART 1 History

Urethra
Cooper's
and neck
lig.
of bladder Symphysis

Cooper’s lig.
Symph

Perivaginal
Arcus fascia
tendineus
Foley
catheter
Perivaginal Bladder
fascia Peritoneum
elevated by
finger in vagina
A B
FIGURE 1.17 Burch urethrovaginal fixation procedure. A, The suture has been passed through the perivaginal fascia and the wall of the
vagina, but not through the mucous membrane. The sutured point is now matched to that point on Cooper’s ligament to which it is most eas-
ily approximated, and the suture passed through this point and tied. B, The lateral edges of the vagina have been approximated to Cooper’s
ligament by three interrupted sutures. (From Burch JC. Urethrovaginal fixation to Cooper’s ligament for correction of stress incontinence, cystocele,
and prolapse. Am J Obstet Gynecol. 1961; 81:281, with permission.)

posterior cul-de-sac by a series of continuous sutures along In 1914, Wilhelm Latzko (1863–1945) introduced a
the length of the uterosacral ligaments. partial-colpocleisis technique for vesicovaginal fistula clo-
Operative laparoscopy was first employed in gyneco- sure following hysterectomy. By dissecting off the vaginal
logic procedures by Raoul Palmer (1905–1985) in 1943. mucosa surrounding the fistula and inverting the denuded
At a time when laparoscopy was largely the domain of sur- area with multiple layers, he effectively obliterated the fis-
geons, he established its role for evaluating infertility and tulous opening.
visualizing pelvic organs by placing the patient in the Tren- From the turn of the nineteenth century and well into
delenburg position and elevating the uterus by means of a the twentieth century, the faculty from the departments
transcervical manipulator. However, credit for devising the of obstetrics and gynecology at The Johns Hopkins Hospi-
earliest endoscope must go to Philipp Bozzini (1773–1809), tal would become a guiding force for the specialty. Among
who described his “lichltleiter” in 1806. He advocated the these leaders is Howard Atwood Kelly (1858–1943), often
inspection of all “interior cavities … by looking through regarded as the father of American gynecology due to his
natural openings or at least small wounds.” Expounding on important role in establishing gynecology as a surgical spe-
the utility of his device, Bozzini wrote, “To give an idea how cialty in America (see Fig. 1.13). For three decades, he was
distinctly the light transmitter reflects the rays, I would like chairman of gynecology at The Johns Hopkins Hospital
to cite just one example: if, observing proper cleanliness, where he established the first residency program in gynecol-
one places a piece of writing in the fundus of the uterus of a ogy, an innovation in surgical training and an important con-
woman who died during delivery, it can be read through the tribution to the development of the specialty. He was by all
vagina with the help of the light transmitter containing an measures a prolific author. By 1919, he had published 485
ordinary wax candle as clearly as by light of a candle stand- titles, of books, journal articles, and pamphlets. In 1899,
ing at the same distance on a table.” Furthermore, he cor- Kelly consented to the department’s division and delegated
rectly predicted the development of operative endoscopy, responsibility for obstetrics to John Whitridge Williams
writing, “Surgery will not only develop new and previously (1866–1931). Williams along with Kelly introduced a new
impossible procedures, but all uncertain operations which standard of scholarship into America’s obstetric and gyne-
rely on luck and approximation will become safe under the cologic literature and teaching. For three decades, Williams
influence of direct vision, since the surgeon’s hand will now exercised a near monopoly in filling the chairs of obstet-
be guided by his eyes.” Amazingly, Bozzini was formally rep- rics and gynecology at the country’s major universities. His
rimanded for his “undue curiosity” after visualizing the inte- widely popular textbook, Williams Gynecology, continues
rior of the urethra of a living patient, a reaction that repeats to bear his name under new editorship. Later, Richard Wes-
itself on many occasions throughout history as innovations ley Te Linde (1894–1989) was appointed chairman in 1939,
or new ideas are initially put forth. a post he held for 21 years. During his tenure, he played a
CHAPTER 1  Historical Milestones in Female Pelvic Surgery, Gynecology, and Female Urology 15

role in the development of fascial slings for stress incon- Langenbeck CJM. Geschichte einer von mir glucklich verichteten extirpa-
tinence in the United States and performed much of the tion der ganger gebarmutter. Biblioth Chir Ophth Hanover. 1817;1:557.
Latzko W. Behandlung hochsitzender blasen und mastdarmscheidenfisteln
preliminary work in delineating the diagnosis of and appro- nach uterusextipation mit hohem schedienverschluss. Zentbl Gynak.
priate treatment for cervical carcinoma in situ. Perhaps Te 1914;38:906.
Linde is best known for his text Operative Gynecology, Latzko W. Postoperative vesicovaginal fistulas: genesis and therapy. Am J
which was published in 1946 and was destined to be and Surg. 1942;58:211.
Le Fort L. Nouveau procédé pour la guérison du prolapsus utérin. Bull Gen
remains the standard American work on the subject under Therapie. 1877;92:337.
successive authors. Mackenrodt A. Uber die Ursachen der normalen und pathologischen Lagen
Thus, we owe a great debt of gratitude to these and many des Uterus. Arch Gynakol. 1895;48:394.
others who established the foundation for successful pel- Marshall VF, Marchetti AA, Krantz KE. The correction of stress incontinence
vic surgery and ultimately for our specialty. Perhaps Kelly, by simple vesicourethral suspension. Surg Gynecol Obstet. 1949;88:509.
McCall ML. Posterior culdeplasty: surgical correction of enterocele during
himself an avid historian and bibliophile, summarized it best vaginal hysterectomy; a preliminary report. Obstet Gynecol. 1957;10:595.
stating, “No group should ever neglect to honor the fore- McDowell E. Three cases of extirpation of diseased ovaria. Eclect Repertory
bears upon whom their contributions are based. Great is Analyst Re Phila. 1817;7:242.
the loss to anyone who neglects to study the lives of those Mettauer JP. Vesico-vaginal fistula. Boston Med Surg J. 1840;22:154.
Moschcowitz AV. The pathogenesis, anatomy and cure of prolapse of the
he follows.” rectum. Surg Gynecol Obstet. 1912;15:7.
Nitze M. Lehrbuch der kystoskopie; ihre technik und klinische bedeutung.
Bibliography Wiesbaden; 1907.
Aldridge AH. Transplantation of fascia for relief of urinary stress inconti- Palmer R. La coelioscopie gynécologique. Acad Chir. 1946;72:363.
nence. Am J Obstet Gynecol. 1942;44:398. Pare A. The Works of Ambroise Parey [Johnson TH, Trans.]. London: Clark
American Armamentarium Chirurgicum (intro by Edmonson JM, Ham- Publishing; 1678.
brecht FT), Centennial ed. George Tiemann & Company: San Francisco/ Pfannenstiel J. Uber die vortheile des wuprasymphysaren Fascienquer-
Boston; 1989. schnitts fur die Gynakologischen Koliotomein zugleich ein Beitrag zu
Baldy JM. A new operation for retrodisplacement. Am J Obstet. 1902;45:650. der Indikationsstellung der Operationswerge. Samml Klin Vortr Leipzig.
Baskett TF. Eponyms and Names in Obstetrics and Gynaecology. London, 1900;268:1753.
UK: RCOG Press; 1996. Retzius AA. Uber das ligamentum Pelvoprostaticum oder den apparat,
Bourgery JM. Traité Complet De l’Anatomie De L’ Homme Comprenant la durch welchen die Harnblasee, die Prostata und die Harnrohre an den
Médecine Opératoire. Paris: Guerin; 1866–1868. untern Beckenoffnung befestigt sind. Muller’s Arch Anat Physiol Wiss
Bush RB, Leonhardt H, Bush IM, Landes RR. Dr. Bozzini’s lichtleiter: a Med. 1849;11:182.
translation of his original article (1806). Urology. 1974;3:119. Ricci JV. The Geneaology of Gynecology: History of the Development of
Burch JC. Uretrovaginal fixation to Cooper’s ligament for correction Gynecology throughout the Ages. 2000 BC – AD 1800. Philadelphia: The
of stress incontinence, cystocele and prolapse. Am J Obstet Gynecol. Blakiston Company; 1972.
1961;81:281. Ricci JV. The Vaginal Speculum and Its Modifications Throughout the Ages.
Choulant L. History and Bibliography of Anatomic Illustration (reprint; New York: New York Medical College; 1948–1949.
originally published in 1852). New York: Hafner Publishing; 1962. Scultetus J. Arsenal de Chirurgie. Lyon: Antoine Cellier; 1653.
De Graaf R. De Mulierum Organis Generationi Inservientbus. Leyden: Schultheiss D, Udo J. Max Brödel (1870–1941) and Howard A. Kelly
Hackiana; 1672. (1858–1943) – Urogynecology and the birth of modern medical illustra-
Donald A. Operation in cases of complete prolapse. J Obstet Gynaecol Br tion. Eur J Obstet Gynecol. 1999;86:113.
Emp. 1908;13:195. Sims JY. Silver Sutures in Surgery. The Anniversary Discourse before the
Douglas J. A Description of the Peritoneum and of that Part of the Membrana New York Academy of Medicine. New York: Samuel S. and William Wood;
Cellularis Which Lies on its Outside. London: J. Roberts; 1730. 1858.
Fallopius G. Observationes Anatomicae: Marco Antonio Ulmun, Venice; Sims JY. Clinical notes on Uterine Surgery. London: Robert Hardwicke;
1561:221. 1866.
Fothergill WE. Anterior colporrhaphy and its combination with amputation Soranus’ Gynecology[Temkin O, Trans.]. Baltimore: Johns Hopkins Univer-
of the cervix as a single operation. J Obstet Gynaecol Br Emp. 1915;27:146. sity Press; 1956.
Goebell R. Zur operativen Beesitigung der Angelborenen Incontinez Vesi- Speert H. Obstetric and Gynecologic Milestones: Essays in Eponymy. New
cae. Z Gynaek Urol. 1910;2:187. York: Macmillian; 1958.
Graves TW. A new vaginal speculum. NY Med J. 1878;28:506. Speert H. Obstetrics and Gynecology in America: A History. Chicago:
Heaney NS. A report of 565 vaginal hysterectomies performed for benign ACOG; 1980.
pelvic disease. Am J Obstet Gynecol. 1934;28:751. Stoeckel W. The use of the pyramidal muscle in the surgical treatment of
Hodge HL. On Diseases Peculiar to Women, Including Displacements of the urinary incontinence. Zentralbl Gynakol. 1917;41:11.
Uterus. Philadelphia: Blanchard and Lea; 1860. Stromayr C. Die Handschrift des Schnitt-und Augenarztes Caspar Stromayr
Hunter W. The Anatomy of the Human Gravid Uterus. Birmingham, Eng- Lindau Munscript; 1559.
land: John Baskerville; 1774. Te Linde RW. Operative Gynecology. 1st ed. Philadelphia: Lippincott; 1946.
Kelly HA. The examination of the female bladder and the catheterization of Te Linde RW. The modified Goebell-Stoeckel operation for urinary incon-
the ureters under direct inspection. Bull Johns Hopkins Hosp. 1893;4:101. tinence. Southern Med J. 1934;27:193.
Kelly HA. Operative Gynecology. 2 vols. New York: D. Appleton and Co.; Watkins TJ. The treatment of cystocele and uterine prolapse after the
1898. menopause. Am J Obstet Dis Wom. 1899;15:420.
Kelly HA. Incontinence of urine in women. Urol Cutaneous Rev. Webster JC. A satisfactory operation for certain cases of retroversion of the
1913;17:291. uterus. JAMA. 1901;37:913.
Kelly HA, Burnam CS. Diseases of the Kidneys, Ureters, and Bladder. 2 vols. Wertheim E. Zur Frage der Radicaloperation beim uteruskrebs. Arch Gyn-
New York: D. Appleton and Co.; 1914. akol. 1900;61:627.
CHAPTER 2

Anatomy of the
Lower Urinary Tract,
Pelvic Floor, and
Rectum
Kevin J. Stepp
Mark D. Walters

Pelvic Anatomy Chapter Outline


Bones of the Pelvis
The bones of the pelvis are the rigid foundation to which Pelvic Anatomy
all of the pelvic structures are ultimately anchored. In the Bones of the Pelvis
standing position, forces are dispersed to minimize the pres- Pelvic Floor and Sidewalls
sures on the pelvic viscera and musculature and disperse the Abdominal Wall
forces to the bones that are better suited to the long-term, Nerves of the Pelvis
cumulative stress of daily life. In the upright position, the
pubic rami are oriented in an almost vertical plane. Simi- Uterus and Ovaries
lar to the supports of an archway or bridge, the weight of Vagina
the woman is transmitted along these bony supports to Perineum
her femurs. Where the pubic rami articulate in the mid- Bladder
line, they are nearly horizontal. Much of the weight of the Trigone
abdominal and pelvic viscera is inferiorly supported by the
Urethra
bony articulation.
The pelvic bones are the ilium, ischium, pubic rami, Pelvic Ureter
sacrum, and coccyx (Fig. 2.1A and B). The sacrum is com- Transobturator Anatomy
posed of five sacral vertebrae that are fused together. The Rectum and Anal Sphincters
nerve foramina are positioned anterior and laterally. Overly-
Pelvic Organ Support
ing the middle of the sacrum is a rich neurovascular bed.
The coccyx is inferiorly attached and is the posterior border Support of the Uterus and Vagina
of the pelvic outlet. Urethral Support
Several landmarks are important to the pelvic surgeon.
The anterior superior iliac spine (ASIS) is easily identifiable
and is anterior and laterally located on the superior ileum.
The ischium is fused to the ilium. The medial surface of The ischial spine can be palpated easily through a vaginal,
the ilium forms the lateral borders of the pelvic outlet. rectal, or retropubic approach, and many supportive struc-
The superior greater sciatic notch and inferior lesser sciatic tures attach to it. The ischial spine is useful as a fixed point
notch are medially separated by a projection, the ischial to describe the relative position of other anatomic struc-
spine. The sacrospinous ligament, triangular in form, is lat- tures and as a landmark in various reconstructive surgeries
erally attached by its apex to the ischial spine; its broader for pelvic organ prolapse.
base arises from the side of the lower sacral and coccygeal The superior and inferior pubic rami are anteriorly
segments. This ligament converts the greater sciatic notch located and articulate in the midline at the pubic symphysis.
into the greater sciatic foramen (see Fig. 2.1B). Through The ridge along the superior, medial surface of the superior
this foramen pass the piriformis muscle and all of the ves- pubic rami is called the pectineal line, or Cooper’s ligament
sels and nerves that leave the pelvis for the gluteal region (see also Figs 21.2 and 21.3).
and back of the thigh. The sacrospinous ligament and the In the standing position, the ASIS and pubic symphysis
dorsal sacrotuberous ligament also convert the lesser sciatic are in the same vertical plane (Fig. 2.1B). This directs the
notch to the lesser sciatic foramen. Through this foramen pressure of the intra-abdominal and pelvic contents toward
pass the tendon and nerve of the internal obturator muscle, the bones of the pelvis instead of the muscles and endopelvic
the pudendal nerve, and the internal pudendal vessels. fascia attachments of the pelvic floor. The posterior surface of
19
20 PART 2  Basic Science

Anterior
Inferior Pubic superior
pubic ramus symphysis iliac spine
Anterior
Acetabulum superior Sacral
iliac spine promontory
Ischial Greater
tuberosity sciatic
Ischial foramen
Sacral spine
promontory
Sacrospinous
Sacrotuberous ligament
ligament Lesser
Sacrotuberous sciatic
ligament (cut) foramen
Sacrospinous
ligament
Sacrotuberous
Obturator
ligament
Coccyx foramen
Sacrospinous Ischial
A ligament B tuberosity
FIGURE 2.1  A, Bones and ligaments of the pelvis. Lithotomy view shows the relationships of the ligaments to the pelvic outlet and bony struc-
tures. B, Bones and ligaments of the pelvis. Sagittal view shows the nearly vertical distribution of weight (arrows) toward the pubic symphysis.
The ischial spine is at approximately the level of the pubic symphysis.

the pubic symphysis is located in a plane approximately 2 to levator ani. The levator ani muscle complex consists of the
3 cm inferior to the ischial spine. Therefore, a line drawn puborectalis, pubococcygeus, and iliococcygeus muscles
connecting the two structures would be almost horizontal as classically described by Woodburne (1976) and Net-
in the standing position. This has important implications for ter (1997) (Fig. 2.2). The more medial puborectalis arises
the support of pelvic organs, and it will be discussed later from the posterior inferior pubic rami and passes posteri-
in the chapter. orly forming a sling around the vagina, rectum, and perineal
body to form the anorectal angle and contribute to fecal
continence. Some of the fibers of the muscle blend with the
Pelvic Floor and Sidewalls
muscularis of the vagina, perineal body, and anal canal and
The obturator internus and piriformis make up the pelvic intermingle with the anal sphincter muscle. The pubococ-
sidewalls (Fig. 2.2). The obturator membrane is a fibrous cygeus has a similar origin, but it inserts in the midline onto
membrane that covers the obturator foramen. The obtura- the anococcygeal raphe and the anterolateral borders of the
tor internus muscle lies on the superior (intrapelvic) side of coccyx. The iliococcygeus extends along the arcus tendineus
the obturator membrane. The obturator internus origin is levator ani from the pubis to the ischial spine to insert in the
on the inferior margin of the superior pubic ramus and the midline onto the anococcygeal raphe and coccyx.
pelvic surface of the obturator membrane. Its tendon passes Changes in the terminology of the levator ani muscle have
through the lesser sciatic foramen to insert onto the greater more recently been proposed to be more in line with the ori-
trochanter of the femur to laterally rotate the thigh. The gin and insertion of the various components (Kearney et al.,
obturator internus receives its innervation from the obtura- 2004). The pubovisceral muscle encompasses all levator mus-
tor nerve originating from L5-S2. The obturator vessels and cles medial to the ileococcygeus. It is the thick U-shaped
nerve pass through the anterior and lateral border of the muscle that arises from the pubic bone on each side of the
obturator membrane, in the obturator canal, to their desti- midline and inserts into, or forms a sling around, the urethra,
nation in the adductor compartment of the leg. vagina, and rectum. On the basis of specific insertion points,
The piriformis is part of the pelvic sidewall and is located segments of the pubovisceral muscle include the puboperi-
dorsal and lateral to the coccygeus. It extends from the nealis, pubovaginalis, and puboanalis. The puborectalis origi-
anterolateral sacrum to pass through the greater sciatic fora- nates from the pubic bone and forms a sling dorsal to the
men and insert onto the greater trochanter. Lying on top of anorectal angle, just cranial to the external anal sphincter.
the piriformis is a particularly large neurovascular plexus, The coccygeus, although not part of the levator ani,
the lumbosacral plexus. does make up the posterior part of the pelvic floor, and it
There is a linear thickening of the fascial covering of the plays a role in support. Its origin is on the ischial spine and
obturator internus muscle called the arcus tendineus levator sacrospinous ligament. It inserts on the lateral lower sacrum
ani. This thickened fascia forms an identifiable line from and coccyx, and it overlies the sacrospinous ligament. The
the ischial spine to the posterior surface of the ipsilateral muscle becomes thin and fibrous with age. The coccygeus
superior pubic ramus. The muscles of the levator ani origi- often blends with the sacrospinous ligament, and it can be
nate from this musculofascial attachment. difficult to distinguish the two because they have the same
The pelvic diaphragm is defined as the levator ani mus- origin and insertion.
cles and the coccygeus muscle. It is stretched hammock-like The space between the levator ani musculature through
between the pubis in front and the coccyx behind, and it is which the urethra, vagina, and rectum pass is called the
attached along the lateral pelvic walls to the arcus tendineus levator (genital) hiatus. The fusion of levator ani where they
CHAPTER 2  Anatomy of the Lower Urinary Tract, Pelvic Floor, and Rectum 21

FIGURE 2.2  The relationships of the muscles of the pelvic floor and sidewalls and their attachments from an abdominal view. The arcus ten-
dineus fasciae pelvis has been removed on the left, showing the origins of the levator ani muscles. On the right, the arcus tendineus fasciae
pelvis remains intact, showing the attachment of the lateral vagina via the endopelvic fascia (cut away).

meet in the midline creates the levator plate. The levator loosely arranged collagen, elastin, and adipose tissue through
plate forms the basis for pelvic support. The levator ani may which the blood vessels, lymphatics, and nerves travel to
be very thin and attenuated, especially in elderly patients reach the pelvic organs. By surgical convention, condensa-
and those with pelvic organ prolapse. tions of the visceral endopelvic fascia of the pelvis have been
With the change from plantigrade to erect posture, the described as discrete “ligaments,” such as the cardinal or
pelvis and vertebral column of humans underwent various uterosacral ligaments. The role of the endopelvic fascia in
evolutionary changes that restored the balance between pelvic organ support will be discussed in detail later in this
intra-abdominal pressure and visceral support. The lum- chapter.
bosacral curve, a specific human characteristic, directs The pelvic floor muscles have constant tone except dur-
abdominal pressure forward onto the abdominal wall and ing voiding and defecation, and they can be voluntarily
the nearly horizontal, flattened pubic bones. Downward contracted. This muscle tone serves as a constant support
pressure is directed backward onto the sacrum and the rear- for the pelvic viscera. The levator muscles and the skeletal
ranged pelvic muscles, which now fill in the pelvic cavity to components of the urethral and anal sphincters all have the
form the pelvic floor and sidewalls. ability to contract quickly at the time of an acute stress,
The pelvic floor and sidewalls are made up of muscular such as a cough or sneeze, to maintain continence. The mus-
and fascial structures that enclose the abdominal-pelvic cav- cles contain type I (slow-twitch) fibers to maintain constant
ity, the external vaginal opening (for intercourse and partu- tone, and type II (fast-twitch) fibers to provide reflex and
rition), and the urethra and rectum (for elimination). The voluntary contractions. Although the muscles of the pelvic
fascial components consist of two types of fascia: parietal floor were initially thought to have innervation from direct
and visceral (endopelvic). Parietal fascia covers the pelvic branches of the sacral nerves on the pelvic surface and via
skeletal muscles and provides attachment of muscles to the pudendal nerve on the perineal surface, recent ana-
the bony pelvis; it is characterized histologically by regular tomic, neurophysiologic, and experimental evidence indi-
arrangements of collagen. Visceral endopelvic fascia is less cates that these standard descriptions are inaccurate and
discrete and exists throughout the pelvis as a meshwork of that the levator ani muscles are predominantly innervated
22 PART 2  Basic Science

by a nerve traveling on the superior (intrapelvic) surface of Posterior division


the muscles without contribution of the pudendal nerve. of internal iliac a.
Common
There are small branches that penetrate the body of each Iliolumbar a. iliac a.
muscle as the nerve traverses them.
Superior Ureter
gluteal a. Internal
Abdominal Wall iliac a.
Lateral
The abdominal wall comprises several layers. Inferior to the sacral a.
External
iliac a.
umbilicus and beneath the skin, the subcutaneous tissue
Obturator
forms two distinct layers: the subcutaneous fat (Camper’s n. and a.
Inferior
fascia) and an inner membranous layer (Scarpa’s fascia). gluteal a. Obliterated
These layers come together in the midline at the linea alba. umbilical a.
The umbilicus consists of an umbilical ring through the linea Superior
Pudendal a. vesicle a.
alba, and it is the thinnest part of the abdominal wall. There
Uterine a.
are laterally three layers of muscles: the external oblique,
Vaginal a.
the internal oblique, and the transversus abdominis muscles. Middle
rectal a.
Near the midline are the rectus abdominus and the pyrami- Levator ani n.
dalis muscles. The three lateral muscles come together near Inferior
the midline to envelope the rectus abdominus muscles in vesicle a.
the rectus sheath. The innermost layer of the sheath (pos- FIGURE 2.3 View of the nerves and blood vessels of the lateral
terior rectus sheath) is only present above the approximate wall of the pelvis. The sacral plexus is shown in yellow. The smaller
position of halfway between the umbilicus and the pubic branches innervating the muscles of the pelvic floor can be seen sup-
symphysis. This point of transition is called the arcuate line. plying the levator ani muscles (S3, S4).
Below the arcuate line, there is no posterior rectus sheath.
The transversalis fascia and the peritoneum cover the inter- The sciatic and gluteal nerves innervate the lower limb
nal surface of the entire anterior abdominal wall. and buttock. Other branches include the pudendal nerve
The ilioinguinal and iliohypogastric nerves are located in (S2-S4), the anococcygeal nerves, the nerve to levator ani
the space between the internal and external oblique mus- (S3, S4), the nerves to the piriformis and obturator inter-
cles. Abdominal wall surgical sites below the level of the nus, the pelvic splanchnic nerves, and the cutaneous nerves.
anterior superior iliac spine have the potential for ilioingui- The superior hypogastric plexus contains the sympathetic,
nal and iliohypogastric nerve injury. parasympathetic, and visceral afferent fibers; it is located
Important folds located on the internal surface of the anterior to L5 between the sacral promontory and the aortic
anterior abdominal wall include the median and medial bifurcation before proceeding to the pelvic sidewalls (Fig.
umbilical folds. The paired obliterated remnants of the 2.4). This plexus of nerves leaves the sacral surface to fan
umbilical arteries course posterior to the rectus muscles. out on either side of the rectum approximately 3 to 4 cm
The single median umbilical fold is located in the midline superior to the pelvic floor muscles then disperses through-
and is the remnant of the embryologic urachus. Each infe- out the pelvis through the endopelvic fascia.
rior epigastric artery originates from the external iliac artery
and ascends medial to the inguinal ring to lie along the lat-
Uterus and Ovaries
eral border of the rectus abdominus.
The uterus is a muscular organ consisting of the uterine fun-
dus, isthmus, and cervix. The uterus and cervix are con-
Nerves of the Pelvis
tinuous with the anterior apical portion of the vagina and
Although the muscles of the pelvic floor were initially are connected superiorly to the ovaries via the utero-ovarian
thought to have innervation from direct branches of the ligaments. The ovaries receive their blood supply from the
sacral nerves on the pelvic surface and via the pudendal ovarian (gonadal) vessels that originate from the aorta. The
nerve on the perineal surface, evidence indicates that these uterus receives most its blood supply bilaterally from the
standard descriptions are inaccurate and that the levator ani uterine arteries. The uterine arteries originate at the ante-
muscles are innervated solely by a nerve traveling on the rior division of the internal iliac artery and reach the lower
superior (intrapelvic) surface of the muscles without contri- uterine segment within the cardinal ligament. The artery
bution of the pudendal nerve (Fig. 2.3). caudally gives off the vaginal branches and continues along
In the pelvis, the sympathetic nerves to the pelvis origi- the lateral surface of the uterus to anastomose with the
nate at the T5 to L2 spinal level and act to promote storage ovarian blood supply (see Fig. 2.3).
by causing relaxation of the bladder and rectum and con- The uterus is a midline organ positioned posterior to
traction of the smooth muscle components of the urethral the bladder and anterior to the rectum. Condensations of
and anal sphincters. The parasympathetic nerve supply to peritoneum form the cardinal and broad ligaments, round
the pelvic viscera originates from the second, third, and ligament, and the suspensory ligament of the ovary (infun-
fourth sacral nerves (Fig. 2.4). dibulopelvic ligament).
The sacral plexus is formed by the nerve roots of L4, L5, The cardinal ligament is a condensation of the endopelvic
and S1 to S4 and is located on the anterior surface of the fascia that is part of the supportive structure of the uterus.
piriformis muscle on the lateral pelvic floor and sidewalls. It extends outward and laterally from the uterine isthmus
The sacral plexus gives rise to multiple nerve branches. and cervix in a three-dimensional fan-like manner, and it
CHAPTER 2  Anatomy of the Lower Urinary Tract, Pelvic Floor, and Rectum 23

FIGURE 2.4  The sympathetic and parasympathetic nerves entering the pelvis. The superior hypogastric plexus can be seen lying directly over
the sacral promontory until it divides to the right and left sides of pelvis.

is continuous with the endopelvic fascia of the pelvic side- is surrounded by an adventitial layer, which is a variably dis-
wall. In addition to playing a role in upper vaginal support, crete layer of collagen, elastin, and adipose tissue containing
it divides the deeper pelvis into avascular planes anteriorly blood vessels, lymphatics, and nerves. The adventitia repre-
called the paravesical space and posteriorly called the para- sents an extension of the visceral endopelvic fascia that sur-
rectal space. The space of Retzius is continuous with the rounds the vagina and adjacent pelvic organs, and it allows
paravesical space. The borders of the paravesical space are for their independent expansion and contraction.
the obturator internus and neurovascular bundle laterally, The walls of the vagina are in contact except where
the cardinal ligament posteriorly, the pubic symphysis ante- its lumen is held open by the cervix. The vagina has an
riorly, and the obliterated umbilical artery medially. The H-shaped lumen, with the principal dimension being
borders of the pararectal space are the cardinal ligament transverse. In addition, the upper vagina is supported by
anteriorly, the rectum medially, the internal iliac artery lat- connective tissue attachments to the sacrum, coccyx, and
erally, and the sacrum posteriorly. lateral pelvic sidewalls; these are identified at surgery as
the cardinal and uterosacral ligament complex. The pres-
ence of a true fascia between the vagina and adjacent organs
Vagina
has been debated. Surgical terms such as pubocervical and
The vagina is a hollow, fibromuscular tube with rugal folds rectovaginal fascia refer to layers that are developed as a
that extends from the vestibule to the uterine cervix. In result of separating the vaginal epithelium from the muscu-
the standing woman, the upper two thirds of the vagina is laris or by splitting the vaginal muscularis layer. Anteriorly,
almost horizontal whereas the lower one third is nearly ver- the vagina lies adjacent to and supports the bladder base,
tical. The vaginal wall is histologically composed of three from which it is separated by the vesicovaginal adventitia
layers. It is lined by a nonkeratinized stratified squamous (endopelvic fascia). The urethra is fused with the anterior
epithelium that lies over a thin, loose layer of connective vagina, with no distinct adventitial layer separating them.
tissue, the lamina propria. The lamina propria contains no The terminal portions of the ureters cross the lateral for-
glands. Coursing through the lamina propria are small blood nices of the vagina on their way to the bladder base. Poste-
vessels. Vaginal lubrication is via a transudate from the ves- riorly, the vagina is related to the cul-de-sac, to the rectal
sels, cervix, and from the Bartholin’s and Skene’s glands. ampulla, and inferiorly to the perineal body. Embryologi-
Beneath this is the vaginal muscularis, a well-developed cally, an extension and fusion of the peritoneum from the
fibromuscular layer consisting primarily of smooth muscle cul-de-sac attached to the posterior surface of the vagi-
with smaller amounts of collagen and elastin. The muscularis nal muscularis forms the rectovaginal septum. A layer of
24 PART 2  Basic Science

adventitia separates the muscular layer of the rectum from supply the perineum: clitoral, perineal, and inferior rectal
the rectovaginal septum, except at the level of the peri- (inferior hemorrhoidal). The blood supply to the perineum
neal body, where there is fusion of the vaginal muscula- is from the pudendal artery, which travels with the puden-
ris and connective tissue of the perineal body. The dense dal nerve to exit the pelvis. Similar to the nerve, there are
connective tissue of the perineal body extends 2 to 3 cm three main branches with rich collateral anastomoses.
cephalad from the hymenal ring along the posterior vagi-
nal wall and forms what some have called the rectovaginal
Bladder
fascia. Although at the time of surgery there appears to
be an identifiable fascial plane, Weber and Walters (1997) The bladder is a hollow, muscular organ that is the reservoir
and DeLancey (1999) have each concluded that between for the urinary system. The bladder is flat when empty and
the adjacent organs is primarily vaginal muscularis and no globular when distended. The superior surface and upper 1
fascia is histologically present. to 2 cm of the posterior aspect of the bladder are covered
by peritoneum, which sweeps off of the bladder into the
vesicouterine pouch. The anterior bladder is extraperitoneal
Perineum
and adjacent to the retropubic space (space of Retzius).
The perineum is divided into two compartments: superficial Between the bladder and pubic bones, within the space
and deep. These are separated by a fibrous connective tissue of Retzius, lie adipose tissue, pubovesical ligaments and
layer called the perineal membrane. The perineal membrane muscle, and a prominent venous plexus. The bladder rests
is a triangular sheet of dense fibromuscular tissue that spans inferiorly on the anterior vagina and lower uterine segment,
the anterior half of the pelvic outlet. It had previously been separated by an envelope of adventitia (endopelvic fascia).
called the urogenital diaphragm; this change in name reflects The epithelium lining the bladder lumen is loosely
the appreciation that it is not a two-layered structure with attached to the underlying musculature, except at the tri-
muscle in between, as had been thought. The perineal mem- gone, where it is firmly adherent. The bladder lining con-
brane provides support to the vagina and urethra as they sists of a transitional epithelium (urothelium) supported
pass through it. Cephalad to the perineal membrane lies the by a layer of loose connective tissue, the lamina propria.
striated urogenital sphincter muscle, which compresses the The internal surface of the bladder has a rugose appearance
mid- and distal urethra (see Fig. 2.7). The borders of the formed by mucosal folds in the contracted state. In the dis-
perineum are the ischiopubic rami, the ischial tuberosities, tended state, a variably prominent meshlike appearance is
the sacrotuberous ligaments, and the coccyx. A line con- formed by mucosa-covered detrusor musculature.
necting the ischial tuberosities divides the perineum into The bladder wall musculature is often described as hav-
the urogenital triangle anteriorly and the anal triangle pos- ing three layers: inner longitudinal, middle circular, and
teriorly. The perineal body marks the point of convergence outer longitudinal. However, this layering occurs only at the
of the bulbospongiosus muscles, the superficial and deep bladder neck; the remainder of the bladder musculature is
transverse perinei, the perineal membrane, the external anal composed of fibers that run in many directions within and
sphincter, the posterior vaginal muscularis, and the insertion between layers. This plexiform arrangement of detrusor
of the puborectalis and pubococcygeus muscles. The bulbo- muscle bundles is ideally suited to reduce all dimensions of
spongiosus originates on the inferior surface of the superior the bladder lumen on contraction.
pubic rami and the crura of the clitoris. It inserts on the peri- The inner longitudinal layer has widely separated muscle
neal body, where its fibers blend with the superficial trans- fibers that course multidirectionally. Near the bladder neck,
verse perinei and the external anal sphincter. It is innervated these muscle fibers assume a longitudinal pattern that is
by the pudendal nerve. The superficial transverse perinei are contiguous through the trigone and, according to Tanagho
bilateral muscles that extend from the medial ischial tuber- (1986), into the inner longitudinal muscular layer of the ure-
osities to insert on the perineal body. Some fibers blend thra. The middle circular layer is prominent at the bladder
with the bulbospongiosus and the external anal sphincter. It neck, where it fuses with the deep trigonal muscle, forming
is innervated by the pudendal nerve. The ischiocavernosus a muscular ring. This layer does not continue into the ure-
muscles originate from the medial ischial tuberosities and thra. The outer longitudinal layer forms a sheet of muscle
ischiopubic rami. They insert on the inferior aspect of the bundles around the bladder wall above the level of the blad-
pubic angle and they are innervated by the pudendal nerve. der neck. Anteriorly, these fibers continue past the vesical
The deep perineal compartment is composed of the deep neck as the pubovesical muscles and insert into tissues on
transverse perineus muscle, portions of the external urethral the posterior surface of the pubic symphysis. The pubovesi-
sphincter muscles (compressor urethrae and urethrovaginal cal muscles may facilitate bladder neck opening during void-
sphincter), portions of the anal sphincter, and the vaginal ing. Posteriorly, the longitudinal fibers fuse with the deep
musculofascial attachments. surface of the trigonal apex and communicate with several
The neurovascular anatomy of the perineum is illus- detrusor muscle loops at the bladder base; these loops prob-
trated in Figure 2.5. The motor and sensory innervation ably aid in bladder neck closure.
of the perineum is via the pudendal nerve. The pudendal
nerve originates from S2 to S4 and exits the pelvis through
Trigone
the greater sciatic foramen, hooks around the ischial spine,
and then travels along the medial surface of the obturator In the bladder base is a triangular area, the trigone. The tri-
internus through the ischiorectal fossa in a thickening of fas- gone has a flattened appearance with a smooth epithelial
cia called Alcock’s canal. It immerges posterior and medial covering. The corners of the trigone are formed by three
to the ischial tuberosity and divides into three branches to orifices: the paired ureteral orifices and the internal urethral
CHAPTER 2  Anatomy of the Lower Urinary Tract, Pelvic Floor, and Rectum 25

FIGURE 2.5  Neurovascular anatomy of perineum, illustrating the muscles and nerves of the perineum, including the distribution of the puden-
dal and ilioinguinal innervation (shaded on left).

orifice. The superior boundary of the trigone is a slightly directly above the vaginal opening. Throughout its length,
raised area between the two ureteric orifices called the the urethra is embedded in the adventitia of the anterior
interureteric ridge. The two ureteral openings are slitlike vagina.
and, in an undistended organ, lie approximately 3 cm apart. The urethral epithelium has longitudinal folds and many
The trigone has two muscular layers: superficial and small glands, which open into the urethra throughout its
deep. The superficial layer is directly continuous with lon- entire length. The epithelium is continuous externally with
gitudinal fibers of the distal ureter and is continuous poste- that of the vulva and internally with that of the bladder.
riorly with the smooth muscle of the proximal urethra. The It is primarily stratified squamous epithelium that becomes
deep muscular layer of the trigone forms a dense, compact transitional near the bladder.
layer that fuses somewhat with the detrusor muscle fibers. The epithelium is supported by a layer of loose fibroelas-
The deep layer is in direct communication with a fibromus- tic connective tissue, the lamina propria. The lamina propria
cular sheath, Waldeyer’s sheath, in the intravesical portion contains many bundles of collagen fibrils and fibrocytes and
of the ureter (Fig. 2.6). The deep trigonal muscle has auto- an abundance of elastic fibers oriented longitudinally and
nomic innervation identical to that of the detrusor, being circularly around the urethra. Numerous thin-walled veins
rich in cholinergic (parasympathetic) nerves and sparse in are another characteristic feature. This rich vascular supply
noradrenergic (sympathetic) nerves. In contrast, the super- contributes to urethral resistance.
ficial trigonal muscle has few cholinergic nerves but more The urethral smooth muscle is composed primarily of
noradrenergic nerves. oblique and longitudinal muscle fibers, with a few circularly
oriented outer fibers. This muscle and the detrusor muscle
in the bladder base form what can be called the intrinsic
Urethra
urethral sphincter mechanism. This smooth muscle is usu-
The female urethra is approximately 4 cm long and averages ally noted to be under alpha-adrenergic and cholinergic
6 mm in diameter. Its lumen is slightly curved as it passes control, although Gosling et al. (1981) found an extensive
from the retropubic space, perforates the perineal mem- cholinergic nerve supply with few noradrenergic nerves.
brane, and ends with its external orifice in the vestibule The longitudinally directed muscles probably shorten and
26 PART 2  Basic Science

B
FIGURE 2.6  Normal ureterovesico–trigonal complex. A, Side view with Waldeyer’s muscular sheath surrounding vestige of the intravesical
ureter and continuing downward as the deep trigone, which extends to the bladder neck. The ureteral musculature becomes the superficial
trigone, which extends to just short of the external meatus in the female. B, Waldeyer’s sheath connected by a few fibers to the detrusor
muscle in the ureteral hiatus. This muscular sheath inferior to the ureteral orifice becomes the deep trigone. The musculature of the ureters
continues downward as the superficial trigone. From Tanagho (1986).

widen the urethral lumen during micturition, whereas the


Pelvic Ureter
circular smooth muscle (along with the striated urogenital
sphincter muscle) contributes to urethral resistance to out- As it courses retroperitoneally from the renal pelvis to the
flow at rest. bladder, the ureter is divided anatomically into abdominal
The striated urethral and periurethral muscles form the and pelvic segments, which are approximately equal in length,
extrinsic urethral sphincter mechanism. It has two compo- 12 to 15 cm each. The ureter enters the pelvis by crossing
nents: an inner portion, which lies within and adjacent to over the iliac vessels where the common iliac artery divides
the urethral wall, and an outer portion, composed of skel- into the external iliac and internal iliac (hypogastric) artery.
etal muscle fibers of the pelvic diaphragm. The inner por- It travels lateral to the hypogastric artery, but it eventually
tion is made up of the sphincter urethrae, a striated band crosses to lie medial to the branches of the anterior division
of muscle that surrounds the proximal two thirds of the of the hypogastric artery and lateral to the peritoneum of
urethra, and the compressor urethrae and urethrovaginal the cul-de-sac. It is attached to the peritoneum of the lateral
sphincter (known together formerly as the deep transverse pelvic wall. As it proceeds more distally, the ureter courses
perineus muscle), which consist of two straplike bands of along the lateral side of the uterosacral ligament and enters
striated muscle that arch over the ventral surface of the dis- the endopelvic fascia of the parametrium (cardinal ligament).
tal one third of the urethra (Fig. 2.7). These three muscles, The ureter courses medially as the uterosacral ligament is
which function as a single unit, have been called by Oelrich traced from the sacrum toward the vagina. At the level of the
(1983) the striated urogenital sphincter. The striated uro- ischial spine, the ureter is approximately 2 to 3 cm lateral to
genital sphincter is primarily composed of small-diameter, the uterosacral ligament (Buller et al. 2001). The ureter is
slow-twitch muscle, making it ideally suited to exert tone closest to the uterosacral ligament at its distal end, approxi-
on the urethral lumen over prolonged time periods. These mately 1 cm. The ureter passes beneath the uterine artery
muscles may also contribute (along with the levator ani) to approximately 1.5 cm lateral to the cervix. The distal ureter
voluntary interruption of the urine stream and to urethral then moves medially over the lateral vaginal fornix and travels
closure with stress via reflex muscle contraction. through the wall of the bladder until reaching the trigone.
CHAPTER 2  Anatomy of the Lower Urinary Tract, Pelvic Floor, and Rectum 27

FIGURE 2.7  Diagrammatic representation showing the component parts of the urethral support and sphincteric mechanisms. Note that the
proximal urethra and bladder neck are supported by the anterior vaginal wall and its musculofascial attachments to the pelvic diaphragm.
Inset, Contraction of the levator ani muscles elevates the anterior vagina and overlying bladder neck and proximal urethra, contributing
to bladder neck closure. The sphincter urethrae, urethrovaginal sphincter, and compressor urethrae are all parts of the striated urogenital
sphincter.

The ureter has only one muscular coat that forms an and posterior divisions traveling distally down the thigh to
irregular, helical pattern of muscle bundles with fibers ori- supply the muscles of the adductor compartment. With
ented in almost every direction. As the ureter approaches the patient in the dorsal lithotomy position, the nerves and
and enters the bladder wall, its helical fibers elongate and vessels follow the thigh and course laterally away from the
become parallel to its lumen. The intravesical ureter is ischiopubic ramus.
approximately 1.5 cm long and is divided into an intramu-
ral segment, totally surrounded by the bladder wall, and a
Rectum and Anal Sphincters
submucosal segment directly under the urothelium. The
longitudinal muscle fibers of the distal ureter proceed unin- The rectum extends from its junction with the sigmoid colon
terrupted into the superficial trigonal muscle. to the anal orifice. The distribution of smooth muscle is
The distal and intramural segments of the ureter are sur- typical for the intestinal tract, with inner circular and outer
rounded by Waldeyer’s sheath. Waldeyer’s sheath fuses proxi- longitudinal layers of muscle. At the perineal flexure of the
mally with the intrinsic musculature of the ureter and distally rectum, the inner circular layer increases in thickness to form
acts as an added fixation, linking the ureter proper to the detru- the internal anal sphincter. The internal anal sphincter is
sor muscle (see Fig. 2.6). Waldeyer’s sheath has been described under autonomic control (sympathetic and parasympathetic)
thoroughly by Tanagho (1986) and Woodburne (1968). and is responsible for 85% of the resting anal pressure. The
outer longitudinal layer of smooth muscle becomes concen-
trated on the anterior and posterior walls of the rectum, with
Transobturator Anatomy
connections to the perineal body and coccyx, and then passes
The obturator membrane is a fibrous sheath that spans the inferiorly on both sides of the external anal sphincter.
obturator foramen through which the obturator neurovas- The external anal sphincter is composed of striated
cular bundle penetrates via the obturator canal. The obtu- muscle that is tonically contracted most of the time, and it
rator artery and vein originate as branches of the internal can also be voluntarily contracted. Various divisions of the
iliac vessels. As they emerge from the inferior side of the external anal sphincter have been described, and although
obturator membrane and enter the obturator space, they there is no consensus, recent descriptions favor superficial
divide into many small branches supplying the muscles of (combining the previous superficial and subcutaneous com-
the adductor compartment of the thigh. Cadaver work by ponents) and deep compartments. The external anal sphinc-
Whiteside et al. (2004) has contradicted previous reports ter functions as a unit with the puborectalis portion of the
of the obturator vessels bifurcating into medial and lat- levator ani muscle group.
eral branches. Rather, the vessels are predominantly small The anal sphincter mechanism comprises the internal anal
(<5 mm diameter) and splinter into variable courses. The sphincter, the external anal sphincter, and the puborectalis
muscles of the medial thigh and adductor compartment are, muscle (Fig. 2.9). As with the bladder neck and urethra, a spinal
from superficial to deep, the gracilis, the adductor longus, reflex causes the striated sphincter to contract during sudden
the adductor brevis, the adductor magnus, and the obtura- increases in intra-abdominal pressure, such as coughing. The
tor externus muscles (Fig. 2.8). anorectal angle is produced by the anterior pull of the puborec-
In contrast to the vessels, the obturator nerve emerges talis muscles. These muscles posteriorly form a sling around
from the obturator membrane and bifurcates into anterior the anorectal junction. The anorectal angle was previously
28 PART 2  Basic Science

FIGURE 2.8 Transobturator anatomy. Diagrammatic representation showing the muscles of the obturator compartment. The superficial
muscles are illustrated on the left. On the right, the superficial muscles have been made transparent to illustrate the deeper muscles.

thought to be important in maintaining fecal continence, but


its importance has been questioned. More recent studies sug-
gest that fecal incontinence in women is often related to dener-
vation of the muscles of the pelvic diaphragm and to disruption
and denervation of the external anal sphincter.

Pelvic Organ Support


Support of the Uterus and Vagina
Normal pelvic support is provided by interaction between
the pelvic floor muscles and connective tissue attachments.
Under most conditions, the pelvic muscles are the primary
support for the pelvic organs, providing a firm yet elastic
base on which they rest. The connective tissue (endopelvic
fascia) attachments keep the pelvic organs in the proper ori-
entation so that they may be supported by the pelvic floor
musculature. When the pelvic muscles are relaxed, as dur-
ing micturition or defecation, the connective tissue attach-
ments temporarily hold up the pelvic organs.
The endopelvic fascia is a connective tissue network of
FIGURE 2.9 Diagram of the rectum, anal canal, and surrounding the retroperitoneum that envelopes all of the organs of the
muscles. The puborectalis muscle posteriorly forms a sling around pelvis and connects them loosely to the supportive muscu-
the anorectal junction. The external anal sphincter (skeletal muscle) lature and bones of the pelvis. The term endopelvic fascia is
surrounds the anal canal and is closely associated with the puborec- used here to describe the tissues located between the sur-
talis muscle. The internal anal sphincter muscle (smooth muscle) lies faces of the peritoneum, muscles, and pelvic organs. Histo-
within the ring of the external sphincter muscle and is a continuation logically, it is composed of collagen, elastin, adipose tissue,
of the inner circular layer of the smooth muscle of the rectal wall. nerves, vessels, lymph channels, and smooth muscle. Its
From Madoff et al. (1992). properties provide stabilization and support, but they allow
for mobility, expansion, and contraction of the viscera to
permit storage of urine and stool, coitus, parturition, and
defecation.
CHAPTER 2  Anatomy of the Lower Urinary Tract, Pelvic Floor, and Rectum 29

FIGURE 2.10  Integrated levels of support. Illustrates the three levels of support of the vagina and uterus showing the continuity of supportive
structures throughout the entire length of the genital tract. In Level I, the endopelvic fascia suspends the upper vagina and cervix from the
lateral pelvic walls. The fibers of Level I extend vertically and posteriorly toward the sacrum. In Level II, the vagina is attached to the arcus ten-
dineus fasciae pelvis and to the superior fascia of the levator ani muscles. In Level III, the distal vagina is supported by the perineal membrane
and muscles.

Other than the cervix, the uterus does not have fixed individually. However, it is important to remember that
supports, as indicated by its ability to enlarge without Levels I, II, and III are all connected through a continuation
restriction during pregnancy. Several areas of the endopelvic of the endopelvic fascia.
fascia (and its associated peritoneum) have been named by Comprising Level I support, the cardinal and uterosacral
anatomists. These are really condensations of the endopel- ligaments attach to the cervix from the lateral and posterior
vic fascia and not true ligaments and include the uterosacral sides, respectively, with fibers intermingling. The cardinal
ligament, cardinal ligament, broad ligament, meso-ovarium, ligaments blend with the uterosacral ligaments, and they are
mesosalpinx, and round ligament. The broad ligament, difficult, if not impossible, to precisely delineate from one
meso-ovarium, mesosalpinx, and round ligament do not play another. Fibers traveling predominately laterally make up
a role in support of the pelvic organs. the cardinal ligaments, whereas fibers going to the sacrum
Connective tissue attachments stabilize the vagina at make up the uterosacral ligaments. These fibers form a three-
different levels, as described by DeLancey (1992) and oth- dimensional complex attaching the upper vagina, cervix,
ers (Fig. 2.10). Level I refers to the uterosacral ligament/ and lower uterine segment to the sacrum and lateral pelvic
cardinal ligament complex and represents the most cepha- sidewalls at the piriformis, coccygeus, levator ani, and per-
lad supporting structures. Level II support is provided by haps the obturator internus fascia overlying the ischial spine.
the anterior and posterior paravaginal attachments along Together, the uterosacral/cardinal ligament complex supports
the length of the vagina. Level III support describes the the cervix and upper vagina to maintain vaginal length and to
most inferior or distal portions of the vagina including keep the vaginal axis nearly horizontal so that it rests on the
the perineum. Each of these areas plays a significant role rectum and can be supported by the levator plate. This keeps
in maintaining pelvic organ support and will be discussed the cervix just superior to the level of the ischial spine.
30 PART 2  Basic Science

Contiguous with the cardinal/uterosacral ligament com- When the vagina, bladder, and rectum are kept in the
plex at the location of the ischial spine is Level II support— horizontal plane over the levator plate and pelvic floor mus-
the paravaginal attachments. These are the connections of cles, intra-abdominal and gravitational forces are applied
the lateral vagina and endopelvic fascia anteriorly to the perpendicular to the vagina and pelvic floor while the pelvic
arcus tendineus fasciae pelvis and posteriorly to the arcus floor musculature counters those forces with its constant
tendineus rectovaginalis. Level II support functions to keep tone. It is this horizontal position and support by the levator
the vagina midline, directly over the rectum. ani that maintain pelvic organ support. With proper tone
The arcus tendineus fasciae pelvis, or “white line,” is a of the pelvic floor muscles (levator ani), stress on the lat-
thickened condensation of the parietal fascia into which the eral paravaginal attachments is minimized. Furthermore, in
paravaginal endopelvic fascia connects, supporting and cre- times of acute stress such as a cough or sneeze, there is a
ating the anterior lateral vaginal sulci. Similar to the arcus reflex contraction of the pelvic floor musculature counter-
tendineus levator ani, it originates on the ischial spine. How- ing and further stabilizing the viscera. The genital hiatus
ever, as it approaches the pubic symphysis, the arcus ten- also responds by narrowing to maintain Level III support.
dineus fasciae pelvis travels medially and inferiorly to the With pelvic floor weakness, such as with neuropathic injury
arcus tendineus levator ani, inserting on the inferior aspect or mechanical muscular damage, the endopelvic fascia
of the superior pubic rami over the origin of the puborec- becomes the primary mechanism of support. Over time,
talis muscle. The axes of the arcus tendineus levator ani this stress can overcome the endopelvic fascial attachments
and the arcus tendineus fasciae pelvis are nearly horizontal and result in loss of the normal anatomic position through
in the standing woman, establishing the normal axis of the breaks, stretching, or attenuation of endopelvic fascia sup-
upper vagina. ports. This can result in changes in the vector forces applied
Similar to the anterior paravaginal supports, there to the viscera and may lead to pelvic organ prolapse and/or
are also posterior lateral supports. The endopelvic fascia visceral dysfunction. Re-creation of these supportive con-
extends posteriorly from the posterior lateral vagina sulci nections and proper position of the organs while maintain-
around the rectum to attach the vagina to the pelvic floor. ing adequate vaginal length to keep the vaginal apex in a
These fibers blend with the vaginal muscularis anteriorly, natural position should be the goal of reconstructive pelvic
the rectal muscularis posteriorly, and the perineal body surgery.
inferiorly. The lateral endopelvic fascia attachments of the
posterior vaginal wall do not have significant connections
Urethral Support
across the midline. Rather, they anchor the posterior lateral
vaginal sulci to the ipsilateral levator ani. The posterior vagi- When the vagina is normally supported, it provides sup-
nal muscularis is attached through this endopelvic fascia to port to the bladder and urethra. Support of the urethra and
the fascia of the levator ani laterally at the arcus tendineus bladder neck was traditionally thought to be provided by
rectovaginalis. The arcus tendineus rectovaginalis represents the interaction of the pubourethral ligaments, the perineal
a condensation of the parietal fascia of the levator ani cours- membrane, and the muscles of the pelvic floor. Numerous
ing from the perineal body inferiorly, along the levator ani investigators have described the so-called pubourethral liga-
laterally, where it intersects the midpoint of the arcus ten- ments as extending from the inferior surface of the pubic
dineus fasciae pelvis (see Fig. 2.10). The arcus tendineus bones to the urethra. Milley and Nichols (1971) found
rectovaginalis is approximately 4 cm in length. The connec- bilaterally symmetric anterior, posterior, and intermediate
tion to the arcus tendineus rectovaginalis creates the change pubourethral ligaments and stated that the anterior and
in axis toward vertical of the distal vagina. posterior ligaments were formed, respectively, by the infe-
Level III support is provided by the perineal body, the rior and superior fascial layers of the perineal membrane.
perineal membrane, the superficial and deep perineal mus- An anatomic defect of the pubourethral ligaments has been
cles, and the endopelvic fascia. These structures support and cited as a contributing factor to stress urinary incontinence
maintain the normal position of the distal one third of the in women.
vagina and introitus. The endopelvic fascia anteriorly blends Studies by DeLancey (1986, 1988, 1989, 1991) pro-
with the vaginal muscularis and is continuous with the sup- vide a more complete view of urethral support. Rather than
portive structures of the urethra. The perineal body is criti- being suspended ventrally by ligamentous structures, the
cal for support of the lower part of the vagina and proper proximal urethra and bladder base are supported in a sling-
function of the anal canal. The perineal membrane anchors like fashion by the anterior vaginal wall, which is attached
the perineal body and distal vagina laterally and anteriorly to bilaterally to the muscles of the pelvic diaphragm (levator
the ischiopubic rami. Separation of the perineal body from ani muscles) at the arcus tendineus fasciae pelvis. Similar
the perineal membrane results in perineal decent and can anatomic connections between the pelvic diaphragm and
contribute to defecatory dysfunction. vagina have been described by Olesen and Grau (1976)
The three levels of support are connected and interde- and others. These attachments extend caudally and blend
pendent. Level III structures are connected to the endopel- with the superior fibers of the perineal membrane. The tis-
vic fascia that surrounds the vagina and rectum; therefore, sues, described as pubourethral ligaments, are made up of
they are continuous with Level II support. Level II support the perineal membrane and the most caudal portion of the
is connected to Level I support through the confluence of arcus tendineus fasciae pelvis, which fix the distal urethra
the lateral endopelvic fascia attachments and the uterosac- beneath the pubic bone. Figure 2.7 illustrates the anatomic
ral ligament/cardinal ligament complex. Adequate support structures that contribute to urethral support and closure.
at all levels maintains the pelvic organs in their normal ana- Anterior vaginal attachment at the arcus tendineus fas-
tomic positions. ciae pelvis may contribute to urethral closure by providing
CHAPTER 2  Anatomy of the Lower Urinary Tract, Pelvic Floor, and Rectum 31

a stable base onto which the bladder neck and proximal Gosling JA, Dixon JS, Humpherson JR. Functional anatomy of the urinary
urethra are compressed with increases in intra-abdominal tract: an integrated text and color atlas. Baltimore: University Park Press;
1982.
pressure. These attachments also are responsible for the Halban J, Tandler J. Anatomie und Atiologie der Genital-prolapse (Trans-
posterior movement of the vesical neck seen at the onset lated by Porges RF, Porges JC. The anatomy and etiology of genital pro-
of micturition (when the pelvic floor relaxes) and for the lapse in women). Obstet Gynecol. 1960;15:790.
elevation noted when a patient is instructed to arrest her Kearney R, Sawhney R, DeLancey JOL. Levator ani muscle anatomy by
urinary stream (see Fig. 2.7, inset). Defects in these attach- origin-insertion pairs. Obstet Gynecol. 2004;104:168.
Krantz KE. The anatomy of the urethra and anterior vaginal wall. Am J
ments probably result in proximal urethral support defects Obstet Gynecol. 1951;62:374.
(urethral hypermobility) and anterior vaginal prolapse (cys- Lawson JO. Pelvic anatomy. I. Pelvic floor muscles. Ann R Coll Surg Engl.
tocele), conditions associated with stress urinary incon- 1974;52:244.
tinence. These defects also correspond to the paravaginal Leffler KS, Thompson JR, Cundiff GW, et al. Attachment of the recto-
vaginal septum to the pelvic sidewall. Am J Obstet Gynecol. 2001;185:41.
fascial defects, with detachment of the vagina from its lat- Lund CJ, Fullerton RE, Tristan TA. Cinefluorographic studies of the bladder
eral connective tissue supports, described by Richardson and urethra in women. Am J Obstet Gynecol. 1959;78:706.
et al. (1976). Madoff RD, Williams JG, Caushaj PF. Fecal incontinence. N Engl J Med.
1992;326:1003.
Bibliography Margulies RU, Hsu Y, Kearney R, Stein T, Umek WH, DeLancey JOL.
Appearance of the levator ani muscle subdivisions in magnetic resonance
Aronson MP, Lee RA, Berquist TH. Anatomy of anal sphincters and related images. Obstet Gynecol. 2006;107:1064.
structures in continent women studied with magnetic resonance imaging. McGuire EJ. The innervation and function of the lower urinary tract. J Neu-
Obstet Gynecol. 1990;76:846. rosurg. 1986;65:278.
Barber MD, Bremer RE, Thor KB, et al. Innervation of the female levator Mengert WF. Mechanics of uterine support and position. Am J Obstet
ani muscles. Am J Obstet Gynecol. 2002;187:64. Gynecol. 1936;31:775.
Buller JL, Thompson JR, Cundiff GW, et al. Uterosacral ligament: descrip- Milley PS, Nichols DH. The relationship between the pubo-urethral liga-
tion of anatomic relationships to optimize surgical safety. Obstet Gynecol. ments and the urogenital diaphragm in the human female. Anat Rec.
2001;97:873. 1971;170:281.
Curtis AH, Anson BJ, Ashley FL. Further studies in gynecological anatomy Netter FH, Dalley II AF, eds. Atlas of Human Anatomy. 2nd ed. Summit:
and related clinical problems. Surg Gynecol Obstet. 1942;74:709. Hoechstetter Printing; 1997.
Curtis AH, Anson BJ, McVay CB. The anatomy of the pelvic and urogeni- Oelrich TM. The striated urogenital sphincter muscle in the female. Anat
tal diaphragms, in relation to urethrocele and cystocele. Surg Gynecol Rec. 1983;205:223.
Obstet. 1939;68:161. Olesen KP, Grau V. The suspensory apparatus of the female bladder neck.
Dalley AF. The riddle of the sphincters: the morphophysiology of the ano- Urol Int. 1976;31:33.
rectal mechanism reviewed. Am Surgeon. 1987;53:298. Pierce LM, Reyes M, Thor KB, et al. Innervation of the levator ani muscles
DeLancey JOL. Correlative study of paraurethral anatomy. Obstet Gynecol. in the female squirrel monkey. Am J Obstet Gynecol. 2003;188:1141.
1986;68:91. Redman JF. Anatomy of the genitourinary system. In: Gillenwater JY,
DeLancey JOL. Structural aspects of the extrinsic continence mechanism. Grayhack JT, Howards SS, Duckett JW, eds. Adult and Pediatric Urol-
Obstet Gynecol. 1988;72:296. ogy. vol. 1. Chicago: Mosby; 1987.
DeLancey JOL. Pubovesical ligament: a separate structure from the urethral Richardson AC, Lyon JB, Williams NL. A new look at pelvic relaxation. Am
supports (“pubo-urethral ligaments”). Neurourol Urodyn. 1989;8:53. J Obstet Gynecol. 1976;126:568.
DeLancey JOL. Anatomic aspects of vaginal eversion after hysterectomy. Ridgeway BM, Arias BE, Barber MD. Variation of the obturator foramen and
Am J Obstet Gynecol. 1992;166:1717. pubic arch of the female bony pelvis. Am J Obstet Gynecol. 2008;198.
DeLancey JOL. Anatomy of the pelvis. In: Thompson JD, Rock JA, eds. 546.e1.
Telinde’s Operative Gynecology. 7th ed. Philadelphia: JB Lippincott; Tanagho EA. Anatomy of the lower urinary tract. In: Walsh PC, Gittes RF,
1992. Perlmutter AD, Stamey TA, eds. Campbell’s Urology. 5th ed. Philadel-
DeLancey JOL, Starr RA. Histology of the connection between the vagina phia: WB Saunders; 1986.
and levator ani muscles. J Reprod Med. 1990;35:765. Weber AM, Walters MD. Anterior vaginal prolapse: review of anatomy and
DeLancey JOL. Structural anatomy of the posterior pelvic compartment as techniques of surgical repair. Obstet Gynecol. 1997;89:331.
it relates to rectocele. Am J Obstet Gynecol. 1999;180:815. Whiteside JL, Barber MD, Walters MD, Falcone T. Anatomy of ilioinguinal
DeLancey JOL. Anatomy. In: Cardozo L, Staskin D, eds. Textbook of Female and iliohypogastric nerves in relation to trocar placement and low trans-
Urology and Urogynecology. 3rd ed London, UK: Informa Healthcare; verse incisions. Am J Obstet Gynecol. 2003;189:1574.
2010. Whiteside JL, Walters MD. Anatomy of the obturator region: relations to a
Dickinson RL. Studies of the levator ani muscle. Am J Obstet Dis Women transobturator sling. Int Urogynecol J. 2004;15:223.
Child. 1889;22:897. Wood BA, Kelly AJ. Anatomy of the anal sphincters and pelvic floor. In:
Elbadawi A. Neuromorphologic basis of vesicourethral function: I. Histo- Henry MM, Swash M, eds. Coloproctology and The Pelvic Floor. 5th ed.
chemistry, ultrastructure and function of the intrinsic nerves of the blad- Oxford: Butterworth-Heinemann; 1992.
der and urethra. Neurourol Urodyn. 1982;1:3. Woodburne RT. Anatomy of the bladder and bladder outlet. J Urol.
Funt MI, Thompson JD, Birch H. Normal vaginal axis. South Med J. 1968;100:474.
1978;71:1534. Woodburne RT. Essentials of Human Anatomy. 5th ed. New York: Oxford
Gosling JA, Dixon JS, Critchley HO, et al. A comparative study of the University Press; 1976.
human external sphincter and periurethral levator ani muscles. Br J Urol. Zacharin RF. The suspensory mechanism of the female urethra. J Anat.
1981;53:35. 1963;97:423.
CHAPTER 3

Embryology
and Congenital
Anomalies of the
Urinary Tract,
Rectum, and Female
Genital System
Beri M. Ridgeway
Marjan Attaran

Chapter Outline
Embryology Classification
Formation of the Mesoderm Müllerian Agenesis (Mayer Rokitansky Kuster
Urinary System Hauser Syndrome)
Kidney and Ureter Receptor Abnormalities and Enzyme Deficiencies
Bladder, Trigone, and Urethra Complete Androgen Insensitivity Syndrome
Congenital Anomalies of the Urinary Tract Treatment of Congenital Absence of the Vagina
Rectum and Anal Sphincters and Uterus
Normal Development of the Hindgut Vaginal Dilation
Congenital Anomalies of the Rectum Vecchietti Procedure
and Anal Sphincters McIndoe Procedure
Female Genital System Peritoneal Graft: Davydov Procedure
Gonads Adhesion Barrier Lining
Genital Ducts, Sexually Indifferent Stage Tissue Engineering
Sexual Differentiation Muscle and Skin Flap
Vagina Bowel Vaginoplasty
External Genitalia Longitudinal Vaginal Septum
Nonobstructing Longitudinal Vaginal Septum
Congenital Anomalies of the Female Genital
Obstructing Longitudinal Vaginal Septum
System
Transverse Vaginal Septum
Congenital Anomalies of the Female Genital
System Presenting as Congenital Absence of the Anomalies of the Hymen
Vagina and Uterus Summary

Embryology the ectodermal and endodermal layers of the embryo. At


approximately the sixteenth day of development, the pos-
Formation of the Mesoderm
terior wall of the yolk sac forms a small diverticulum, the
The period of organogenesis, also called the embryonic allantois, which extends into the connecting stalk. The hind-
period, spans from the third to eighth week of development. gut undergoes slight dilation to form the cloaca; it ventrally
At approximately 15 days after fertilization, invagination receives the allantois and it laterally receives the two meso-
and lateral migration of mesodermal cells occur between nephric ducts. By the seventeenth day of development, the
32
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 33

This chapter will explore the embryology and basic con-


genital anomalies of the urinary tract, rectum, and anal
sphincters. It will delineate the embryology of female geni-
tal organs and discuss congenital anomalies and their treat-
ments in detail.

Urinary System
Kidney and Ureter
The urinary system begins to take shape before any gonadal
development is evident. The kidney exists in three distinct
Mesonephric duct
but slightly overlapping forms during development. The first
is the pronephros, which is present at approximately 22 days
of gestation and is rudimentary and nonfunctioning. The sec-
Cloacal Cloaca ond form, the mesonephros, likely functions for a short time
membrane during the early fetal period. The excretory tubules of the
Ureter mesonephros enter the longitudinal collecting duct (primary
nephric duct). These formations go on to form the meso-
nephric duct, which is crucial in the formation of the male
genital system, but disappears in the female. By the end of
the fourth week, the mesonephric ducts attach to the cloaca
Ventral urogenital and a continuous lumen is present. The ureteric bud is an epi-
sinus
thelial outgrowth of the portion of the mesonephric duct near
the attachment to the cloaca. The bud penetrates the meso-
Urorectal septum Dorsal rectum dermal tissue and ultimately forms the renal calyces, ureter,
FIGURE 3.1 Embryo approximately 32 days (8-mm crown-rump renal pelvis, and collecting tubules. Interactions between the
length) after fertilization. The urorectal septum is shown dividing mesoderm and ureteric bud form the third and permanent
the cloaca into a ventral urogenital sinus and dorsal rectum. Defini- form of kidney, the metanephros (Fig. 3.2). The excretory
tive ureter and mesonephric ducts share a common opening into a units of the kidney develop from the metanephric mesoderm.
partially divided cloaca. Note the ureter has induced formation of a The definitive kidney, formed from the metanephros,
kidney from metanephrogenic blastema.
begins to function around the twelfth week of develop-
ment. Urine is passed and mixes with amniotic fluid. The
endoderm and ectoderm layers are separated entirely by the fetus swallows this and recycles it through the kidney. Dur-
mesoderm layer, with the exception of the prochordal plate ing fetal life, it is the placenta that is responsible for waste
cephalically and the cloacal plate caudally. The cloacal plate excretion, not the kidney.
consists of tightly adherent endodermal and ectodermal lay- The kidney is initially positioned in the pelvic region,
ers. With ventral bending of the embryo, the connecting but it begins a caudal ascent secondary to lumbar and sacral
stalk and contained allantois, as well as the cloacal mem- body growth in the late embryonic and early fetal periods.
brane, are displaced onto the ventral aspect of the embryo. If a kidney fails to ascend, then it remains close to the iliac
A spur of mesodermal tissue migrates from the base of vessels and is known as a pelvic kidney. The kidneys are
the allantois toward the cloacal membrane at approximately occasionally so close in proximity that the lower poles fuse,
28 days after fertilization, forming the urorectal septum (Fig. leading to development of a horseshoe kidney. This struc-
3.1). This structure partitions the cloaca into a ventral uro- ture often cannot ascend completely because it cannot pass
genital sinus and a dorsal rectum. After this, each of the three the inferior mesenteric artery root.
germ layers—the endoderm, mesoderm, and ectoderm—give
rise to specific tissues and organs. The intermediate mesoderm Bladder, Trigone, and Urethra
differentiates into the urogenital structures. Other portions of During the fourth to seventh week of development, the
the mesoderm form multiple structures including the vascular cloaca divides into two separate structures: the urogenital
system, spleen, connective tissue, and the wall of the gut tube. sinus (anteriorly) and the anal canal (posteriorly). These
At birth, the urogenital system can be divided function- structures are separated by a mesodermal structure, the
ally into two different systems: the urinary system and the urorectal septum. The tip of this septum eventually forms
genital system. However, embryologically and anatomi- the perineal body. The upper and largest portion of the uro-
cally, they are intimately connected because both develop genital sinus forms the urinary bladder, which is of endo-
from a common mesodermal ridge known as the intermedi- dermal origin. The bladder is initially continuous with the
ate mesoderm. Both systems share a common origin with allantois (rudimentary structure primarily involved in nutri-
significant interaction between the components of each tion and waste excretion in the embryo), but the lumen of
system during the later stages of development. Epithelial- the allantois becomes obliterated and forms a fibrous cord
mesenchymal interactions are primarily responsible for the called the urachus, which runs from the bladder dome to
maintenance and differentiation of many of the structures the umbilicus and is called the median umbilical ligament in
of the urogenital system. Furthermore, male and female the adult. The middle portion of the urogenital sinus forms
sexual differentiation is dependent on the presence of spe- the prostatic and membranous parts of the urethra, and the
cific promoting or inhibiting factors. distal portion forms the phallic portion.
34 PART 2  Basic Science

FIGURE 3.2  By day 37 to 40, the


kidney has continued to ascend
and undergo medial rotation and
the mesonephric ducts and future
ureter have separated. In addi-
tion, the cloaca has been divided
into ventral urogenital and dorsal
alimentary parts. The inset dem-
onstrates the urogenital sinus and
associated ducts at approximately
40 days (17-mm crown-rump
length) after fertilization. The tri-
gone lies between the separate
ureteric and mesonephric ducts.

The expanding wall of the bladder grows and incorpo- Table 3.1  Timetable of Events in the
rates the mesonephric ducts and ureteric buds, forming Development of the Lower Urinary Tract
the bladder trigone. This structure provides a mesodermal
contribution to the endodermal wall of the vesicourethral 15 days Ingrowth of intraembryonic mesoderm
canal. At approximately 42 days after fertilization, the tri- 16-17 days Allantois appears
17 days Cloacal plate forms
gone may be defined as the region of the vesicourethral canal 22 days Pronephros present
lying between the ureteric orifices and the termination of 28 days Mesonephric duct reaches cloaca; ureteric bud
the mesonephric ducts (Fig. 3.2). The caudal portion of the appears
vesicourethral canal remains narrow and forms the entire 28-49 days Partitioning of cloaca by urorectal septum
urethra. The urethra consists of an epithelium that is derived 30-37 days Ureteric bud initiates formation of metanephros
(permanent kidney)
from endoderm whereas the surrounding connective tissue 41 days Lumen of urethra is discrete; genital tubercles
and smooth muscle is mesodermal in origin. In females, the prominent
cranial portion of the urethra gives rise to the urethral and 42-44 days Mesonephric ducts and ureters drain separately
paraurethral glands. A timetable and schematic representa- into urogenital sinus, defining boundaries of
trigone
tion of the embryologic contributions of the various struc- 51-52 days Kidneys in lumbar region; glomeruli appear in
tures of the urogenital system are shown in Table 3.1 and kidney
Figure 3.3, respectively. 12 weeks Renal function initiates
The separate development of the trigone and bladder 13 weeks Bladder becomes muscularized
may explain why the muscle laminae of the trigone are 20-40 weeks Further growth and development complete the
urogenital organs
contiguous with the muscle of the ureter, but not with the
detrusor muscle of the bladder. This separate development
also may account for pharmacologic responses of the muscu-
lature of the bladder neck and trigone, which partially differ the multiple congenital anomalies of the upper and lower
from those of the detrusor. Because of its embryonic origins urinary tracts. Selected congenital anomalies of the urinary
(mesonephric ducts and ureters), the bladder mucosa is ini- tract and their embryologic causes are shown in Table 3.2.
tially mesodermal, but with time, this lining is replaced by
endodermal epithelia from the hindgut. Rectum and Anal Sphincters
Congenital Anomalies of the Urinary Tract Normal Development of the Hindgut
Anomalies of the urinary system are common (3% to 4% In the early embryo, the caudal portion of the primitive
of live births). Knowledge of the embryology of the genito- gut forms the hindgut. The hindgut extends from the
urinary system is necessary for understanding the causes of posterior intestinal portal to the cloacal membrane and
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 35

FIGURE 3.3 Schematic represen-


tation of the embryologic con-
tributions of various structures of
the female urogenital system.

During further development, a transverse ridge called


Table 3.2  Selected Congenital Anomalies of the
the urorectal septum arises from mesoderm between the
Urinary Tract and Their Embryologic Causes
allantois and the hindgut. This septum gradually grows cau-
Condition Embryologic Cause dally, thereby dividing the cloaca into an anterior portion,
Renal agenesis Faulty interaction between the ureteric bud the primitive urogenital sinus, and a posterior portion, the
and metanephrogenic mesenchyme anorectal canal. The primitive perineum is formed when the
Pelvic kidney Failure of kidney to ascend to the lumbar urorectal septum reaches the cloacal membrane when the
region embryo is 7 weeks. At this time, the cloacal membrane rup-
Horseshoe Fusion of lower poles of both kidneys; ascent
kidney to lumbar region prevented by root of infe-
tures, creating an anal opening for the hindgut and a ventral
rior mesenteric artery opening for the urogenital sinus.
Urachal fistula, Variable persistence of the intraembryonic por- Ectoderm on the surface portion of the cloaca proliferates
cyst, sinus tion of allantois; from bladder to umbilicus and invaginates to create the anal pit. Degeneration of the anal
Double ureter Early splitting of the ureteric bud membrane (formerly cloacal membrane) establishes continuity
Ectopic ureter Two ureteric buds develop from one meso-
nephric duct. One bud is in normal position; between the upper and lower anal canal. Thus, the upper part
the abnormal bud moves downward with of the anal canal is endodermal in origin; the lower third of the
the mesonephric duct to enter into the anal canal is ectodermal. The junction between these regions is
urethra, vagina, vestibule, or uterus delineated by the pectinate or dentate line. The embryologic
Bladder exstro- Insufficiency of mesoderm of the ventral
phy abdominal wall leading to abdominal
origin of the anus explains the differing blood supplies and epi-
ectodermal breakdown and degeneration of thelial cell types of the upper and lower anal canal.
the anterior bladder wall; the bladder opens The external anal sphincter appears in human embryos at
broadly onto the abdominal wall approximately 7 to 8 weeks. This sphincter, together with
the levator ani, is believed to originate from hypaxial myo-
tomes. Although the anal sphincter and levator ani may arise
gives rise to the distal third of the transverse colon, the from distinct primordia, their relationship is very close.
descending colon, the sigmoid, the rectum, and the upper
part of the anal canal. The terminal portion of the hindgut Congenital Anomalies of the Rectum
enters into the cloaca, an endoderm-lined cavity that is in and Anal Sphincters
direct contact with the surface ectoderm. This boundary Imperforate anus is one of the more common abnormalities
between the endoderm and ectoderm forms the cloacal of the hindgut. In simple cases, the anal canal ends blindly at
membrane. the anal membrane, which then forms a diaphragm between
36 PART 2  Basic Science

A B
FIGURE 3.4  A, A 3-week embryo showing the primordial germ cells in the wall of the yolk sac close to the attachment of the allantois.
B, Migrational path of the primordial germ cells along the wall of the hindgut and the dorsal mesentery into the genital ridge. This takes place
between approximately 4 to 6 weeks after fertilization.

the endodermal and ectodermal portions of the anal migrate along the dorsal mesentery of the hindgut and
canal. This occurs when the anal membrane fails to break arrive at the primitive gonads at the beginning of the
down. In more severe cases, a thick layer of connective fifth week, and they invade the genital ridges in the sixth
tissue may be found between the terminal end of the rec- week. Approximately 1000 to 2000 primordial germ cells
tum and the surface because of either a failure of the enter the genital ridges. If the primordial germ cells fail
anal pit to develop or atresia of the ampullar part of the to reach the genital ridge, then the gonads do not develop.
rectum. Vascular accidents in this region are the likely In the female, once the primordial germ cells reach the
cause of rectoanal atresias. These vary greatly and present genital ridge, they are called oogonia. Oogonia begin to
as a fibrous remnant or loss of a segment of the rectum proliferate at this stage which continues into the fourth
or anus. month. Once these cells proliferate via mitosis, they are
Rectourethral and rectovaginal fistulas are likely caused called oocytes.
by abnormalities in the formation of the cloaca or urorectal In the absence of the Y chromosome (XX or XO) and
septum. If the urorectal septum does not extend far enough in the presence of the appropriate somatic cell environ-
caudally or it shifts anteriorly, then the hindgut opens into ment, the primitive sex cords (medullary cords) regress
the urethra or vagina, creating a fistula. (Fig. 3.5A). However, the surface epithelium continues
to proliferate and develops a second generation of cords
Female Genital System called cortical cords. Cells in these cords surround each
oocyte with a layer of epithelial cells called follicular
Gonads cells. Together, the oocyte and follicular cells constitute
Gonads appear in early development as a pair of longi- a primary follicle (Fig. 3.5B). These enter meiosis until
tudinal ridges of steroidgenic mesoderm called the geni- prophase I, when meiosis is arrested. The oocytes remain
tal or gonadal ridges, which are formed by proliferation in this phase until ovulation, which may be up to approxi-
of the epithelium and condensation of the underlying mately 50 years later.
mesenchyme. These initially do not contain germ cells.
Primordial germ cells originate in the epiblast, migrate Genital Ducts, Sexually Indifferent Stage
through the primitive streak, and by the third week reside As in gonadal development, the embryo genital ducts go
in the posterior wall of the yolk sac (Fig. 3.4). They then through a sexually indifferent stage. Until approximately
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 37

The mesonephric ducts open into the urogenital sinus on


either side of this tubercle.
Sexual Differentiation
Sexual differentiation is determined genetically at the time
of fertilization, but the gonads do not acquire sex-specific
morphologic characteristics until the seventh week of devel-
opment. Sexual differentiation is a complex process that
depends on the presence or absence of the Y chromosome,
which contains the testis-determining gene, SRY (sex deter-
mining region on Y). Under its influence, male development
occurs; in its absence, female development occurs.
The way in which the genital ducts undergo sexual dif-
ferentiation is an intricate process that involves multiple
A levels of molecular regulation, of which only part is under-
stood. The SRY protein, autosomal gene SOX9, and mül-
lerian inhibiting substance all play important roles. SRY
is a transcription factor that acts in conjunction with the
autosomal gene SOX9. When the Y chromosome is pres-
ent, SRY and SOX9 influence multiple pathways that lead
to testes development and testosterone production in the
male. SOX9 is also known to bind to the promoter region
of the gene for müllerian inhibiting substance (MIS). MIS
is critical in sexual differentiation because its presence
leads to regression of the paramesonephric ducts (Fig. 3.6).
When the Y chromosome is not present, WNT4, called the
ovary-determining gene, inhibits the function of SOX9 and
regulates the expression of other genes responsible for ovar-
ian differentiation. Estrogens are also important in sexual
differentiation because they stimulate the paramesonephric
ducts to form the uterus, fallopian tubes, cervix, and upper
vagina. They also act on external genitalia.
Once sexual differentiation begins at approximately
7 to 8 weeks, the paramesonephric ducts develop into three
main sections: (1) the cranial portion that opens into the
abdominal cavity, (2) the horizontal portion that crosses the
mesonephric duct, and (3) the fused caudal portion located
medial to the mesonephric duct (Fig. 3.7A). As the parame-
sonephric ducts move medially, a pelvic fold is formed from
the pelvis to the fused paramesonephric ducts, forming the
broad ligament. The two most cranial portions develop into
B the fallopian tubes, and the fused distal portion forms the
FIGURE 3.5  A, Transverse section of the ovary at the seventh week uterus and cervix (Fig. 3.7B).
showing degeneration of the primitive (medullary) sex cords and
formation of the cortical cords. B, Ovary and genital ducts in the Vagina
fifth month. Note degeneration of the medullary cords. The corti- After the solid tip of the paramesonephric ducts reaches
cal zone of the ovary contains a group of oogonia surrounded by the urogenital sinus, two solid evaginations, known as the
follicular cells.
sinovaginal bulbs, grow out from the pelvic part of the sinus
(Fig. 3.8A). These bulbs proliferate and form the solid vagi-
8 weeks, male and female embryos contain two pairs of nal plate. Proliferation continues at the cranial plate, which
genital ducts: paramesonephric (müllerian) ducts and meso- increases the distance between the uterus and urogenital
nephric (wolffian) ducts. The paramesonephric ducts are a sinus (Fig. 3.8B). The solid plate becomes canalized by the
longitudinal invagination of the epithelium of the urogenital fifth month of development (Fig. 3.8C). This demonstrates
ridge. The ducts open cranially into the intra-abdominal cav- that the vagina has two origins: the upper vagina originates
ity and extend caudally. The paramesonephric ducts travel from the paramesonephric ducts and the lower vagina from
lateral to the mesonephric ducts and move medially, cross- the urogenital sinus. The lumen of the vagina remains sepa-
ing the mesonephric ducts ventrally and coming into close rated from the urogenital sinus by the hymen, which con-
proximity in the midline. The paired paramesonephric ducts sists of the epithelial lining of the sinus and a thin layer of
initially are separated by a septum but later fuse to form the vaginal cells.
uterine canal. Once these ducts are combined, the fused tip Although the mesonephric ducts regress in a devel-
projects into the posterior wall of the urogenital sinus where oping female embryo, in some females, a remnant of
it causes a small swelling called the paramesonephric tubule. these ducts persists. If a small cranial portion persists,
38 PART 2  Basic Science

FIGURE 3.6  Factors involved in sexual differentiation of the genital tract.

then it forms the epoohoron or the paroophoron. Most urethra and vagina open (Fig. 3.9C). Table 3.3 delineates the
of these regress during further embryonic development embryologic origin of the major female genital structures.
but the most cranial portion (found in the epoophoron)
and most caudal portion (found in the wall of uterus or
vagina and called Gartner’s cyst) may be found in adult Congenital Anomalies of the Female
women (Fig. 3.7B). Genital System
External Genitalia Congenital Anomalies of the Female Genital
System Presenting as Congenital Absence of
Cloacal folds form around the cloacal membrane in the third
the Vagina and Uterus
week of development. Cranial to the cloacal membrane,
these folds fuse to form the genital tubercle (Fig. 3.9A). Malformations of the müllerian ducts and the external geni-
Caudally, the folds are subdivided into urogenital folds talia can have a significant effect on reproductive potential
anteriorly and anal folds posteriorly. A second set of tissue and sexual function. When a patient presents with such an
elevations, the genital swellings, becomes visible on each abnormality, it is important to put significant thought and
side of the urogenital folds (Fig. 3.9B). When the original time into determining the correct diagnosis and subsequent
cloacal membrane breaks down during the eighth week, the treatment.
urogenital sinus opens between the genital folds directly to The literature reports the rate of female congenital
the outside. Estrogens further stimulate development of the anomalies to be between 0.2% and 0.4% of the general
external genitalia. The genital tubercle elongates and forms population. However, the prevalence of female congenital
the clitoris. The urogenital folds form the labia minora, and anomalies may be as high as 7% when using some of the
the genital swellings form the labia majora. The urogenital newer diagnostic methods. These rates are much higher
sinus remains open and forms the vestibule, into which the when looking at subgroups of patients with recurrent
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 39

A B
FIGURE 3.7  A, Genital ducts in the female at the end of the 8 weeks. The paramesonephric ducts cross the mesonephric ducts to fuse in the
midline and form the uterine canal. B, Genital ducts after descent of the ovary. The only remnants from the mesonephric duct system are the
epoohoron, paroophoron, and Gartner’s cyst.

pregnancy loss and infertility. However, in many instances vagina as well as unicornuate and bicornuate uteri and
these anomalies are asymptomatic. related abnormalities.
Although sex steroid receptor abnormalities and enzyme There are endless variations to müllerian and vagi-
deficiencies are not considered malformations of the mül- nal anomalies. It is impossible to effectively note these
lerian ducts, they often have similar clinical presentations variations in any one classification system. The most
and should be considered in the differential. The workup accepted classification of uterine anomalies, published
and diagnosis of these disorders are beyond the scope of by the American Society of Reproductive Medicine
this chapter; however, similar reconstructive techniques are (ASRM), places uterine anomalies into distinct groups
often utilized. on the basis of anatomic configuration (Table 3.4).
Because vaginal anomalies are not included in this clas-
Classification sification, they must be described along with the uter-
The classification of müllerian anomalies helps with the ine anomaly. This classification does not give insight
diagnosis and the comparison of outcomes after various into pathophysiology, but it is an effective way to com-
modes of management. However, there is no single clas- municate observations for the purposes of treatment
sification that encompasses all anomalies that have been and prognosis. Other, more comprehensive classification
reported in the literature. systems do exist, however, they are utilized less in the
Although the direct cause of most of these anomalies United States.
is not known, on the basis of our embryologic knowl-
edge, the pathogenesis of most of these anomalies can Müllerian Agenesis (Mayer Rokitansky Kuster
be understood. On the basis of pathophysiology, mülle- Hauser Syndrome)
rian anomalies can be broadly classified as being related Müllerian agenesis (i.e., Mayer Rokitansky Kuster Hauser
to (1) agenesis, (2) vertical fusion defects, or (3) lateral syndrome) was first described in 1829. Its incidence is
fusion defects. Compared with other anomalies, agenesis reported to be 1 in every 5000 newborn females. The etiol-
of the uterus and vagina are relatively common abnor- ogy of müllerian agenesis remains unknown. It appears to be
malities. Vertical fusion defects are usually the result of influenced by multifactorial inheritance, and rare familial
abnormal canalization of the vaginal plate and result in cases have been reported. It does not appear to be transmit-
defects such as a transverse vaginal septum and imper- ted in an autosomal dominant inheritance pattern because
forate hymen. Lateral fusion defects can be symmetrical none of the female offspring of women with müllerian agen-
or asymmetrical and include septum of the uterus and esis (born via in vitro fertilization and surrogacy) have shown
40 PART 2  Basic Science

A B C

FIGURE 3.8  Coronal and sagittal sections demonstrating the formation of the uterus and vagina. A, At approximately 9 weeks the paramesonephric
ducts meet the urogenital sinus. In addition, the uterine septum begins to degenerate. B, At 12 weeks, the sinovaginal bulbs proliferate, creating
a solid vaginal plate, which increases the distance between the uterus and urogenital sinus. C, The fornices and upper portion of the vagina are
formed by vacuolization of the paramesonephric tissue whereas the lower portion of the vagina is formed by vacuolization of the sinovaginal bulbs.

A B C
FIGURE 3.9  A, Sexually indifferent stage of external genitalia development at approximately 4 to 5 weeks. B, At 20 weeks, sexual differentia-
tion of the female external genitalia is evident. C, Newborn.
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 41

Table 3.3  Embryologic Origin and transverse septum. Because these patients have a 46XX
Female Derivative karyotype, normal ovaries will be present in the pelvis. Ovu-
lation can be documented as a shift in basal body tempera-
Indifferent Structure Female Derivative ture. These patients’ hormonal levels are normal and their
Genital ridge Ovary cycle length on the basis of hormonal studies varies from 30
Primordial germ cells Ova to 34 days. In addition, they may experience the monthly
Sex cords Follicular (granulosa) cells
pain (mittleschmerz) that is indicative of ovulation.
Müllerian agenesis is associated with renal and skeletal sys-
Mesonephric tubules Oophoron
tem anomalies. Renal abnormalities are noted in 40% of these
Paroophoron
patients. These include complete agenesis of a kidney, malposi-
Mesonephric ducts Appendix of ovary tion of a kidney, and changes in renal structure. Skeletal abnor-
Gartner’s duct cyst malities are noted in 12% of patients and include primarily
Paramesonephric ducts Fallopian tubes spine defects and limb and rib defects. Patients with müllerian
Uterus agenesis should be actively assessed for these associated anom-
Upper vagina alies. Hearing difficulties also have been reported in patients
Definitive urogenital sinus (lower Lower vagina with müllerian agenesis. A higher rate of auditory defects has
part) Vulvar vestibule been noted in general in patients with müllerian anomalies
Early urogenital sinus (upper part) Urinary bladder compared with those with normal müllerian structures.
Urethra
The diagnosis of müllerian agenesis is confirmed via imaging
techniques. Abdominal ultrasonography will demonstrate the
Genital tubercle Clitoris
lack of a uterus and the existence of ovaries. The presence of a
Urogenital folds Labia minora
midline mass consistent with a blood collection usually indicates
Genital swellings Labial majora an obstructive müllerian anomaly. The distinction between mül-
lerian agenesis and obstruction is extremely important because
an incorrect diagnosis can jeopardize appropriate management.
With the advent of magnetic resonance imaging (MRI), lapa-
Table 3.4  ASRM Classification of Müllerian roscopy is no longer considered necessary to make this diag-
Anomalies nosis. Typical findings in the pelvis include normal ovaries and
I. Hypoplasia/agenesis a. Vaginal fallopian tubes, and usually small müllerian remnants attached
b. Cervical to the proximal portion of the fallopian tubes, which may be
c. Fundal solid or have functioning endometrial tissue. Direct commu-
d. Tubal
e. Combined
nication with the radiologist about the differential diagnosis
before imaging studies is important. On occasion, the unsus-
II. Unicornuate a. Communicating
b. Noncommunicating pecting radiologist may interpret the small uterine remnants
c. No cavity as a uterus. Careful attention to the very small dimensions of
d. No horn this structure will alert the physician to this possibility. MRI is
III. Didelphus also important to evaluate co-existing anomalies of the urinary
IV. Bicornuate a. Complete tract such as renal agenesis and other renal malformations. It is
b. Partial critical to diagnose these before surgical treatment.
V. Septate a. Complete The diagnosis, usually made in early adolescence, must be
b. Partial explained to the patient with great sensitivity. At a time when
VI. Arcuate being like her peers is extremely important, knowledge of
VII. Diethylstilbestrol (DES) this diagnosis can be psychologically devastating. Each patient
related must be reassured that her external genitalia appear normal
and that they will be able to have a normal sex life after the
creation of a normally functioning vagina. Although usually
evidence of vaginal agenesis. Because the vagina and associ- not voiced, the inability to subsequently bear children is a
ated uterine structures do not develop with this disorder, it major disappointment to teenagers. Fortunately, with assisted
is an ASRM Class IA müllerian anomaly. Patients typically reproductive technology procedures including in vitro fertil-
present during their adolescent years with the complaint ization and surrogacy, having her own genetic child will be an
of primary amenorrhea. As a cause of primary amenorrhea, option for many of these young women.
müllerian agenesis is second only to gonadal dysgenesis.
Patients with müllerian agenesis will have normal onset of Receptor Abnormalities and
puberty and appropriate secondary sexual characteristics but Enzyme Deficiencies
do not start menstruating. They do not complain of cyclic These disorders are secondary to enzyme deficiencies or
pelvic pain like patients with obstructive müllerian anoma- defects in the hormone receptors of the sex steroid pathways.
lies. The external genitalia appear completely normal, with Because these affect sex steroid production during embryo-
normal pubic hair growth and normal size labia minora, which genesis, development of the embryo and fetus can be greatly
is in contrast to patients with complete androgen insensitivity affected. Often affecting the embryo during the sexually
syndrome. Hymenal fringes may be evident, but the vaginal indifferent stage, the absence of specific receptors or enzymes
opening is absent. No pelvic masses suggestive of hematocol- can completely change the hormonal environment, which
pos will be evident, which is in contrast to cases of complete leads to discrepancies between genotype and phenotype. The
42 PART 2  Basic Science

most common syndromes include complete and incomplete Table 3.5  Differences in Clinical Presentations
androgen insensitivity syndrome, 5-α-reductase deficiency, of Mullerian Agenesis and Complete Androgen
17-α-hydroxylase deficiency, vanishing testes syndrome, and Insensitivity Syndrome
absent testis-determining factor.
These disorders, with the exception of complete andro- Complete Androgen
gen insensitivity syndrome, often have variable presenta- Müllerian Agenesis Insensitivity Syndrome
tions including ambiguous genitalia at birth, inappropriate Uterus Absent Absent
virilization at puberty, and/or lack of pubertal development. Ovaries Present Absent
These are rare, complex disorders that require the attention Testes Absent Present (undescended)
Breast Normal Normal
of a subspecialist for proper diagnosis. development
Vagina Foreshortened Foreshortened
Complete Androgen Insensitivity Syndrome Hormone Normal estrogen Normal male
This is an X-linked recessive disorder in which there is assay testosterone
a defect in the androgen receptor leading to testosterone Karyotype XX XY
resistance. This resistance leads to developmental failure
of all of the male sexual characteristics that are dependent
on testosterone. These individuals have a karyotype of XY, preferred method for many years. The success of any tech-
and they have a normal functioning SRY. The testes develop nique depends in large part on the emotional maturity of
normally during embryogenesis and produce normal levels the patient. Pretreatment counseling and continued support
of testosterone. However, because the receptor is defec- during treatment are important.
tive, all downstream development dependent on testoster-
one does not occur. Specifically, the active development Vaginal Dilation
of the mesonephric ducts does not take place, leading to The simplicity and ease of vaginal dilation and its low com-
absence of the seminal vesicle, prostate, ductus deferens, plication rate compared with surgical vaginoplasty dictates
and epididymis and maturation and descent of the testes. its use as the initial form of therapy for most patients. The
Because the embryo testis is normal, it produces MIS, American College of Obstetrics and Gynecology released
leading to active regression of the paramesonephric ducts. a committee opinion in 2002 that recommends nonsurgi-
This prevents further development of the uterus, fallopian cal management of vaginal agenesis as the first mode of
tubes, and upper vagina (Fig. 3.6). These individuals are treatment.
genetically male and have testes but are typically female Frank’s technique of dilation involves actively plac-
in appearance. The testes are not fully developed and are ing pressure with the dilators against the vaginal dimple
often located in the abdomen, inguinal canal, or labia. The (Fig. 3.10). The patient is not only in an awkward posi-
external genitalia appear normal for a female infant at tion but the hand applying the pressure can become tired.
birth. At puberty, the testes make normal or high levels of In 1981, Ingram proposed the concept of passive dilation,
testosterone, which are aromatized to estrogen in the cell, in which pressure is placed on the dilator by sitting on a
leading to normal female secondary sexual characteristics. bicycle seat. Roberts reported a success rate of 92% in
At puberty, breast development occurs, but the areolas are women who dilated the vagina via the Ingram technique
pale and the pubic and axillary hair is sparse. Similar to for 20 min three times a day (2001). The average time to
those with müllerian agenesis, these patients often pres- creation of a functional vagina was 11 months. This series
ent with primary amenorrhea. The diagnosis of complete demonstrated that an initial dimple smaller than 0.5 cm
androgen insensitivity syndrome is made with physical was all that was necessary to achieve adequate dilation.
examination and imaging demonstrating normal female Failure of this technique was not related to the length of
external genitalia; absence of the upper vagina, uterus, the vaginal dimple but rather more closely associated with
ovaries, and fallopian tubes; high serum testosterone con- the patient’s youth. Failure of this technique was more
centrations; and 46 XY karyotype. Please see Table 3.5 for common in patients younger than 18 years of age.
the differences between complete androgen insensitivity When the patient expresses a desire to proceed with
syndrome and müllerian agenesis. Because both disorders therapy, she is shown the exact location of her vaginal dim-
present without a vagina, the treatment options are the ple. The axis of dilator placement is also demonstrated (Fig.
same. However, those with complete androgen insensitiv- 3.11). The process is initiated by placement of the small-
ity syndrome should undergo surgical excision of the testes est dilator against the dimple. Pressure is kept on the distal
after puberty because of the increased risk of developing aspect of the dilator by sitting upon a stool while leaning
testicular cancer after age 25. slightly forward. When the dilator fits comfortably, she
moves to the next size dilator. The patient is instructed
to use this technique a minimum of 20 min a day, but she
Treatment of Congenital Absence of the
is encouraged to dilate up to two to three times a day. In
Vagina and Uterus
motivated patients, a functional vagina can be created in as
The first goal of treatment of congenital absences of the few as 12 weeks. Counseling and psychologic support are
vagina, including müllerian agenesis and complete androgen integral to successful treatment. Patients are requested to
insensitivity syndrome, is creation of a functional vagina to return to the office frequently to allow providers to monitor
allow for intercourse. Frank first proposed vaginal dilatation their progress and provide guidance and an opportunity to
with the use of a dilator as a means of creating a neovagina answer questions. Intercourse may be attempted once the
in 1938. However, surgical vaginoplasty has remained the largest dilator fits comfortably.
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 43

tension device on the lower abdomen. Although the


original description of the Vecchietti procedure utilized
laparotomy, this technique is currently performed via
laparoscopy.
The first step in this procedure is to use a sharp liga-
ture carrier (similar to a Stamey needle) to insert one
end of a No. 2 polyglycolic acid suture through the ret-
rohymenal dimple into the peritoneal cavity between the
bladder and the rectum under laparoscopic guidance. The
other end of this suture is placed through a 3-cm acrylic
olive or stent. The next step is to use a curved blunt lig-
ature carrier to retroperitoneally burrow from a lateral
suprapubic laparoscopic port site to the peritoneal fold
between the bladder and the uterine rudiment. The end
of the suture introduced with the sharp ligature carrier
is placed through the eye of this curved ligature carrier
and pulled retroperitoneally back through the abdominal
FIGURE 3.10  Examples of vaginal dilators of different sizes. wall port site incision. This procedure is repeated on the
opposite side with the other end of the suture. After the
laparoscope is removed and the abdominal wall incisions
Anterior
abdominal wall
are closed, the ends of the suture are attached to a supra-
pubic Vecchietti spring traction device located externally
on the abdomen.
Constant traction is applied postoperatively to the
perineal olive by daily readjustment of the tension of the
Bladder sutures and traction device. The neovagina lengthens by
1 to 2 cm per day, such that a 10- to 12-cm vagina is cre-
ated in 7 to 9 days. After creation of the vagina, the olive
Posterior Peritoneal
cavity (now located at the apex of the neovagina) is removed
angle
and the patient is sent home with a vaginal mold in place.
After surgery, it is important to initiate regular sexual
intercourse or routinely use dilators to maintain vaginal
length.
Vecchietti reported a series of over 500 patients with a
Rectum success rate of 100% and only nine complications, includ-
ing one bladder and one rectal fistula (1992). Several
smaller studies have subsequently been reported by other
surgeons with similar outcomes. A 3-year follow-up study
by Kaloo assessed functional and psychologic outcomes
in five patients (2002). All five subjects reported having
FIGURE 3.11  Schematic drawing of angle of dilator placement. The a functioning vagina allowing satisfactory intercourse and
patient is viewed in the lithotomy position and the axis is directed
improvement in general well-being.
away from the bladder.
McIndoe Procedure
Multiple types of graduated dilators made of vari- The traditional surgical management of vaginal agenesis is
ous materials are present on the market, all of which are to create a vaginal space followed by placement of a lining
equivalent in achieving successful outcomes. Patients may to prevent stenosis. Multiple native tissue grafts and at least
stop and reinitiate dilation at any time without any nega- one synthetic graft have been used to line this cavity with
tive long-term sequelae. Patients are most often interested varying degrees of success in preventing subsequent stenosis
in initiating this therapy the summer before college when of the neovagina (Table 3.6).
they are mature enough and motivated to create the vagina. The most widely used surgical technique for creation of
However, the timing of therapy is purely dependent on the a neovagina is the McIndoe operation. The first step of the
patient’s goals and desires. procedure is obtaining the split thickness skin graft. The
plastic surgery team typically acquires the skin graft from
Vecchietti Procedure the buttock or inner thigh—two locations usually covered
Giuseppe Vecchietti described this method of creat- by clothing. The patient is placed in either the lithotomy
ing a neovagina in 1965. Similar to vaginal dilation, this or the prone position, and the site is cleansed with an anti-
method avoids the use of a graft. The Vecchietti pro- septic solution and then soaked with an epinephrine saline
cedure is a one-step procedure in which a neovagina is gauze to allow for vasoconstriction of small punctuate
created in approximately 7 days by continuous pressure bleeding sites. Mineral oil is applied to the donor site, and
on the vaginal dimple using an external acrylic “olive” the skin is held taught while the electrodermatome device
that is connected by retroperitoneal sutures to a spring is used to obtain a thick split thickness skin graft. The skin
44 PART 2  Basic Science

Table 3.6  Surgical Methods of Creating a


Neovagina
Dissection of a perineal Split thickness skin graft (McIndoe)
space Full thickness skin graft
Peritoneum (Davydov)
Tissue engineering
Muscle and skin flap
Adhesion barriers
Tissue expansion
Bowel vaginoplasty Sigmoid colon
Vulvovaginal pouch Williams vaginoplasty
Traction on retrohymeneal Vecchietti
fovea

FIGURE 3.12  Skin graft is sutured around a mold.


FIGURE 3.13  The initial transverse cut is made on the tissue between
the urethra and rectum.
graft should be 0.015 to 0.018 inches thick. After applica-
tion of an antiseptic solution, the donor site is covered with
a transparent adhesive film which is fixed in place by several After creation of the vaginal space, the mold covered
stitches. Within 2 to 3 weeks the area heals with accept- with the skin graft is placed inside of the cavity (Fig. 3.15).
able scarring. The skin graft is placed thru a 1:5 ratio skin At the introitus, the skin graft is attached with several sepa-
mesher. The purpose of meshing the skin is not to stretch rate 3-0 absorbable stitches. To hold the mold in place, sev-
the skin but rather to allow for escape of any underlying eral loose, nonreactive sutures such as 2-0 silk are used to
blood clots or serous fluids. This skin graft is sutured around approximate the labia minor in the midline.
a mold with 4-0 absorbable suture (Fig. 3.12). It is impor- During the ensuing week, the patient is maintained on
tant that the mold is covered completely by the graft. Any bed rest with broad-spectrum antibiotics, a low-residue
uncovered sites due to lack of sufficient tissue or a gaping diet, an indwelling catheter, and an agent to decrease bowel
hole in the suture line tend to result in the formation of motility. Upon return to the operating room in 1 week, the
granulation tissue. Thus, great care must be taken to obtain mold is carefully removed. After the vaginal cavity is irri-
a sufficient amount of graft for this procedure. gated with warm saline, the graft site is carefully assessed
The patient is placed in the dorsolithotomy position. A for any signs of necrosis or underlying hematoma. Another
transverse incision is made in the vaginal vestibule, between soft mold is then reinserted and kept in place for the next
the rectum and urethral openings (Fig. 3.13). In a patient 3 months except during defecation and urination. Night-
who has not had prior surgery or radiation in the area, areo- time usage of the mold is recommended for the next 6
lar tissue is now encountered. This tissue is easily dissected months. To prevent contracture of the vagina, the patient
with either fingers or a Hagar dilator on either side of a is instructed to reinsert the mold during extended times of
median raphe (Fig. 3.14). The dissection is continued for at sexual inactivity.
least the length of the mold without entering the peritoneal Because of concern regarding tissue necrosis from mold
cavity. By cutting the median raphe, the two channels are pressure and subsequent fistula formation, rigid and soft
then connected. If the dissection is performed in this man- molds have been used for this procedure (Figs 3.16 and 3.17).
ner, then minimal bleeding is encountered. Any bleeding Soft molds theoretically decrease the risk of fistula formation
sites must be controlled meticulously to avoid lifting of the that can result from avascular necrosis. A soft mold can be
graft from the newly created vaginal wall and subsequent created by covering a foam rubber block with a condom. The
nonadherence and necrosis. foam is able to expand and fit the neovaginal space, thereby
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 45

FIGURE 3.14 Placement of Hagar dilator to create space for the FIGURE 3.15  The mold with the graft in placed in the space. Notice
graft. The direction of the Hagar dilators is posterior. that the space to be created must completely accommodate the
mold.

providing equal pressure throughout the canal. However, a


report by Alessandrescu on the use of a rigid mold on 201
patients who underwent the McIndoe operation demon-
strated a fistula formation rate of less than 1% (1996). There
is no study comparing the outcomes of soft versus rigid molds
in this operation. Typically, a rigid mold is used initially, but
the patient is sent home with a soft mold in place.
Difficulty in dissecting the space between the bladder
and rectum and increased probability of bleeding and fistula
formation are encountered in the patient with a prior vagino-
plasty procedure. Other problems that may be encountered
include a narrow pubic arch, strong levators, a short perineum,
prior hymenectomy, and a congenitally deep cul-de-sac. Sur-
gical complications include postoperative infection and hem-
orrhage, failure of graft and formation of granulation tissue,
and fistula formation. In general, the incidence of complica-
FIGURE 3.16  Hard glass mold.
tions is low: rectal perforation in 1%, graft infection in 4%,
and graft site infection in 5.5% of patients. In a review of 50
patients by Buss, two rectovaginal fistulas and one graft fail- for prolonged use of the mold. Indeed, part of the presur-
ure were reported (1989). Five patients (10%) required an gical assessment involves determination of patient matu-
additional operative procedure. Eighty-five percent of these rity and motivation concerning use of dilators. Lack of
patients considered their surgery to be a success. compliance with the postoperative use of dilators will lead
An 80% success rate has been reported with this pro- to contracture and diminishment of vaginal length. Long-
cedure. Because success rates are highest in those patients term data on the McIndoe procedure, although limited,
that have not undergone prior vaginoplasty, patients must consistently indicate an improvement in quality of life. In
be counseled extensively before surgery regarding the need a series published by Mobus of 44 patients who underwent
46 PART 2  Basic Science

prolapse or enterocele formation. Minor granulation tissue


was noted at the vaginal cuff, but the vault was primarily
covered with squamous epithelial tissue.
Adhesion Barrier Lining
Jackson first described the use of an adhesion barrier to
line the neovagina in 1994. Oxidized regenerated cellulose
(INTERCEED®; Johnson and Johnson Patient Care, Inc.,
New Brunswick, NJ) forms a gelatinous barrier on raw sur-
faces; thus, it prevents adhesion formation. After creation
of the vaginal space, sheets of cloth-like oxidized regener-
ated cellulose are wrapped around the mold and placed in
the vagina in a manner similar to the McIndoe procedure.
The neovaginal space must be free of any bleeding. Epitheli-
alization is noted to occur within 3 to 6 months. Small areas
FIGURE 3.17  Adjustable vaginal mold by Mentor, Minneapolis, MN. of granulation tissue may be seen at the apex of the vagina
and resolve after application of silver nitrate. The average
vaginal depth ranges from 6 to 12 cm. Continuous use of
a surgical procedure to create the vagina, 82% achieved a the mold is encouraged until complete epithelialization has
functional satisfactory postoperative result (1996). Vaginal occurred.
length varied from 3.5 to 15 cm. In another long-term study A case series by Motoyama et al. (2003) assessed the
by Klingele evaluating women who underwent a McIndoe outcome of this technique on ten patients with vaginal agen-
procedure, 79% of the patients reported improved quality esis. Complete squamous epithelialization was noted within
of life, 91% remained sexually active, and 75% regularly 1 to 4 months. When compared with a normal vagina, fern
achieved orgasm (2003). formation was noted and the vaginal pH was always acidic.
The newly created vagina must be inspected at the time However, none of the women complained of vaginal dry-
of the yearly pelvic examination. Hair growth has been ness or foul-smelling discharge. Patients who were sexually
reported to be a problem with some skin grafts. Transfor- active did not report any problems.
mation to squamous cell carcinoma from skin graft has been The advantages of the use of oxidized regenerated cel-
described. lulose include avoidance of any scars, a readily available
product, and low expense. In addition, the surgical proce-
Peritoneal Graft: Davydov Procedure dure is simplified into a one-stage procedure. Although the
Use of the peritoneum to line the newly created vaginal reported data appear encouraging, confirmatory studies are
space was popularized by Davydov, a Russian gynecologist, required before the use of oxidized regenerated cellulose
and it was first described by Rothman in the United States can be recommended without reservation.
in 1972. In the original description, a laparotomy is per-
formed after creation of the vaginal space as described in Tissue Engineering
the previous section for the McIndoe operation. The first case in which in vitro cultured vaginal tissue was
A cut is made on the peritoneum overlying the new used to line the neovagina was published by Panici et al.
vagina. Long sutures are applied to the anterior posterior (2007). A 1-cm2 biopsy was performed from the vulvar ves-
and lateral sides of this peritoneum. The sutures are then tibule. Autologous keratinocyte cultures were created from
pulled down through the vaginal space, thus pulling the this biopsy. The McIndoe procedure was used to create the
peritoneum to the introitus. The edge of the peritoneum vaginal space, and the autologous in vitro cultured tissue was
is then stitched to the epithelium of the introitus. Clos- used to line the cavity. The length of the vagina was reported
ing the peritoneum on the abdominal side forms the top to be normal. Of course, long-term data are currently lack-
of the vagina. Several investigators have also described the ing, as is information on vaginal stenosis. However, if proven
laparoscopic modification of this procedure. This procedure to be effective, this method of creating a vagina may lead to
may have several advantages compared with the traditional increasing popularity of the McIndoe procedure given the
McIndoe procedure. The most significant advantage is the lack of concomitant scars on the skin.
avoidance of donor-site morbidity or cosmetic compromise
that is typically associated with the McIndoe procedure. In Muscle and Skin Flap
addition, there is no unappealing hair growth or risk of graft These approaches are not the procedures of choice for
rejection with the Davydov procedure. women with congenital absence of the vagina. However,
In Davydov’s first reported series in 1980, sexual inter- they may be used for those who require vaginal reconstruc-
course was initiated within several weeks of surgery in all tion after exposure to radiation or multiple surgical proce-
but 1 of his 30 patients. On follow-up, the length of the dures. The advantage of using a full-thickness skin flap is
vagina was noted to be 8 to 11 cm. Soong et al. (1996) that it avoids the problem of contracture encountered with
published a series of 18 patients who underwent the lap- split thickness grafts.
aroscopic modification of this procedure: 85% reported The use of gracilis myocutaneous flaps and rectus
being sexually satisfied during an 8- to 40-month follow- abdominus myocutaneous flaps for vaginal reconstruction
up. Although there was one report of a rectovaginal fistula have been reported. These approaches have been asso-
18 months after the surgery, there was no evidence of vault ciated with a conspicuous scar and a higher failure rate.
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 47

An alternative approach, introduced by Wee and Joseph


in Singapore, created flaps that maintained good blood
supply and innervation (1989). Known as a “pudendal-
thigh flap vaginoplasty,” this technique has been particu-
larly successful in patients with vulvar anomalies. In one
study by Monstrey et al. (2001) of patients with mülle-
rian agenesis, 100% success in creating a functional vagina
was reported.
The patient’s own labia majora and labia minora have also
been used to create a vagina. Tissue expansion has also been
advocated to create labiovaginal flaps, which are then used
to line the neovagina. Other modifications of this procedure
have been reported.
Bowel Vaginoplasty
Similar to muscle and skin flaps, bowel vaginoplasty is not FIGURE 3.18  Nonobstructing longitudinal vaginal septum.
the procedure of choice in women with congenital absence
of the vagina. However, this technique can be used for to have a bicornuate uterus. Other investigators have noted
vaginal reconstruction in patients who have either under- a predominance of didelphic uteri in such cases.
gone pelvic radiation or in cases of previously failed vagi- A longitudinal vaginal septum should be removed in
noplasty procedures. For this procedure, also known as a patients with complaints of dyspareunia and those who
colocolpopoiesis, a portion of the large bowel or sigmoid desire to be able to effectively use a tampon. In cases of
colon with its preserved vascular pedicle is sutured into didelphic uteri, removal of the septum may be necessary
the neovagina. Continuous use of dilators is not considered to allow for sufficient access to each cervix for pap smears.
necessary, although constriction has been noted when the Some obstetricians advocate removal of a longitudinal vagi-
ilium has been used. Success rates of up to 90% have been nal septum before delivery to avoid potential dystocia and
reported, but reported complications include profuse vagi- laceration of the septum. The number of patients with vagi-
nal discharge, prolapse, introital stenosis, bowel obstruc- nal septa who have had successful vaginal deliveries remains
tion, and colitis. Finally, there is a report of a mucinous unknown. However, emergent resection of a vaginal sep-
adenocarcinoma arising in a neovagina lined with the sig- tum at the time of delivery to resolve dystocia has been
moid colon. A laparoscopic modification of this procedure reported. It seems reasonable to remove a thick longitudinal
has also been described. Given the increased complica- septum before pregnancy or before delivery if discovered
tion rates, it seems appropriate to reserve this treatment during pregnancy.
modality for complex situations in which a prior vagino- The goal of surgery is removal of a wedge of tissue with-
plasty technique has failed or when there are multiple uro- out damaging the cervix, bladder, or rectum. A Foley cath-
genital malformations. eter is placed in the bladder. Because longitudinal vaginal
septa are well vascularized, the anterior border of the sep-
tum, followed by the posterior border, are removed using
Longitudinal Vaginal Septum
unipolar electrosurgery. Care must be taken not to remove
A longitudinal vaginal septum is an example of a lateral the septum too close to the vaginal wall because this will
fusion defect and is typically associated with uterine anoma- leave larger mucosa defects. The edges of these mucosal
lies such as septate uterus and uterus didelphyis. The sep- defects are reapproximated with 2-0 absorbable suture.
tum that divides the vagina can be either nonobstructing Postoperative use of a vaginal mold is not necessary.
or obstructing. A nonobstructing vaginal septum is often
asymptomatic and discovered at the time of a pelvic exam Obstructing Longitudinal Vaginal Septum
or childbirth. A woman with an obstructing vaginal septum Women with an obstructing longitudinal septum usually
often presents with increasingly severe dysmenorrhea and a have normal-onset menarche and increasingly severe dys-
unilateral vaginal mass. menorrhea. These patients are most likely to have a didel-
phic uterus. One of the uteri has a patent outlet; the other
Nonobstructing Longitudinal Vaginal Septum is obstructed (Fig. 3.19). If the obstruction is low in the
Nonobstructing longitudinal vaginal septa account for 12% vagina, then eventually a bulge may be noted upon examina-
of the malformations of the vagina. Although most are tion of the lower canal. However a higher obstruction may
asymptomatic, some patients complain of continued vaginal be completely missed with just visual inspection, which is
bleeding despite placement of a tampon, difficulty remov- frequently the case in an adolescent. Digital examination
ing a tampon, or dyspareunia. The septum may be complete may reveal a tense bulge in the vaginal wall (Fig. 3.20). In
or partial and can exist in any portion of the vagina (Fig. many instances the bulge is toward the anterior portion
3.18). The vaginal cavities created by a septum may be dis- of the vagina between the 12:00 to 3:00 positions or the
proportionate in size and therefore the septum may be eas- 9:00 to 12:00 positions because of the rotation of the two
ily missed during physical examination. Once the diagnosis cervices.
is made, the uterus and renal anatomy should be assessed for Ultrasonography of the pelvis will usually show a pel-
associated anomalies. In one study by Haddad et al. (1997), vic mass, which can be misleading unless a vaginal septum
60% of patients with longitudinal vaginal septa were found is considered in the differential diagnosis. MRI is the best
48 PART 2  Basic Science

obstructed vagina. Allis clamps are placed on the edges


of this incision, and the cavity is assessed. When remov-
ing the medial border of this septum, care must be taken
to avoid damaging the urethra. The septum should be
removed in its entirety to allow easy access to the second
cervix for pap smears. The raw mucosal edges are approxi-
mated with 2-0 absorbable suture. Use of a vaginal mold
after surgery is not necessary because it would be impos-
sible for the patient to consistently place the stent in the
correct position. In difficult cases, use of either a resecto-
scope or hysteroscope to remove the longitudinal vaginal
septum has been described.
The previously hidden cervix and obstructed vaginal
canal will often appear abnormal. The cervix is usually flush
with the vaginal fornix and often appears erythematous
and glandular. Histologically, the obstructed vaginal canal
and septum on its obstructed side will have a columnar
epithelium and glandular crypts. Some patients may com-
plain of profuse vaginal discharge after removal of the sep-
tum. Metaplastic transformation of the vaginal mucosa to a
FIGURE 3.19  Schematic of obstructing longitudinal septum.
mature squamous epithelium can take many years.
Simultaneous laparoscopy during removal of a vaginal sep-
tum is not recommended unless the diagnosis is unclear on
MRI or imaging studies indicate concomitant pelvic masses. As
in all cases of obstructive müllerian anomalies, endometriosis
is frequently encountered, even if the septum is only partially
obstructing. With the possible exception of endometriomas,
excision of the endometriosis is not recommended because
these lesions will regress after removal of the obstruction. The
obstetric outcome of such patients is similar to that reported
for patients with simple uterine didelphis. Pregnancy rates of
87% and live birth rates of 77% have been reported.

Transverse Vaginal Septum


A transverse vaginal septum results when there is fail-
ure of fusion and/or canalization of the urogenital sinus
and paramesonephric ducts. The incidence of a transverse
vaginal septum appears to be between 1 in 21,000 and 1
in 72,000. A transverse vaginal septum may be located in
FIGURE 3.20  An obstructing longitudinal septum usually presents as the upper (46%), middle (40%), and lower (14%) third of
a bulge in the vagina. the vagina. A transverse vaginal septum may be complete
or incomplete and varies in thickness (Figs 3.21 and 3.22).
imaging mode for definitively diagnosing this abnormality. Patients with a complete transverse vaginal septum gen-
Like other müllerian anomalies, a longitudinal vaginal sep- erally complain of primary amenorrhea in early to midpu-
tum is associated with renal abnormalities, including absent berty. Pelvic pain is a common, but not universal, presenting
kidneys, pelvic kidneys, and duplicate ureters. complaint. Patients with high transverse vaginal septa are
Some longitudinal septa will be found to be only par- most likely to experience pelvic pain, and the pain will man-
tially obstructing, and a small opening in the septum can be ifest earlier than in patients with septa located lower in the
found during menses with close inspection. Symptoms may vagina. This is believed to be secondary to decreased space
vary from irregular and prolonged bleeding to profuse vagi- for the hematocolpos that ensues after initiation of menses.
nal discharge. Occasionally, the pinpoint opening provides a Patients with an incomplete transverse vaginal septum may
pathway for organisms to access the obstructed vagina lead- complain of profuse vaginal discharge, dyspareunia, inability
ing to pelvic infection and pyocolpos. Physical examination to insert a tampon, or tear during intercourse with resul-
is unlikely to reveal a tense bulge, but a slight fullness may tant bleeding. If asymptomatic, then it may not be discov-
sometimes be appreciated in the paravaginal area. ered until a routine gynecologic examination. Very rarely a
Accurate delineation of anatomy is a prerequisite for transverse vaginal septum may be detected in an infant or
surgical excision of a noncommunicating longitudinal vagi- young child. In such instances, a mucocolpos can present
nal septum. The first step is to place a needle into the as an abdominal mass. If large enough, then this mass may
bulging vaginal wall to identify the correct plane of dissec- cause ureteral obstruction with secondary hydronephrosis.
tion. Once blood extrudes from the needle, the adjacent Compression of the vena cava and cardiopulmonary failure
tissue is incised with electrosurgery to gain access into the has also been reported.
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 49

By increasing intra-abdominal pressure and increasing the


bulge of the imperforate hymen, the Valsalva maneuver
may further assist in this differentiation. If an opening to
the vagina is noted, then a manual or speculum exam may
reveal a higher location of the septum. A rectal exam is very
helpful in detecting a hematocolpos because the bulge is
readily palpable.
Transperineal and transabdominal ultrasonography can
sometimes diagnose and determine the thickness of a trans-
verse vaginal septum. However, in most cases an MRI of
the pelvis will be required to differentiate a transverse vagi-
nal septum from other müllerian anomalies such as cervical
agenesis. These patients should also be evaluated for asso-
ciated anomalies, including aortic coarctation, atrial septal
defects, urinary tract anomalies, and malformations of the
FIGURE 3.21  Complete transverse septum. Notice that there is no lumbar spine.
bulge with a Valsalva maneuver that would be seen with an imper- Surgical removal of a transverse vaginal septum is rec-
forate hymen. ommended as soon as practical after diagnosis to avoid
continued retrograde menstruation. Endometriosis is com-
mon in patients with a transverse vaginal septum. How-
ever, removal of endometriosis lesions is not recommended
because relief of the obstruction leads to their spontaneous
resolution. Delay in detection or treatment of a transverse
vaginal septum may impair fertility secondary to irreversible
pelvic adhesions, hematosalpingies, and endometriosis. In
one long-term follow-up study by Rock of 19 patients with
transverse septa, 47% became pregnant (1982). However,
a small study in Finland by Joki-Erkkila showed a consider-
ably higher live birth rate in women who had undergone
very early diagnosis and management of their transverse
vaginal septa (2003).
The unfortunate consequence of very early surgical man-
agement is an increased rate of vaginal stenosis after surgical
repair. This is most likely due to inconsistent use of vaginal
dilators by young adolescents, which are a necessary part of
treatment of a thick vaginal septum (see next paragraph).
An alternative to early surgery for very young patients is
medical termination of monthly endometrial shedding using
depot medroxyprogesterone to postpone surgery. The young
girl can be instructed to dilate the distal vagina to stretch the
distal vaginal mucosa, potentially decreasing the need for a
graft, and to prepare her for postoperative use of the dilator.
The thickness and location of the septum will determine
the best approach to surgery. Thin, low, transverse vaginal
septa are much easier to repair than thick, usually high
septa. Transverse septa that are thin and low in the vagina
can usually be excised without difficulty. If a slight bulge
cannot visually be appreciated on examination, then an
angiocath needle is placed through the septum (Fig. 3.23).
With return of thick blood through the angiocath, the plane
of dissection becomes clear. Access is gained into the upper
vaginal cavity by perforating the transverse septum with
unipolar electrosurgery or scissors (Fig. 3.24). Concomi-
FIGURE 3.22  Partial transverse septum. tant pelvic ultrasound can also assist with the correct axis
of incision. The septum is excised in its entirety, and the
upper vaginal mucosa is reapproximated to the lower vagi-
Manual and speculum examination provide the most nal mucosa using 2-0 absorbable suture (Fig. 3.25). In most
important information for diagnosis of a transverse vaginal instances, to prevent stenosis of the vagina, continual use
septum. If the septum is very low, then a vaginal opening of a mold is recommended for several weeks after surgery.
may not be appreciated on evaluation of the external geni- Managing thick transverse septa can be quite challenging.
talia. A low transverse vaginal septum can usually be differ- Before surgery, the patient must be prepared for prolonged
entiated from an imperforate hymen by visual inspection. use of a mold and a possible split thickness skin graft to
50 PART 2  Basic Science

FIGURE 3.25  Reapproximation of distal and proximal vagina mucosa


FIGURE 3.23  Placement of angiocath into the transverse septum.
after excision of the septum.

If a thick septum is completely incised, then the distance


between the vaginal mucosa of the proximal and distal por-
tions of the vagina may be so great that the edges cannot be
reapproximated without tension. For this reason, a z-plasty
technique, as first described by Garcia et al. (1967), should
be considered for correction of thick transverse vaginal septa
or when the vagina is short. For this technique, four lower
mucosal flaps are created by making oblique crossed inci-
sions through the vaginal tissue on the perineal side of the
transverse septum, taking great care to avoid injuring either
the bladder or rectum. Four upper mucosal flaps are cre-
ated by making oblique crossed incisions through the vaginal
tissue on the hematocolpos side of the transverse septum.
Transverse The upper and lower mucosal flaps are separated by sharp
vaginal
septum
and blunt dissection and are sutured together at their free
edges to form a continuous z-plasty. Excellent results have
been noted by Wierrani et al. (2003) on 13 patients who
underwent this procedure. A vaginal mold must be used for
5 to 8 weeks after the procedure to avoid vaginal stenosis. If
the girl is not sexually active, then a dilator should be used
FIGURE 3.24  Angle of incision into septum.
at night for 6 to 8 additional months. The patient should
be instructed in self-examination and should return if she
line the vagina. The main concern is potential rectal injury; notices any signs of early stenosis. In cases of a thick septum
therefore, a mechanical bowel preparation or preoperative in which a z-plasty technique is not used, a skin graft may
enema is recommended. During surgery, a bulge will not be be required. The technique used is similar to that described
seen in the presence of a thick transverse septum. The cor- for the McIndoe procedure. Prolonged use of a mold is post-
rect angle of dissection can be determined by inserting an operatively required.
angiocath needle into the hematocolpos under ultrasound
guidance. In difficult cases, the septum can be approached
Anomalies of the Hymen
transfundally via the uterus using laparoscopy or laparotomy.
The dissection is performed taking care to protect the Hymenal anomalies are derived from the incomplete degen-
bladder and rectum. A Foley catheter is placed into the blad- eration of the hymen at birth. There are several variants,
der. As the loose areolar tissue is being dissected, the rec- including imperforate, microperforate, septate, and cribi-
tum is frequently examined to ensure an appropriate angle form. Imperforate hymen is the most common congenital
of dissection. If there is inadvertent entry into the bladder anomaly of the female reproductive tract, occurring in 1 in
or the rectum, then the procedure should be stopped and 1000 women. Females present either at birth with a bulging
completed at a future date. After the cervix is visualized, hymen secondary to mucocolpos or at menarche with cyclic
the goal is to reapproximate the upper vaginal epithelial tis- pelvic pain and hematocolpos. Distension of the vagina may
sue to the lower vaginal epithelium. lead to additional symptoms of a hymenal membrane with
CHAPTER 3  Embryology and Congenital Anomalies of the Urinary Tract, Rectum, and Female Genital System 51

bluish discoloration and defecatory and voiding dysfunc- Davydov SN. 12-year experience with colpopoiesis using the peritoneum.
tion. An imperforate hymen is sometimes discovered during Gynakologe. 1980;13:120.
Fedele L, Bianchi S, Zanconato G, Raffaelli R. Laparoscopic creation of a
a well-child check at the pediatrician. neovagina in patients with Rokitansky syndrome: analysis of 52 cases. Fertil
Repair of the imperforate hymen is best undertaken after Steril. 2000;74:384.
the tissue has undergone estrogenic stimulation. Therefore, Frank RT. The formation of an artificial vagina without operation. Am J
the ideal time is as a neonate (because of maternal estrogenic Obstet Gynecol. 1938;35:1053.
Garcia RF. Z-plasty for correction of congenital transverse vaginal septum.
effects) or in the postpubertal/premenarchal girl. Repair of Am J Obstet Gynecol. 1967;99:1164.
the imperforate hymen is not recommended between these Gidwani G, Falcone T. Congenital Malformations of the Female Genital
times because of a lack of estrogen in the pediatric vagina. Tract: Diagnosis and Management. Philadelphia: Lippincott Williams &
Under anesthesia, an incision is made in the imperforate Wilkins; 1999.
hymen. This can be a stellate or elliptical incision. The bor- Gosling JA. Anatomy. In: Stanton SL, ed. Clinical Gynecologic Urology.
St Louis: Mosby; 1984.
ders of the incision should approximate the hymenal ring. Gosling JA, Dixon J, Humpherson JR. Functional Anatomy of the Urinary
Excess tissue is excised with electrocautery to create a nor- Tract. London: Gower; 1982.
mal-sized orifice and the vaginal epithelium is sutured to Haddad B, Louis-Sylvestre C, Poitout P, Paniel BJ. Longitudinal vaginal
the hymenal ring using absorbable suture. septum: a retrospective study of 202 cases. Eur J Obstet Gynecol Reprod
Biol. 1997;74:197.
Hojsgaard A, Villadsen I. McIndoe procedure for congenital vaginal agen-
Summary esis: complications and results. Br J Plastic Surg. 1995;48:97.
Ingram JM. The bicycle seat stool in the treatment of vaginal agenesis and
Anomalies of the genitourinary tract are common, and a stenosis: a preliminary report. Am J Obstet Gynecol. 1981;140:867.
basic knowledge of the embryology of this system is nec- Jackson ND, Rosenblatt PL. Use of interceed absorbable adhesion barrier
for vaginoplasty. Obstet Gynecol. 1994;84:1048.
essary for the diagnosis and successful treatment of these Joki-Erkkila MM, Heinonen PK. Presenting and long-term clinical implica-
patients. A careful history, physical examination, and tions and fecundity in females with obstructing vaginal malformations.
imaging (most often MRI) are critical to make the correct J Pediatr Adolesc Gynecol. 2003;16:307.
diagnosis and subsequently offer appropriate treatment. Joseph VT. Pudendal-thigh flap vaginoplasty in the reconstruction of genital
anomalies. J Pediatr Surg. 1997;32:62.
Because of the close embryologic development of the uri- Kaloo P, Cooper M. Laparoscopic-assisted Vecchietti procedure for creation
nary and genital systems, patients with congenital anoma- of a neovagina: an analysis of five cases. Aust N Z J Obstet Gynaecol.
lies of the genital tract must also be evaluated for anomalies 2002;42:307.
of the urinary tract, such as renal anomalies. Management Klingele CJ, Gebhart JB, Croak AJ, DiMarco CS, Lesnick TG, Lee RA.
is based on the type of anomaly. Although the first-line McIndoe procedure for vaginal agenesis: long-term outcome and effect
on quality of life. Am J Obstet Gynecol. 2003;189:1569.
treatment is usually conservative management with vaginal Langman J. Medical Embryology. Baltimore: Williams & Wilkins; 1976.
dilation for patients with congenital absence of the vagina, Maizels M. Normal development of the urinary tract. In: Walsh PC, Gittes
surgical treatment is often required for these patients. Sur- RF, Perlmutter AD, Stamey TA, eds. Campbell’s Urology. 5th ed. Phila-
gical management is often most appropriate for those with delphia: WB Saunders; 1986.
Mobus VJ, Kortenhorn K, Kreienberg R, Friedberg V. Long-term results
other types müllerian anomalies such as vaginal septum and after operative correction of vaginal aplasia. Am J Obstet Gynecol.
imperforate hymen. 1996;175:617.
Monstrey S, Blondeel P, Van Landuyt K, Verpaele A, Tonnard P, Matton
G. The versatility of the pudendal thigh fasciocutaneous flap used as an
Bibliography island flap. Plast Reconstr Surg. 2001;107:719.
Acién P, Acién MI. The history of female genital tract malformation clas- Motoyama S, Laoag-Fernandez JB, Mochizuki S, Yamabe S, Maruo T.
sifications and proposal of an updated system. Hum Reprod Update. Vaginoplasty with interceed absorbable adhesion barrier for complete
2011;17:693. squamous epithelialization in vaginal agenesis. Am J Obstet Gynecol.
Alessandrescu D, Peltecu GC, Buhimschi CS, Buhimschi IA. Neocol- 2003;188:1260.
popoiesis with split-thickness skin graft as a surgical treatment of vagi- Oppelt P, Renner S, Brucker S. The VCUAM classification: a new classifica-
nal agenesis: retrospective review of 201 cases. Am J Obstet Gynecol. tion for genital malformations. Fertil Steril. 2005;84:1493.
1996;175:131. Panici PB, Bellati F, Boni T, Francescangeli F, Frati L, Marchese C. Vagi-
ACOG Committee on Adolescent Health Care. ACOG Committee Opin- noplasty using autologous in vitro cultured vaginal tissue in a patient
ion No. 355: Vaginal agenesis: diagnosis, management, and routine care. with Mayer–von–Rokitansky–Kuster–Hauser syndrome. Hum Reprod.
Obstet Gynecol. 2006;108(6):1605-1609. 2007;22:2025.
American Fertility Society. Classifications of adnexal adhesions, distal Petrozza JC, Gray MR, Davis AJ, Reindollar RH. Congenital absence
tubal occlusion, tubal occlusion secondary to tubal ligation, tubal preg- of the uterus and vagina is not commonly transmitted as a domi-
nancies, Mullerian anomalies, and intrauterine adhesions. Fertil Steril. nant genetic trait: outcomes of surrogate pregnancies. Fertil Steril.
1988;49:944. 1997;67:387.
Borruto F. Mayer–Rokitansky–Kuster syndrome: Vecchietti’s personal Roberts CP, Haber MJ, Rock JA. Vaginal creation for mullerian agenesis.
series. Clin Exp Obstet Gynecol. 1992;19:273. Am J Obstet Gynecol. 2001;185:1349.
Borruto F, Chasen ST, Chervenak FA, Fedele L. The Vecchietti procedure Rock JA, Zacur HA, Dlugi AM, Jones HW, Telinde RW. Pregnancy success
for surgical treatment of vaginal agenesis: comparison of laparoscopy and following surgical correction of imperforate hymen and complete trans-
laparotomy. Int J Gynaecol Obstet. 1999;64:153. verse vaginal septum. Obstet Gynecol. 1982;59:448.
Buss JG, Lee RA. McIndoe procedure for vaginal agenesis: results and com- Romao RL, Salle JL, Wherrett DK. Update on the management of disorders
plications. Mayo Clin Proc. 1989;64:758. of sex development. Pediatr Clin North Am. 2012;59:853.
Byrne J, Nussbaum-Blask A, Taylor WS, et al. Prevalence of Müllerian duct Rothman D. The use of peritoneum in the construction of a vagina. Obstet
anomalies detected at ultrasound. Am J Med Genet. 2000;94:9. Gynecol. 1972;40:835.
Candiani GB, Fedele L, Candiani M. Double uterus, blind hemivagina, and Sadler TW. Langman’s Medical Embryology. 11th ed. Baltimore: Lippincott
ipsilateral renal agenesis: 36 cases and long-term follow-up. Obstet Gynecol. Williams & Wilkins; 2010.
1997;90:26. Saravelos SH, Cocksedge KA, Li TC. Prevalence and diagnosis of congenital
Carlson BM. Human Embryology and Developmental Biology. 4th ed. Phila- uterine anomalies in women with reproductive failure: a critical appraisal.
delphia: Mosby, Inc.; 2009. Hum Reprod Update. 2008;14:415.
Davydov SN. Colpopoeisis from the peritoneum of the uterorectal space. Shapiro E, Huang H, Wu XR. New concepts on the development of the
Akush Ginekol (Mosk). 1969;45:55. vagina. Adv Exp Med Bio. 2004;545:173.
52 PART 2  Basic Science

Snyder HM. Anomalies of the ureter. In: Gillenwater JY, Grayhack JT, Verp MS, Simpson JL. Abnormal sexual differentiation and neoplasia.
Howards SS, Duckett JW, eds. Adult and Pediatric Urology. ;vol. 2. Chicago: Cancer Genet Cytogenet. 1987;25:191.
Mosby; 1987. Walters MD, Karram MM, eds. Urogynecology and Reconstructive Pelvic
Soong YK, Chang FH, Lai YM, Lee CL, Chou HH. Results of modified Surgery. 3rd ed. Philadelphia: Mosby, Inc.; 2007.
laparoscopically assisted neovaginoplasty in 18 patients with congenital Wee JT, Joseph VT. A new technique of vaginal reconstruction using neuro-
absence of vagina. Hum Reprod. 1996;11:200. vascular pudendal-thigh flaps: a preliminary report. Plast Reconstr Surg.
Stenchever MA, Droegemueller W, Herbst AL, Mishell DR, eds. Compre- 1989;83:701.
hensive Gynecology. 4th ed. Philadelphia: Mosby, Inc; 2001. Wierrani F, Bodner K, Spangler B, Grunberger W. “Z”-plasty of the trans-
Vechietti G. Neovagina nella sindrome di rokitansky kuster-hauser. Attual verse vaginal septum using Garcia’s procedure and the Greenberger mod-
Obstet Gynecol. 1965;11:131. ification. Fertil Steril. 2003;79:608.
Veronikis DK, McClure GB, Nichols DH. The Vecchietti operation for Willemsen WN. Renal–skeletal–ear- and facial-anomalies in combination
constructing a neovagina: indications, instrumentation, and techniques. with the Mayer–Rokitansky–Kuster (MRK) syndrome. Eur J Obstet
Obstet Gynecol. 1997;90:301. Gynecol Reprod Biol. 1982;14:121.
CHAPTER 4

Neurophysiology
and Pharmacology
of the Lower
Urinary Tract
Douglass S. Hale
Mark D. Walters

Introduction Chapter Outline


The two functions of the lower urinary tract are the stor-
age of urine within the bladder and the timely expulsion Introduction
of urine from the urethra. The precise neurologic path- General Nervous System Arrangements
ways and neurophysiologic mechanisms that control these Neural Control of the Lower Urinary Tract
functions of storage and micturition are complex and not
completely understood, with many of these pathways Autonomic Nervous System
adapted from animal models. Understanding the inter- Sympathetic Actions on Detrusor Muscle and Ganglia
action of the autonomic nervous system, the peripheral Parasympathetic Actions on Detrusor Muscle
nervous system, and the central nervous system (CNS) Smooth Muscle of Trigone and Urethra
in lower urinary tract function is critical to patient care. Skeletal Muscle of Lower Urinary Tract: Somatic
Until recently, neural pathways were thought to be static Innervation
with little opportunity for change. However, an extremely Sensory Innervation
important concept, appreciated for its application to Central Nervous System Modulation
treatment of lower urinary tract dysfunction, is the prin-
Cortical and Subcortical Pathways
ciple of neuroplasticity as it applies to the pathways and
mechanisms. The nervous system is composed of varying Spinal Cord
sizes and types of nerves. They are classified generally Mechanisms of Normal Bladder Filling, Storage,
by size. The largest, myelinated, fast-conducting A alpha and Voiding
nerves are sensory (afferent) nerves conveying touch, or Filling and Storage
motor (efferent) nerves activating large muscles. The Voiding
smallest, nonmyelinated C nerve fibers are slow-con-
ducting nerves that convey pain and temperature on the Clinical Effects of Neurologic Disease
sensory side or act as postganglionic autonomic nerves on on Lower Urinary Tract Function
the motor side. The bladder afferent nerves are largely C Brainstem Lesions
fibers at birth, until maturation changes the afferents to Spinal Cord Disease
A delta (lightly myelinated, small) fibers. It is now appre- Cauda Equina
ciated that bladder insults, such as obstruction, bladder
inflammation, or spinal cord disease, affecting pathways Peripheral Innervation and Bladder Dysfunction
involved in lower urinary tract function lead to neuroplas- Pelvic Nerve Injury
tic changes in which the afferents again become C fibers Clinical Pharmacology of the Lower Urinary Tract
as the bladder’s response to the insults. Understanding Therapy to Facilitate Bladder Emptying
the anatomy and physiology of the basic reflex pathways Increasing Intravesical Pressure
and central voluntary control involved in lower urinary Decreasing Outlet Resistance
tract function is necessary, but appreciating the dynamic
ability of the neurons to modify these pathways is essen- Therapy to Facilitate Urine Storage
tial to the application of modern therapies. This chapter Decreasing Bladder Contractility
reviews normal and abnormal function, neurologic con- Promoting Bladder Storage
trol, and clinical pharmacology of the lower urinary tract Increasing Outlet Resistance
in women.
53
54 PART 2  Basic Science

column of the 12 thoracic and first two lumbar segments of


General Nervous System Arrangements the spinal cord constitute the sympathetic division (thoraco-
The nervous system is composed of neurons (nerve cells) lumbar) of the autonomic nervous system. The parasympa-
with characteristic functions of propagation and transmis- thetic division (craniosacral) consists of fibers arising from
sion of signals. A neuron propagates a signal, the “action the second through the fourth intermediolateral cell column
potential,” along an axon and then transmits the signal to sacral segments and from cranial outflows.
another neuron or an end organ to elicit a response (e.g., Sympathetic nerves to the pelvic cavity originate in cord
a muscle contraction). The neural propagation depends levels T5 to L2. Generally, their two-neuron chain consists
on electrical events, with channels allowing ions to move of short preganglionic fibers and long postganglionic fibers.
through the cell membrane that depolarizes the mem- Some preganglionic axons pass via white rami communican-
brane and establishes electrical current (saltatory conduc- tes to the paravertebral sympathetic chain, synapse, and pass
tion in myelinated nerves) that conveys action potentials by gray rami communicantes to the skeletal nerves. These
to the junctions of the nerve with another nerve or with constitute the paravertebral sympathetics, and they gener-
end organs. At this site, chemical events that depend on ally follow the segmental nerves to somatic structures. The
neurotransmitters and receptors affect action potentials in other preganglionic sympathetic axons pass directly through
the second nerve or end organ to elicit the response. Neu- the paravertebral ganglia to the prevertebral ganglia located
rotransmitters are chemicals, selectively released from a at roots of arteries, for which they are named (e.g., lumbar
nerve terminal by an action potential, that interact with a splanchnic nerves terminate in inferior mesenteric and hypo-
specific receptor on an adjacent structure and elicit a spe- gastric ganglia). After synapsing in these ganglia, the post-
cific physiologic response. Most neurotransmitters come ganglionic nerves travel through the right or left hypogastric
from the nine essential amino acids. Some neurons modify nerve to join the pelvic plexus and follow the visceral arteries
the amino acid to form “amine” transmitters; for example, to the organs of the lower abdomen and pelvis. These consti-
norepinephrine (NE), serotonin, acetylcholine, and others tute the prevertebral sympathetics. In addition to these two
combine to form peptides. The chemical event at the junc- pathways, preganglionic sympathetic fibers may also ascend
tion gives origin to further electrical events in the secondary or descend within the paravertebral ganglia chain before syn-
neurons or in the end organs. These chemical synapses can apsing or passing through to the prevertebral ganglia.
be excitatory (Na+ channels open, and Na+ influx depolar- Pelvic parasympathetic system preganglionic fibers origi-
izes and creates action potentials) or inhibitory (Cl− and nate in spinal segments S2 through S4. The long pregan-
K+ channels allow influx and egress, and hyperpolarization glionic fibers travel through the pelvic nerve to join the
develops, preventing action potential development). hypogastric nerve in forming the pelvic plexus. These fibers
The nervous system is arranged into the central and the continue to ganglia located within or very near the organs
peripheral systems. The CNS includes the brain and spinal that they supply, thus having very short postganglionic fibers
cord. Within the brain and spinal cord, nerve cell bodies are and much longer preganglionic fibers.
arranged in groups of various sizes and shapes called nuclei.
Fibers with a common origin and destination are called a Neural Control of the Lower
tract; some are so anatomically distinct that they may be
called fasciculus, brachium, peduncle, column, or lemniscus.
Urinary Tract
Synaptic relationships in the CNS are very complex, with Local innervation is chiefly by parasympathetic and sym-
contacts occurring between axons and cell bodies, axons and pathetic autonomic and peripheral somatic motor and sen-
dendrites, cell body and cell body, or dendrite and dendrite. sory systems. A summary of the neural pathways involved in
Twelve pairs of cranial and 31 pairs of spinal nerves with bladder filling and voiding is shown in Figures 4.1 and 4.2.
their ganglia compose the peripheral nervous system. Syn-
aptic relationships in the peripheral nervous system involve
Autonomic Nervous System
only neuron–neuron or neuron–effector interactions. The
somatic component of the peripheral system innervates The autonomic nervous system controls the lower urinary
skeletal muscle and receives somatic sensory input. tract by its actions on the ganglia, detrusor muscle, and
The autonomic division innervates cardiac muscle, smooth muscle of the trigone and urethra.
smooth muscle, and glands; is involved with ganglionic activi-
ties; and is indirectly involved in conveying visceral afferent Sympathetic Actions on Detrusor Muscle
input. The autonomic nervous system consists, in part, of and Ganglia
general visceral efferent fibers, supplying the smooth muscle During physiologic bladder filling, little or no increase in
of viscera. General visceral afferent fibers are closely asso- intravesical pressure is observed, despite large increases in
ciated with the autonomic efferents, and both the motor urine volume. This process, called accommodation, is caused
and sensory visceral neural activities ordinarily function at primarily by passive elastic and viscoelastic properties of the
a subconscious level. Unlike the somatic motor system, the smooth muscle and connective tissue of the bladder wall.
peripheral efferent autonomic fibers reach the effector organ During filling, muscle bundles in the bladder wall undergo
by at least a two-neuron chain, constituting a preganglionic reorganization, and the muscle cells are elongated up to four
and a postganglionic neuron. The preganglionic neuron arises times their length. As bladder filling progresses, at a certain
in the intermediolateral cell column of the brainstem or spi- bladder wall tension, a desire to void is felt, although it has
nal cord and terminates at an outlying ganglion, where the not been determined where this sensation is processed in the
postganglionic neuron continues the impulse transmission to brain. Mechanoreceptors in the bladder wall are activated
the end organ. Fibers arising from the intermediolateral cell (Aδ fibers), and action potentials run with afferents following
CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 55

10
11 Hypogastric nerve

12
1
Beta
2
Pelvic Alpha
plexus Bladder

Pelvic Trigone
nerve
2 Levator ani
Striated
Proximal portion
3 urogenital
Distal portion
sphincter
4
To perineal muscles
and external anal sphincter

FIGURE 4.1  Peripheral innervation of the female Pudendal nerve


lower urinary tract.

Filling/storage Voiding

Inhibition of Stimulation of
parasympathetics parasympathetics

Stimulation of Inhibition of
sympathetics: sympathetics
alpha-contraction
beta-relaxation

FIGURE 4.2  Actions of the autonomic


Stimulation of Inhibition of
and somatic nervous systems during
somatic nerves to somatic nerves to
bladder filling/storage and voiding. striated urogenital striated urogenital
Only sympathetic receptors (α and β) sphincter sphincter
are shown.

parasympathetic pelvic nerves to the spinal cord at the S2 to behind and below the ureter. This location is ironically the
S4 and with afferents following sympathetic nerves to the same area where uterosacral sutures are placed for vaginal
thoracolumbar cord (de Groat and Lalley, 1972; Floyd et al., vault suspension. After these neurons join the pelvic nerves,
1976). As filling increases to a critical intravesical pressure, the pelvic plexus is formed, running below and medial to the
or with rapid bladder filling, detrusor muscle contractility is internal iliac vessels overlying the anterior lateral lower rec-
inhibited and urethral sphincter muscle enhanced by acti- tum near the anorectal junction. The plexus spreads in the
vation of a spinal sympathetic reflex—one that stays intact lateral wall of the upper one-third of the vagina beneath the
with spinal cord lesions above the lumbar level (de Groat and uterine artery, medial to the ureter and 2 cm inferolateral to
Lalley, 1972; de Groat and Theobald, 1976). the cervix. Within the vesicovaginal space, the plexus sup-
The sympathetic preganglionic fibers from thoracolum- plies the upper vagina, bladder, proximal urethra, and lower
bar spinal segments form white rami communicantes to ureter. Sympathetic preganglionic neurons generally use
synapse in the paravertebral or prevertebral sympathetic acetylcholine neurotransmitter acting on nicotinic recep-
pathways, the latter predominating. Preganglionic neu- tors. The sympathetic postganglionic fibers are primarily
rons reach their inferior mesenteric ganglia by the lumbar noradrenergic, with norepinephrine being the chief neu-
splanchnic nerves, synapse, and continue as postganglionic rotransmitter. Norepinephrine stimulation of β3-adrenergic
nerves through the hypogastric nerves to the presacral fas- receptors located in the bladder body causes relaxation of
cia, across the upper posterior lateral pelvic wall, 1 to 2 cm the smooth muscle. Stimulation of α1 receptors in bladder
56 PART 2  Basic Science

base and urethral smooth muscle by norepinephrine causes more therapeutic effects against bladder overactivity with
muscle contraction. In addition, norepinephrine also acts fewer side effects.
as a neurotransmitter at the parasympathetic ganglia, and Cholinergic receptors are more present in the body than
α-adrenergic receptors, when stimulated, depress parasym- in the base of the bladder, whereas adrenergic and neuro-
pathetic pelvic ganglion transmission by suppression of pre- peptide receptors are more prevalent in the base of the
synaptic cholinergic neurotransmitter release. bladder. Neuropeptide modulators include vasoactive intes-
Thus, sympathetic relaxation of detrusor body smooth tinal polypeptide and substance P. Histaminic and purinergic
muscle, contraction of bladder base and urethral smooth receptors may also be present in detrusor smooth muscle.
muscle, and depression of parasympathetic ganglionic trans-
mission all act to promote urine storage. Smooth Muscle of Trigone and Urethra
The trigone was originally thought to be of separate embry-
Parasympathetic Actions on Detrusor Muscle ologic origin from the bladder, however, this idea is being
The parasympathetic preganglionic fibers arise from nerve challenged (Shapiro, 2009). The idea of a separate origin
roots S3 and S4 and, occasionally, S2, with the cell bodies being was attractive because of the different innervation of this
in the sacral cord, the conus medullaris. These fibers emerge area compared to the rest of the bladder. The innervation
from the piriformis muscle overlying the sacral foramina and of the trigone smooth muscle fibers is an almost exclusively
enter the presacral fascia near the ischial spine at the poste- adrenergic innervation with chiefly α1 receptors. Choliner-
rior layer of the hypogastric sheath forming the pelvic nerve, gic development in the bladder is present at birth, whereas
where they then contribute to the already described pelvic adrenergic development occurs later. Prostaglandins act as
plexus. The pelvic plexus has freely interconnected nerves in intracellular messengers to relax trigonal muscles.
the pelvic fascia that supply the rectum, genitalia, and lower The proximal urethral smooth muscle is rich in
urinary tract. The parasympathetic fibers to the urinary tract α-adrenergic receptors responsive to norepinephrine neu-
terminate in pelvic ganglia located within the wall of the blad- rotransmitter. Acetylcholine, substance P, vasoactive intes-
der, a location quite vulnerable to end-organ disease, such as tinal polypeptide, and histamine are all additional potential
overstretch, infection, or fibrosis. At the ganglia, excitatory transmitters in the urethra. Nitric oxide (NO) is promi-
transmission occurs from activation of nicotinic acetylcholine nent in the parasympathetic postganglionic innervation of
receptors, with some ganglionic cells having secondary musca- the urethra, and exogenous NO or parasympathetic nerve
rinic receptors. Multiple neuropeptide agents also function at stimulation relaxes urethral smooth muscle.
these ganglia including adrenergic, purinergic, and peptidergic
modulation. Transmission regulation remains complex, and Skeletal Muscle of Lower Urinary Tract:
precise knowledge is not available at present. Somatic Innervation
At the detrusor muscle, postganglionic parasympathetic In the lower urinary tract, the somatic system involves
detrusor nerve fibers diverge and store neurotransmitter skeletal muscle in the lower urinary tract outlet. The neu-
agents in axonal varicosities called synaptic vesicles. The agent ronal cell bodies for the urethral sphincter and for the dis-
is diffused to neuromuscular bundles of 12 to 15 smooth tal periurethral striated muscles and pelvic floor muscles
muscle fibers enclosed in a collagen capsule that acts similarly are located in Onuf ’s (Onufrowicz) somatic nucleus in
to the tendon insertion of a muscle. Stimulating electrical the lateral aspect of the anterior horn of the gray matter
pulses produce two episodes of depolarization, suggesting the of the sacral spinal cord from S2 to S4. This nucleus gives
release of two neurotransmitters. The chief neurotransmit- rise to the pudendal nerve, which is classically thought to
ter is cholinergic, with muscarinic receptors, and a second provide the efferent innervation of the striated sphincter.
major neurotransmitter is noncholinergic and nonadrenergic. Thor (2004) has shown that serotonin and norepinephrine
This observation accounts for detrusor atropine resistance. enhance the effects of glutamate, the primary excitatory
The studies of Burnstock et al. in 1972 demonstrated that neurotransmitter for pudendal motor neurons. This is the
adenosine triphosphate (ATP) was the mediator of these non- proposed mechanism of action of duloxetine (a serotonin-
cholinergic, nonadrenergic contractions. Variability is present norepinephrine reuptake inhibitor) in treating stress incon-
between species, and some studies suggest that the purine tinence. The pudendal nerve, using acetylcholine, activates
(ATP) pathway responses lead to more rapid bladder contrac- nicotinic cholinergic receptors to contract the rhabdo-
tions, perhaps being useful in animals that use short, quick sphincter. The alpha motor neurons of Onuf ’s nucleus are
squirts of urine for geographically marking their territory. unique in many ways including their resistance to polio and
Muscarinic receptors have received much attention by amyotrophic lateral sclerosis (ALS).
pharmaceutical companies. The receptors are present in The exact neuropathways supplying the urethral sphinc-
the CNS, eye lacrimal glands, salivary glands, heart, gall- ter skeletal muscle are controversial. The proximal intramu-
bladder, stomach, and colon. Five types (M1–5) have been ral component of the striated urogenital sphincter muscle
identified. In detrusor muscle, M2 and M3 predominate. (urethral sphincter, rhabdosphincter) is variably innervated
While there are more detrusor M2 receptors, the M3 are by somatic efferent branches of the pelvic nerves, a com-
more important for detrusor contractions. Dry mouth, ponent of the pelvic plexus. Elbadawi (1983) believed
slowed gastrointestinal motility, blurred vision, increased this intramural component to have somatic and autonomic
heart rate, heat intolerance, sedation with reductions in (both cholinergic and adrenergic) innervation. However, the
memory and attention, delirium, drowsiness, fatigue, and more distal periurethral striated muscles (compressor ure-
other cognitive functions are side effects related to the var- thrae and urethrovaginal sphincter) are innervated by the
ious receptors located throughout the body. Anticholinergic pudendal nerve, as is the skeletal muscle of the external anal
medications more selective for M3 receptors should have sphincter and perineal muscles.
CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 57

Typically, somatic motor activity regulates skeletal mus- while others state they travel through the pelvic nerve and
cle contraction by spinal reflexes, with the afferent arm of enter at the sacral levels. A specific nucleus, Gert’s nucleus,
the reflex originating in muscle spindles, synapses taking is located ventrolateral to the dorsal horn cells of S1–S2 and
place in the spinal cord, and the efferent arm originating receives Aδ input from the bladder. Ascending projections
in anterior horn cells with the axon going to the muscle. from here reach to the periaqueductal gray (PAG) area in the
Unlike typical somatic reflex pathways that are regulated by mesencephalon. Afferent fibers travel with their correspond-
sensory nerves from muscle spindles, the afferent regulation ing efferents, and this explains why patients with lesions in
of the urethral sphincter somatic reflex is different because the cauda equina still have some sensory input via the sym-
urethral skeletal muscle has no spindles. pathetic pathways. Both Aδ and unmyelinated C fibers pro-
Embryologic speculation is that pelvic caudal muscles vide the majority of this innervation. Detrusor proprioceptive
(tail waggers), which compose the levator group in humans, endings (Aδ fibers) exist as nerve endings in collagen bundles.
are supplied from the pelvic plexus on the pelvic surface They are stimulated by stretch or contraction and are respon-
side, whereas the sphincter cloacal derivatives are supplied sible for the feeling of bladder fullness. Pain and temperature
from the perineal aspect by the pudendal nerve. nerve endings (C fibers) are free in bladder mucosa and sub-
The pudendal nerve passes between the coccygeus and mucosa. The sensory endings in the detrusor involve multiple
piriformis muscles, leaves the pelvis through the greater sci- neurotransmitters and modulators including substance P,
atic foramen, crosses the ischial spine, and reenters the pelvis vasoactive intestinal peptide, ATP, neurokinins, and calcito-
through the lesser sciatic foramen. Here the nerve accompa- nin gene-related polypeptide among others.
nies the pudendal vessels along the lateral wall of the ischio- Afferent nerves are further influenced by transient recep-
rectal fossa in a tunnel formed by a splitting of the obturator tor potentials (TRPs), transmembrane cation channels that
internus fascia, called Alcock’s canal. At or before the perineal influence cytosolic ion concentration, mainly calcium and
membrane, the nerve divides into the inferior rectal nerve, magnesium as well as affecting other intracellular pathways.
supplying the external anal sphincter, the perineal nerve, and These unique cation channels are described in almost every
the dorsal nerve to the clitoris (Fig. 2.5). The perineal nerve tissue and cell type and play a major role in cellular func-
splits into a superficial branch to the labia and a deep branch tion and sensory input. In addition to the transmembrane
to the periurethral striated muscles. The branching of the channels, intracellular channels (TRPs) in other membranes
pudendal nerve shows considerable variation. (endo and sarcoplasmic reticulum) also exist. These chan-
The urethral sphincter muscle is an integral part of the nels have been divided into six subfamilies, each subfamily
urethral wall and is made up of all slow-twitch (type 1) having several unique channels. The most described of these
fibers. The periurethral muscles (compressor urethrae and channels is the TRP vanilloid subfamily. These channels are
urethrovaginal sphincter) are composed of mostly slow- affected by many different stimuli (both chemical and physi-
twitch fibers with a variable concentration of fast-twitch cal) and play a major role in afferent activity including detec-
(type 2) fibers. These fibers combine to provide constant tion and integration of noxious stimuli. They achieve this by
tonus, with emergency reflex activity mainly in the distal a dual mechanism whereby their intracellular actions (cation
half of the urethra. concentrations) are combined with a second mechanism of
The response of segmental spinal reflex leading to influencing neurotransmitter release including substance P
pudendal nerve function involves several spinal cord seg- and calcitonin gene-related peptide (Furuta et al., 2012).
ments. Afferent fibers involved in the reflex have both seg- Activation of C fibers plays a major role in bladder inflam-
mental and supraspinal routing. This dual routing explains mation and overactivity and in conditions where C fiber
the bimodal response of pudendal motor neurons when afferentation through neuroplastic changes has taken place.
pudendal sensory nerves are stimulated, and it differs from Purinergic receptor stimulation (chemical, C-fiber) in an ani-
stimulation of pelvic detrusor afferents. mal model enhances the spinal neuronal activity already seen
The neurotransmitter at the periurethral skeletal neuro- with intravesical filling (Aδ physical stretch). This increased
muscular junction is acetylcholine and the receptors are nic- spinal activity is diminished or abolished by purine antago-
otinic type. The intimate adherence of the neuromuscular nists. Active research into pharmacologic manipulation of
junction to the striated muscle fibers conveys a resistance to these channels is a potentially new therapeutic option for
blockade by neuromuscular blocking agents. control of conditions such as painful bladder syndrome.
Other neurotransmitters involved with bladder sensation
include ATP, adenosine, nitric oxide, vasoactive intestinal
Sensory Innervation
polypeptide, substance P, and pituitary adenylate cyclase-
The sensory innervation of the lower urinary tract is intri- activating peptide. Not only can some of these act as neu-
cate and complex. A urothelial and suburothelial network has rotransmitters but others like nitric oxide are also released
been described, which provide different sensory input from from the urothelium and act as modulators and messengers.
the lower urinary tract. These interactions involve cell-to-cell The complex interactions of these neurotransmitters are
communication and neural pathways. The sensory nerves are still being investigated, but their role in conditions involving
denser in the urethra and trigone and sparser in the dome of bladder pain is undeniable and will undoubtedly influence
the bladder. The afferent axons join their respective efferent future therapies (Fig. 4.3).
nerves in the previously described paths for the autonomic Urethral sensation is carried principally by the pudendal
and somatic neural pathways. Controversy exists concerning nerve, although the autonomic nervous system also has its
where the major afferent supply travels. Some researchers usual afferent component. Urethral smooth muscle sensory
claim the majority of afferent nerves travel with the hypo- innervation, like that of the detrusor, has both a contralat-
gastric nerve to the thoracolumbar region of the spinal cord, eral and an ipsilateral supply.
58 PART 2  Basic Science

Bladder

Lumen

Urothelium
Connective tissue

Muscularis

Connective tissue

Sensory neuron Spinal cord CNS


NO

Stretch TRPV1
Vanilloids
Acids ATP
Acetylcholine TRPV4
Norepinephrine P2X3
Substance P
Capsaicin
Reflex contraction

TRPV1/4
TRPV3?
Bladder urothelium
TRPA1
B TRPM8

FIGURE 4.3  Involvement of TRPV1 and TRPV4 in regulation of bladder contraction. A, Illustration of the composition of the bladder wall.
B, TRPV1 and TRPV4 are both expressed in the urothelium and can be directly activated by the stimuli shown at the left. Moreover, these
substances can also activate both channels in sensory fibers in the urothelium and the muscularis, which can cause, via the spinal cord, contrac-
tion of the bladder and pain. Stimulation of TRPV1 and TRPV4 in the urothelium induces release of ATP and nitric oxide. ATP can also activate
the sensory fibers via P2X3 receptors. (Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev.
2007;87:165.)

Extensive communication takes place with all these struc-


Central Nervous System Modulation
tures to control storage and voiding. Although many neu-
CNS neurons affecting bladder function may be spinal or rotransmitters are involved in central regulation, the major
supraspinal, with extensive dendritic communications. The CNS neurotransmitters are glutamate and GABA.
chief excitatory neurotransmitter in the CNS is glutamate,
frequently acting on n-methyl-d-aspartate (NMDA) recep- Cortical and Subcortical Pathways
tors, which creates areas of possible therapeutic pharma- The brainstem’s importance in the lower urinary tract func-
ceuticals. The chief inhibitory CNS neurotransmitters are tion has been known since 1921, when Barrington ablated
γ-aminobutyric acid (GABA) and glycine. this area in cats and produced permanent urinary retention.
The detrusor and the periurethral striated muscle mech- He demonstrated that the middle pons was the level in the
anisms have separate cortical and other higher-center reg- brain at which the motor tone of the bladder arises. This
ulation. The effects of such regulation are chiefly on the region in the pons has been called the pontine micturition
brainstem for the detrusor and on the sacral cord for the center or the M region by Holstege et al. (1979). Stimulation
periurethral mechanisms. The brain pathways known to results in the decrease in urethral pressure and silence of pel-
be associated with bladder and pelvic floor activity include vic floor electromyographic (EMG) signal, followed by a rise
cortical pathways originating in the precentral gyrus, lateral in detrusor pressure. Tracing studies reveal direct projections
prefrontal cortex, and anterior cingulate gyrus (ACG). Sub- from the M region to the intermediolateral cell column of the
cortical pathways originate in basal ganglia, brainstem raphe sacral cord and the parasympathetic preganglionic bladder
nuclei, locus ceruleus, hypothalamus, and the midbrain motor neurons. Other projections are to sacral cord interneu-
periaqueductal gray, and affect the brainstem, specifically rons that activate GABA inhibition of Onuf ’s nucleus neu-
the medial (M region analogous to the pontine micturition rons, resulting in relaxation of urethral skeletal muscle. The
center [PMC], or Barrington’s nucleus) and lateral (L) pons. detrusor motor nuclei in the pons receive input from basal
CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 59

ganglia and coordinating afferents from the cerebellum and Pudendal cortical pathways affect periurethral striated
the PAG. Recall that the PAG receives input from the disten- muscle innervation by direct descending paths originating in
sion receptors in the bladder via fibers ascending from Gert’s the central vertex of the pudendal cerebral cortical area and
nucleus. The PAG then communicates with the M region to going to pudendal nuclei in the ventromedial portion of the
stimulate micturition. In addition to these important supra- ventral gray matter of the S1 to S3 cord segments. At this
spinal tracts, there is evidence that spinal reflexes may also level, the pudendal motor nuclei act as described to affect
facilitate voiding. Electrical stimulation of urethral afferents lower urinary tract skeletal muscle activity.
can stimulate detrusor activity in spinal cord patients. This Ascending axons from periurethral striated muscle go to
reflex has been postulated to augment bladder emptying by the pudendal cortical area, possibly synapsing in the nucleus
being activated when urine enters the urethra. ventralis posterolateralis of the thalamus, the brain’s chief
Brainstem neurotransmitters include substance P, GABA, relay station.
and serotonin, which is produced from tryptophan. Stimula- Sensory afferents from both pudendal and detrusor pel-
tion of the same level of the pons at a more lateral position, vic nerves send input to the anterior vermis of the cerebel-
the L region, results in contraction of the urethral sphincter by lum, which then originates an axon relay to the cortex in
fibers in Onuf ’s nucleus. Direct cortical relay to the L region the dentate nucleus. Fibers for both detrusor and puden-
gives voluntary micturition control. These brainstem activities, dal proprioception and exteroception (pain, temperature,
which are important for continence (L region) and micturition and touch) ascend in posterior columns and spinothalamic
(M region) in adults, are replaced by reemerging pathologic tracts, respectively.
primitive reflexes in disease states. Most important in this Neurotransmitters involved in these pathways include
respect is the C-fiber–mediated reflex that emerges follow- acetylcholine and peptides, especially substance P and
ing disconnection from pontine regulatory influences as a con- enkephalin. Neurotransmitter agents are stored in astro-
sequence of spinal cord disease. These effects are mediated cytes, which may also regulate extracellular concentrations.
by sensory neurotransmitters that are prompted to appear The limbic system in the temporal lobes exerts controls
by nerve growth factors, as shown by Steers et al. (1996), affecting all autonomic functions and is a favored site for
and that are alleviated by intravesical capsaicinoids. Similar epileptiform activity. Enkephalin is a notable neurotrans-
development of C-fiber–afferentation is seen with bladder mitter here as well as in the reticular formation. The cer-
outlet obstruction and with bladder inflammatory states. In ebellum, where GABA is prominent along with standard
addition, with spinal cord injury it appears that the C fibers neurotransmitters, regulates muscle tone and coordinates
become sensitized to mechanical distension, a role reserved movement. Disease in this area produces spontaneous, high-
for Aδ fibers in the normal bladder. This leads to further acti- amplitude detrusor overactivity.
vation of primitive, ineffective voiding reflexes, which are fur- The ACG and the prefrontal cortex have rich communica-
ther modulated by TRP channels acting on the sensory side. tions with the brainstem areas concerned with lower urinary
The basal ganglia are associated with the production of tract function. The ACG shows increased activity with imag-
dopamine, one of the catecholamine neurotransmitters that ing studies during filling and voiding (Athwal et al., 2001). It
is largely inhibitory to bladder activity. Seventy-five percent projects heavily to the PAG, which in turn connects to the
of patients with decreased dopamine resulting from Parkin- M-region in the pons. Depending on the area affected within
son’s disease have slowness of movement, gait disturbance, the ACG, lesions may lead to bladder overactivity or urinary
and tremor; 45% to 75% have bladder overactivity. The retention (Andrew and Nathan, 1964; Duffau and Capelle,
vast majority of cell bodies of origin for serotonin are in the 2005). The prefrontal cortex is thought to play a major role
raphe nuclei. Serotonin acts to inhibit reflex bladder and in volitional voiding and deciding the social appropriateness of
pelvic nerve activity by suppressing afferent bladder infor- voiding. Lesions here lead to inappropriate bladder overactiv-
mation. The sympathetic autonomic nuclei and the sphinc- ity and voiding (Griffiths et al., 2005).
ter motor nuclei also receive a serotonergic input from the
raphe nucleus. Fibers from the raphe nuclei of the reticular Spinal Cord
formation may moderate responsiveness to different phases By adolescence, disparity in growth of the spinal cord and
of the sleep–wake cycle or emotional states. the vertebral column leads to the cord’s terminating around
The locus ceruleus is the brainstem’s CNS container of the first lumbar vertebra. The adult conus medullaris is quite
norepinephrine cell bodies. Norepinephrine acts to tonically short and contains the entire S1 to S5 segment. Because the
facilitate continence-related reflexes. spinal cord terminates well above the respective segmental
The hypothalamus and midbrain PAG are activated during foramina, the cauda equina describes the terminal ventral
micturition. The paraventricular nucleus of the hypothalamus and dorsal nerve roots as they travel through the spinal canal
has connections to the sacral parasympathetic nucleus (SPN) to exit. The cauda equina is subject to various spinal pathol-
and the sphincter motor neurons. The anterior hypothalamus ogies including lumbar disk disease, trauma, tethered cord,
and PAG projects to the pons M region and can induce bladder and spinal stenosis. Although the thoracolumbar levels are
contraction via pontine parasympathetic pathways. The poste- important in sympathetic autonomic influence of the lower
rior hypothalamus has sympathetic inhibitory pathways. The urinary tract, the conus medullaris has greater significance
hypothalamus function, although poorly delineated, is known because autonomic detrusor nuclei and pudendal somatic
to involve β-endorphin neurotransmitters, the opioid peptides nuclei are housed in the intermediolateral and ventromedial
constituting an entire class of brain neurotransmitters. Inter- anterior gray matter, respectively. The conus medullaris also
neurons in the lumbosacral cord project strongly to the PAG, houses neurons involved with defecation and sexual func-
which in turn projects to the pons M region, thus making the tion, with relays for cortical separation of these visceral
PAG an important component in bladder reflex activities. functions (encephalization) developing after birth.
60 PART 2  Basic Science

tracts involving the L region of the pons also take part in the
Mechanisms of Normal Bladder Filling, voluntary assistance to storage.
Storage, and Voiding
Filling and Storage Voiding
Storage depends on sympathetic neural activity. As noted The mechanisms responsible for switching reflexes from
by McGuire (1986), three sympathetic neural responses storage to voiding, that is, from chiefly sympathetic to
to afferent pelvic nerve firing associated with increasing parasympathetic, or adrenergic to cholinergic, or spinal to
bladder volume have been demonstrated experimen- supraspinal reflex pathways, rely on axodendritic contacts
tally: β-receptor–mediated relaxation of the detrusor between parasympathetic, sympathetic, and somatic path-
musculature; α-receptor–mediated increase in urethral ways in the spinal cord.
smooth muscle activity and urethral pressure; and inhi- Voiding is largely a parasympathetic event. Our under-
bition of ganglionic transmission in the pelvic (vesical) standing of the neurophysiology of micturition developed
ganglia, which, in effect, inhibits sacral parasympathetic from a large body of literature based primarily on animal
outflow to the bladder. These actions are illustrated in models. Precise neural pathways involved in voiding remain
Figure 4.2. controversial. The concepts presented here are based pri-
Somatic activation of lower urinary tract outlet is regu- marily on those by Bradley et al. (1974) and de Groat et al.
lated by afferent pelvic nerve spinal reflexes that keep tonic (1979), as synthesized by Blaivas (1982) and McGuire
resistance to the urethra so that urethral pressure is greater (1986). Figure 4.4 is a summary of the major neurologic
than detrusor pressure. Cortical tracts to the urethra and pathways involved in bladder filling and voiding.

Filling and
storage Voiding Stop voiding

Pontine
micturition
center

Corticospinal
tract

Sympathetic

Pudendal
nucleus

Pelvic
nerves
Pudendal
Pelvic Pelvic
Plexus Plexus

Pudendal
Pudendal
Afferent
Efferent
FIGURE 4.4  Summary of major neurologic pathways involved in bladder function. Storage: Bladder distention results in afferent pelvic nerve dis-
charge. After synapse in pudendal nucleus, efferent pudendal nerve impulses result in contraction of external urethral sphincter. At the same time,
afferent sympathetic discharges traverse hypogastric nerve. After synapse in sympathetic nuclei, efferent firing causes (1) inhibition of transmission
of postganglionic parasympathetic neuron, which inhibits detrusor contraction, and (2) increased tone at bladder neck. Net effect is that urethral
pressure remains greater than detrusor pressure, facilitating urine storage. Voiding: Afferent pelvic nerve discharges ascend in spinal cord and synapse
in pontine micturition center. Descending efferent pathways cause (1) inhibition of pudendal firing, which relaxes external sphincter, (2) inhibition
of sympathetic firing, which opens bladder neck and permits postganglionic parasympathetic transmission, and (3) pelvic parasympathetic firing,
which causes detrusor contraction. Net result is that relaxation of external sphincter causes decrease in urethral pressure, followed almost imme-
diately by detrusor contraction, and voiding ensues. Stop: Voluntary interruption of urinary stream. Descending corticospinal pathways emanating
from motor complex synapse in pudendal nucleus, resulting in contraction of external sphincter. Urethral pressure increases above detrusor pressure,
interrupting stream. (Modified with permission from Blaivas JG. The neurophysiology of micturition: a clinical study of 550 patients. J Urol. 1982;127:958.)
CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 61

Normal voiding is a voluntary act involving reflex-­ NMDA receptors and is modulated by serotonergic and nor-
coordinated relaxation of the urethra and sustained contrac- adrenergic systems of brainstem that tend to support stor-
tion of the bladder until emptying is complete. In healthy age reflexes. Fight-or-flight situations affect micturition via
women, the micturition reflex is probably not a simple seg- 5-hydroxytryptamine (5-HT) and NE modulation. The high-
mental sacral reflex but is modulated supraspinally in the est densities of 5-HT and NE in lower urinary tract reflex
PMC. Voluntary control of the micturition reflex is mediated pathways are in the lateral pathway (LP), primary afferents
by connections between the prefrontal cerebral cortex and in sacral dorsal horn, SPN and Onuf ’s nucleus, and lumbar
the pons. Voluntary control of the external urethral sphincter sympathetic intermediolateral nucleus. 5-HT neurons are
is via the corticospinal pathway connecting the frontal cortex also located in medullary neurons (raphe magnus) and NE
with the pudendal nucleus in the ventral horn of the sacral neurons in medullary and pontine nuclei, for example, locus
spinal cord. Bradley et al. (1974) believe that connections ceruleus (pons), and Kolliker-Fuse nucleus (pontomedul-
between the sensorimotor cortex and the pudendal nucleus lary junction). Aδ afferents, activated by stretch, travel via
control voluntary sphincter activity and that voiding is con- Lissauer’s tract to the PAG to constitute a spinobulbospinal
trolled voluntarily by complex interactions among cortical reflex. The efferent arm from the M region activates sacral
areas (prefrontal cortex), subcortical areas (thalamus, hypo- parasympathetic neurons that travel to the pelvic nerve, with
thalamus, basal ganglia, and limbic system), and brainstem acetylcholine neurotransmitters acting on M2 and M3 recep-
(mesencephalic-pontine-medullary reticular formation). tors, and via interneuron GABA activity inhibiting Onuf ’s
With filling to bladder capacity, stimuli from the bladder nucleus.
cause afferent discharges, which traverse pathways in the Urodynamically, the micturition reflex begins with sud-
spinal cord to synapse largely in the PAG. Voiding is initi- den and complete relaxation of the striated muscles of the
ated voluntarily or when the bladder volume is so large that urethra and pelvic floor and a decrease in urethral pressure.
it is no longer possible to suppress micturition. To initiate Several seconds later, intravesical pressure is increased by a
voiding, the external urethral sphincter relaxes voluntarily via highly controlled coordinated contraction of the bulk of the
inhibition of somatic motor neurons from the ventral horn. detrusor muscle. Descent and funneling of the bladder neck
Efferent impulses from the PMC run in the reticulospinal and proximal urethra occur and urine flow begins (Fig. 4.5).
tracts to inhibit pudendal firing (relaxing the external sphinc- Afferent feedback from the urethra to the spinal cord when
ter) and to stimulate parasympathetic neurons situated in urine enters the proximal urethra further augments bladder
the intermediolateral cell column at levels S2–S4, causing contraction to complete emptying.
detrusor contraction. During voiding, sympathetic efferents Brainstem modulation of the micturition reflex allows for
are inhibited, which opens the bladder neck and permits a detrusor contraction long enough to completely evacuate
postganglionic parasympathetic transmission. The micturi- intravesical contents. With voluntary termination of voiding
tion reflex depends upon glutamate activation of α-amino- or with the stop test, the striated muscles of the urethra and
3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and pelvic floor contract to elevate the bladder base, increase
intraurethral pressure, and empty the urethra of urine. The
detrusor muscle is reflexly inhibited, and intravesical pres-
sure returns to normal.
AB C
Clinical Effects of Neurologic Disease
on Lower Urinary Tract Function
Clinical studies of patients with brain lesions demonstrate
urgency and frequency with urodynamic studies revealing
“neurogenic detrusor overactivity” with coordinated detru-
sor and sphincter function if the lesion is above the pons
(Fig. 4.6B). Lesions below the pons interfere with detru-
sor and sphincter coordination, so the neurogenic detrusor
overactivity is not associated with coordinated outlet activ-
ity and may result in detrusor-sphincter dyssynergia (DSD;
Fig. 4.6C). If the brain lesion is limited to small frontal lobe
areas, the patients are generally socially aware, understand-
ingly embarrassed, and without dementia.
In patients with Parkinsonism, a diagnosis of multiple
system atrophy (MSA) should be considered if urinary
symptoms are severe. MSA involves processes of atrophy
FIGURE 4.5 Urodynamic representation of normal female micturi- of neurons, and urinary dysfunction can be the presenting
tion. A, Voluntary initiation of voiding with relaxation of external symptom in up to 83% of patients (Stefanova et al., 2009).
urethral sphincter and pelvic floor muscles and associated decrease
Thus, neurogenic detrusor overactivity in these patients
in urethral pressure. B, Detrusor contraction occurs with increase in
intravesical pressure; intraurethral pressure equals intravesical pres-
may be due to cell loss in the brainstem region, and incom-
sure, and urine flow is initiated. C, Voluntary termination of void- plete bladder emptying may be due to loss of parasympa-
ing. (From Walters MD. Mechanisms of continence and voiding, with thetic drive with atrophy of intermediolateral cell columns.
International Continence Society classification of dysfunction. Obstet Weakening of the sphincter may be due to loss of cells in
Gynecol Clin North Am. 1989;16:773, with permission.) Onuf ’s nucleus; anal sphincter needle EMG may be helpful
62 PART 2  Basic Science

bladder dysfunction resulting from pons lesions because of


A the proximity of the medial longitudinal fasciculus to the
PMC. The bladder dysfunctions associated with brainstem
lesions include emptying disorders, nocturnal urinary fre-
B quency, and urgency with neurogenic detrusor overactivity.

Pons Spinal Cord Disease


Urinary storage and micturition are dependent upon spinal
cord reflexes. Storage reflexes include direct spinal acti-
vation of Onuf ’s nucleus to activate tonic, somatic, and
skeletal periurethral muscle. Sympathetic reflexes involve
low-level bladder afferent firing, which traverses the spinal
cord, activating lumbar sympathetic preganglionic neurons.
Secondary sympathetic neurons, chiefly via the preverte-
bral hypogastric postganglionic nerves, cause bladder outlet
C
contraction and parasympathetic ganglionic inhibition by
α-receptor activity and detrusor relaxation by β-receptor
Hypogastric activity.
T10 nerve Micturition reflexes involve GABA inhibition of urethral
T11 sphincter EMG activity. This activity is initiated in the PMC
T12 (M region) and involves the spinal cord for transmission.
L1 The PMC is also associated with stimulating sacral pregan-
L2 Pelvic plexus
glionic parasympathetic bladder contraction via glutamic
acid neurotransmission and NMDA and non-NMDA gluta-
minergic receptors. Thus, trans-spinal pathways to connect
D the PMC and the sacral cord are necessary to effect coordi-
nated bladder and outlet activities so detrusor contraction
S2
S3
and sphincter relaxation may be synchronous with voiding,
S4 Pudendal and detrusor relaxation and sphincter contraction may act in
Pelvic nerve harmony for urinary storage. Following disconnection from
nerve
the pons, this synergistic activity is altered, and the detrusor
and the sphincter tend to contract simultaneously, leading
FIGURE 4.6 Interruption of nervous system at various levels and to a pathologic condition, DSD. The International Conti-
subsequent voiding dysfunction. A, Lesions in higher cortical centers nence Society (ICS) defines DSD as a detrusor contrac-
have various effects, including inability to voluntarily postpone void- tion synchronous with contraction of the urethral and/or
ing, urge incontinence, enuresis, urethral spasm, and loss of social periurethral striated muscles. It is diagnosed using cystom-
concern about incontinence. B, Suprapontine lesions result in invol- etry with simultaneous surface patch electrodes, urethral
untary detrusor contractions with coordinated urethral relaxation. needle EMG, urethral pressures, or videocystourethrog-
C, High spinal cord (upper motor neuron) lesions lead to neuro- raphy. Diagnosis is not standardized and can be difficult.
genic detrusor overactivity without coordinated urethral relaxation
Different classification schemes have been proposed but
(detrusor-sphincter dyssynergia). D, Lower motor neuron lesions
cause detrusor areflexia.
not widely adopted. Continuous versus intermittent EMG
activity is proposed to occur with complete or incomplete
cord injury, respectively. Therapy is directed at protect-
in diagnosis. The cells of Onuf ’s nucleus are susceptible to ing the patient from upper tract disease and may involve
MSA where they are uniquely resistant to the effects of anticholinergic, tricyclic antidepressant, or α-blocker medi-
polio and ALS. cations; intrasphincteric botulinum-A toxin; intermittent
Multiple sclerosis exists in several forms and may affect self-catheterization; or urinary diversion. Also reported are
the brain or spinal cord, explaining the variety of clinical sphincterotomy and anterior nerve root stimulation follow-
presentations. Lower urinary tract symptoms are the first ing dorsal root rhizotomy.
manifestations of the disease in 5% to 9% of patients, and in With spinal cord transection above the level of the lum-
later stages of multiple sclerosis, 80% to 90% exhibit blad- bosacral cord, “spinal shock” occurs and the bladder is ini-
der dysfunction. Detrusor hyperreflexia is the presenting tially acontractile. Intermittent drainage to the bladder must
symptom with lesions above the pons, while DSD with or be provided to avoid upper tract damage during this time.
without detrusor hyperreflexia presents with lesions below In a few weeks, the bladder develops new reflexes leading
the coordinating pons. to detrusor hyperreflexia, C fibers become the major affer-
ents of these poorly effective reflexes, and the Aδ fibers no
longer appear to function. The bladder capacity is dimin-
Brainstem Lesions
ished. Detrusor-sphincter dyssynergia commonly develops
Nearly half of all patients with brainstem lesions have uri- in patients with spinal cord disease, whether acute as with
nary symptoms, especially voiding difficulty, as shown by trauma or chronic as with multiple sclerosis. The detrusor-
Betts et al. (1992). Eye movement disorders may accompany sphincter dyssynergia causes poor bladder emptying. Hence,
CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 63

both storage and emptying phases of bladder function are not decrease, sublingual nifedipine (10 mg) is administered.
altered, although the resulting symptoms are chiefly problems Patients and caretakers should be educated about the condi-
of storage. The overactive, small capacity bladder with rela- tion, its symptoms, and care, with patients by always carry-
tive outlet obstruction leads to the development of urgency/ ing nifedipine capsules with them.
frequency and urge incontinence as the chief symptoms.
An important clinical note presented by Fowler (1999)
Cauda Equina
is that unless completely restricted to the conus medullaris,
spinal cord disease, which is responsible for the develop- Damage in cauda equina syndromes involves both anterior
ment of a neurogenic bladder, will produce clinical signs and posterior sacral roots and hence has somatic and para-
in the lower limbs because the innervation of the bladder sympathetic motor effects and somatic and visceral sen-
arises more caudally than the innervation of the lower limbs. sory effects. The clinical picture involves sensory loss, in a
Because spinal cord injury is a nonprogressive neurologic patchy “saddle hypesthesia” pattern and variable loss of anal
disease, and because the neurogenic detrusor overactivity and urethral and sexual response functions. Disk disease is
and DSD and loss of bladder compliance can cause ureteric a frequent cause but trauma, spinal stenosis, and tethered
reflux and resultant upper renal tract damage, therapy must cord also may result in damage to the cauda equina.
be directed to prevention of upper tract disease. Loss of com-
pliance is not always part of DSD and is poorly defined, but
Peripheral Innervation and Bladder
needs monitoring in these patients. Loss of compliance has
Dysfunction
been defined in a range of 1–20 mL/cm H2O (Park, 2010).
In neurologically intact patients, bladder compliance below Bladder disturbances are seen in peripheral neuropathies
40 mL/cm H2O was associated with an increase in detru- that involve small fibers, for example, diabetes, amyloidosis,
sor overactivity incontinence. McGuire et al. (1981) have and panautonomic neuropathy. The most common in devel-
shown that ureteral reflux occurs when detrusor leak point oped countries is diabetes, which typically involves small
pressures exceed 40 cm H2O, which places the upper tracts sensory and postganglionic parasympathetic fibers, leading
at risk of damage. In a group of patients with spinal cord to excessive accommodation, reduced bladder sensation,
disease, dual or triple medical therapy has been suggested increased residual urine, decreased urine flow, and markedly
as treatment for loss of compliance, which includes an anti- increased capacity. Other signs of neurologic disturbance are
cholinergic agent combined with an α-blocker, tricyclic anti- common, and bladder dysfunction in isolation is not seen.
depressant (imipramine), or both (Cameron et al., 2009).
These medications work synergistically to reduce detrusor
Pelvic Nerve Injury
pressure and decrease outlet resistance. Another example of
therapy to protect upper tracts is the avoidance of sustained Pelvic nerve injury, resulting in bladder dysfunctions, can be
bladder drainage, which may add to compliance loss. In con- produced by resection surgery (e.g., radical hysterectomy
trast, progressive spinal cord disease (e.g., multiple sclerosis) or rectal carcinoma or prostate excision surgery). The chief
very rarely causes upper tract involvement. The therapies, damage is to the parasympathetic innervation. Nerve injury
therefore, may be more symptomatic. Transverse myelitis may also be seen with vaginal deliveries. Nerves may be
has a consistent, surprising finding in that although there injured by compression, stretch, or transection. At the pres-
may be excellent clinical recovery from tetraparesis, bladder ent time, recovery is unpredictable in compression or stretch
dysfunction remains as a sole residual neurologic complaint. injuries involving the pelvis. Another common type of injury
Spinal cord injuries at T6 and above are associated with may result from bladder overdistention, which is seen in con-
a serious condition, autonomic dysreflexia. Resulting from junction with epidural anesthesia and labor and where blad-
loss of supraspinal and baroreptor control of the sympa- der volumes are not consistently known. Varying degrees of
thetic system below the lesion, autonomic dysreflexia urinary retention are seen with overdistention injuries.
results clinically in signs of hypertension, pilomotor contrac- Urinary retention in young girls without evidence of
tion, and diaphoresis. It is considered a medical emergency neurologic disease may be seen in conjunction with pseudo-
and can result in stroke, convulsions, cardiac arrhythmia, myotonia, a distinct auditory and waveform pattern seen on
and death. Segmental reflexes are responsible for this sym- needle examination of the urethral sphincter. This type of
pathetic response, and bladder or bowel distension are well- EMG activity is not specific and may also be seen in other
known triggers. Bladder distention has been identified as types of bladder dysfunction or in patients with normal
the trigger in up to 75% to 85% of the cases; other causes lower urinary tract function. Some patients with urinary
are fecal impaction, urinary tract infection, or other abdom- retention and EMG abnormality have polycystic ovaries,
inopelvic inflammatory conditions. Prompt identification of suggesting the possibility of a linkage of disturbances to a
the cause is needed, and immediate relief (unblockage of hormonal abnormality, the overall condition referred to as
bladder drainage due to a defective or obstructed catheter Fowler’s syndrome. The syndrome appears to be responsive
or fecal disimpaction) is required. Important for the uro- to sacral neuromodulation therapy.
gynecologist is that urodynamics or urethrocystoscopy may
also trigger this event, making monitoring of blood pressure Clinical Pharmacology of the Lower
mandatory during these procedures in spinal cord patients.
A rise in blood pressure of 20–40 mm Hg (systolic or dia-
Urinary Tract
stolic) is usually considered diagnostic of autonomic dysre- Thorough understanding of the neurologic control of the
flexia. If this occurs during urodynamics or cystoscopy, the urinary bladder and its outlet allows one to intelligently use
procedure should be stopped. If the blood pressure does pharmacologic agents to manage many types of lower urinary
64 PART 2  Basic Science

tract dysfunction. Basic concepts of pharmacologic treat- neuromuscular junction. Parasympathetic nerve stimulation
ment are summarized within a functional scheme of therapy causes the release of acetylcholine at postsynaptic, parasym-
for micturition disorders, as developed by Wein et al. (1991; pathetic receptor sites. Acetylcholine release produces mus-
see Box 8.2). More specific guidelines for pharmacologic carinic and nicotinic effects; one of the muscarinic effects
treatments of various lower urinary tract complaints and is contraction of the detrusor muscle and relaxation of the
reviews of the clinical studies using these agents are found in trigone. Acetylcholine itself cannot be used for therapeutic
the chapters describing individual urogynecologic disorders. purposes because of actions at central and ganglionic levels
Most pharmacologic agents produce their effects by and because of its rapid hydrolysis by acetylcholinesterase
combining with cell receptors. The drug–receptor interac- and nonspecific cholinesterase. Bethanechol chloride exhib-
tion initiates a series of biochemical and physiologic changes its a selective acetylcholine-like action on the urinary blad-
that characterize the effects produced by the agent. In gen- der and gut, with little or no action at therapeutic dosages
eral, drugs alter lower urinary tract function by affecting on ganglia or the cardiovascular system. Bethanechol chlo-
synthesis, transport, storage, and release of the neurotrans- ride is cholinesterase resistant and causes a contraction of
mitter; the combination of the neurotransmitter with smooth muscle from the bladder, bladder neck, and ure-
postjunctional receptors; or the inactivation, degradation, or thra, thus preventing coordinated and complete bladder
reuptake of the neurotransmitter. Most drugs used to treat emptying. Although bethanechol chloride has been used
lower urinary tract disorders were developed originally for extensively for treatment of postoperative and postpartum
their actions on other organ systems whose functions are urinary retention, it is no longer considered to be effective
also controlled by innervation or drug–receptor interac- to facilitate voiding.
tion. The pharmacologic effects on other organ systems are Other pharmacologic methods of achieving a cholinergic
responsible for many of the unwanted side effects of these effect include the use of cholinesterase agents, dopamine
agents. Improving specificity and selectivity of the thera- antagonists (metoclopramide), and α-adrenergic blocking
peutic agents is an important area of future development agents (to block the inhibitory effect of sympathetics on pel-
in uropharmacology. Clinically, pharmacologic agents can vic parasympathetic ganglionic transmission). In addition,
be grouped into those that facilitate bladder emptying and prostaglandins may facilitate bladder emptying by inducing
those that facilitate urine storage (Box 4.1). Patients with detrusor contraction and maintaining smooth muscle tone.
disorders of bladder emptying have voiding dysfunction; Unfortunately, drug therapy is generally ineffective in caus-
theoretically, drugs that improve bladder emptying would ing detrusor contraction and improving voiding, especially
do so by increasing bladder contractility or by decreasing in the presence of neurogenic disease. The best treatments
outlet resistance. Patients with disorders of urine storage remain intermittent self-catheterization and sacral neuro-
often present with urinary frequency, urgency, or urinary modulation (see Chapters 37 and 43).
incontinence (stress and/or urge), which is usually caused
by either an overactive detrusor or an incompetent urethral Decreasing Outlet Resistance
sphincter mechanism. Agents that facilitate urine storage act The lower urinary tract has α- and β-adrenergic receptor
by inhibiting bladder contractility—thereby increasing blad- sites, the functions of which have been discussed. Facilita-
der capacity—by increasing outlet resistance or by reducing tion of bladder emptying could be achieved by the use of
sensation or afferent input necessary to trigger voiding. The α-adrenergic antagonists, which decrease outlet resistance by
most effective and commonly used agents act on either the smooth muscle relaxation of the bladder neck and proximal
parasympathetic or sympathetic systems. urethra. Some investigators have suggested that these agents
may also affect striated sphincter tone. Alpha-sympathetic
Therapy to Facilitate Bladder Emptying blocking agents have thus been used to treat both smooth
sphincter dyssynergia and detrusor-striated sphincter dys-
Increasing Intravesical Pressure synergia. Wein et al. (1991) published a review of the effec-
A major portion of the final common pathway in a physiologic tiveness of these agents.
bladder contraction is stimulation of the muscarinic cholin- Botulinum-A toxin, a substance that inhibits acetylcho-
ergic receptor sites at the postganglionic, parasympathetic line release from cholinergic nerve terminals, is a presynaptic

Box 4.1  Drug Effects on Lower Urinary Tract Function


Therapy to Facilitate Bladder Emptying Therapy to Facilitate Urine Storage
Increasing intravesical pressure/bladder contractility Inhibiting bladder contractility/increasing bladder capacity
Parasympathomimetic agents, prostaglandins, blockers of Antimuscarinic agents, anticholinergic agents, β-adrenergic
inhibition, α-adrenergic antagonists, opioid antagonists agonists, prostaglandin inhibitors, tricyclic antidepressants,
botulinum-A toxin, potassium channel openers
Decreasing outlet resistance at the level of the smooth Increasing outlet resistance
sphincter
β-adrenergic agonists, α-adrenergic antagonists α-adrenergic agonists, tricyclic antidepressants, SNRI,
β-adrenergic antagonists, estrogen, β-adrenergic agonists
At the level of the striated sphincter Afferent nerve inhibitors/decreasing sensory input
Skeletal muscle relaxants, centrally acting relaxants, botulinum-A Botulinum-A toxin, local anesthetics, dimethyl sulfoxide, vanilloid
toxin, dantrolene, baclofen, α-adrenergic antagonists receptor agonists

SNRI, serotonin (5-HT)—norepinephrine reuptake inhibitor.


CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 65

neuromuscular blocking agent inducing selective and revers- and hippocampus (working memory and inhibition), M2
ible muscle weakness for up to several months when injected affects flexibility and memory, and M3 and M5 affect learn-
intramuscularly in minute quantities. Food and Drug ing. Darifenacin is more selective for M3 and least likely
Administration (FDA) approvals were gained for neurogenic to block M1. Oxybutynin has small molecular weight, high
detrusor overactivity in 2011 and for refractory idiopathic lipophilicity, and neutral polarity, making it more likely to
detrusor overactivity in 2013. Other potential indications cross the barrier than larger, less lipophilic, polarized drugs,
for botulinum-A toxin include detrusor-sphincter dyssyn- such as darifenacin, tolterodine, and trospium. Trospium is
ergia, motor and sensory urge, and certain pain disorders. a quarternary amine that is also less lipophilic and less likely
Botulinum-A toxin appears to be effective to treat detrusor- to cross the blood–brain barrier in patients where CNS side
sphincter dyssynergia when injected either transurethrally effects are of concern.
or transperineally into the external urethral sphincter. Best Tricyclic antidepressants, particularly imipramine hydro-
indications seem to be multiple sclerosis and incomplete chloride, have prominent systemic anticholinergic effects,
spinal cord injury patients suffering from neurogenic detru- weak antimuscarinic effects on bladder smooth muscle,
sor overactivity and detrusor-sphincter dyssynergia. Besides antihistaminic effects, and local anesthetic properties. Imip-
acting presynaptically to prevent release of acetylcholine, ramine also appears to increase bladder outlet resistance by
botulinum-A toxin appears to act on the sensory side of the a peripheral blockade of noradrenaline uptake. Thus, it may
bladder and may work by affecting the TRP channels, thus be effective for the treatment of urine storage disorders by
showing promise for disease states where C fiber activation both decreasing bladder contractility and increasing outlet
is the major pathology leading to overactive bladder or pain- resistance.
ful bladder syndrome (Ikeda et al., 2012). Injections of botulinum-A toxin into the detrusor muscle
were first tested to treat neurogenic detrusor overactivity in
Therapy to Facilitate Urine Storage spinal cord–injured patients and in myelomeningocele chil-
dren. Excellent results of this therapy into the detrusor in
Decreasing Bladder Contractility neurogenic detrusor overactivity led to an expansion of this
Overactivity of the bladder during filling may present as treatment to incontinence due to idiopathic detrusor over-
involuntary detrusor contractions, decreased bladder com- activity. Dosages from 100 to 200 units of onabotulinum-A
pliance, and/or urgency with or without incontinence. The toxin have been recommended, although treatment can be
pathophysiology and treatments of detrusor overactivity are individualized.
discussed thoroughly in Chapter 35. Pharmacologic agents Several intravesical treatment options to treat neuro-
used to treat detrusor overactivity are directed toward inhib- genic detrusor overactivity have been attempted. Currently
iting bladder contractility or decreasing sensory input during available intravesical treatments either act on the afferent
filling. Atropine and atropine-like agents depress detrusor arc of the reflex, such as local anesthetics or vanilloid, or
overactivity of any cause by inhibiting muscarinic choliner- on the efferent cholinergic transmission to the detrusor
gic receptor sites. Propantheline bromide is an oral agent muscle, such as intravesical oxybutynin or botulinum-A
with this mechanism of action; however, side effects limit toxin. TRP vanilloid receptor agonists reduce sensation or
its use. Currently available anticholinergic agents include afferent input that is necessary to trigger micturition. These
oxybutynin, tolterodine, propiverine, trospium chloride, drugs include capsaicin and resiniferatoxin. Resiniferatoxin
solifenacin, and darifenacin. Oral and transdermal prepara- (RTX) is a pungent substance from a cactus that is 1000
tions are available. Direct instillation into the bladder has times more potent than capsaicin in interacting with vanil-
also been described. Efficacy for the treatment of overactive loid receptors to excite and then desensitize afferent nerves,
bladder is probably similar among these agents, although particularly C fiber or bladder afferents, while being much
their side effect profiles may differ somewhat. This is prob- less painful than capsaicin for bladder injection. These drugs
ably due, at least in part, to their differing selectivity for might raise volume threshold for micturition and are poten-
muscarinic receptor subtypes, and thus they have different tially useful for pain disorders and overactive bladder, with
effects on the body in addition to their actions on the blad- or without urge incontinence. Clinical application of these
der. Oxybutynin has moderate selectivity for M3 over M2, substances has been limited. Capsaicin has proven too pain-
M4, and M5 receptors but greater affinity for M3 and M1 ful for patient use, and problems with manufacturing RTX
receptors. Tolterodine, propiverine, and trospium chloride have not been overcome.
have only modest selectivity for one type of muscarinic Other drugs that have been used to decrease bladder
receptor compared to another. Solifenacin, like oxybutynin, contractility include prostaglandin inhibitors and dimethyl
is more selective for M1 and M3 receptors over other types, sulfoxide. The overall clinical response has generally been
and darifenacin shows the highest selectivity for M3 recep- small with these agents.
tors. The impact of these differences in receptor selectivity
is probably responsible for some of the differences between Promoting Bladder Storage
drugs in rates of dry mouth, slowed gastrointestinal motility, The β-adrenergic agonists offer a unique solution to bladder
blurred vision, heart rate changes, and sedation. overactivity. Rather than act on the contractility (acetylcho-
Patients can also have reductions in memory and atten- line receptors) side of the bladder by blocking contrac-
tion, delirium, drowsiness, and fatigue, and these changes are tions, β3 agonists promote urine storage by stimulating
partially due to the drug’s relative ability to cross the blood– their receptors. Solabegron has shown promise in European
brain barrier. Blood–brain barrier permeability increases with studies with a decrease in weekly incontinence episode of
age, stress, and certain diseases. All five receptor subtypes 20.9% compared to placebo, a decrease in micturitions over
are expressed in the brain. M1 is predominant in forebrain 24 h, and an increase in voided volume. Side effects were
66 PART 2  Basic Science

similar among placebo and treatment groups and may pro- Burnstock G, Dumsday B, Smythe A. Atropine resistant excitation of the
vide an alternative to anticholinergic medications and their urinary bladder: the possibility of transmission via nerves releasing a
purine nucleotide. Br J Pharmacol. 1972;44:451.
side effect profiles. Mirabegron, another β3 agonist, has Cameron AP, Clemens JQ, Latini JM, McGuire EJ. Combination drug
shown similar results with an improved side effect profile therapy improves compliance of the neurogenic bladder. J Urol.
compared to anticholinergics (Tyagi et al., 2011) and is now 2009;182:1062.
approved for use in the United States. Cardozo L, Drutz HP, Baygani SK, Bump RC. Pharmacological treatment of
women awaiting surgery for stress urinary incontinence. Obstet Gynecol.
Increasing Outlet Resistance 2004;104:511.
Chancellor MB, de Groat WC. Intravesical capsaicin and resinifera-
Because of the preponderance of α-adrenergic receptor sites toxin therapy: spicing up ways to treat the overactive bladder. J Urol.
in the bladder neck and proximal urethra, α-adrenergic ago- 1999;162:3.
nists have been used to produce urethral smooth muscle Cruz F. Mechanisms involved in new therapies for overactive bladder. Urol-
ogy. 2004;63:65.
contraction, thereby increasing resting urethral pressure and Downie JW, Armour JA. Relation of afferent nerve activity in the pelvic
resistance to outflow. Beta-adrenergic blocking agents may plexus with pressure, length, and wall strain in the urinary bladder of the
be expected to increase urethral resistance as well, poten- cat. Soc Neurosci Abstr. 1982;8:858.
tiating an α-adrenergic effect. However, few studies have Duffau H, Capelle L. Incontinence after brain glioma surgery: new insights
into the cortical control of micturition and continence. Case report.
tested this hypothesis, and the clinical effects of either drug J Neurosurg. 2005;102:148.
type are relatively small. Edvardsen P. Changes in urinary-bladder motility following lesions in the
Duloxetine is a potent and balanced dual serotonin nervous system in cats. Acta Neurol Scand. 1966;42:25.
(5-HT)-norepinephrine reuptake inhibitor (SNRI) that Elbadawi A. Neuromorphologic basis of vesicourethral function. I. Histo-
potentiates the physiologic actions of endogenous serotonin chemistry, ultrastructure, and function of intrinsic nerves of the bladder
and urethra. Neurourol Urodyn. 1982;1:3.
and NE (by inhibiting the reuptake of these neurotransmit- Elbadawi A. Autonomic muscular innervation of the vesical outlet and its
ters in the presynaptic element) and thereby enhancing role in micturition. In: Hinman Jr F, ed. Benign Prostatic Hypertrophy.
the CNS continence control mechanisms. Duloxetine is New York: Springer-Verlag; 1983:330.
believed to stimulate pudendal nerve motor output result- Finkbeiner A, Welch L, Bissada N. Uropharmacology. IX. Direct acting
smooth muscle stimulants and depressants. Urology. 1978;12:128.
ing from increased levels of 5-HT and norepinephrine in Fletcher TF, Bradley WE. Neuroanatomy of the bladder-urethra. J Urol.
the pudendal motor nucleus. This appears to improve ure- 1978;119:153.
thral closure pressure and urethral resistance. Studies have Floyd K, Hick VE, Morrison JF. Mechanosensitive afferent units in the
shown an improvement in stress incontinence symptoms in hypogastric nerve of the cat. J Physiol. 1976;259:457.
over 60% of women and a decrease in incontinence episodes Fowler CJ. Neurological disorders of micturition and their treatment. Brain.
1999;122:1213.
by over 50%, with variable side effects. Although approved Fowler CJ, Auerbach S, Ginsberg D, et al. OnabotulinumtoxinA improves
in Europe, duloxetine was withdrawn from further study in health-related quality of life in patients with urinary incontinence due to
the United States. idiopathic overactive bladder: a 36-week, double-blind, placebo-controlled,
Estrogens affect adrenergic nerves by influencing excit- randomized, dose-ranging trial. Eur Urol. 2012;62:148.
Fowler CJ, Christmas TJ, Chapple CR, et al. Abnormal electromyographic
ability, neuronal influences on the muscle, receptor density activity of the urethral sphincter, voiding dysfunction, and polycystic ova-
and sensitivity, and transmitter metabolism. The clinical use ries: a new syndrome? Br Med J. 1988;297:1436.
of estrogen to augment lower urinary tract function is dis- Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N. Transient receptor
cussed in Chapter 17. potential A1 receptor-mediated neural cross-talk and afferent sensitiza-
tion induced by oxidative stress: implication for the pathogenesis of inter-
Bibliography stitial cystitis/bladder pain syndrome. Int J Urol. 2012;19:429.
Gibson A. The influence of endocrine hormones on the autonomic nervous
Andrew J, Nathan PW. Lesions on the anterior frontal lobes and distur- system. J Auton Pharmacol. 1981;1:331.
bances of micturation and defaecation. Brain. 1964;87:233. Gosling JA, Dixon JS. The structure and innervation of smooth muscle in
Athwal BS, Berkley KJ, Hussain I, et al. Brain responses to changes in blad- the wall of the bladder neck and proximal urethra. Br J Urol. 1975;47:549.
der volume and urge to void in healthy men. Brain. 2001;124:369. Gosling JA, Dixon JS, Critchley HO. A comparative study of the human exter-
Bacsu CD, Chan L, Tse V. Diagnosing detrusor sphincter dyssynergia in the nal sphincter and periurethral levator ani muscles. Br J Urol. 1981;53:35.
neurological patient. BJU Int. 2012;109(suppl 3):31. Griffiths D, Derbyshire S, Stenger A, Resnick N. Brain control of normal
Barrington FJ. The nervous mechanism of micturition. Q J Exp Physiol. and overactive bladder. J Urol. 2005;174:1862.
1914;8:33. de Groat WC. Nervous control of the urinary bladder in the cat. Brain Res.
Barrington FJ. The relation of the hind-brain to micturition. Brain. 1975;87:201.
1921;44:23. de Groat WC. Integrative control of the lower urinary tract: preclinical per-
Beck RP. Neuropharmacology of the lower urinary tract in women. Obstet spective. Br J Pharmacol. 2006;147(suppl 2):S25.
Gynecol Clin North Am. 1989;16:753. de Groat WC, Booth AM, Krier J, et al. Neural control of the urinary blad-
Bennett BC, Kruse MN, Roppolo JR, et al. Neural control of urethral outlet der and large intestine. In: Brooks CM, Koizumi K, Sato A, eds. Integra-
activity in vivo: role of nitric oxide. J Urol. 1995;153:2004. tive Functions of the Autonomic Nervous System. North Holland, Elsevier,
Betts CD, Kapoor R, Fowler CJ. Pontine pathology and voiding dysfunction. Amsterdam, Biomedical Press; 1979.
Br J Urol. 1992;70:100. de Groat WC, Lalley PM. Reflex firing in the lumbar sympathetic outflow
Blaivas JG. The neurophysiology of micturition: a clinical study of 550 to activation of vesical afferent fibres. J Physiol. 1972;226:289.
patients. J Urol. 1982;127:958. de Groat WC, Ryall RW. Recurrent inhibition in sacral parasympathetic
Blaivas JG. Pathophysiology of lower urinary tract dysfunction. Urol Clin pathways to the bladder. J Physiol. 1968;196:579.
North Am. 1985;12:216. de Groat WC, Saum WR. Sympathetic inhibition of the urinary bladder
Bradley WE. Cerebro-cortical innervation of the urinary bladder. Tohoku J and of pelvic ganglionic transmission in the cat. J Physiol. 1972;220:297.
Exp Med. 1980;131:7. de Groat WC, Theobald RJ. Reflex activation of sympathetic pathways to
Bradley WE, Timm GW, Scott FB. Innervation of the detrusor muscle and vesical smooth muscle and parasympathetic ganglia by electrical stimula-
urethra. Urol Clin North Am. 1974;1:3. tion of vesical afferents. J Physiol. 1976;259:223.
de Groat WC, Yoshimura N. Pharmacology of the lower urinary tract. Ann
Rev Pharmacol Toxicol. 2001;41:691.
CHAPTER 4  Neurophysiology and Pharmacology of the Lower Urinary Tract 67

Holstege G. Micturition and the soul. J Comp Neurol. 2005;493:15. Reitz A, Schurch B. Intravesical therapy options for neurogenic detrusor
Holstege G, Kuypers HG, Boer RC. Anatomical evidence for direct brain overactivity. Spinal Cord. 2004;42:267.
stem projections to the somatic motoneuronal cell groups and autonomic Reitz A, Stohrer M, Kramer G, et al. European experience of 200 cases
preganglionic cell groups in cat spinal cord. Brain Res. 1979;171:329. treated with botulinum-A toxin injections into the detrusor muscle for
Huang YH, Bih LI, Chen GD, Lin CC, Chen SL, Chen WW. Autonomic urinary incontinence due to neurogenic detrusor overactivity. Eur Urol.
dysreflexia during urodynamic examinations in patients with suprasacral 2004;45:510.
spinal cord injury. Arch Phys Med Rehabil. 2011;92:1450. Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturition disturbance in
Ikeda Y, Zabbarova IV, Birder LA, et al. Botulinum neurotoxin serotype acute transverse myelitis. Spinal Cord. 1996;34:481.
A suppresses neurotransmitter release from afferent as well as efferent Shapiro E. Clinical implications of genitourinary embryology. Curr Opin
nerves in the urinary bladder. Eur Urol. 2012;62:1157. Urol. 2009;19:427.
Ioanid CP, Noica N, Pop T. Incidence and diagnostic aspects of the bladder Shergill IS, Arya M, Hamid R, Khastgir J, Patel HR, Shah PJ. The impor-
disorders in diabetics. Eur Urol. 1981;7:211. tance of autonomic dysreflexia to the urologist. BJU Int. 2004;93:923.
Jünemann K, Thüroff J. Innervation. In: Brubaker LT, Saclarides TJ, eds. Sillen U. Central neurotransmitter mechanisms involved in the control of
The Female Pelvic Floor: Disorders of Function and Support. Philadelphia: urinary bladder function. Scand J Urol Nephrol. 1980;58:1.
F.A. Davis; 1996. Sirls LT, Zimmern PE, Leach GE. Role of limited evaluation and aggres-
Keast JR, Kawatani M, De Groat WC. Sympathetic modulation of cholin- sive medical management in multiple sclerosis: a review of 113 patients.
ergic transmission in cat vesical ganglia is mediated by alpha 1- and alpha J Urol. 1994;151:946.
2-adrenoceptors. Am J Physiol. 1990;258:R44. Steers WD. Physiology and pharmacology of the bladder and urethra. In:
Kelin LA. Urge incontinence can be a disease of bladder sensors. J Urol. Walsh PC, Retik AB, Vaughan ED, et al., eds. Campbell’s Urology. 7th ed.
1988;139:1010. Philadelphia: WB Saunders; 1998.
van Kerrebroeck P, Abrams P, Lange R, et al. Duloxetine versus placebo Steers WD, Creedon D, Tuttle JB. Immunity to NGF prevents afferent plas-
in the treatment of European and Canadian women with stress urinary ticity following hypertrophy of the urinary bladder. J Urol. 1996;155:378.
incontinence. BJOG. 2004;111:249. Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an
Khanna OP. Vesicourethral smooth muscle: function and relation to struc- update. Lancet Neurol. 2009;8:1172.
ture. Urology. 1981;18:211. Stohrer M, Schurch B, Kramer G, Schmid D. Botulinum A toxin detru-
Leippold T, Reitz A, Schurch B. Botulinum toxin as a new therapy option sor injections in the treatment of detrusor hyperreflexia. J Urol.
for voiding disorders: current state of the art. Eur Urol. 2003;44:165. 2000;163:244A.
Lensch E, Jost WH. Autonomic disorders in multiple sclerosis. Autoimmune Swash M. Innervation of the bladder, urethra and pelvic floor. In: Drive JO,
Dis. 2011;2011:803841. Hilton P, Stanton SL, eds. Micturition. London: Springer-Verlag; 1990.
Mahoney DT, Laberte RO, Blais DJ. Integral storage and voiding reflexes: Tanagho EA, Miller ER. Initiation of voiding. Br J Urol. 1970;42:175.
neurophysiologic concept of continence and micturition. Urology. Thor KB. Targeting serotonin and norepinephrine receptors in stress urinary
1977;10:95. incontinence. Int J Gynaecol Obstet. 2004;86(suppl):S38.
McGuire EJ. Experimental observations on the integration of bladder and Todorova A, Vonderheid-Guth B, Dimpfel W. Effects of tolterodine, tro-
urethral function. Invest Urol. 1978;15:303. spium chloride, and oxybutynin on the central nervous system. J Clin
McGuire EJ. The innervation and function of the lower urinary tract. J Neu- Pharmacol. 2001;41:636.
rosurg. 1986;65:278. Tulloch AG. Sympathetic activity of internal urethral sphincter in empty
McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of uro- and partially filled bladder. Urology. 1975;5:353.
dynamic testing in myelodysplastic patients. J Urol. 1981;126:205. Tyagi P, Tyagi V, Chancellor M. Mirabegron: a safety review. Expert Opin
Morrison J, Steers WD, Brading A, et al. Neurophysiology and neurophar- Drug Saf. 2011;10:287.
macology. In: The 3rd International Consultation on Incontinence. Paris: Uvelius B, Gabella G. Relation between cell length and force production in
Health Publication Ltd; 2005. urinary bladder smooth muscle. Acta Physiol Scand. 1980;110:357.
Mundy AP. Clinical physiology of the bladder, urethra and pelvic floor. In: Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem.
Mundy AP, Stephenson TP, Wein AJ, eds. Urodynamics: Principles, Prac- 2007;76:387.
tice and Application. New York: Churchill Livingstone; 1984. Veselá R, Asklund H, Aronsson P, et al. Coupled nitric oxide and autonomic
Munoz A, Smith CP, Boone TB, Somogyi GT. Overactive and underactive receptor functional responses in the normal and inflamed urinary bladder
bladder dysfunction is reflected by alterations in urothelial ATP and NO of the rat. Physiol Res. 2012;61:371.
release. Neurochem Int. 2011;58:295. Walters MD. Mechanisms of continence and voiding, with International
Nakamura T, Yoshimura M, Shinnick-Gallagher P, Gallagher JP, Akasu T. Continence Society classification of dysfunction. Obstet Gynecol Clin
Alpha 2 and alpha 1-adrenoceptors mediate opposing actions on parasym- North Am. 1989;16:773.
pathetic neurons. Brain Res. 1984;323:349. Wang P, Luthin GR, Ruggieri MR. Muscarinic acetylcholine receptor sub-
Nilius B. Transient receptor potential (TRP) cation channels: rewarding types mediating urinary bladder contractility and coupling to GTP bind-
unique proteins. Bull Mem Acad R Med Belg. 2007;162:244. ing proteins. J Pharmacol Exp Ther. 1995;273:959.
Ohlstein EH, von Keitz A, Michel MC. A multicenter, double-blind, ran- Wein AJ. Pharmacology of incontinence. Urol Clin North Am. 1995;22:557.
domized, placebo-controlled trial of the β3-adrenoceptor agonist solabe- Wein AJ, Arsdalen KV, Levin RM. Pharmacologic therapy. In: Krane RJ,
gron for overactive bladder. E­ ur Urol. 2012;62:834. Siroky MB, eds. Clinical Neurourology. 2nd ed. Boston: Little Brown &
Park HW. Management of Low Compliant Bladder in Spinal Cord Injured Co.; 1991.
Patients. LUTS. 2010;2:61. Wein AJ, Barrett DM. Voiding Function and Dysfunction. Chicago: Mosby;
Pernow B. Substance P. Pharmacol Rev. 1983;35:85. 1988.
Raezer D, Wein AJ, Jacobowitz D, et al. Autonomic innervation of canine Winter DL. Receptor characteristics and conduction velocities in bladder
urinary bladder: cholinergic and adrenergic contributions and interac- efferents. J Psychiatr Res. 1971;8:225.
tion of sympathetic and parasympathetic systems in bladder function.
­Urology. 1973;2:211.
CHAPTER 5

Physiology of the
Pelvic Muscles,
Vagina, and
Anorectum
Rebecca Shaffer
Pamela A. Moalli

The pelvic floor musculature is largely composed of skel-


Chapter Outline etal, or striated, muscle. The predominant muscle group is
the levator ani muscles, which are the iliococcygeus, pubo-
Pelvic Floor coccygeus, and puborectalis muscles. The pelvic floor forms
Anatomy and Composition the bottom of a bowl that extends anteriorly to the abdomi-
Function and Biomechanical Properties nal wall and posteriorly to the back and spine. Abnormal
forces originating from the anterior or posterior trunk, from
Vagina within the abdomen, or from the pelvic floor itself may
Anatomy and Composition affect its function. This includes the development of pelvic
Embryology and Innervation floor myalgia as can be seen after lower back injury, or the
Orientation and Structural Support effect of chronic cough as an instigating factor for the devel-
opment of pelvic organ prolapse.
Function
In the human, the nervous system is divided into the
Biomechanical Properties and Histology central and the peripheral nervous systems (see Chapter 4).
Anorectum The central nervous system is typically considered to include
Anatomy and Composition the brain and spinal cord, whereas the peripheral nervous
system encompasses the somatic and autonomic nervous sys-
Innervation
tems. Somatic nerves primarily innervate skeletal muscle and
Intrinsic Enteric Nervous System allow a human to perform voluntary, self-directed actions.
Sympathetic Control Conversely, the autonomic nervous system underlies baseline,
Parasympathetic Control homeostatic functions that occur without conscious thought
Extrinsic Afferents or action. This includes innervation of the smooth muscle of
Defecation and Continence visceral organs, the cardiac system, and glandular functions.
Neurologic Abnormalities Somatic innervation to the levator ani muscles is sup-
plied by efferent (motor) nerves specifically arising from
Assessment of Anal Incontinence
the pelvic nerve (originating from spinal cord levels S2-S4)
supplying the peritoneal aspect and the pudendal nerve
(also from S2-S4) supplying the caudal, or perineal, portion.
The levator ani muscles maintain a baseline contractile tone
Pelvic Floor that helps to preserve the orientation of the pelvic organs
(Parks et al., 1962; Parks et al., 1966), which was originally
Anatomy and Composition
termed the postural reflex of the pelvic floor (Parks et al.,
The pelvic floor is a highly complex heterogeneous struc- 1966). This constant tone is dependent on proprioceptive
ture that orchestrates support to the vagina, which in turn afferent input as processed by the dorsal root ganglia in the
provides support to the pelvic organs. In certain cases, such spine and the normal function of afferent sensory nerves.
as childbirth, substantial stretch and accommodation of pel- Humans can voluntarily increase their pelvic muscle contrac-
vic floor structures must also occur. Although the precise tions, such as in response to an increase in intra-abdominal
physiology by which the pelvic floor provides support to the pressure, but the muscles rapidly fatigue and tone returns
vagina is not understood, it is known to comprise an amalga- to baseline after an average of 1 min (Parks et al., 1962). As
mation of skeletal muscles, connective tissue supports, and humans evolved to become bipedal creatures and obtained
bones. Together, this support mechanism serves to maintain upright postures, new stress forces emerged that began to
the location and orientation of the uterus, cervix, vagina, be countered by the musculature. The pubococcygeus and
bladder, urethra, and the anorectum within the pelvis. puborectalis muscles bilaterally attach to the pubic bone
68
CHAPTER 5  Physiology of the Pelvic Muscles, Vagina, and Anorectum 69

just lateral to midline and wrap posteriorly around the rec- the endopelvic fascia coalesces with the ATFP on either
tum, forming a sling observed anatomically as the anorectal side. More distally, there is also an attachment between the
angle. The iliococcygeus originates from a connective tissue vagina and the arcus tendineus fascia rectovaginalis. Level
condensation (termed the arcus tendineus levator ani) of III is the support of the distal vagina, specifically to the peri-
the lateral pelvis near the ilia of the bony pelvis and attaches neal body and the perineal membrane. Injury at different
to the coccyx. This large muscle has a horizontal orienta- levels will cause different anatomic defects.
tion and coalesces with the pubococcygeus and puborectalis The connective tissue itself is composed of a mixture of
to form the levator plate (median raphe), upon which the collagen, elastin, proteoglycans, and the extracellular matrix
upper two thirds of the vagina and the uterus rest horizon- (ECM) that acts as scaffolding for the other components.
tally. The urethra, vagina, and rectum descend through the Collagen provides the tissue with tensile strength, and elas-
interior of this loop in the space termed the urogenital hia- tin provides resilience, which is the ability for tissue to snap
tus. As the levators contract, they apply pressure to these back into place after it is deformed or stretched. Large and
structures and eliminate potential space. Caudal to the small proteoglycans are extracellular proteins important
levator plate, the vagina and rectum terminate in a vertical for cell-to-cell connections, or connections between cells
orientation. and the ECM. Through the binding of small proteoglycans
Smooth muscle fibers are also present, primarily con- (decorin, fibromodulin, biglycan, luminican, and chon-
tained within viscera, including the bladder, urethra, uterus, droadherin) with glycosaminoglycans, they form complexes
vagina, and bowel. They allow for stretch and accommoda- that occupy space within the ECM and help it to resist com-
tion during filling of the viscera and evacuation of visceral pression (Abramowitch et al., 2009). Other proteoglycans,
contents in combination with autonomic reflexes. Smooth including fibronectin, vitronectin, and laminin, serve to cre-
muscle cells can be found, to varying degree, within the ate cell-to-cell bindings (Tinelli et al., 2010). The composi-
supportive connective tissue. Many of the components of tion of the connective tissue is dynamic, with production
the pelvic floor are noted to be altered in postmenopausal and degradation of collagens occurring as the tissue continu-
women or women with prolapse, and the smooth muscle ously remodels in response to stresses, aging, and injury.
cells are no exception. For example, Ozdegirmenci et al. Tissue breakdown occurs after the enzymatic activity of
(2005), using computer-based analysis, determined that the acid cathepsins, which break down the protein cross-linked
predicted proportion of smooth muscle cells in the round bonds that bind collagen fibers together, and matrix metal-
ligament is decreased in women with prolapse. loproteinases (MMPs), which lead to cleavage of the col-
In orthopedic terminology, ligaments are the dense lagen fibers themselves (Burleigh et al., 1974).
connective tissue connections bridging from bone to bone Of the 19 known types of collagens, types I and III are
whereas tendon is the term given to the connection between found most commonly in epithelial tissues (Jackson et al.,
a muscle and a bone. Within the abdomen and the pelvis, 1996). Overall, type I is the collagen found most commonly
the term ligament is used more variably. A ligament may throughout the body. It forms large fibers and provides
refer to a fold of peritoneum that formed during embryonic much of the tensile strength for tissues. Types II and III
development. An example is the hepatoduodenal ligament, also form strong fibers that do not readily deform. Type III
which contains the portal triad of the hepatic artery, portal fibers are smaller than those formed by type I fibers. Type
vein, and the common bile duct. In the pelvis, the ligaments III collagen is typically found more frequently in tissues that
typically refer to the connective tissue suspensions tethering require flexibility, such as the walls of blood vessels (Moalli
the viscera (such as the uterus, bladder, urethra, vagina, and et al., 2004). Type IV collagen assembles into a network
rectum) to the pelvic sidewall and the bony pelvis. Con- configuration instead of distinct fibers, and it may help form
densations of connective tissues that provide support to the the basement membrane beneath the fibers (Tinelli et al.,
vagina and uterus include the cardinal-uterosacral ligament 2010). Type V collagen forms small fibrils and is frequently
complex and the paravaginal attachments to the arcus ten- found in wound healing. It also likely directs fibrillogene-
dineus fasciae pelvis (ATFP). This is collectively known as sis. Heterogeneous fibrils are formed when type I collagen
the endopelvic fascia. copolymerizes with type III or type V collagens. As the pro-
The endopelvic fascia is a continuation of the web of con- portion of type III and IV collagens increase as compared
nective tissue originating at the level of the uterine artery’s with type I collagen, the tissue becomes weaker.
insertion at the uterus and extending bilaterally to the pel- It is thought that hormones may influence the balance of
vic sidewalls and caudally to suspend the cervix and vagina. collagen types within the tissues. After menopause, if hor-
Close to the uterus and cervix it is termed the parame- mone replacement therapy is not initiated, the amount of
trium, and at the level of the external cervical os it becomes type I collagen decreases by 75% (compared with premeno-
the paracolpium (DeLancey, 1993). This web periodically pausal women) and the ratio of type I-to-type III/V collagen
solidifies into thicker bands called ligaments, which serve to is found to decrease in biopsies from the ATFP (Moalli et al.,
support the internal organs of the pelvis and are primarily 2004). Thus, after menopause, there is an increased propor-
bridges between the viscera and bony structures. DeLancey tion of type III and type V collagens in human connective
and others have previously discussed a conceptual frame- tissue. This group found no difference in the proportion of
work organizing these connective tissue attachments into elastin or smooth muscle between pre- and postmenopausal
levels corresponding to support of different anatomic sites women.
on the vagina (DeLancey, 1992, 1994) (see Fig. 2.10). Level Changes in collagen composition are also likely associ-
I refers to the support of the vagina at its apex, specifically ated with pelvic organ prolapse. Jackson et al. (1996) found
referring to the cardinal and uterosacral ligaments. Level II that the total collagen content of tissue and the solubility of
is the lateral support of the midportion of the vagina, where that collagen were decreased in premenopausal women with
70 PART 2  Basic Science

prolapse as compared with control subjects. In their experi- Ultimate load


ments, there was no change in the collagen I-to-collagen
II ratios. They also found that MMP and cathepsin activ-
ity increased for prolapse patients, leading to more rapid 15
turnover of the collagen (Jackson et al., 1996). Overall, the
Linear
changes in collagen likely change the tensile strength of the
stiffness
tissue, a risk factor for prolapse. It is interesting to note that (slope)
the collagen content is also decreased for women with pro-

Load (N)
lapse in tissues that do not provide structural support, such 10
as the cervix (Wong et al., 2003).
Energy
absorbed
Function and Biomechanical Properties to failure
In nonhuman mammalian species, especially for animals that 5
Ultimate
walk on four legs, the levator ani muscles primarily control elongation
the movement of an animal’s tail, and the connective tissue
alone acts as the primary support structure (Abramowitch 2 4 6
et al., 2009). For example, the rat has connective tissue Elongation (mm)
anatomy that parallels human anatomy in terms of its sup- FIGURE 5.1 Structural properties are frequently measured using a
port. The rat has attachments between the upper vagina uniaxial load-elongation test to failure, resulting in a load-elongation
and the spine, similar to the human uterosacral ligaments curve for the tissue complex. (Modified with permission from Abramow-
and the Level I support; paravaginal attachments between itch SD, Feola A, Jallah Z, Moalli PA. Tissue mechanics, animal models,
the lateral vagina and the dense connective tissue stretching and pelvic organ prolapse: A review. Eur J Obstet Gynecol Reprod Biol.
2009;144(suppl 1):S146–S158.)
from the pubic symphysis to the lateral bony pelvis, similar
to the ATFP at Level II; and attachments emulating Level
III support, connecting the distal vagina with the anterior which is the general term given to the change in size or con-
surface of the ischiopubic rami (Moalli et al., 2005). figuration of a material due to the actions of an external
In humans, because of the adoption of an upright pos- force or change in temperature. Deformation is also called
ture, the levator ani muscles and the connective tissue strain. The force may be a tensile force, occurring because
structures share the load. The muscles and the endopelvic of pulling; a compression force, applied by pushing; or tor-
fascia work together to support the pelvic organs. When sion, which is applied by twisting. The connective tissue
the pelvic floor muscles contract at baseline, the tension within ligaments typically contributes to their viscoelastic
applied to and experienced by the supportive ligaments is property—the ability to initially resist strain, then to stretch
reduced. If the muscles are damaged, such as may happen as they begin to deform, and then to snap back and regain
after childbirth, or if the nerves that supply the muscles are their previous configuration once the force is removed. If
stretched or otherwise damaged, such that the muscles they enough strain is experienced by the tissue, it may lose its
supply are compromised, then the shelf supporting the pel- recoil ability and undergo structural failure, in which rup-
vic organs may sag or the uterus, cervix, bladder, and rectum ture occurs. As an example from the orthopedic literature,
may change their orientation or herniate through the uro- we know that after ligaments are damaged, their collagen
genital hiatus. When the organs change their position, addi- remodels as they heal. After healing from injury, the com-
tional tension is placed on the supporting connective tissue, position of the ligament changes; it is frequently stiffer and
which may then stretch or even rupture, leading to observ- may be permanently stretched and elongated, losing its abil-
able pelvic organ prolapse. It is likely that vaginal childbirth ity to recoil normally (Tinelli et al., 2010).
serves as an initial instigating event for damage, but it is also Biomechanical properties may be structural or mechani-
likely that progressive denervation of the muscles contin- cal. This was well described by Abramowitch et al. (2009).
ues to occur as a woman ages. Some suspect that pudendal Structural properties describe how tissues react when a load
nerve trauma (i.e., stretch and elongation during childbirth) or force is applied; they are dependent on the actual size
may play a role, although this remains a point of conten- and shape of the tested tissue. Thus, a larger tissue sample
tion. Other risks include chronic increased intra-abdominal generally performs better than a smaller tissue sample. An
pressure or repetitive high-pressure straining, such as occurs example is a uniaxial load-elongation test to failure (Fig. 5.1;
for patients with obesity, chronic cough conditions, chronic Abramowitch et al., 2009). In this test, one edge of a tis-
obstructive pulmonary disease, habitual heavy lifting, or sue sample is rigidly fixed, and the other is connected to a
chronic constipation. movable arm, which stretches the tissue until the point of
Recent work has sought to elucidate the biomechanical failure. The length that the tissue stretches as well as the
properties of the pelvic floor. The pelvic floor by default is force applied can be measured. The linear stiffness of the
load-bearing, supporting the pelvic organs against the effects tissue is the slope of the load-elongation curve.
of gravity and applied intra-abdominal pressure. Hence, Measurement of mechanical properties is different
the standard components of biomechanics, including force because these properties take into account the differing
application, stress deformation, and structural movement, sizes and shapes of a tissue sample. To obtain these formu-
will have an obvious effect on its function. las, the force applied to the tissue is divided by the specific
Applicable biomechanical parameters to this discus- cross-sectional area of the tissue; this is the stress. Measure-
sion include materials science terms including deformation, ment of mechanical properties also allows quantification
CHAPTER 5  Physiology of the Pelvic Muscles, Vagina, and Anorectum 71

Tensile strength normal strain described previously. The stretch ratio is a


term referring to the ratio between the length of a tissue
under stretch over the length of the tissue at rest. Brooks
1.5 et al. (1995) determined a maximum stretch ratio of 1.5
before muscle tissue undergoes structural failure, with sub-
Tangent
sequent rupture of muscle fibers. Using computer model-
modulus
ing of magnetic resonance images of the pelvis obtained
Stress (MPa)

(slope)
from a nulliparous woman and simulating the passage of
1.0 a fetal head through the pelvic floor model, Lien et al.
(2004) found that the medial portion of the pubococcygeus
Strain-energy muscles stretched the most, with a stretch ratio of 3.26,
density but that 79% of the simulated muscles had a stretch ratio
greater than 1.5. Thus, it is likely that most vaginal deliver-
0.5 ies lead to some amount of permanent stretch damage to
Ultimate
strain the muscles of the pelvic floor.
Compared with other medical fields such as orthopedic
1 5 10 surgery, female pelvic medicine and reconstructive surgery
Strain (%) is in its infancy in terms of research into the biomechani-
FIGURE 5.2 Mechanical properties are frequently measured using cal principles that apply to our work. We are only begin-
the uniaxial tensile test to failure, resulting in a stress-strain curve. ning to understand the effect of injury of the pelvic floor
(Modified with permission from Abramowitch SD, Feola A, Jallah Z, as a result of childbirth, the application of chronic pressure
Moalli PA. Tissue mechanics, animal models, and pelvic organ pro- because of obesity or recurrent Valsalva with heavy lifting,
lapse: A review. Eur J Obstet Gynecol Reprod Biol. 2009;144(suppl 1): chronic constipation or cough, or other trauma to the pelvic
S146–S158.)
floor. Likewise, we have poor understanding of the healing
and repair mechanisms undertaken by the pelvic soft tis-
of strain by calculating the difference in length from the sues after injury. In the future, it will be critical to improve
original to the stretched tissue after the force is applied. our understanding of all of these components if we are to
As these properties are calculated per unit area, we believe have confidence in our understanding of the mechanisms
they provide a more direct biomechanical measurement of of pelvic organ prolapse and to improve the longevity and
the microcomposition of a tissue. For the particular tissue, specificity of our surgical corrections.
how does its collagen, elastin, and smooth muscle composi-
tion contribute to its function? This is typically measured via
a uniaxial tensile test to failure, also known as a stress-strain Vagina
curve (Fig. 5.2; Abramowitch et al., 2009). Here, the tissue
Anatomy and Composition
is clamped on at least two sides. Lengthening and stress sus-
tained can be measured. The tangent modulus (also called The vagina is composed of muscular and connective tissue
the elastic modulus or Young’s modulus) is the slope of this elements. It is also richly vascular. The vagina is commonly
curve, and the tensile strength of the tissue is the maximal described as a fibromuscular tube extending from the cer-
stress it can support. Of note, the tensile strength of a tissue vix to the perineum. The layers of the vagina include an
may differ depending on the axis in which it is stretched— epithelial surface, the lamina propria, the vaginal muscula-
whether it is pulled linearly to the majority of muscular or ris, and the adventitia. The surface of the vagina is lined
connective tissue components or whether it is pulled per- with stratified squamous epithelial cells that are nonkera-
pendicularly. This differential stretch behavior is termed tinizing. Histologically, there are four main epithelial lay-
anisotropy. ers: (1) most superficially, nonkeratinized cells with small,
Stretch must occur during childbirth. As the fetal head pyknotic nuclei; (2) an intermediate glycogen-containing
descends into the pelvis from the uterus, through the cer- cellular layer; (3) proliferating parabasal cells; and (4) the
vix, and into the vagina, it must by definition pass through basal epithelial layer (Forsberg, 1995). Adjacent to the epi-
the urogenital hiatus. The bones of the fetal skull differen- thelium is the lamina propria, or subepithelium, a layer of
tially deform based on whether the fetus is preterm or is dense connective tissue that is composed of collagen and
at term, the shape of the mother’s pelvis, and the force of elastin. Next is the muscularis, which is largely composed
the expulsive labor efforts, but the head still must narrow of smooth muscle cells. The smooth muscle adopts a circu-
and elongate as molding occurs during the second stage of lar configuration for its inner layer and then a longitudinal
labor. It is estimated that the average suboccipito-bregmatic orientation in its outer layer (Siddique, 2003). Intercalated
diameter, the smallest aspect of the presenting fetal head, is between the smooth muscle bundles of the muscularis
9.2 cm (Pu et al., 2011) after molding. The urogenital hiatus are blood vessels. Finally, the adventitia is a layer of loose
is estimated to be 2.5 cm transversely from medial border connective tissue and contains collagen, elastin, additional
to medial border between the levator ani muscles in an aver- smooth muscle, and additional vasculature. The composi-
age nonpregnant woman without prolapse (DeLancey and tion of the connective tissue here includes 84% collagen and
Hurd, 1998). During delivery, the urogenital hiatus must 13% elastin (Abramowitch et al., 2009; Moalli et al., 2004).
rapidly dilate, similar to the dilation of the cervix but over Overall, the vagina and the endopelvic fascia are very simi-
a much shorter time frame. The particular biomechanical lar in terms of their collagen configurations (Keane et al.,
property affected is the stretch ratio, an extension of the 1997). Thus, clinically obtained vaginal biopsies may allow
72 PART 2  Basic Science

extrapolation to the collagen composition of the endopelvic Sze et al., 2001). In considering these examples, it is impor-
fascia for a particular patient. tant to remember that the normal anatomy has already been
disrupted, leading to the prolapse. However, on the basis of
imaging studies, it appears that sacrocolpopexy leads to a
Embryology and Innervation
better restoration of the normal angle than does sacrospi-
(Also See Chapter 3)
nous ligament fixation.
The innervation differs between the proximal and distal Because of its attachments to the ATFP and the arcus
portions of the vagina, and these differences begin early in tendineus rectovaginalis, the midvagina in cross-section for a
embryogenesis. Embryologically, the distal two thirds of the woman with normal support has an “H” configuration. This
vagina arises from an outgrowth of the endoderm of the has been confirmed on magnetic resonance imaging (Field-
urogenital sinus, the paired sinovaginal bulbs. The proximal ing et al., 1996).
one third of the vagina, as well as the cervix and the uterus, Overall, the vaginal epithelium contributes little struc-
arise from the uterovaginal primordium, which is the result tural strength on its own. Instead, structural integrity is sup-
of fusion of the paramesonephric ducts in the midline. The plied by the deeper layers of connective tissue and smooth
solid sinovaginal bulbs eventually fuse together, grow cepha- muscle (DeLancey, 1992; Moalli et al., 2004).
lad, and then fuse with the uterovaginal primordium. This
whole structure then eventually canalizes to form the vagina.
Function
The original junction between the sinovaginal bulbs and the
urogenital sinus is the site of the future hymen. Reflecting The normal functions of the vagina include response to hor-
differential embryologic origins, innervation to the upper monal stimulation, lubrication and stretch during sexual
portion of the vagina is via the inferior hypogastric nerve activity, immunologic protection to help protect against
plexus, and innervation to the lower vagina and skin is from the acquisition of infectious diseases, and remodeling and
the pudendal nerve. The spinal origin of all of these nerves stretch to allow for vaginal childbirth.
is the sacral levels S2 to S4 (Siddique, 2003). As a premenopausal woman traverses the menstrual
Important to note is the convergence of sensory input cycle, the vaginal epithelium responds to fluctuating hor-
from the pelvis at the level of the spinal cord and the brain. mone levels. Sjoberg et al. (1988) collected vaginal biop-
Although afferent sensations are tracked independently sies from women every third day throughout the menstrual
from various end organs (bladder, ureters, vagina, the skin), cycle. They reported that the epithelium normally thick-
there is dynamic processing of the inputs centrally, such that ens and superficial epithelial cells mature when circulating
pathophysiology from one organ may affect others. This estrogen levels are high. Under high progesterone levels,
helps to explain the expression of numerous pelvic pain syn- superficial cell layers are shed and the basal portion of the
dromes within the same individual, such as endometriosis, epithelium is more quiescent. Proliferation is confined to
interstitial cystitis, irritable bowel syndrome, and fibromy- the parabasal cell layer. At the time of ovulation, the epithe-
algia. There may also be overlap of the sensory nerve fibers lium is maximally thickened and mature.
within the pelvic nerve plexus. One of the consequences of sexual excitation is genital
congestion, which is thought to be a reflexive autonomic
response. The major neurotransmitters involved with this
Orientation and Structural Support
response are nitric oxide, which acts on the clitoris, and
The vagina contains a convex angle, with the uppermost vasoactive intestinal polypeptide (VIP), which affects the
portion in a nearly horizontal orientation as it rests on top of vagina. There may be other neurotransmitters that have not
the levator muscles and the distal portion descending more yet been identified. With this reflexive response, the geni-
vertically. The angle occurs as the vagina descends through tals become engorged and lubrication is increased. This is
the genital hiatus and is caused by the sling of levator mus- partly mediated by increased vascular flow and is depen-
cles contracting at baseline. Funt et al. (1978) found this dent on estrogen. After menopause, paravaginal vasodila-
angle to average 130° in the supine position on X-ray vagino- tion is compromised because of a decrease in the number of
gram. The levator plate helps to withstand downward forces estrogen receptors on the vascular endothelium, and it may
caused by Valsalva maneuvers or other increases in intra- lead to deficits in the genital congestion response (Basson,
abdominal pressure. For example, if this angle is lost because 2009).
of a lack of tone of the puborectalis muscle or a compromise Before menarche, the vaginal epithelium is thin and the
in the connective tissue attachments, the genital hiatus will vaginal pH is relatively high (pH > 4.7). As endogenous estro-
widen and the risk of prolapse and herniation through the gen production is initiated by the ovaries, the vaginal epithe-
genital hiatus increases (Nichols et al., 1970). This clini- lium thickens and glycogen levels in the epithelium increase.
cally has practical effects when considering the approach Once a woman begins menstruating, the vagina maintains a
for a prolapse repair. Any repair that changes the angle of pH in the acidic range (pH < 4.5). It is thought that this
the vagina may circumvent this normal anatomic support. pH level is established as the naturally predominant Lacto-
For example, using magnetic resonance imaging of supine bacillus bacteria ferment the glycogen present in the vagi-
women, the average angle was found to be 145°. Two differ- nal epithelium, converting it into lactic acid (Fettweis et al.,
ent investigative groups confirmed differential postoperative 2012) Lactobacilli also produce hydrogen peroxide, contrib-
angles after different surgical procedures; after abdomi- uting to the acidic environment. After menopause, as serum
nal sacrocolpopexy with Burch colposuspension, the angle estrogen levels decrease, estrogen receptors are subsequently
was 137° to 149°, and after sacrospinous ligament fixation downregulated in the epithelium. The proportion of inter-
the angle was increased at 215° to 220° (Rane et al., 2004; mediate and parabasal cells in the epithelium increases, with
CHAPTER 5  Physiology of the Pelvic Muscles, Vagina, and Anorectum 73

few superficial basal cells seen. There is less vaginal blood of the vagina. Badiou et al. (2008) found a decreased pro-
flow. The vaginal epithelium thins and elasticity is reduced. portion of smooth muscle cells in biopsies from the anterior
Normal vaginal secretions decrease, and glycogen stores vaginal wall of women with prolapse versus controls. Hence,
decrease. This results in a higher baseline vaginal pH level these women have a greater fraction of collagen and ECM
(Tsai et al., 1987). Estrogen receptors are restored and vaginal within the vaginal muscularis. In addition, the normally
pH returns to an acidic level if exogenous estrogen hormone tightly organized smooth muscle bundles were less dense
therapy is administered (Basson, 2009). There is currently a and less rigidly structured.
large body of research examining biofilms and other immuno- Badiou et al. (2008) further present a hypothesis in
logic defenses of the vagina in preventing infection. regards to the decreased smooth muscle cells. One of the
One of the critical functions of the vagina is to stretch to explanations could be apoptosis of these cells. After the pro-
allow for the vaginal delivery of offspring. However, vaginal gramed cellular death of apoptosis, fibroblasts frequently
parturition has long been recognized as a major risk fac- enter the tissue and may produce de novo collagens, chang-
tor in the development of pelvic organ prolapse, and new ing the collagen ratios. As discussed above, this has been
research has attempted to elucidate the mechanism of the observed in human tissue biopsies from various components
development of this disease. Throughout the body, elastin of the pelvic floor and vagina. This may have direct clini-
is generally a stable and permanent component of tissue. It cal ramifications, especially in the consideration of vaginal
is remarkable that, in the vagina, elastin is actually resynthe- graft materials such as synthetic mesh grafts. If the graft
sized after childbirth. Rodent models of pelvic organ prolapse materials also lead to apoptosis, or hasten it in tissue already
have been developed in which proteins important for elastin compromised and prolapsed, then could this hasten abnor-
fiber assembly have been genetically knocked out, includ- mal collagen production? These questions will be critical as
ing null mutations in lysyl oxidase-like-1, as reported by Liu next-generation graft materials are developed.
et al. (2006) and Lee et al. (2008), and fibulin-5, as reported
by Drewes et al. (2007). Both of these rodent models dem-
onstrate pelvic organ prolapse associated with pregnancy. Anorectum
Anatomy and Composition
Biomechanical Properties and Histology
The rectum and anus are the terminal portions of the gastro-
The biomechanical properties of the vagina likely demon- intestinal tract. The rectum is approximately 12 to 15 cm
strate anisotropy, as previously defined. Hence, vaginal tis- long, and the anus is 2 to 4 cm long. Women have a slightly
sue behaves differently when it is stretched longitudinally as shorter anal canal than men, with a mean length of 3.7 cm
compared with when it is stretched circumferentially. This versus 4.6 cm, respectively (Irving and Catchpole, 1992).
is seen with the disproportional circumferential stretch nec- As is seen elsewhere in the gastrointestinal tract, the rectum
essary for vaginal parturition as compared with more mod- as described from its inner to outer layers has a mucosal
erate lengthening of the vagina. surface, a submucosal layer, a muscularis, and a serosal layer
Goh (2002) performed an experiment examining longi- (see Fig. 5.3). The muscular layer is composed of an inner
tudinal anterior vaginal wall tissue samples from pre- and circular layer of smooth muscle fibers and an outer longitu-
postmenopausal women, all with prolapse. This study did dinal layer. As is true for the entire gastrointestinal tract, the
not control for hormone replacement therapy use. Samples rectum includes a network of intrinsic neurons, located in
were normalized by cross-sectional area. No differences in the submucosa (the submucosal or Meissner’s plexus) and
elongation length or deformation amount were found, but between the circular and longitudinal muscle layers (myen-
an increased elastic modulus was found, which indicated teric or Auerbach’s plexus). The rectal mucosal surface and
increased stiffness in postmenopausal tissues. On the basis the proximal portion of the anus are lined with columnar
of the experiment, this may reflect age-related changes, but epithelium until the dentate or pectinate line, located at
conclusions cannot be drawn regarding changes on the basis the midpoint of the anal canal approximately 2 cm proxi-
of prolapse status. mal from the end of the anal canal. The dentate line is the
Subsequently, Lei et al. (2007) used similar techniques point at which the epithelium transitions to squamous epi-
to test the biomechanical properties of pre- and postmeno- thelium (Irving and Catchpole, 1992). The distal portion of
pausal Chinese women with and without prolapse. All vagi- the anus past the dentate line is called the anoderm, and it
nal samples were obtained in a longitudinal orientation from has numerous sensory nerves that allow for determination
the midline anterior vagina at the time of hysterectomy. of tactile and nociceptive signals. This area is important for
Subjects were controlled for hormone use and smoking his- continence because it is one of the final areas to help deter-
tory; no subjects were using hormone therapy, and all were mine the composition of a bolus passing through from the
nonsmokers. The mechanical properties of the tissue were rectum, be it solid, liquid, or gas. The termination of the
measured, and stress-strain curves were calculated. For all anal canal is the anal verge, where the epithelium of the
patients with prolapse, the biomechanical properties of the anus changes to the keratinized epithelium of the perianal
tissues were inferior; they had shorter lengths of maximum skin.
elongation and fracture, and they had an increased elastic The anatomy of the anal canal sphincter complex
modulus. Overall, they concluded that for women with pro- includes the internal anal sphincter (IAS), which is com-
lapse, the connective tissues had decreased elasticity and posed of smooth muscle fibers, and the external anal
increased stiffness. sphincter (EAS), which extends more distally and is made
Thus, independent of postmenopausal status, prolapse of skeletal muscle. It may also include a component of the
itself is associated with histologic changes in the composition puborectalis muscle, one of the levator ani muscles, which
74 PART 2  Basic Science

Myenteric
plexus Extrinsic efferent
and afferent nerves
Circular Deep and vasculature
muscle muscular
Myenteric
plexus
plexus
Submucous
plexus

Longitudinal
muscle

Mucosa Muscularis Mucosal Submucosal


mucosae plexus artery

Submucous Mucosa Deep muscular plexus


A B plexus
FIGURE 5.3  Layers of intestinal wall showing the locations of the submucosal and myenteric nerve plexuses: A, three-dimensional representa-
tion and B, cross-sectional representation. (With permission from Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. 4th ed. New
York, NY: McGraw-Hill; 2000.)

is also composed of skeletal muscle. Above the dentate line, pubic symphysis. Contraction of the puborectalis muscle
the anal mucosa is folded into what is eponymously termed via baseline muscle tone helps form the anorectal angle at
the columns of Morgagni (named after the Italian anatomist 90°, which historically has also been thought to contribute
Giovanni Batista Morgagni, who lived from 1682 to 1771; to baseline fecal continence (Palit et al., 2012).
Haubrich, 2002), a configuration that may contribute to With voluntary squeeze, the anorectal angle narrows
the baseline coaptation of the anal canal. The anal vascular and moves ventrally and cranially. These anatomic changes
cushions, located in the submucosa above the dentate line, contribute to the ability to defer defecation. Using a com-
provide a final passive seal for the anal canal when engorged bination of magnetic resonance imaging, three-dimensional
with blood (Lestar et al., 1992). endoanal ultrasound, and high-definition anal manometry
Continence is complex and requires the coordination of to examine anal sphincter control in humans, Raizada et al.
multiple muscle types. The IAS is the final extension of the (2011) found that the proximal portion of the anal sphinc-
rectal circular smooth muscle fibers and is under autonomic ter mechanism includes some voluntary control supplied
control. The IAS is proximally wrapped by the puborectalis by the puborectalis muscle. Their high-definition manom-
muscle and distally by the EAS. The striated muscle of the etry probe consisted of 256 pressure sensors in a 16 × 16
EAS is innervated by the inferior hemorrhoidal branch of grid over a 64-mm-long pressure discrimination zone. Upon
the pudendal nerve; thus, it is under volitional control. A voluntary squeeze in human subjects, pressure increases
portion of the EAS anteriorly fuses with the perineal body; asymmetrically, with the strongest pressures measured at
fibers laterally and anteriorly fuse with the right and left the anterior and most distal portions of the anal canal. In
transverse perinei muscle bodies (Raizada et al., 2011). The addition, a portion of the puborectalis muscle was found to
EAS works with the IAS to provide the resting pressure of occlude the cranial portion of the anal sphincter (Raizada
the anal canal. Historically, it was established that the IAS et al., 2011), just as the EAS contracts the distal portion.
contributed up to 85% of the resting pressure; thus, it was It is likely that in addition to its effects on the anorectal
a major component of baseline fecal continence (Frenckner angle, the puborectalis muscle contributes to continence
and Euler, 1975). With improved measurement and the abil- as part of the actual anal sphincter mechanism. The exact
ity to perform manometry with concurrent endoanal ultra- contribution of the EAS versus the puborectalis muscle as
sound, we have been able to more precisely determine the applied to the continence status of women has not yet been
anatomy of the canal. An example of this was demonstrated determined.
by Wong et al. (1998), who showed that the EAS may in A clinical example of a malfunctioning anal sphincter
fact play a major role in baseline pressure once measured in mechanism is found in obstructive defecation, also known
an upright position or when physical activity alters abdomi- as pelvic floor dyssynergia or anismus. In this disorder,
nal pressures. The EAS can be further recruited via volun- there is a paradoxical contraction of the anal sphincter
tary control, resulting in increased pressure and improved complex with attempts to defecate. Alternatively, there is
maintenance of continence when rectal filling occurs. This an inability to coordinate the abdominal, rectal, and pelvic
helps to abate feelings of urgency while awaiting a socially floor muscles with defecatory trials. Dyssynergia is impli-
acceptable moment for defecation. cated in the etiology of up to 30% to 50% of patients with
The pubococcygeus and puborectalis muscles wrap pos- chronic constipation (Rao, 2001). Patients with this condi-
terior to the rectum, suspending it anteriorly toward the tion report extended periods of straining in their attempts
CHAPTER 5  Physiology of the Pelvic Muscles, Vagina, and Anorectum 75

to defecate. It has been found that abnormal contractions As previously discussed in this book, the ability of the
of the puborectalis muscle and the EAS contribute to dys- autonomic motor system to affect distant targets in the body
synergic defecation (Dailianas et al., 2000). In conclusion, (smooth muscle, cardiac muscle, glands) involves a chain of
proper function of both of these striated muscles is neces- neural connections. This is in contrast to the somatic motor
sary for normal defecation, with the ability to recruit and system, which innervates skeletal muscle. In the somatic
then relax the muscles on demand. system, a neuronal cell body is typically located within the
central nervous system, and a single, very long axon trav-
Innervation els through the body before synapsing directly on its end
target, the muscle. The autonomic system has an interven-
Intrinsic Enteric Nervous System ing synapse somewhere along its pathway; thus, it has, at
The physiology of colorectal function is dependent on prop- minimum, a two-neuron chain. The term efferent describes
erly functioning innervation of the bowel. We must start pathways traveling away from the central nervous system,
with a discussion of the neurologic control of the gastro- typically descending toward a target and carrying informa-
intestinal tract itself. As previously discussed, the neural tion regarding motor effects. Afferent is the name given
physiology of the body can be divided into the central and to ascending pathways traveling from the end organ back
peripheral nervous systems. The gastrointestinal tract con- toward the central nervous system, typically transmitting
tains yet another distinct component of the nervous system sensory information from the target. For efferent autonomic
that is separate from the central and peripheral divisions. nerves, traveling toward an end target organ, the first neu-
Most nerve control of the colon is supplied via what is ron typically has its neuronal cell body located within the
called the enteric nervous system (ENS), with a network of central nervous system (the spinal cord or the brain stem)
ganglia located in the gut wall controlling basic functions, and synapses onto the cell body of a subsequent neuron
such as peristalsis or secretory reflexes (see Fig. 5.3). In within an autonomic ganglion. Axons of the central neurons
this intrinsic enteric nerve plexus, neuronal cell bodies are traveling toward ganglia are called the preganglionic fibers,
located within the muscularis of the bowel wall itself. It is and axons traveling from the ganglionic cell bodies are called
estimated that there are 80 to 100 million neurons located postganglionic fibers. The postganglionic fibers can then syn-
within the ENS, approximately the same number as might apse onto the final target or onto another intervening cell.
be found in the spinal cord (Kandel et al., 2000). Signals are The sympathetic neurons have cell bodies located within
modulated and propagated quickly along the length of the the spinal cord, in the intermediolateral region (see Fig.
bowel through the release of neurotransmitters. 5.4). Axons leave the spinal cord via the ventral root at the
There are clinical diseases specifically noted to affect the spinal cord level where the cell body is located. They then
ENS ganglia. There are two major examples. The first is run together with the somatic motor nerves in the spinal
Hirschsprung’s disease, a congenital disease resulting from nerve for a short time, but then they enter the sympathetic
an incomplete migration of neural crest cells during devel- nerve trunks, which run parallel to each side of the spinal
opment. This leads to an aganglionic state with no identi- cord and contain periodic ganglia in a paravertebral chain.
fiable ganglion cells within the myenteric plexus for some The connections between the spinal nerve and the paraver-
portion of the intestinal tract, typically in the colon. Disease tebral chains are called white myelinated rami. The axons
sequelae include chronic constipation and proximal dilation can run cephalad or caudad within the paravertebral chains
of the colon due to the contracted distal aganglionic section. as they travel toward their targets. Each preganglionic axon
The dilation is also called congenital megarectum. Biopsies then synapses with multiple postsynaptic cell bodies in dif-
of the rectal wall confirm an absence of neuronal ganglia. ferent ganglia. Postganglionic axons leave the sympathetic
The second is an acquired form, seen in patients with Cha- chain via gray unmyelinated rami and travel in large bundles
gas disease, a tropical parasitic infection. When the disease along spinal nerves projecting to targets in various parts of
becomes chronic, there is a decrease in the ganglionic cells the body. Sympathetic nerve supply to the pelvis comes
identified in the myenteric plexus. The ganglia normally from the T5 to L2 spinal cord levels.
contain nitric-oxide-producing neurons of the ENS, which For the colorectal system, there are some sympathetic
allows inhibition of the IAS, resulting in defecation. For preganglionic fibers that leave the spinal cord, travel through
both of these pathologic conditions, the IAS is unable to the paravertebral chain without forming a synapse, and fol-
relax, resulting in continued tonic contraction and a failure low branches of the splanchnic nerve before synapsing into
to pass the contents of a rectal bolus; ballooning of the rec- postsynaptic cell bodies within the prevertebral ganglia.
tal wall eventually occurs and may result in a megarectum These ganglia are located somewhat away from the spinal
state. cord and include the celiac ganglion, the superior mesen-
teric ganglion, and the inferior mesenteric ganglion (Kandel
Sympathetic Control et al., 2000).
The intrinsic ENS interacts with elements of the somatic In the rectum, sympathetic nerve supply leads to inhibi-
and autonomic nervous systems. Extrinsic nerve supply to tion and thus relaxation of smooth muscle, and it contrib-
the bowel is supplied by the autonomic nervous system— utes to contraction of the IAS (Wester and Brubaker, 1998).
the sympathetic and parasympathetic systems. The extrin-
sic inputs modulate the actions of the intrinsic system, Parasympathetic Control
but the intrinsic system maintains predominant control of In the parasympathetic system, cell bodies are found in spe-
bowel function. These extrinsic nerves directly innervate cific nuclei in the brainstem and in the sacral segments S2
the enteric smooth muscle, and some evidence suggests that to S4 of the spinal cord. As opposed to the sympathetic gan-
they may also innervate the ENS ganglia. glia, the parasympathetic system has very long preganglionic
76 PART 2  Basic Science

Spinal cord Dorsal root Dorsal root


ganglion

Preganglionic
Ventral
neuron
root
Paravertebral chain
ganglion
Sympathetic
nerve trunk
Postganglionic fibers to
peripheral autonomic
effector organs
Intermediolateral FIGURE 5.4 Pictoral representation
gray matter of the sympathetic preganglionic
Gray communicating ramus
and postganglionic axons. (With per-
Prevertebral White communicating ramus mission from Kandel ER, Schwartz JH,
ganglion Jessell TM. Principles of Neural Sci-
Postganglionic neuron
ence. 4th ed. New York, NY: McGraw-
Adrenal medulla
Hill; 2000.)

nerves and very short postganglionic connections, such that afferents are polymodal in that they can be activated by
the ganglia in most instances are located within the wall of different stimulus modalities. The best characterized affer-
the end target organ. Thus, the relay point in these connec- ents are mechanosensitive and respond to distention of the
tions is located in the periphery of the body. This has prac- colon, conveying a sense of fullness or even urgency. How-
tical importance for pathologic conditions. For example, if ever, afferents can also respond to chemical signals, such
urinary retention occurs, the bladder wall may stretch and as inflammatory cytokines, which may contribute to tenes-
could potentially lead to irreversible damage to the parasym- mus and frequent low-volume or even frustrated defeca-
pathetic neural connections located within the visceral wall. tion attempts in affected patients. In addition, the afferents
The parasympathetic nerve supply for the upper colon likely communicate information when the colonic wall con-
arises from the vagus nerve, and for the distal colon and rec- tracts; this may be the origination of the visceral pain sen-
tum it arises from the sacral nerve plexus. The innervation sations that are experienced as colonic spasms or “colicky
from the vagus nerve travels along the course of the superior pain,” as is sometimes described by patients.
mesenteric artery. The innervation of the sacral nerve plexus Clinically, the importance of balancing excitatory and
parallels the course of the inferior mesenteric artery. The inhibitory influences can be highlighted by the example of
dorsal vagal nucleus is located in the brainstem and contains patients with spinal cord injuries (SCIs) who develop neu-
parasympathetic neuronal cell bodies; preganglionic fibers then rogenic bowel symptoms. For these patients, constipation
project through via an association with Cranial Nerve X before is the most prevalent problem, likely resulting from inad-
synapsing in ganglia associated with thoracic and abdominal equate sensory afferent input. However, these patients may
targets, including the upper gastrointestinal tract. Where the also experience fecal impaction, with a lack of control when
sacral nerve arises in segments S2 to S4 of the sacral spinal a bowel movement arrives, resulting in fecal incontinence.
cord, the parasympathetic preganglionic cell bodies also lie in Here, inhibitory control is inadequate. One rare and extreme
the intermediolateral column of the spinal cord and exit the treatment example involves a posterior sacral rhizotomy, in
ventral roots of the cord parallel to the sympathetic fibers. The which the posterior nerve roots at the S2 to S4 levels are
parasympathetic nerves then travel in the pelvic nerve toward ligated to decrease irritative or spastic sensations from reach-
the pelvic ganglion nerve plexus (Kandel et al., 2000). ing the spinal cord via the normal reflex arc (Ebert, 2012).
In the rectum, parasympathetic nerve supply activates Reflexive defecation can no longer occur because the reflex
smooth muscle and leads to contraction of the rectum, arc has been interrupted, but it improves control for patients
and it contributes to relaxation of the IAS (Wester and because the risk of incontinence is much lower once the
Brubaker, 1998). These actions are necessary for defecation spastic activity is truncated. Manual rectal stimulation or the
in addition to the intrinsically-mediated actions. implantation of sacral nerve electrical stimulators that stimu-
late the anterior sacral nerve roots must be used to initiate
Extrinsic Afferents the defecatory sequence after posterior sacral rhizotomy.
Sensory afferent information from the bowel is commu-
nicated directly to the spinal cord via sensory nerves that
Defecation and Continence
travel through posterior sacral nerve roots to level S2 to
S4. Information from sensory afferents passes through two The normal control of defecation is a combination of reflexive
major neural pathways: one originating from the lumbar action and voluntary control. The act of defecation has been
splanchnic/colonic nerves and one traveling via the pelvic/ proposed to consist of four distinct phases: (1) the transit of
rectal nerves. As is true for most visceral afferents, rectal stool in an antegrade direction because of colonic propulsion,
CHAPTER 5  Physiology of the Pelvic Muscles, Vagina, and Anorectum 77

(2) storage of stool in the rectum until a convenient defeca- In addition to the smooth muscle cells, a cellular popu-
tory time is available, (3) passage of stool, and (4) the resolu- lation known as the interstitial cells of Cajal (ICCs) help to
tion of defecation (Palit et al., 2012). The body’s mechanism control peristalsis and are thought to act as “intrinsic pace-
for defecation involves the interaction of enteric neurologic makers” (Brookes et al., 2009). The ICCs are mesenchymal
control, stool composition and consistency, spinal reflexes, cells formed from the same common precursor stem cells
and voluntary control as established at the time of toilet as the smooth muscle cells. They contain c-kit, a tyrosine
training. kinase that is activated by stem cell factor and that pref-
The ENS is responsible for most bowel actions, such as erentially influences the ICCs over smooth muscle cells.
peristalsis or gut secretory functions. Peristalsis involves the The ICCs have unique properties that lead to rhythmic
sequential contraction of adjacent segments of the bowel changes in their membrane potentials, which are rapidly
wall. At the time of contraction, the smooth muscle fibers and passively conducted along the network of ICCs and
shorten and waste contents progress in the direction of a spread to neighboring smooth muscle cells. Some evidence
propagating wave if not impeded by a downstream obstruc- suggests direct activation of the ICCs by sympathetic
tion. The obstruction typically presents in the form of extrinsic nerves. ICC activation results in wave patterns
a functional rather than a structural change. Functional that are characteristic with unique frequencies for differ-
obstructions include retained fecal matter or contracted ent areas of the gastrointestinal tract. For example, the
segments of the colon. Normal peristaltic movement is actions of the ICCs lead to the propagation of slow (Smith
accompanied by the maintenance of a low intraluminal pres- et al., 1987b) and faster waves that propagate toward the
sure (Brookes et al., 2009). However, if obstruction occurs rectum (Smith et al., 1987a). The slow waves (oscillat-
and resistance is met, pressure in the segment increases, the ing 3-6 times/min) were first observed to originate from
smooth muscle does not shorten, and the contents do not ICCs near the submucosal border in the canine gut, and
advance. fast waves (15-20 waves/min) were observed to originate
Once food and waste passes through the ileocecal valve from ICCs near the myenteric border. Similar pacemaker
into the large intestine, colonic contractions may then move cells have been observed in vitro in the human colon by
contents either antegrade toward the rectum (aboral) or Rae et al. (1998).
retrograde back toward the mouth (oral). Within the colon Hormones, neurotransmitters, and other stimuli can
there is typically a mix of antegrade and retrograde contrac- alter the amplitude of the slow waves triggered by the ICCs.
tions, with the balance normally toward antegrade such that If the amplitude exceeds a predetermined threshold, then
there is net forward propulsion of colonic contents. Unlike depolarization occurs and superimposed spikes of action
the more proximal areas of the gastrointestinal tract, the potentials will be triggered. These action potentials are
colon does not exhibit stereotypic patterns of motor activ- associated with calcium increases in the adjacent smooth
ity, with many of the ongoing contractions leading only to muscle cells, leading to contractions. Current evidence sug-
segmentation or transit over short distances (i.e., nonpropa- gests that the ICC network ensures the rapid spread of elec-
gating waves). However, occasional powerful contractions trical signals; thus, it coordinates the effector cells (smooth
originate in the proximal colon and migrate distally, typi- muscle cells) within functional units of the gastrointestinal
cally resulting in defecation. These enterically controlled tract. In addition, this network translates neuronal signals;
propagating waves are termed mass movements or giant thus, it is an important intermediary. Clinically, preliminary
migrating contractions, and they were first described in the studies suggest a role of the ICCs in colorectal disorders
intestines of cats by Cannon (1902). There appears to be because chronic constipation has been associated with a
a circadian rhythm pattern for peristalsis, with propagating decrease in ICCs.
and nonpropagating waves occurring less frequently at night Colonic peristalsis has traditionally been measured using
(Brookes et al., 2009; Rao et al., 2004). colonic manometry with sensors spaced every 10 cm along
Likewise, in the rectum, enterically controlled periodic the length of the gastrointestinal tract to record pressure
contractions seem to be the dominant motor activity as changes. Newer techniques include 24-h spatiotempo-
opposed to the predominant propagating waves seen more ral manometric recording techniques that may allow for
proximally in the bowel. Kumar et al. (1989) recorded what improved spatial resolution with closer sensors and the abil-
are termed rectal motor complexes (RMCs) in humans. The ity to correlate pressure changes with specific events such as
RMCs exhibit activity 3 to 6 times/min. Episodes of activity ingestion of food or defecation (Dinning et al., 2008).
last for 3 to 30 min and occur intermittently, approximately Gastrointestinal transit time affects stool volume and
every 80 to 90 min during the day and twice as frequently consistency (Palit et al., 2012). It has been shown that males
at night. At least one study suggests that in the rectum, ret- have a shorter gastrointestinal transit time than females as
rograde contractions predominate. Rao et al. (2004) found measured by transit of radioisotopes as well as radio-opaque
that 4% to 5% of contractions in the rectum propagated markers (Degen and Phillips, 1996). In terms of the bowel
in an antegrade direction and 14% to 36% of contractions itself, various circulating hormones such as somatostatin;
propagate retrograde. The remaining contractions either menstrual hormones; and humoral factors such as substance
propagated bidirectionally or were confined to the rectum P, VIP, and cholecystokinin may affect gastrointestinal
and did not move rectal contents (Rao and Welcher, 1996). motility. They act on the intrinsic enteric nerve plexus to
In this case, the local pressure likely increases and tension is regulate contractility.
sensed in the rectum. It is thought that nonpropagating and As waste contents progress through the length of the
retrograde contractions may enable the rectum to function in intestinal tract, they typically become progressively more
its storage capacity rather than continuing to move the stool viscous as water is absorbed through the bowel wall. Fur-
antegrade. thermore, there is a complex interaction between the
78 PART 2  Basic Science

composition of stool and the bowel itself. For example, rectum and at the midpoint of the anal canal, they deter-
stool with a high osmotic load, as is seen in patients with mined that the anal sphincter relaxed and allowed pres-
lactose intolerance, experiences more rapid colonic transit sures to equalize in these two locations approximately seven
than other compositions of stool (Rao, 2004). times hourly. The relative importance of this sampling has
Reflexes play a role in normal physiologic function. Def- been shown in patients with fecal incontinence who have
ecation may be thought to be initiated by the gastrocolic decreased sensory discrimination capabilities in the anal
reflex, in which stretching of the stomach leads to increased canal and decreased capabilities to determine temperature
gastrointestinal peristalsis. Other important reflexes for def- differentials between the rectum and the anal canal (Miller
ecation include the rectosphincteric inhibitory reflex or the et al., 1988).
rectoanal inhibitory reflex (RAIR). Here, distention of the In summary, after a waste bolus moves into position
rectum with solid stool or gas leads to relaxation of the IAS. In in the rectum, the rectum distends, the IAS relaxes, the
infants and “spinalized” individuals, this leads to evacuation. puborectalis muscles and EAS are voluntarily relaxed, and
To counteract the RAIR, humans learn to voluntarily contract the abdominal musculature is recruited to further increase
the EAS and to delay defecation. The RAIR is largely enteri- intra-abdominal pressure. After these actions, defecation
cally controlled, although there is also an element of para- occurs.
sympathetic control contributing to relaxation of the IAS. A Final reflexes include the closing reflex or the postdef-
fall of at least 10% of the resting anal pressure (as measured ecation reflex, which engages after the rectum is emptied
by anorectal manometry) is considered normal relaxation and defecation is completed, when the pelvic floor muscles
(Dailianas et al., 2000). In Hirschsprung’s disease, because contract and are elevated to their baseline positions, restor-
of a lack of enteric ganglia, patients do not exhibit the usual ing continence (Parks et al., 1966).
IAS relaxation.
Voluntary control of defecation is instilled after toilet
Neurologic Abnormalities
training and allows an adult to suppress defecation until a
socially acceptable environment is established (i.e., at a toi- Neurologic abnormalities, which contribute to patho-
let). Voluntary relaxation of the pelvic floor muscles is then logic disease states in humans, may occur in the central or
necessary to initiate defecation. Defecation can only occur peripheral nervous systems. Much research involving the
when the puborectalis muscle and the EAS relax. In addi- central nervous system has investigated the effects of SCIs.
tion, humans voluntarily increase intra-abdominal pressure Patients with SCIs frequently have abnormalities of bowel
to complete the defecatory process. This typically occurs by and bladder function. Indeed, population studies show that
tensing the abdominal musculature. 27% to 62% of SCI patients will have colorectal problems
During the interval of voluntary suppression of defeca- (Ebert, 2012). Other central neurologic disease processes
tion, distention of the rectum occurs and is termed accom- that affect colorectal function include multiple sclerosis and
modation. This is very important for the storage capacity Parkinson’s disease.
of the rectum. In animal studies in guinea pigs and mice, For those with spinal cord lesions found at higher levels
a population of mechanosensitive afferent nerves that are of the spine, deficits typically result in constipation because
activated by low levels of stretch has been identified in of slower colonic transit time in the sigmoid colon, allowing
the rectum (Lynn et al., 2003). These afferent nerves are for extended absorption of water and more viscous stool
activated by small changes in the amount of distension of content. These patients also have decreased rectal compli-
the rectum and by low levels of muscular contractions in ance; however, digital stimulation of the anorectum can
that area. It may be that this particular nerve population is trigger defecation because other colonic reflex arcs remain
important for the accommodation ability of the rectum. It functional (Gutman and Ellerkmann, 2003). Patients with
is also hypothesized that this population provides the major- higher level lesions also have a risk of fecal incontinence
ity of afferent synaptic input to the sacral parasympathetic because they cannot feel and voluntarily activate the EAS.
nucleus (Yamanouchi et al., 2002). Overall, it has been Patients with SCIs above the level of S2 to S4 must
shown that the rectum may accommodate stool volumes up develop alternative methods for increasing intra-abdominal
to 400 mL (Irving and Catchpole, 1992). pressure. Those with injuries above the level of T5 recruit
The next step in the regulation of defecation and the contraction of the intercostal muscles and the diaphragm;
maintenance of continence is sampling, a term originated patients with injuries at the level of the cervical spine exclu-
by Duthie and Bennett (1963). Sampling describes the sively contract the diaphragm (Ebert, 2012). However, this
relaxation of the cephalic portion of the anal sphincter still requires stabilization of the abdominal wall (i.e., so that
after distension of the rectum, which allows the pressure it will not balloon outward as pressure increases). This is the
between the rectum and the anal canal to equilibrate. As the precise difficulty that affects many patients with SCIs. In
pressures equalize, the contents of the rectum come into this case, they then must rely only on colonic mechanisms
contact with the anal mucosa and the very sensitive ano- for defecation.
derm, ultimately allowing humans to determine whether Lower spinal cord lesions, especially at the level of the
gas, liquid, or solid contents are contained within the rec- sacral nerves (S2-S4), will affect parasympathetic control of
tum and only allowing voluntary release of rectal contents the bowel. These patients also may have problems with con-
when appropriate. Miller et al. (1988) further described a stipation and incontinence. Constipation may arise because
thermal temperature gradient that was observed to occur of decreased motility of the descending colon. Problems
between the rectum and the upper, middle, and lower por- with defecation due to decreased rectal sensation, increased
tions of the anal canal as measured via a transrectal thermal rectal distention, and decreased rectal tone may lead to
electrode. In addition, by measuring pressure within the fecal incontinence (Gutman and Ellerkmann, 2003).
CHAPTER 5  Physiology of the Pelvic Muscles, Vagina, and Anorectum 79

or pelvic floor. The individual results are then extrapolated


Assessment of Anal Incontinence
to describe the contraction or function of an entire muscle
Various modalities have been used to explore the mecha- (Parks et al., 1962). EMG may also be performed via the
nisms of anal function and continence (see also Chapters use of external sensors rather than with needle insertion.
31 and 32). Visual inspection of the perineum will initially The bulbocavernosus reflex may be more formally tested
provide clues as to the function of the anal sphincter. Are using concentric needle EMG testing (Vodusek, 2011).
scars present, indicating previous surgical intervention or
healed obstetrical lacerations? Is dermatitis visualized, pos- Acknowledgments
sibly due to fecal incontinence? Is the anal canal closed? Are The authors thank Klaus Bielefeldt, MD, PhD, for his assistance
any fistulous tracts or fissures present? Visual examination with this chapter.
can also help the clinician estimate the amount of baseline
perineal descent. Abnormal perineal descent is noted if Bibliography
the perineum at the level of the anal verge is several cen- Abramowitch SD, Feola A, Jallah Z, et al. Tissue mechanics, animal models,
timeters below the pubococcygeal line in a sagittal section and pelvic organ prolapse: A review. Eur J Obstet Gynecol Reprod Biol.
2009;144(suppl 1):S146.
(Parks et al., 1966), either at baseline or with Valsalva. Sen- Badiou W, Granier G, Bousquet P-J, et al. Comparative histological anal-
sation to light touch on the perineum should be assessed. ysis of anterior vaginal wall in women with pelvic organ prolapse or
The bulbocavernosus reflex, a polysynaptic sacral reflex, control subjects. A pilot study. Int Urogynecol J Pelvic Floor Dysfunct.
can be assessed by monitoring for anal sphincter contrac- 2008;19:723.
Basson R. Pharmacotherapy for women’s sexual dysfunction. Expert Opin
tion in response to stimulation of the labia minora lateral
Pharmacother. 2009;10:1631.
to the clitoris; sphincter contraction indicates intact spinal Brookes SJ, Dinning PG, Gladman MA. Neuroanatomy and physiology of
reflexes with the afferent input being the clitoral branch of colorectal function and defaecation: from basic science to human clinical
the pudendal nerve and the efferent input being the inferior studies. Neurogastroenterol Motil. 2009;21(suppl 2):9.
hemorrhoidal branch of the pudendal nerve (Wester et al., Brooks SV, Zerba E, Faulkner JA. Injury to muscle fibres after single
stretches of passive and maximally stimulated muscles in mice. J Physiol.
2003). The patient should be asked to Valsalva or strain as 1995;488(Pt 2):459.
if initiating defecation and to squeeze the EAS. The pelvic Burleigh MC, Barrett AJ, Lazarus GS. Cathepsin b1. A lysosomal enzyme
floor should be observed to incrementally move down with that degrades native collagen. Biochem J. 1974;137:387.
maneuvers for defecation, or up with squeeze of the EAS. Cannon WB. The movements of the intestines studied by means of the
röntgen rays. J Med Res. 1902;7:72.
Large movements may indicate neurologic impairment.
Dailianas A, Skandalis N, Rimikis MN, et al. Pelvic floor study in
Function can then be assessed via the digital rectal exam. patients with obstructive defecation: influence of biofeedback. J Clin
This allows for further assessment of neurologic and muscu- Gastroenterol. 2000;30:176.
lar control. Baseline sphincter tone should be present, and Degen LP, Phillips SF. Variability of gastrointestinal transit in healthy
the patient should be able to further contract the EAS on women and men. Gut. 1996;39:299.
DeLancey JO. Anatomic aspects of vaginal eversion after hysterectomy.
command. Sphincter tone as assessed on digital exam can Am J Obstet Gynecol. 1992;166:1717.
be described in terms of symmetry and whether tone is cir- DeLancey JO. Anatomy and biomechanics of genital prolapse. Clin Obstet
cumferentially equal. Quantification of muscular strength Gynecol. 1993;36:897.
can be estimated. Duration of voluntary contraction can be DeLancey JO. The anatomy of the pelvic floor. Curr Opin Obstet Gynecol.
1994;6:313.
measured. The length of the anal canal can be estimated,
DeLancey JOL, Hurd WW. Size of the urogenital hiatus in the levator ani
and the length should be noted to increase during squeeze. muscles in normal women and women with pelvic organ prolapse. Obstet
Finally, tone should be maintained even if the clinician’s Gynecol. 1998;91:364.
finger is moved in an anterior or posterior direction; if the Dinning PG, Szczesniak MM, Cook IJ. Twenty-four hour spatiotemporal
muscle fatigues and the canal opens, then it may be a sign of mapping of colonic propagating sequences provides pathophysiological
insight into constipation. Neurogastroenterol Motil. 2008;20:1017.
severe neuromuscular impairment. Drewes PG, Yanagisawa H, Starcher B, et al. Pelvic organ prolapse in fibu-
Proctoscopy in the operating room allows for direct visu- lin-5 knockout mice: pregnancy-induced changes in elastic fiber homeo-
alization of anatomy and may reveal pathology that could stasis in mouse vagina. Am J Pathol. 2007;170:578.
compromise anal sphincter function. However, it is diffi- Duthie HL, Bennett RC. The relation of sensation in the anal canal to
the functional anal sphincter: a possible factor in anal continence. Gut.
cult to assess the functional status of the sphincter under
1963;4:179.
anesthesia. Ebert E. Gastrointestinal involvement in spinal cord injury: a clinical per-
Imaging studies to assess anorectal structure and func- spective. J Gastrointestin Liver Dis. 2012;21:75.
tion include defecography, in which radio-opaque contrast Fettweis JM, Serrano MG, Girerd PH, et al. A new era of the vaginal micro-
dye such as barium is transanally instilled and radiographic biome: advances using next-generation sequencing. Chem Biodivers.
2012;9:965.
images are obtained in real time as the subject voluntarily Fielding JR, Versi E, Mulkern RV, et al. MR imaging of the female pelvic floor
strains to empty their bowels. Defecography can also reveal in the supine and upright positions. J Magn Reson Imaging. 1996;6:961.
anatomic abnormalities such as intussusception, rectal pro- Forsberg JG. A morphologist’s approach to the vagina–age-related changes
lapse, or malignancy that may be causing problems with and estrogen sensitivity. Maturitas. 1995;22(suppl):S7.
Frenckner B, Euler CV. Influence of pudendal block on the function of the
defecation.
anal sphincters. Gut. 1975;16:482.
Other assessments include rectal manometry or electro- Funt MI, Thompson JD, Birch H. Normal vaginal axis. South Med J.
myography (EMG). In rectal manometry a fluid-filled bal- 1978;71:1534.
loon catheter is transrectally placed and connected to an Goh JT. Biomechanical properties of prolapsed vaginal tissue in pre- and post-
external electrode or transducer to measure intrarectal pres- menopausal women. Int Urogynecol J Pelvic Floor Dysfunct. 2002;13:76.
Gutman RE, Ellerkmann RM. Colo-rectal-anal pathophysiology and phar-
sures. EMG examines muscle function by placing needle macology. J Pelvic Med Surg. 2003;9:149.
electrodes into muscles to record the electrical potentials of Haubrich WS. Morgagni of the foramen and columns of Morgagni.
individual muscle units within striated muscles of the EAS Gastroenterology. 2002;123:424.
80 PART 2  Basic Science

Irving MH, Catchpole B. ABC of colorectal diseases. Anatomy and physiol- Pu F, Xu L, Li D, et al. Effect of different labor forces on fetal skull molding.
ogy of the colon, rectum, and anus. BMJ. 1992;304:1106. Med Eng Phys. 2011;33:620.
Jackson SR, Avery NC, Tarlton JF, et al. Changes in metabolism of collagen Rae MG, Fleming N, McGregor DB, et al. Control of motility patterns in
in genitourinary prolapse. Lancet. 1996;347:1658. the human colonic circular muscle layer by pacemaker activity. J Physiol.
Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. 4th ed. 1998;510(Pt 1):309.
New York: McGraw-Hill; 2000. Raizada V, Bhargava V, Karsten A, et al. Functional morphology of anal
Keane DP, Sims TJ, Abrams P, et al. Analysis of collagen status in premeno- sphincter complex unveiled by high definition anal manometery and
pausal nulliparous women with genuine stress incontinence. Br J Obstet three dimensional ultrasound imaging. Neurogastroenterol Motil.
Gynaecol. 1997;104:994. 2011;23:1013.
Kumar D, Williams NS, Waldron D, et al. Prolonged manometric record- Rane A, Lim YN, Withey G, et al. Magnetic resonance imaging findings
ing of anorectal motor activity in ambulant human subjects: evidence of following three different vaginal vault prolapse repair procedures: a ran-
periodic activity. Gut. 1989;30:1007. domised study. Aust N Z J Obstet Gynaecol. 2004;44:135.
Lee UJ, Gustilo-Ashby AM, Daneshgari F, et al. Lower urogenital tract ana- Rao SS. Dyssynergic defecation. Gastroenterol Clin North Am. 2001;30:97.
tomical and functional phenotype in lysyl oxidase like-1 knockout mice Rao SS. Pathophysiology of adult fecal incontinence. Gastroenterology.
resembles female pelvic floor dysfunction in humans. Am J Physio Renal 2004;126:S14.
Physiol. 2008;295:F545. Rao SS, Sadeghi P, Beaty J, et al. Ambulatory 24-hour colonic manometry in
Lei L, Song Y, Chen R. Biomechanical properties of prolapsed vaginal tis- slow-transit constipation. Am J Gastroenterol. 2004;99:2405.
sue in pre- and postmenopausal women. Int Urogynecol J Pelvic Floor Rao SS, Welcher K. Periodic rectal motor activity: the intrinsic colonic gate-
­Dysfunct. 2007;18:603. keeper? Am J Gastroenterol. 1996;91:890.
Lestar B, Penninckx F, Rigauts H, et al. The internal anal sphincter can not Siddique SA. Vaginal anatomy and physiology. J Pelvic Med Surg. 2003;
close the anal canal completely. Int J Colorectal Dis. 1992;7:159. 9:263.
Lien KC, Mooney B, DeLancey JOL, et al. Levator ani muscle stretch Sjoberg I, Cajander S, Rylander E. Morphometric characteristics of the
induced by simulated vaginal birth. Obstet Gynecol. 2004;103:31. vaginal epithelium during the menstrual cycle. Gynecol Obstet Invest.
Liu X, Zhao Y, Pawlyk B, et al. Failure of elastic fiber homeostasis leads to 1988;26:136.
pelvic floor disorders. Am J Pathol. 2006;168:519. Smith TK, Reed JB, Sanders KM. Origin and propagation of electrical slow
Lynn PA, Olsson C, Zagorodnyuk V, et al. Rectal intraganglionic laminar waves in circular muscle of canine proximal colon. Am J Physiol. 1987a;
endings are transduction sites of extrinsic mechanoreceptors in the guinea 252:C215.
pig rectum. Gastroenterology. 2003;125:786. Smith TK, Reed JB, Sanders KM. Interaction of two electrical pacemakers
Miller R, Bartolo DC, Roe A, et al. Anal sensation and the continence mech- in muscularis of canine proximal colon. Am J Physiol. 1987b;252:C290.
anism. Dis Colon Rectum. 1988;31:433. Sze EH, Meranus J, Kohli N, et al. Vaginal configuration on MRI after
Miller R, Lewis GT, Bartolo DCC, et al. Sensory discrimination and abdominal sacrocolpopexy and sacrospinous ligament suspension. Int
dynamic activity in the anorectum – evidence using a new ambulatory Urogynecol J Pelvic Floor Dysfunct. 2001;12:375.
technique. Br J Surg. 1988;75:1003. Tinelli A, Malvasi A, Rahimi S, et al. Age-related pelvic floor modifica-
Moalli PA, Howden NS, Lowder JL, et al. A rat model to study the struc- tions and prolapse risk factors in postmenopausal women. Menopause.
tural properties of the vagina and its supportive tissues. Am J Obstet 2010;17:204.
Gynecol. 2005;192:80. Tsai CC, Semmens JP, Semmens EC, et al. Vaginal physiology in postmeno-
Moalli PA, Talarico LC, Sung VW, et al. Impact of menopause on collagen pausal women: Ph value, transvaginal electropotential difference, and
subtypes in the arcus tendineous fasciae pelvis. Am J Obstet Gynecol. estimated blood flow. South Med J. 1987;80:987.
2004;190:620. Vodusek DB. The role of clinical neurophysiology in urogynecology. Int
Nichols DH, Milley PS, Randall CL. Significance of restoration of normal ­Urogynecol J. 2011;22:1473.
vaginal depth and axis. Obstet Gynecol. 1970;36:251. Wester C, Brubaker L. Normal pelvic floor physiology. Obstet Gynecol Clin
Nyirjesy P. Postmenopausal vaginitis. Curr Infect Dis Rep. 2007;9:480. North Am. 1998;25:707.
Ozdegirmenci O, Karslioglu Y, Dede S, et al. Smooth muscle fraction of Wester C, FitzGerald MP, Brubaker L, et al. Validation of the clinical bulbo-
the round ligament in women with pelvic organ prolapse: a computer- cavernosus reflex. Neurourol Urodyn. 2003;22:589.
based morphometric analysis. Int Urogynecol J Pelvic Floor Dysfunct. Wong MY, Harmanli OH, Agar M, et al. Collagen content of nonsupport tis-
2005;16:39. sue in pelvic organ prolapse and stress urinary incontinence. Am J Obstet
Palit S, Lunniss PJ, Scott SM. The physiology of human defecation. Dig Dis Gynecol. 2003;189:1597.
Sci. 2012;57:1445. Wong RF, Bonapace Jr ES, Chung CY, et al. Simultaneous endoluminal
Parks AG, Porter NH, Hardcastle J. The syndrome of the descending sonography and manometry to assess anal sphincter complex in normal
perineum. Proc R Soc Med. 1966;59:477. subjects. Dig Dis Sci. 1998;43:2363.
Parks AG, Porter NH, Melzak J. Experimental study of the reflex mecha- Yamanouchi M, Shimatani H, Kadowaki M, et al. Integrative control of rec-
nism controlling the muscles of the pelvic floor. Dis Colon Rectum. toanal reflex in guinea pigs through lumbar colonic nerves. Am J Physiol
1962;5:407. Gastrointest Liver Physiol. 2002;283:G148.
CHAPTER 6

Female Sexual
Function and
Dysfunction:
Assessment and
Treatment
Roya L. Rezaee
Sheryl A. Kingsberg

Introduction
Sexual health is an important component of a woman’s well-
Chapter Outline
being. Evidence suggests that healthy sexual functioning is a
fundamental component of a woman’s sense of self and qual- Introduction
ity of life. Lesser sexual function is related to advancing age, Models of Female Sexual Response
menopause, and economic and health problems (Ornat et al.,
Physiology
2013; Cabral et al., 2013). Sexual dysfunction has been shown
to be associated with a statistically significant decrease in men- Female Sexual Disorders
tal health, vitality, and social function and is associated with Sexual Desire Disorders
relationship problems and undiagnosed medical conditions Hypoactive Sexual Desire Disorder
(Biddle et al., 2009). Sexual problems are highly prevalent Sexual Aversion Disorder
in women and in the United States: about 40% have sexual
Female Sexual Arousal Disorder
concerns and 12% report distress (Shifren et al., 2008). This
sense of dysfunction takes different forms and treatment typi- Female Orgasmic Disorder
cally is individualized and tailored to the diagnosis and to the Sexual Pain Disorders
underlying psychological, physical, and medical conditions. Variables That Can Affect Sexual Function
The World Health Organization has stipulated that the
Pregnancy and the Postpartum
maintenance of sexual health is the physician’s responsibility
(WHO, 2000). In 2001, the U.S. Surgeon General, in his Pelvic Floor Disorders
Call to Action to promote sexual health as one of the goals of Myofascial Pelvic Pain
Healthy People 2010, described the role of health care pro- Overactive Bladder
fessionals and the need for better education and preparation Incontinence and Prolapse
(Office of the Surgeon General, 2001). For these concerns Surgery and Sexual Dysfunction
to be addressed, health care professionals must understand
Screening and Evaluation for Sexual
what constitutes functional sexuality. Unfortunately, sexual
Dysfunction
medicine is not given a high priority in medical education,
which leaves many providers uncomfortable; this discom- Identification and Assessment of a Sexual
fort, ultimately, is an obstacle to competency. Additionally, Problem
many patients are hesitant to discuss these problems with Evaluation of an Identified Problem
their providers, and this also contributes to the underdiag- Treatment of Female Sexual Disorders
nosis and undertreatment of female sexual dysfunction.
Hypoactive Sexual Desire Disorder
The Diagnostic and Statistical Manual of Mental Disor-
ders, Fourth Edition, Revised (DSMR-IV) lists six primary Sexual Aversion Disorders
female sexual disorders: hypoactive sexual desire disorder, Female Sexual Arousal Disorders
sexual aversion disorder, female sexual arousal disorder Anorgasmia
(FSAD), female orgasmic disorder, dyspareunia, and vagi- Dyspareunia
nismus. This chapter will offer the provider an opportunity
Vaginismus
to have a working knowledge of the evolving theoretical
models to describe the healthy sexual response as well as Conclusion
an understanding of the neurobiology of sexual function.
81
82 PART 2  Basic Science

Additionally, a framework for assessment, diagnosis, and sexual thoughts, and genital sensations. It is influenced by neu-
management of sexual dysfunction in women will be out- roendocrine mechanisms. The second component is a sociocul-
lined and will include surgical and medical conditions that tural or expectation component that reflects a woman’s beliefs
can contribute to the development of sexual dysfunction. and values about sex. The third component is the motivation
component and is the emotional or interpersonal aspect of
desire that is characterized by a women’s willingness to engage
Models of Female Sexual Response in sexual activity. Motivation is often the most important factor
The female sexual response is complex in nature. It was and is affected by psychological function, relationship quality,
first described by Masters and Johnson (1966) as a linear and concerns about health, occupation, or family. The interplay
model of discrete events in which excitement always pre- and input of all of these realms yields one’s sexual response and
cedes arousal and then is followed by orgasm and resolution therefore the clinician’s differential diagnosis must be broad.
(Fig. 6.1). It then was modified by Kaplan (1979) and Leif One additional theory of sexual response to consider
(1977) independently to a triphasic model that emphasized that also keeps to a biopsychosocial perspective is Bancroft’s
desire as the first stage of the sexual response in contrast to Dual Control Model. This model proposes that sexual
physiologic genital arousal leading to response. response occurs as an interaction between sexual excitatory
In the late 1990s, Basson first published her intimacy- and sexual inhibitory processes. The model further suggests
based, circular model to help explain the multifactorial char- that individuals vary in their propensity for both sexual exci-
acter of the female sexual response. This model includes the tation and sexual inhibition (Bancroft et al., 2009).
interplay of emotional intimacy, sexual stimuli, psychological These theoretical models of sexual response may reflect
factors and relationship satisfaction. This model also intro- the variation that women experience in sexuality. This was
duces the concept of receptive desire, the idea that arousal demonstrated by The Nurses’ Sexuality Study in which
often precedes desire and that women often begin a sexual a sample of nurses was asked to endorse the model that
encounter from a position of sexual neutrality (Basson 2001). best fit their response (Sands and Fisher, 2007). Approxi-
It encompasses the impact of biologic and nonbiologic fac- mately 33% endorsed the Masters and Johnson model, 33%
tors on a woman’s sexual response like motivation, interper- endorsed Kaplan’s models, and 33% endorsed Basson’s
sonal issues, cultural and religious beliefs, partner health, model. Of note, the women who had sexual concerns were
relationship quality, past sexual abuse, and distractions. more likely to endorse Basson’s model of sexual response.
Desire is a deceptively complex concept that is best under-
stood by differentiating sexual drive and sexual motivation.
A biopsychosocial model (see Fig. 6.2) of desire outlined by
Physiology
Levine (2004) suggests that desire is comprised of three indi- The physiologic pathway of arousal in women is an intri-
vidual but interrelated components. Drive is the biological cate neurobiologic process that is not fully understood. The
component that is a spontaneous and variable sexual interest female sexual anatomy includes the mons pubis; the vulva,
made up of cravings for sexual activity, dreams, unprompted including the labia majora, labia minora, interlabial space,
and the clitoris; and the inner genitalia, including the vesti-
bule, periurethral glans and vagina, uterus, fallopian tubes,
Desire and ovaries (Salonia et al., 2010). The cycle of arousal is
• Excitement Divided initiated by genital vasocongestion. The vulva swells expos-
Arousal ing the introitus; the vagina lengthens and dilates; the outer
• Plateau third of the vagina tightens; the clitoris increases in length
• Orgasm and diameter; and the uterus rises above the levator plate.
Stimulation of the pelvic nerves induces smooth muscle
• Resolution relaxation and decreases the resistance within the arteries,
leading to increased blood flow to the clitoris. This blood
Linear progression flow results from active neurogenic dilation of the sinusoi-
FIGURE 6.1 Human sexual response: classic models. (From: Masters dal blood spaces, which causes the corpora cavernosa of
and Johnson, 1966; Kaplan, 1979; Leif, 1977.) the clitoris to become engorged, and the clitoris becomes

(e.g., physical health, (e.g., performance


neurobiology, anxiety, depression)
endocrine function)
Biology Psychology

(e.g., upbringing, (e.g., quality of current


cultural norms and and past relationships,
expectations)
Sociocultural Interpersonal intervals of abstinence,
life stressors, finances)

FIGURE 6.2 Biopsychosocial model of female sexual response. (Modified from Kingsberg SA, Rezaee RL. Hypoactive sexual desire in women.
Menopause. 2013; 20:1284.)
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 83

progressively more prominent. It has been noted that the Table 6.1A  DSM-IV-TR Definitions of Female
vulvar structures become engorged, but they do not become Sexual Dysfunctions
erect because the thinner tunica in women does not trap
venous blood, and therefore it pools with persistent inflow Disorder Definition
and outflow (Basson, 2003). In addition, vaginal lubrication Sexual Desire Disorders
occurs as a result of increased pressure in the capillaries of Hypoactive sexual desire Deficiency or absence of sexual
the genital vasculature and transudation of fluid through the disorder fantasies or desire for sexual
subepithelium of the vaginal walls. activity
Although the exact central neuroendocrine mechanisms Sexual aversion disorder Aversion to and active avoidance of
genital sexual contact
remain undiscovered, several areas of the brain appear to be
involved, including the brain stem, hypothalamus, and fore- Sexual Arousal Disorders
brain including the amygdala (Clayton, 2004). It is an active Female sexual arousal Inability to attain or maintain
process that balances both excitatory and inhibitory factors. disorder adequate lubrication-swelling
response or sexual excitement
Excitatory factors include estrogen, testosterone, melano-
cortin, and oxytocin and the neurotransmitters dopamine Orgasmic Disorders
and norepinephrine. Inhibitory factors include serotonin, Female orgasmic disorder Delay in or absence of orgasm after
prolactin, and endogenous opioids; this has been referenced normal sexual excitement phase
as the “sexual tipping point” (Perleman, 2009). Pain Disorders
It is likely that nitric oxide (NO), vasoactive peptide (VIP), Dyspareunia Genital pain associated with sexual
and acetylcholine (ACh) play significant roles in sexual arousal penetration activity
(Meston and Frolich, 2000). Most of what we understand Vaginismus Recurrent or persistent involun-
tary contraction of the perineal
about their roles in female sexual excitement and response muscles preventing vaginal
is a result of the study of penile erection and sexual biology penetration
in animal models. Sexual stimulation releases NO from the
vascular endothelium, which stimulates the release of guanyl- Adapted from American Psychiatric Association. Diagnostic and Statistical
ate cyclase, which in turn converts guanosine triphosphate Manual of Mental Disorders. 4th ed. Text Revision, Washington, DC:
American Psychiatric Association; 2000.
into cyclic guanosine monophosphate (cGMP) (Salonia et al.,
2010). This stimulates smooth muscle relaxation in the penile
arteries and corpora cavernosum, causing blood flow to the
penis. VIP and ACh also have been shown to relax smooth Table 6.1B  DSM-5 Classifications of Female
muscle and increase blood flow in the penis in animal models. Sexual Disorders
It is hypothesized that desire (drive) is triggered in areas
of the hypothalamus and with the activation of the dopa- Female Orgasmic Disorder 302.73 (F52.31)
mine system. This system is activated early and, along with Presence of either of the following on all or almost all (75–100%)
occasions of sexual activity:
norepinephrine, increases sexual excitation and the desire to 1. Marked delay in, marked infrequency of, or absence of orgasm
continue sexual activity. The increasing state of excitement as 2. Markedly reduced intensity of orgasmic sensations
evidenced by increasing heart rate and blood pressure suggests
Female Sexual Interest/Arousal Disorder 302.72 (F52.22)
that the noradrenergic system also is involved in the sexual
Lack of, or significantly reduced, sexual interest/arousal as mani-
response. The actual neurobiology of the orgasm is unknown, fested by three of the following:
although it appears to include the mesolimbic dopamine path- 1. Absent/Reduced interest in sexual activity
way as well as the pudendal, pelvic, and hypogastric nerves. 2. Absent/Reduced sexual/erotic thoughts or fantasies
Orgasm occurs with the release of contraction-producing 3. No/Reduced initiation of sexual activity and unreceptive to
agents, such as serotonin and oxytocin, which leads to rhyth- partner’s attempts to initiate
4. Absent/Reduced sexual excitement/pleasure during sexual
mic contractions of the levator plate, uterus, and vagina and activity in almost all or all (75–100%) sexual encounters
multiple orgasms may occur if stimulation continues. The 5. Absent/Reduced sexual interest/arousal in response to any
time for resolution to take place varies among women. internal or external sexual/erotic cues (written, verbal, visual)
6. Absent/Reduced genital or nongenital sensations during
sexual activity in almost all or all (75–100%) sexual encounters
Female Sexual Disorders Genito-pelvic Pain/Penetration Disorder 302.76 (F52.6)
Persistent or recurrent difficulties with 1 or more of the following:
Sexual Desire Disorders 1. Vaginal penetration during intercourse
2. Marked vulvovaginal or pelvic pain during intercourse or
Female sexual dysfunction disorders most commonly are penetration attempts
classified by the DSM-IV-TR (2000). There are six disorders 3. Marked fear or anxiety about vulvovaginal or pelvic pain in
of female sexual function: Sexual desire disorder (hypoac- anticipation of, during, or as a result of vaginal penetration
tive sexual desire disorder (HSDD) and sexual aversion 4. Marked tensing or tightening of the pelvic floor muscles dur-
disorder), sexual arousal disorder, orgasmic disorder, and ing attempted vaginal penetration
sexual pain disorders (dyspareunia and vaginismus) (see Symptoms persisted a minimum of 6 months and not better explained
Table 6.1A). To make a diagnosis of a sexual disorder, the by a nonsexual mental disorder or consequence of severe relationship
symptoms must cause personal or interpersonal distress or distress or other significant stressors and not due to effects of
substance/medication or other medical conditions.
difficulty and must not be better accounted for by another From American Psychiatric Association. Diagnostic and Statistical Manual of
category of psychiatric disorder or due exclusively to the Mental Disorders. 5th ed. DSM-5. Washington, DC: American Psychiatric
direct physiological effects of a substance or gynecologic or Publishing; 2013.
84 PART 2  Basic Science

Table 6.2  Example of Psychiatric and General Table 6.3  Medications Associated with Sexual
Health Problems That May Affect Sexual Function Dysfunction
General Health Examples Psychoactive medications SSRIs, SNRIs, antipsychotics,
Urogynecologic Urinary tract infections, pelvic organ barbiturates, benzodiazepines,
problems prolapse, urinary and fecal inconti- tricyclic antidepressants,
nence lithium, MAOIs, antiepileptics
Gynecologic Pelvic pain, fibroids, unpredictable Antithypertensive Lipid-lowering agents, digoxin,
problems bleeding, oral contraceptive pills, and cardiovascular beta blockers, alpha blockers,
vulvovaginal atrophy, postpartum medications diuretics
period, breastfeeding, sexually Hormones Antiandrogens, progestins, oral
transmitted infections contraceptives, GnRH agonists,
Endocrine Diabetes mellitus, thyroid disorders, estrogens
hyperprolactinemia Antihistamines and H2
Chronic illness Back pain, cancer, psoriasis, rheuma- receptor blockers
toid arthritis, degenerative arthritis, Narcotics
hypertension, coronary artery Amphetamines, weight loss
disease, neurologic conditions agents
Steroids
Psychiatric Chemotherapeutic agents
Mood disorders Major depression, bipolar depression Immunosuppressants
Anxiety disorders
Psychotic illness SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin-
norepinephrine reuptake inhibitors; MAOIs, monoamine oxidase
inhibitors.
Adapted from Kingsberg S, Althof SE. Evaluation and treatment of female
general medical condition (see Table 6.2). Each disorder is sexual disorders. Int Urogynecol J. 2009;20(Suppl 1):S33.
then further subtyped into lifelong versus acquired and gen-
eralized versus situational. Sexual problems tend to overlap a treatment plan can be often-times confusing for both the
with one another and so the best approach for clinical prac- patient and the clinician. Desire is a compilation of drive,
tice is to identify the most problematic or primary issue and expectations, beliefs, and motivation and is affected by the
focus initial treatment there. interactions of sex steroids and neurotransmitters. Declining
levels of androgens parallel increasing age and contribute to
Hypoactive Sexual Desire Disorder the decline in sexual desire, arousal, and orgasm. Menopause
This disorder is defined as a persistent or recurring defi- has long been assumed to result in a decreased libido because
ciency or absence of sexual thoughts, fantasies, or desire for of the decline in ovarian testosterone production. This is par-
sexual activity. It causes marked personal distress or personal ticularly true for women who experience a sudden loss of
difficulties and can not be better accounted for by another testosterone accompanying a surgical or chemical menopause.
primary disorder, drug or medication, or general medical Recent longitudinal studies, however, suggest that relationship
condition. The judgment of deficiency by the clinician is factors and other nonbiological changes have a stronger impact
subjective and must take into account the normal fluctua- on overall sexual desire than menopause alone (Hayes and
tion seen with relationships over time, age, personal health, Dennerstein, 2005). Many medications can cause sexual side
and life circumstances. Decreased sexual desire is associated effects (see Table 6.3). It is essential to distinguish between
with negative effects, such as poor self-image, mood instabil- the various components of desire because treatments can vary
ity, depression, and strained relationships with partners. based on which components have been impaired.
The prevalence of HSDD is difficult to determine as it Although testosterone plays a role in drive, motivation,
varies depending on the population surveyed. Segraves and and sexual sensation, it is important to understand that
Woodard (2006) suggested that if the population studied were there is little correlation between HSDD and serum andro-
restricted to those reporting frequent problems with desire, gen levels, and so they should not be used as a diagnostic
then the prevalence of HSDD would be between 5.4% and measure of sexual dysfunction (Davis et al., 2005). If hor-
13.6%. The Prevalence of Female Sexual Problems Associated mone assays are utilized, then it is important of include the
with Distress and Determinants of Treatment Seeking (PRE- measurement of sex hormone-binding globulin (SHBG)
SIDE) survey included a validated measure to evaluate more and to calculate the free androgen index (total testoster-
than 31,000 women over the age of 18 (Shifren et al., 2008). one/SHBG), which is a more accurate reflection of the
In this study, 8.9% of women 18 to 44 years of age, 12.3% of hormonal milieu than the total testosterone or bioavailable–
women 45 to 64 years of age, and 7.4% of women ≥65 years free testosterone alone. SHBG is synthesized in the liver
of age had low desire and distress. The Women’s International and serves as the carrier protein for estrogen and testos-
Study of Health and Sexuality (WISHeS) included women terone. It regulates the amount of free hormone circulating
20 to 70 years of age from the United States and Europe. It in the blood. Estrogen stimulates SHBG production while
indicated that the prevalence of HSDD in the United States increased levels of testosterone decrease SHBG synthesis.
was 14% for premenopausal women, 9% in naturally meno- SHBG can be affected by the use of medications through
pausal women, 26% in surgically menopausal women 20 to the hepatic first-pass metabolism.
49 years of age, and 14% in surgically menopausal women 50
to 70 years of age (Leiblum et al., 2006). Sexual Aversion Disorder
As already mentioned, desire is such a complex concept The DSM-IV-TR defines this disorder as the persistent
that identifying the etiology of the problem and developing or recurrent extreme aversion to, and avoidance of, all or
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 85

almost all genital sexual contact with a partner. The distur- The typical comorbid medical conditions associated with
bance must cause marked personal difficulty and distress. FSAD are menopause, vascular disease associate with coro-
This disorder contains elements of revulsion and disgust nary artery disease and diabetes, smoking, and side effects
that can not be explained by a simple phobia. It is a lifelong of medications.
or acquired conditioned response that affects more women
than men and often is associated with a history of sexual
Female Orgasmic Disorder
trauma, abuse, or pain. It typically encompasses physiologic
responses (e.g., nausea, shortness of breath, panic) and can This disorder as defined by the DSM-IV-TR is the persis-
be situational or global. The prevalence of this disorder is tent or recurrent delay in or the absence of orgasm following
not well established because many women avoid sexual normal sexual excitement. Orgasm is best understood as a
contact and do not report this problem until a relationship transient peak sensation of intense pleasure following suf-
becomes dysfunctional (Kingsberg and Janata, 2007). ficient sexual stimulation and arousal. It is accompanied by
A careful sexual history emphasizing the distinction rhythmic contractions of the perineal, bulbocavernosus, and
between potential initiating events and current behavior pubococcygeus muscles.
that may reinforce the continued aversion response must be The cause of orgasmic dysfunction is likely multifacto-
included in the assessment of this condition. The problem rial, making the prevalence difficult to evaluate, but it has
must be identified so that proper referral for care by a sex been reported as 3.4% to 5.8% (Shifren et al., 2008). It may
therapist can be made and the patient reassured that this be more accurate to view the ability to orgasm as situational,
can be treated. Behavioral treatment is essential. Avoidance in that many women can attain orgasm with a specific form
of sexual behavior reinforces aversion. Therefore, a gradu- of sexual stimulation (manual or oral) or with a specific
ated paradigm of exposure is central to the treatment plan. partner. Intercourse is not a reliable way for many women
The modality pairs relaxation exercises with graded and to achieve orgasm. Primary orgasmic disorder is defined as
patient-controlled reintroduction of sexual behavior. Often never having experienced an orgasm. These women may
time, substantial anxiety accompanies this disorder and the even have normal levels of desire, but they are unable to
use of psychotropic medications such as selective serotonin attain climax. There are likely multifactorial causes, includ-
reuptake inhibitors (SSRI) may be indicated. ing physiologic, performance anxiety, psychosocial factors
(cultural messages, history of trauma), or just unfamiliar-
ity with one’s body and physiology (Meston et al., 2004).
Female Sexual Arousal Disorder
Acquired orgasmic disorder is the inability to experience
The DSM-IV-TR defines FSAD as a persistent or recurrent orgasm that develops after one has had reliable orgasmic
impairment or absence of physiologic responsiveness (i.e., attainment. It is often linked to HSDD (either the result of
genital lubrication and swelling) to sexual stimulation. The or leading to HSDD), but it can be associated with pelvic
inability to attain or maintain this sexual responsiveness and surgery and medications, such as antidepressants.
the resulting marked personal or interpersonal distress is
central to the diagnosis. The disorder frequently is associated
Sexual Pain Disorders
with pain and avoidance of sexual contact. The prevalence of
lack of vaginal lubrication has been found to be anywhere The reported incidence of dyspareunia ranges between 8%
from 5% to 20% in the United States (Shifren et al., 2008; and 22% (Latthe et al., 2006). Dyspareunia is defined in the
Laumann et al., 1999). DSM-IV-TR as persistent or recurrent urogenital pain occur-
The American Foundation for Urologic Disease (AFUD) ring before, during, or after sexual intercourse that is not
consensus panel suggests that FSAD may be better under- caused exclusively by the lack of lubrication or by vaginismus.
stood if further subdivided into the following subtypes: It is further delineated into superficial and deep dyspareunia.
subjective arousal disorder, genital arousal disorder, or gen- Current theory has called this definition into question, and
eralized (combined subjective and genital) arousal disorder instead, characterizes dyspareunia as a pain disorder that
(Basson et al., 2000; Basson et al., 2003). Subjective arousal interferes with sexuality as opposed to a sexual disorder
disorder subtype is the absence of or significantly dimin- characterized by pain (Binik et al., 2002). This makes sense
ished feelings of sexual pleasure and excitement despite because urogenital pain occurs in other nonsexual situations.
the presence of stimulation and vaginal lubrication. Genital Dyspareunia, then, is considered a chronic pain disorder
arousal disorder subtype is absent or impaired vulvar swell- that has multiple etiologies with interdependent psychologi-
ing or lubrication or reduced sexual sensations from any cal and biological contributors. Even when an anatomic or
form of sexual stimulation despite subjective arousal being organic cause is found, there is typically considerable stress
present. Excitement still occurs from nongenital stimuli so and anxiety that maintain the pain and promote a continued
these women may report subjective arousal, but they have avoidance of intercourse and negative sexual expectations.
a loss of intensity of any genital response including orgasm. This cycle of pain results in a loss of desire and arousal, which
This might be found in women who have estrogen deficiency only perpetuate the problem. Dyspareunia is considered to
or nerve damage and who do not exhibit vasocongestion or be a common problem over the life span of women largely
engorgement of the genitals. The combined generalized due to the multiple potential causes (see Table 6.4).
subtype is the most common presentation in which these A third type of sexual pain disorder is Noncoital Sexual
women feel no excitement and no engorgement. A Missed Pain Disorder, which is recurrent or persistent genital pain
Arousal Disorder subtype also has been identified that induced by noncoital sexual stimulation (Basson et al., 2000).
occurs when engorgement is present, but not attended to or The DSM-IV-TR defines vaginismus as involuntary,
there is no awareness. recurrent, or persistent spasm of muscles surrounding the
86 PART 2  Basic Science

Table 6.4  Causes of Dyspareunia Variables That Can Affect Sexual


Condition Examples Function
Superficial Pregnancy and the Postpartum
Anatomic variations Congenital anomalies, labial
hypertrophy, urethral Pregnancy and childbirth are central periods in a woman’s
diverticulum life. Although sexuality during pregnancy and the post-
Vulvovaginal atrophy Estrogen deficiency, radiation partum period has been insufficiently researched using
Injury or trauma Childbirth-related, surgery,
female circumcision
validated sexual function questionnaires, data show that
Inflammation or infection Vulvar, vaginal, cervical, sexual function is altered and many factors may contribute
lower urinary tract to this. At 12 weeks postpartum some of the most com-
Generalized vulvodynia mon issues include marital dissatisfaction, dyspareunia,
Vestibulodynia/Vulvar fatigue, depression, and breastfeeding (De Judicibus and
vestibulitis syndrome
Vulvar dystrophies Lichen sclerosis, lichen planus McCabe, 2002). Just as during other periods in a woman’s
Inadequate lubrication/dryness life, during the time of pregnancy and the postpartum,
Deep
women who were more satisfied with their relationships
reported higher sexual function and satisfaction and greater
Endometriosis
Myofascial pelvic pain Hypertonus of levator frequency of activity than women who were less satisfied
muscles (Wittig et al., 2008).
Interstitial cystitis Low desire during pregnancy and the postpartum period
Infection Cervical, uterine, lower urinary is not unusual and it is well-known that it fluctuates dur-
tract
Uterine fibroids
ing pregnancy typically decreasing in the third trimester.
Adhesions Prior surgery, prior infection Women report worsened sexual function, including dimin-
Prolapse disorders Uterine, vaginal cuff, vaginal ished sexual satisfaction, during pregnancy which often
wall/bladder/rectum persists for 6 to 12 months postpartum. Furthermore,
Uterine position variations Retroflexed, retroverted although 80% to 93% of women have resumed intercourse
Adnexal pathology Ovarian/tubal cyst or
neoplasm at 12 weeks postpartum, more than 80% of them report
Intestinal and/or rectal Irritable bowel, inflammatory sexual problems during that time (Glazener, 1997). At
pathology bowel, dermatitis, fissure, 6 months, 18% to 30% of these women still may be expe-
prolapse riencing sexual problems, including dyspareunia (Rogers
Other et al., 2009). Fatigue commonly is reported to cause loss
Psychological problems Depression, anxiety, of desire, infrequent activity and lack of enjoyment, and
body-image issues, stress the fatigue and its impact continues well past 6 months.
History of sexual abuse Even breastfeeding negatively affects sexual function due
or negative experiences
to associated vaginal dryness.
Obstetrical events such as massive hemorrhage, pre-
eclampsia, sepsis, and uterine rupture lead to significant
changes in sexual health and well-being in the women who
outer third of the vagina that interferes with vaginal pen- experience this morbidity. For some it is the physical com-
etration (American Psychiatric Association, 2000). A preva- plications of such events, whereas for others, it is a loss of
lence rate of 1% to 6% has been reported (Basson, 2001). interest and a fear of conceiving (Watersone et al., 2003).
This definition has been challenged because women may not The role of body image cannot be overlooked and seems to
feel pain despite the presence of vaginismus. Whether or have a variable impact. At times it has been correlated posi-
not muscle spasm occurs also has been called into question. tively with the highest sexual function prepregnancy, but it
The 2nd Consultation on Erectile and Sexual Dysfunction also has been shown to decline between the first and third
developed the following alternative definition: “the persis- trimesters and is the lowest postpartum and remains low
tent or recurrent difficulties of the woman to allow vaginal until 6 months postpartum (Pauls et al., 2008).
entry of a penis, finger, and/or any object despite the wom- Childbirth negatively affects a woman’s sexual function
an’s expressed wish to do so” (Lue et al., 2004). Although through physical trauma, such as perineal laceration and
penetration is difficult or impossible, many women can pudendal neuropathy. These effects can be temporary or
enjoy other sexual activity and can achieve orgasm. Vaginis- enduring. There is an obvious connection perineal trauma
mus occurs as a result of the anticipation of the pain with and pain leading to problems with intercourse. Women who
penetration, muscle tension, and avoidance behavior. have an episiotomy complain of increased pain and delayed
At the time of submission of this chapter the DSM-5 sexual relations compared with women who delivery over an
(American Psychiatric Association. Diagnostic and Statistical intact perineum. Overall, dyspareunia is reported in about
Manual of Mental Disorders, 5th ed., DSM-5, 2013) was 41% to 67% of women 2 to 3 months after birth (Handa,
published. As of May 2013, the DSM-5 classification sys- 2006). Persistent dyspareunia is associated strongly with
tem essentially has combined the six categories of the operative vaginal delivery and severity of the perineal trauma
DSM-IV-TR into three categories and virtually omitted the and, additionally, women who experience high-order peri-
diagnosis of aversion disorder. This change has resulted in neal lacerations demonstrate less desire to engage in sexual
considerable debate and its clinical utility and acceptance is activities, such as touching and stroking. Women who have
in its infancy (See Table 6.1B). fourth-degree tears into the anal sphincter are much more
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 87

likely to report pain with intercourse than women who did symptoms typically are localized and may occur in the pel-
not experience lacerations at birth (Signorello et al., 2001). vis, vulva, bladder, and rectum. As the trigger points persist,
The impact of the route of delivery and the resulting the muscles weaken and over time, the surrounding muscles
effects on long-term pelvic floor health continues to be groups become affected and more distant areas, such as the
investigated. In addition to the potential of causing perineal buttocks, thighs, and abdomen, become involved (Fitzgerald
lacerations, the process of vaginal birth has been implicated and Kotarinos 2003b). Pelvic floor muscle hypertonus has
in the damage of the innervation to the pelvic floor. Com- been associated with interstitial cystitis, provoked vestibu-
pression or stretch injury that occurs during delivery leads to lodynia, and generalized vulvodynia and dyspareunia.
neuropathy of the pudendal nerve, which can lead to urinary The hypertonus can be a result of pain or injury but also
and anorectal incontinence and pelvic organ prolapse. Birth can be the origin of pain. Childbirth, surgery, chronic low
may cause or worsen previously existing hypertonicity of the back or hip pain, pelvic pain, recurrent vaginitis, bladder
pelvic floor or trigger points. Spasm induced by contraction infections, dysmenorrhea, constipation or irritable bowel,
of the muscles can cause referred pain or irritative symptoms neuromuscular and inflammatory disorders, chronic pain
throughout the path of the pudendal nerve and adjacent syndromes, and anxiety can all be underlying etiologies.
structures. Because the pudendal nerve mediates some of Many women without obvious organic disease such as posi-
the reflex pathways of the inherent female sexual response, tive urine cultures, vaginitis, or adnexal pathology may find
the damage can result in physiologic causes of female sexual that their clinicians are unable to find the cause of their
dysfunction. symptoms. This may be due to a lack of recognition or
This neuropathic injury may be less likely to occur when training of this diagnosis as a cause of sexual pain or sexual
cesarean section is performed before the onset of labor by dysfunction. A thorough history and directed physical exam
avoiding direct perineal trauma and pudendal neuropathy. will uncover myofascial pelvic pain as a possible cause of
The supposed possible protective benefits of scheduled dyspareunia. Treatment involves validating the presence of
cesarean section, however, remain inconsistent. The National pain even in the absence of clear pathology and including a
Institutes of Health (NIH) State-of-the Science Conference multidisciplinary approach to resolve the identified aspects
on Cesarean Delivery on Maternal Request indicated that by of the sexual dysfunction. Pelvic floor physical therapy
6 months postpartum, there is no difference in overall sexual involving pelvic floor surface electromyography (sEMG)
function based on route of delivery alone, although they rec- biofeedback is utilized to treat hypertonus of the pelvic floor
ognize that anal sphincter tears may be a risk factor for fecal that is related to vulvar pain syndromes and can be effec-
incontinence, and vaginal delivery is a risk factor for severe tive when accompanied by a home exercise plan. A variety
perineal lacerations (NIH Consensus SC Statement, 2006). of manual therapy techniques such as myofascial release,
Data using validated sexual health questionnaires suggest myofascial trigger point release, visceral manipulation, and
that women who undergo cesarean delivery have an elevated neural mobilizations, as well as therapeutic exercises such
risk of sexual dysfunction that is nondyspareunia related in as pelvic floor retraining with dilators, core stabilization,
origin. Any protective effect of caesarean delivery on sexual and behavioral therapies are utilized to benefit women with
function appears to be limited to the early postnatal period sexual pain problems. The use of botulinum toxin injected
and is related to the absence of perineal injury. into the levator muscles is demonstrating an additive effect
There is evidence that breastfeeding reduces a woman’s to pain treatment.
sexual desire and frequency of intercourse. This happens as
a result of decreased vaginal lubrication from high levels of Overactive Bladder
prolactin; nipple sensitivity and discomfort with the poten- Overactive bladder (OAB) is characterized by urinary urgency,
tial erotic feelings from breastfeeding as a result of oxytocin with or without urinary incontinence, urinary frequency, and
production leading to a sense of sexual arousal and orgasm; nocturia. It often is associated with detrusor overactivity.
and sleep disturbances that contribute to fatigue, exhaus- These symptoms can be quite bothersome and have a nega-
tion, and partner isolation. Finally, postnatal depression tive effect on the overall quality of life and daily functioning.
and emotional lability are related inversely to sexual enjoy- The fear of leakage during sexual stimulation and intercourse
ment, interest, and activity. The use of SSRI medication can as well as the urgency and frequency felt afterward interfere
compound this problem because they are agents commonly with a woman’s enjoyment of sexual relations (Coyne et al.,
associated with female sexual dysfunction. 2007). There is evidence that treatment with antimuscarinic
drugs and neuromodulation significantly improves sexual
Pelvic Floor Disorders frequency, desire, lubrication, orgasm, satisfaction, pain, and
total Female Sexual Function Index 6-item (FSFI) scoring
Myofascial Pelvic Pain when study populations were compared at baseline and then
Various terminologies have been used to describe hyper- 3 to 12 months post-treatment (Pauls et al., 2007; Rogers
tonus disorders of the pelvic floor, including pelvic floor et al., 2008).
dysfunction, levator ani syndrome, pelvic floor tension
myalgia, pelvic floor myofascial pain, pelvic floor spasm, and Incontinence and Prolapse
shortened pelvic floor (Fitzgerald and Kotarinos, 2003a). Stress urinary incontinence (SUI), anal incontinence (AI),
Although the mechanism of pelvic floor dysfunction is and pelvic organ prolapse (POP) have been shown to have
incompletely understood, myofascial pain or pelvic floor deleterious effects on the overall health of women because
hypertonicity has been described as a disorder in which they affect the social, occupational, physiologic, physical,
pain is attributed to short, tight, tender pelvic floor muscles domestic, and sexual well-being of women. Studying the
in which trigger points are present. The pain or irritative effects of pelvic floor disorders on sexual function has been
88 PART 2  Basic Science

challenging because of the inherent differences between the due to focal pain even after the vaginal cuff has healed.
populations studied, the characterization of sexual dysfunc- Treatment depends on the location and suspected origin of
tion, and the use of condition nonspecific questionnaires or the pain. Lidocaine, antidepressants, and even surgical resec-
unvalidated measures. These issues likely do not allow for tion for focal areas of neuropathic pain and recurrent disease
the full capture of the effects of these disorders on sexual may be helpful. Physical therapy can be particularly effec-
satisfaction and function and so have resulted in conflicting tive for pain because of levator spasm (Lamvu et al., 2004).
data when evaluating women with pelvic floor disorders. Add Most studies evaluating sexual function after surgery for
to this uncertainty the fact that sexual function is multidi- SUI are small, retrospective, do not use validated question-
mensional, and it is not hard to understand why there is con- naires, and do not include women who were not sexually
fusion. Overall, however, the effects of urinary incontinence active. Additionally, often there is no assessment of baseline
and POP do appear to adversely affect sexual relationships preoperative sexual function and ultimately there are a variety
and seem to depend on the severity of the symptoms since of anti-incontinence and reconstructive surgeries included.
the more significant the disorder, the greater the decrease in Traditionally, maintenance of sexual function was mostly
sexual activity and satisfaction (Tannenbaum et al., 2006). directed at the question of preserving vaginal length and cali-
Pelvic floor symptoms are associated with poorer genital ber to allow for adequate mechanics of sexual intercourse.
body image and reduced arousal, infrequent orgasm, and Vaginal anatomy assessed in this fashion previously had been
dyspareunia (Handa et al., 2008; Zielinski et al., 2012). found to not correlate well with sexual function and still
Urinary incontinence has been associated with low libido, appears to be unrelated to sexual satisfaction (Weber et al.,
vaginal dryness, and dyspareunia, while low stage or asymp- 1995; Weber et al. 2000). Multiple studies employing condi-
tomatic POP has not been associated with sexual complaints tion-specific questionnaires such as the Pelvic Organ Prolapse/
(Handa et al., 2004). Coital incontinence can occur with Urinary Incontinence Sexual Function Questionnaire (PISQ)
vaginal penetration in women with stress incontinence and have demonstrated that surgical treatment for POP and
with orgasm in women with overactive bladder and can be SUI improves sexual function in both physical and partner
problematic for some women. domains with coital incontinence and subsequent embarrass-
Anal incontinence commonly occurs in combination with ment resolving in the majority of women (Rogers et al., 2006;
POP and SUI and as a result of high-order perineal lacera- Jha et al., 2007; Roos et al., 2014). Most prospective studies
tions, median episiotomy, and instrumentation. Anal sphinc- demonstrate that a woman’s overall sexual function improves
ter laceration is found to be associated with a delay in the after prolapse surgery because of a resolution of preexisting
return to sexual activity at 6 months postpartum (Brubaker dyspareunia as well as the interference of the bulge and that
et al., 2008). Posterior compartment POP can lead to def- vaginal length and caliber do not appear to be related to sexual
ecatory dysfunction and sexual dysfunction. Detachments satisfaction (Handa et al., 2007).
of the rectovaginal fascia from the perineal body can result Evidence indicates that surgery for POP also can lead to
in perineal descent, which has been associated with a vari- deterioration of sexual function. Reasons for this are dys-
ety of defecatory disorders, including constipation, rectal pareunia, fear of causing damage to the surgical result, new
pain, and fecal incontinence (Bartolo et al., 1983). Pudendal symptoms, and a disappointing result of surgery (Roos et al.,
neuropathy also can be a result of perineal descent separate 2014). The complaint of pain postoperatively is not uncom-
from rectocele or laceration findings and has been identified mon and typically a period of 6 months is considered to be
as a mechanism for fecal incontinence. One study looking an adequate time for symptom resolution given that surgery
at women with anal sphincter lacerations and women with- often requires vaginal dissection. De novo dyspareunia can
out also found that these women appeared to be as sexually occur in up to 26% of women, particularly after posterior
active, not more likely to complain of dyspareunia, and did colporrhaphy and levator plication (Cundiff and Fenner,
not avoid intercourse because of pain, but they were more 2004). Site-specific repair does not include plication of the
likely to report that their incontinence affected their sexual levator musculature and may have a lower rate of new onset
relationship (Pierce et al., 2006). Furthermore, although dyspareunia. The new onset pain also may be a result of a
many women who have had anal sphincter repair for anal tight vaginal introitus. The general guidelines of tightness
incontinence still report some incontinence, it does not cor- of “2 to 3 fingerbreadths” may not be ideal when partner
relate well with sexual function (Trowbridge et al., 2006). anatomy and vulvovaginal atrophy is taken into consider-
Clinicians who care for women with anal sphincter disrup- ation. Finally, synthetic graft material may have an impact
tion and anal incontinence know how devastating these on dyspareunia by affecting the pliability and movement of
injuries can be. More studies are needed to demonstrate the vagina. Controversy now surrounds some of these grafts
the sexual dysfunction and relationship interference that is because they have been implicated in vaginal exposure and
associated with anal incontinence. scarring that contributes to pain.
Few published studies have evaluated the effect on sexual
Surgery and Sexual Dysfunction function after anal sphincteroplasty for anal incontinence,
Few studies are designed specifically to address the role of and even fewer in which validated scales measuring func-
pelvic surgery on benign gynecologic issues and female sex- tion and fecal incontinence were used. Additionally, it is dif-
ual dysfunction. Surgery to resolve gynecologic indications ficult to assess sexual function in this population of women
may improve, worsen, or have no effect on sexual function. because their surgeries often are performed as a combination
Pelvic pain and dyspareunia due to endometriosis or adhe- of procedures for SUI and POP. Unfortunately, regardless
sions may be improved after surgery or hormonal therapies of repair technique, the success rate of these procedures in
(Ferrero et al., 2005). Touching the vaginal apex with the preventing future episodes of anal incontinence often is not
penis, digit, or cotton swab may be painful posthysterectomy greater than 40% (Trowbridge et al., 2006). Some studies
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 89

demonstrate that women postsurgery do report improve- the PEARLS model can provide a useful structure to elicit
ment in sexual sensation and satisfaction and being more empathy and open communication (See Table 6.6).
able emotionally to engage in sexual activity (Lewicky et al., It is important to ask about the gender of partners and
2004). Other authors report no difference in sexual func- also not to assume that the woman’s sexual behavior is lim-
tioning in the anal repair group when compared with con- ited to one partner or even to an identified partner or spouse.
trols. Fecal incontinence of solid stool is recognized as the
most severe form of AI and this type of AI, as well as the
Evaluation of an Identified Problem
presence of symptoms of depression related to fecal inconti-
nence, appears most likely to be correlated with poor sexual Any office visit can include a brief assessment of sexual func-
function (Pauls et al., 2007). tion. Many screening tools for sexual dysfunction are compli-
cated and more useful in the research setting than in clinical
practice. Commonly used validated scales include those
Screening and Evaluation for Sexual in Table 6.7. The questions listed in Table 6.8 can be used
Dysfunction for an initial screen for sexual problems. The Brief Sexual
Symptoms Checklist (Table 6.9) also may prove to be help-
Identification and Assessment of a Sexual
ful. These questions help to identify the specific components
Problem
Because sexual functioning is multifactorial, a thorough
Table 6.6  PEARLS Model
sexual history and physical examination should assess med-
ical, reproductive, surgical, psychiatric, social, and sexual P The clinician should acknowledge that this is a Partnership
information. Numerous barriers interfere with communica- and that they are in it together
tion of sexual function concerns during the typical patient– E The clinician should express understanding and Empathy
A The clinician should address any unmet expectation with
physician interaction. This lack of discussion regarding an Apology
sexual concerns may be the result of incomplete or insuf- R The clinician should acknowledge any patient suffering or
ficient knowledge on the part of the provider, poor training dissatisfaction with Respect/Reflection/Reinforce
in the taking of an effective sexual history, a perceived lack L The clinician should Legitimize the patient’s concerns and
feelings
of office time, a limited number of approved pharmacologic S The clinician should Support the patient and emphasize
options for treatment, and an uneasiness on both the part of that they will continue to work with the patient
the patient and the provider about discussing such issues.
Sexual problem identification should be a routine part This is a useful structure for the health professional to use in order to
of primary care and the review of systems can be an ideal demonstrate empathy and therefore open communication, which
ultimately will allow for a productive interview with the patient.
time to elicit such concerns. Postpartum and postsurgical Cohen-Cole S. The Medical Interview: The Three Function Approach. St. Louis:
periods must include such a discussion and assessment as Mosby-Yearbook, 1991.
well. Direct questioning is critical to uncovering a patient’s
sexual concerns and also signals that you are comfortable
with discussing sexual health concerns. Studies have shown Table 6.7  Validated Tools That Can Be Used
that patients are reluctant to initiate discussions about sex- to Measure Female Sexual Dysfunction
ual concerns, but very much want their provider to set up
Tool Assessed Area
the environment and open dialogue for this to take place
(Berman et al., 2003). The PLISSIT model can be a help- Female Sexual Function Index (FSFI) Desire, arousal,
ful tool for discussing health concerns with patients (Annon, (Rosen et al., 2000) orgasm, and pain
Female Sexual Function Index-6 Item Desire, arousal,
1976) (See Table 6.5). Also, when conducting the interview, (FSFI-6) (Isidori et al., 2010) orgasm, and pain
The McCoy Female Sexual Function
Questionnaire* (McCoy 2000)
The Brief Sexual Symptoms Checklist
Table 6.5  PLISSIT Model (Hatzichristou et al., 2010)
The Female Sexual Distress Distress
P Given the patient Permission to talk about her sexual Scale-Revised (Derogatis et al., 2008)
concerns by asking open-ended questions The Intimate Relationship Scale Changes in sexual
LI Provide the patient with Limited Information such as (Fischman et al., 1986)* relationship
education about female anatomy and physiology and Sexual Quality of Life-Female (SQoL-F) Quality of life in
basic changes in sexual function throughout the aging (Symonds et al., 2005) women with
process. Not all information must be provided at one female sexual
encounter. Patients should be encouraged to make dysfunction
follow-up appointments for continued discussion and Golombok Rust Inventory of Sexual Quality of sexual
management as needed Satisfaction (GRISS) (Rust and relationship
SS Make specific Suggestions in response to the problem Golombok, 1985)
(i.e., suggest lubricant use for vaginal dryness) Decreased Sexual Desire Screener Brief diagnostic tool
IT A referral to a specialist for Intensive Therapy may be more (DSDS) (Clayton et al., 2009) for HSDD
appropriate after your basic education and sugges- Pelvic Organ Prolapse/Urinary Sexual function in
tions. It is best if the clinician explains this collaborative Incontinence Sexual Questionnaire women with pro-
multidisciplinary approach so that the patient does not (PISQ-12) (Rogers et al., 2003) lapse or urinary
feel abandoned incontinence

Based on the work of Annon J. Behavioral Treatment of Sexual Problems. HSDD, hypoactive sexual desire disorder; FSD, female sexual dysfunction.
Hagerston, MD: Harper & Row; 1976. *Validated in pregnant and/or postpartum women.
90 PART 2  Basic Science

of the sexual problem and address the patient’s perceptions woman with a history of abuse or pain. The provider should
of the problem and the timeline, context, and other health attempt to increase the patient’s sense of control and estab-
problems that might contribute to a sexual complaint. lish a foundation of trust. The examination also is an oppor-
Once a problem is identified it is still important to specify tunity to provide education about anatomy and female sexual
the components of the sexual response that are compromised function especially if the partner is with her.
(see Table 6.8 of Key Questions). Answers to these questions When choosing a questionnaire, a clinician must con-
not only assist in isolating the key issues and etiologies, but sider what they are hoping to accomplish and whether they
also serve as a basis for treatment considerations. A thorough are looking for generic or condition-specific information.
sexual history or physical examination must be pursued to A validated scale that was developed specifically for use by
uncover the physiologic and anatomic factors involved with clinicians not specifically trained in sexual medicine is the
the sexual complaint (Tables 6.10 and 6.11). No standard Decreased Sexual Desire Screener (Clayton et al., 2009).
laboratory tests or imaging studies are required for the initial It is a five-question self-administered survey to help iden-
evaluation of a patient with a normal exam. It is imperative tify generalized acquired HSDD in pre- and postmenopausal
that the clinician pay special attention to the physical features women in a time efficient manner. Another validated tool for
relevant to sexual function. Each step of the exam should be office-based use is the Brief Profile of Female Sexual Func-
explained and agreed on by the patient, particularly in the tion (B-PFSF) (Rust et al., 2007). This seven-question self-
administered survey measures the loss of sexual desire and
function in postmenopausal women with HSDD. The Pelvic
Table 6.8  Suggested Sexual Assessment Organ Prolapse/Urinary Incontinence Sexual Questionnaire
Questions (PISQ-12) is a short-form 12-question, self-administered
How does the patient describe the problem? test that measures sexual function in women with POP or
How long has the problem been present? urinary incontinence (Rogers et al., 2003). The FSFI 6-item is
Was the onset sudden or gradual? a brief self-reporting instrument to assess the areas of desire,
Is the problem specific to a situation or partner or is it generalized?
Were there any precipitating events?
arousal, orgasm, and pain (Isidori et al., 2010) (see Table 6.7).
Are there problems in the women’s primary sexual relationship The original 19-item version often is used in clinical trials.
or any sexual relationship?
Are there current life stressors that might be contributing to
sexual problems? Treatment of Female Sexual Disorders
Is there guilt, depression, or anger that is not being directly
acknowledged? Sexual function does not exist in a vacuum. Women often
Are there physical problems such as pain? present with reports of sexual problems, but they have little
Are there problems in desire, arousal, or orgasm? insight into how or when the problem occurred. Sexuality
Is there a history of physical, emotional, or sexual abuse? and desire can be deeply affected by the quality and stability
Does the partner have any sexual problems?

Adapted from Basson R. Taking the sexual history, part 1: eliciting the
sexual concerns of your patient in primary care. Med Aspects Human Sex. Table 6.10  The Components of a Detailed
2000;1:13. Sexual History
Psychosocial Issues Details
Table 6.9  Brief Sexual Symptoms Checklist for First sexual encounter Age, events surrounding
History of abuse Verbal, emotional, physical,
Women (BSSC-W) sexual
Please answer the following questions about your overall sexual Number and gender of
function previous partners
Nature of current relationship
1. Are you satisfied with your sexual function? Specific sexual behaviors Masturbation, oral, anal, inter-
  ___ Yes course, accessories, erotica
  ___ No Religious and/or cultural
If no, then please continue. influences
2. How long have you been dissatisfied with your sexual Medical Issues
function? Alcohol, illicit drug and/or
3a. The problem(s) with your sexual function is: (Mark one or tobacco use
more) Current health status
  ___ 1 problem with little or no interest in sex Medications
  ___ 2 problem with decreased genital sensation (feeling) Reproductive history and Menarche, menstrual history,
  ___ 3 problem with decreased vaginal lubrication (dryness) current status obstetric and gynecologic
  ___ 4 problem with reaching orgasm history, hormone use,
  ___ 5 problem with pain during sex contraception, infertility,
  ___ 6 other urologic issues, pain, sexually
transmitted infections
3b. Which problem is the most bothersome (circle) 1 2 3 4 5 6
4. Would you like to talk about it with your doctor? Surgical History
  ___ Yes Medical conditions Neurologic, endocrine, car-
  ___ No diovascular, dermatologic,
autoimmune disorders,
Reprinted from Hatzichristou D, Rosen RC, Derogatis LR, et al. Recom- cancer
mendations for the clinical evaluation of men and women with sexual Psychiatric illnesses
dysfunction. J Sex Med. 2010;7:337.
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 91

of a relationship with a sexual partner. In addition to this, an abrupt onset of severe menopausal symptoms, including
her partner’s own sexual health and well-being can affect her decreased sex drive. Changes in overall health status with
sexual activity. Differing expectations based on religious and the development of chronic diseases and the use of medica-
cultural norms may be underlying an unsatisfying sexual expe- tions to manage these conditions can lead to reduced sexual
rience. Also affecting female sexual function is a history of function (see Tables 6.2 and 6.3). Pelvic floor disorders and
sexual abuse, negative sexual experiences, poor body image, issues of incontinence also contribute to a woman’s sense
lack of feeling safe, low sexual self-image, stress, fatigue, and of well-being and her sexual response, as noted previously.
mood or anxiety disorders (Bancroft et al., 2003). In general, treatment of sexual concerns demands an
Hormonal milieu has long been thought to play a role individualized approach. The foundation for treating sexual
in sexual function and dysfunction. Many women who concerns includes using the PLISSIT model for history-
seek assistance for sexual dissatisfaction report that their taking and therapy; facilitating both patient and partner
problem first arose during pregnancy or in the postpartum education; identifying and treating medical conditions that
period. We know that estrogen and testosterone decline contribute, considering both the past and present use of
with age and through the menopause. Women achieve peak medications and substances as a causative role; providing
androgen production in their mid-20s and gradually lose sexual counseling, coaching, and referring for psychother-
circulating testosterone and the adrenal preandrogens in an apy or intensive sex therapy when indicated. The patient
age-dependent fashion. By the time women reach their 60s, is much more likely to comply with referral if the clinician
testosterone levels are half of what they were before age verbalizes both the nature of the problem and the use of a
40 years. Menopause and this state of declining steroid hor- specialist or multidisciplinary approach.
mones have long been associated with a women’s perceived
change in her sexual activity and response. Postmenopausal
Hypoactive Sexual Desire Disorder
estrogen deficiency leads to vulvovaginal atrophy, dryness,
reduced clitoral blood flow, and decreased clitoral sensitiv- The treatment for HSDD depends on which component of
ity. This may result in dyspareunia and orgasmic dysfunction. desire is impaired. Sex therapy–cognitive behavioral psy-
Surgical menopause with removal of the ovaries can lead to chotherapy (CBT) either as an individual or couples is indi-
cated if the primary component impaired is interpersonal or
psychological. This methodology can assist in educating the
individual or couple about normal sexual function, anatomy,
Table 6.11  Components and Related Conditions
and physiology. CBT helps an individual navigate areas of
of a Thorough Physical Examination in Sexual
poor communication skills and imbalanced expectations.
Function Assessment
It allows for more productive interactions and role playing
Inspection of the External Genitalia that ultimately can lead to resolution of resentment, avoid-
Vulvar skin turgor, thickness, Lichen sclerosus/planus, atrophy, ant behavior, and conflict resulting in better intimacy.
color, integrity dermatologic conditions Pharmacologic treatment would be the first-line option
Pubic hair amount and Androgen level for women whose primary component is physiologic. Over
distribution
Labial abnormalities Previous circumcision, congeni-
the past decade, numerous well-powered, well-designed
tal variations, clitoromegaly clinical trials have shown that transdermal testosterone in
Cotton swab test Pain mapping of the vulva and physiologic to slightly supraphysiologic doses is effective
vestibule in the treatment of HSDD in the postmenopausal woman
Hymenal and urethral Urethral diverticulum (Buster et al., 2005; Braunstein et al., 2005; Shifren et al.,
abnormalities
Vestibular, skene, and Cyst, abscess 2006). Presently, no testosterone product is approved by the
bartholin glands U.S. Food and Drug Administration (FDA) for the treat-
Speculum exam Vaginal pH, genital cultures, ment of HSDD. Long-term safety concerns have stalled
examination for atrophy, the FDA approval of topical testosterone therapy for post-
assessment for prolapse
menopausal women. The European Medicines Agency of the
Monomanual/Bimanual Examination European Union has approved the use of the 300 mcg/day
Introital assessment Contraction, relaxation ability, testosterone matrix patch since 2007. Several testosterone
tenderness, scarring therapy options have been utilized off-label by U.S. clini-
Bladder, urethra, levator Assess for muscle tension,
muscles, pelvic floor tenderness and trigger points
cians. Transdermal testosterone gels are FDA-approved for
assessment men and are used sometimes for women in an off-label fash-
Uterus and adnexa, Palpate for mobility, fixed cul- ion by reducing the amount applied to estimate what has
rectovaginal exam de-sac, uterosacral ligaments, been shown to be the effective dose in women (300 mcg/
vaginal length, prolapse day.) These patients are carefully consented and monitored
General examination
for side-effects and therapeutic delivery to avoid supraphys-
Evaluation of signs of anemia, Palor, hair loss, thyromegaly,
endocrine disorders striae
iologic dosing. Alternatively, some practitioners are utilizing
Evaluate for signs of Dryness consistent with compounding pharmacies to formulate testosterone in vari-
connective tissue disease Sjogren’s syndrome, sclero- ous vehicles: Transderma PLO (Premium Lecithin Organo-
derma, other gel) gel dispensed in 5 mL syringes, pellets of 25 to 100 mg
Evaluation for disabilities of Neurologic disease, arthritis, inserted with local anesthesia every 3 to 4 months, and sub-
movement or sensation chronic pain, fibromyalgia
lingual and buccal formulations. Dehydroepiandrosterone
Adapted from Phillips NA. The clinical evaluation of dyspareunia. Int J Impot (DHEA) is a prohormone of testosterone that is available
Res. 1998;10:S117. as over-the-counter supplements in tablets of 25 to 50 mg.
92 PART 2  Basic Science

Clinical trials now are being conducted utilizing DHEA in a reproductive tract and is combined with a skin penetration
transdermal approach for the treatment of HSDD, vaginal enhancer (DDAIP), an ester of N,N-dimethylalanine and
atrophy, and prevention of osteoporosis (Labrie et al., 2009). dodecanol.
Bupropion is an antidepressant that has been shown to Apomorphine is a dopamine agonist that has been used
have a moderate prosexual effect and is utilized to treat the as a subcutaneous injection for the treatment of Parkinson’s
sexual side effects of selective serotonin reuptake inhibi- disease and has been researched as an oral treatment for
tors. It has both dopamine and norepinephrine reuptake arousal disorder.
inhibition. Bremelanotide is a melanocortin receptor-4 agonist
(MCR4 agonist) for the treatment of HSDD and FSAD
Bremelanotide is a synthetic analog of a-melanocyte stimu-
Sexual Aversion Disorders
lating hormone and is an agonist that activates the melano-
Central to the treatment of this disorder is distinguishing cortin receptors MC3-R and MC4-R in the central nervous
the events that may lead to its development and current system. It initially was delivered as a nasal spray, and Phase
behavior that may be reinforcing it. Treatment is based on II results were promising but development was stopped
a graduated exposure paradigm in which the patient pairs because of adverse effects on blood pressure. It recently has
relaxation exercises with patient-controlled reintroduction been reformulated in a lower dose as a subcutaneous injec-
of sexual behavior. SSRIs and anxiolytics may be employed, tion and a Phase IIb study in premenopausal women with
but a referral to a professionally trained clinician in this HSDD and/or FSAD found that it improved both.
disorder is of the utmost importance.
Anorgasmia
Female Sexual Arousal Disorders
The most effective treatment for the patient with orgasmic
First, the clinician should identify which subtypes of this dysfunction is usually cognitive behavioral therapy and edu-
disorder may be present or overlapping. Current options of cation. Many of these women with primary anorgasmia need
treatment include learning to adequately attend to sexual sen- to learn to become comfortable with their bodies and their
sations using masturbation and self-stimulation training alone sexual response, and this is achieved by altering negative
or with one’s partner, and improving communication with perspectives and decreasing anxiety. The therapy uses tech-
one’s partner to include frank discussions of what promotes niques of directed masturbation, sensate focus exercises,
romance and intimacy and what interferes. The use of erotica, and systematic desensitization. One of the most important
fantasy, and sexual accessories such as adjunctive aids can be things that a clinician can do is to educate about the female
encouraged. Physiologic strategies employing phosphodies- sexual response, to give the woman permission to explore
terase inhibitors (Sildenafil) have been studied in hopes of and understand her body, and to debunk the myths that con-
overcoming the problems of poor vasocongestion and blood tribute to the negativity directed at self-stimulation. Women
flow, but engorgement did not conclusively result in subjective with secondary anorgasmia or dysfunction need to have an
arousal (Berman et al., 2003). assessment of the possible contributions of health conditions
Systemic and locally administered estrogen therapy often and medications to their sexual concerns as well as an under-
helps postmenopausal women with FSAD due to genital standing that orgasmic function also can change with age.
insensitivity, vaginal atrophy, lack of lubrication, and genital Many of the techniques employed to treat sexual arousal dis-
vasocongestion. Vulvovaginal symptoms do not improve over orders can be utilized for orgasmic disorders as well.
time as do the vasomotor symptoms of low estrogen states Few pharmacologic options have been researched for the
and the menopausal transition. Because of the complexity treatment of orgasmic disorder. Currently, an intranasal low-
and possible side effects and risk factors associated with sys- dose nasal gel formulation of testosterone is being investigated
temic estrogen usage, many patients and clinicians have opted as an on-demand treatment option. There is currently a Phase
for the vaginally administered minimally absorbed estro- II trial under way in the U.S., Canada, and Australia.
gen, which has been shown to be effective for and is FDA-
approved for the use in dyspareunia caused by vulvovaginal
Dyspareunia
atrophy. This manner of estrogen administration can be found
in many delivery forms, such as creams, tablets, and ring. In determining a treatment strategy for dyspareunia, it is
DHEA presently is being studied in a vaginally-administered imperative that the clinician identify a broad differential diag-
formulation for the treatment of HSDD and FSAD as it is nosis so that treatment can be directed appropriately at the
converted to estrogen locally by the vaginal tissue and is mini- underlying physiologic, anatomic, or psychological source of
mally absorbed systemically (Labrie et al., 2009). the pain. A careful and in-depth evaluation must take place.
The EROS™ Clitoral Therapy System is the only FDA- The pain must be identified by its character, initial onset, ini-
approved device currently available to treat female sexual tiating and alleviating factors, duration, severity, impact on self
dysfunction. It produces clitoral vascular congestion through and partner, and previous treatments. The examination con-
a vacuum apparatus and is designed to help with arousal tains a thorough inspection of the anatomy of the vulva and
problems. It is prescription only, but it can be used in con- may or may not include a speculum if the patient can tolerate
junction with manual vibrators and hand-held massagers. it. A cotton swab test of the vulvar vestibule and palpation of
Femprox® is an alprostadil-based cream intended for the the pelvic floor musculature must be included. Collection of
treatment of FSAD. Alprostadil (PGE1) (FEMPROX) is vaginal discharge for testing can take place if appropriate. It
a naturally occurring potent vasodilator that has an impor- often helps to separate the location of dyspareunia into catego-
tant role in the regulation of blood flow to the female ries: superficial (introital), pelvic (deep), and emotional factors.
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 93

Because dyspareunia may be understood as a symptom Basson R. Sexuality and sexual disorders. In: Clinical Updates in Women’s
itself instead of a dysfunction, treatment is individualized Healthcare. Spring; 2003:1.
Basson R, Berman J, Burnett A, et al. Report of the international consensus
to the specific origin of the pain and to any related behav- development conference on female sexual dysfunction: definitions and
ioral causes or repercussions. Patient counseling, education, classifications. J Urol. 2000;163:888.
and referral to a qualified therapist should be provided, as Basson R, Leiblum S, Brotto L, et al. Definitions of women’s sexual dysfunc-
needed. tion reconsidered: advocating expansion and revision. J Psychosom Obstet
Gynecol. 2003;24:221.
Benson JT, McClellan E. The effect of vaginal dissection on the pudendal
Vaginismus nerve. Obstet Gynecol. 1993;82:387.
Berman JR, Bassuk J. Physiology and pathophysiology of female sexual
During an assessment where vaginismus is considered to be function and dysfunction. World J Urol. 2002;20:111.
a possibility, the clinician must remember that vaginismus Berman JR, Berman LA, Toler SM, et al. Safety and efficacy of sildenafil
citrate for the treatment of female sexual arousal disorder: a double-
still can be present without reported pain, and it can be blinded, placebo controlled study. J Urol. 2003;170:2333.
limited to sexual activity only, pelvic examination only, or Berman L, Berman J, Felder S, et al. Seeking help for sexual function com-
combination of the two. Because it is essentially an anxiety- plaints: what gynecologists need to know about the female patient’s expe-
mediated disorder, treatment usually is comprised of a com- rience. Fertil Steril. 2003;79:572.
Biddle AK, West SL, D’Alosio AA, Wheeler SB, Borisov NN. Hypoactive
bination of cognitive and behavioral therapeutic approaches sexual desire disorder in postmenopausal women: quality of life and
that are geared toward helping the woman to alleviate her health burden. Value Health. 2009;12:763.
fear and anxiety about penetration. This systematic desen- Binik Y, Reissing E, Pukall C, Flory N, Payne K, Khalife S. The female sex-
sitization also includes a program during which the woman ual pain disorders: Genital pain or sexual dysfunction? Arch Sex Behav.
learns progressive muscle relaxation techniques to help her 2002;31:45.
Braunstein GD, Sundwall DA, Katz M, et al. Safety and efficacy of a tes-
to achieve a sense of control over sexual activity or pelvic tosterone patch for the treatment of hypoactive sexual desire disorder
exams. Pelvic floor physical therapy provides guidance and in surgically menopausal women: a placebo-controlled trial. Arch Intern
reassurance and measures progress, especially if there is Med. 2005;165:1571.
myofascial pain or hypertonicity associated with the vagi- Brubaker L, Handa VL, Bradley CS, et al. Sexual function 6 months after
first delivery. Obstet Gynecol. 2008;111:1040.
nismus. In time, the woman also can be instructed on how Buster JE, Kingsberg SA, Aguirre O, et al. Testosterone patch for low sexual
to progressively insert graduated vaginal dilators so that she desire in surgically menopausal women: a randomized trial. Obstet Gynecol.
may learn to understand that she is no longer in danger of 2005;105:944.
experiencing pain from penetration. Cabral PU, Canário AC, Spyrides MH, Uchôa SA, Eleutério Jr J, Gonçalves AK.
Determinants of sexual dysfunction among middle-aged women. Int J
Gynaecol Obstet. 2013;120:271.
Conclusion Chiaffarino F, Parazzini F, Lavezzari M, Giambanco V. Impact of uri-
nary incontinence and overactive bladder on quality of life. Eur Urol.
It is well understood that providers of health care to 2003;43:535.
women have a duty to promote patient well-being. Provid- Clayton AH. Epidemiology and neurobiology of female sexual dysfunction.
J Sex Med. 2004;4:260.
ing education about sexual health and function, addressing Clayton AH, Goldfischer ER, Goldstein I, Derogatis L, Lewis-D’Agostino DJ,
changes in sexual function, and evaluating and addressing Pyke R. Validation of the decreased sexual desire screener (DSDS): a
sexual complaints must be part of the standard care that is brief diagnostic instrument for generalized acquired female hypoactive
given. The task of screening for sexual dysfunction requires sexual desire disorder (HSDD). J Sex Med. 2009;6:730.
knowledge of the complexity of the female sexual response Cohen-Cole S. The Medical Interview: The Three Function Approach.
St. Louis: Mosby Yearbook; 1991.
and the factors that affect it. Viewing this process through Coyne KS, Margolis MK, Brewster-Jordan J, et al. Evaluating the impact
a biopsychosocial perspective and treating patients in an of overactive bladder on sexual health in women: what is relevant? J Sex
individualized fashion via a multidisciplinary approach is Med. 2007;4:124.
likely to lead to more successful outcomes. Cundiff GW, Fenner D. Evaluation and treatment of women with rectocele:
focus on associated defecatory and sexual dysfunction. Obstet Gynecol.
2004;104:1403.
Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and
Bibliography self-reported sexual function in women. JAMA. 2005;294:91.
Althof SE, Leiblum SR, Chevret-Measson M, et al. Psychological and De Judicibus MA, McCabe MP. Psychological factors and sexuality of pregnant
interpersonal dimensions of sexual function and dysfunction. J Sex Med. and postpartum women. J Sex Res. 2002;39:94.
2005;2:793. Derogatis L, Clayton A, Lewis-D’Agostino D, Wunderlich G, Fu Y. Valida-
American Psychiatric Association. Diagnostic and Statistical Manual of tion of the female sexual distress scale-revised for assessing distress in
Mental Disorders: DSM-IV-TR text revision. 4th ed. Washington, DC: women with hypoactive sexual desire disorder. J Sex Med. 2008;5:357.
American Psychiatric Association; 2000. Fenner DE, Genberg B, Brahma P, et al. Fecal and urinary incontinence after
American Psychiatric Association. Diagnostic and Statistical Manual of vaginal delivery with anal sphincter disruption in an obstetrics unit in the
Mental Disorders: DSM-V. 5th ed. Washington, DC: American Psychiatric United States. Am J Obstet Gynecol. 2003;189:1543.
Publishing; 2013. Ferrero S, Esposito F, Abbamonte LH, et al. Quality of sex life in women
Bancroft J, Graham CA, Janssen E, Sanders SA. The dual control model: with endometriosis and deep dyspareunia. Fertil Steril. 2005;83:573.
current status and future directions. J Sex Res. 2009;46:121. Fischman SH, Rankin EA, Soeken KL, Lenz ER. Changes in sexual relation-
Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women ships in postpartum couples. JOGNN. 1986;15:58.
in heterosexual relationships. Arch Sex Behav. 2003;32:193. Fitzgerald MP, Kotarinos R. Rehabilitation of the short pelvic floor. I: back-
Barber MD, Dowsett SA, Mullen KJ, et al. The impact of stress urinary ground and patient evaluation. Int Urogynecol J Pelvic Floor Dysfunct.
incontinence on sexual activity in women. Cleve Clin J Med. 2005;72:225. 2003a;14:261.
Barrett G, Peacock J, Victor C, Thakar R, Manyonda I. Cesarean section and Fitzgerald MP, Kotarinos R. Rehabilitation of the short pelvic floor. I: treat-
postnatal sexual health. Birth. 2005;32:306. ment of the patient with the short pelvic floor. Int Urogynecol J Pelvic
Bartolo DC, Read NW, Jarratt JA, et al. Differences in anal sphincter Floor Dysfunct. 2003b;14:269.
function and clinical presentation in patients with pelvic floor descent. Glazener CM. Sexual function after childbirth: women’s experiences, persis-
Gastroenterology. 1983:858. tent morbidity and lack of professional recognition. Br J Obstet Gynaecol.
Basson R. Human sex-response cycles. J Sex Marital Ther. 2001;27:33. 1997;104:330.
94 PART 2  Basic Science

Glazer HI. Dysesthetic vulvodynia. Long-term follow-up after treatment Lydon-Rochelle MT, Holt VL, Martin DP. Delivery method and self-
with surface electromyography-assisted pelvic floor muscle rehabilitation. reported postpartum general health status among primiparous women.
J Reprod Med. 2008;45:798. Paediatr Perinat Epidemiol. 2001;15:232.
Handa VL. Sexual function and childbirth. Semin Perinatol. 2006;30:253. Masters WH, Johnson VE. Human Sexual Response. Boston, MA: Little
Handa VL, Cundiff GW, Change HH, Helzlsouer KJ. Female sexual function Brown; 1966.
and pelvic floor disorders. Obstet Gynecol. 2008;111:1045. McCoy NL. The McCoy Female Sexuality Questionnaire. 2000;9:739.
Handa VL, Harvery L, Cundiff GW, Siddique SA, Kjeurulff KH. Sexual Meston CM, Frolich PE. The neurobiology of sexual function. Arch Gen
function among women with urinary incontinence and pelvic organ pro- Psychiatry. 2000;57:1012.
lapse. Am J Obstet Gynecol. 2004;191:751. Meston CM, Levin RJ, Sipski ML, Hull EM, Heiman JR. Woman’s orgasm.
Handa VL, Zyczynski HM, Brubaker L, et al. Sexual function before and Ann Rev Sex Res. 2004;15:173.
after sacrocolpopexy for pelvic organ prolapse. Am J Obstet Gynecol. NIH Sate-of-the Science Conference Statement on Cesarean Delivery on
2007;197:629. Maternal Request. NIH Consensus SC Statements. 2006;23:1.
Handbook on Female Sexual Health and Wellness. Washington, DC: Associa- Office of the Surgeon General (US); Office of Population Affairs (US).
tion of Reproductive Health Professionals; September 2011. Available at: The Surgeon General’s Call to Action to Promote Sexual Health and
www.arhp.org. Accessed 22.12.12. Respon­sible Sexual Behavior. Rockville, Maryland: Office of the Surgeon
Hatzichristou D, Rosen RC, Broderick G, et al. Clinical evaluation and man- General (US); 2001. Available at: http://www.ncbi.nlm.nih.gov/books/
agement strategy for sexual dysfunction in men and women. J Sex Med. NBK44216/. Accessed 12/12/12.
2004;1:49. Ornat L, Martínez-Dearth R, Muñoz A, et al. Sexual function, satisfaction
Hatzichristou D, Rosen RC, Derogatis LR, et al. Recommendations for with life and menopausal symptoms in middle-aged women. Maturitas.
the clinical evaluation of men and women with sexual dysfunction. 2013;75:261.
J Sex Med. 2010;7:337. Pauls RN, Marinkovic SP, Silva WA, Rooney CM, Kleeman SD, Karram
Hayes R, Dennerstein L. The impact of aging on sexual function and sexual MM. Effects of sacral neuromodulation on female sexual function. Int
dysfunction in women: A review of population based studies. J Sex Med. Urogynecol J Pelvic Floor Dysfunct. 2007;18:391.
2005;2:317. Pauls RN, Occhino JA, Dryfhout VL. Effects of pregnancy on female sexual
Hi YH, Goh HS. The neurophysiological significance of perineal descent. function and body image: a prospective study. J Sex Med. 2008;5:1915.
Int J Colorectal Dis. 1995;10:107. Pauls RN, Silva WA, Rooney CM, et al. Sexual function after vaginal surgery
Isidori AM, Pozza C, Esposito K, et al. The Female Sexual Function Index for pelvic organ prolapse and urinary incontinence. Am J Obstet Gynecol.
(FSFI): Development and validation of a 6-item version of the female 2007;197:622.
sexual function index (FSFI) as a diagnostic tool for female sexual dys- Pauls RN, Silva WA, Rooney CM, et al. Sexual function following anal sphinc-
function. J Sex Med. 2010;7:1139. teroplasty for fecal incontinence. Am J Obstet Gynecol. 2007;197:618.
Jackson SL, Weber AM, Hull TL, Mitchinson AR, Walters MD. Fecal incon- Perelman MA. The sexual tipping point: a mind/body model for sexual
tinence in women with urinary incontinency and pelvic organ prolapse. medicine. J Sex Med. 2009;6:629.
Obstet Gynecol. 1997;89:423. Peters KM, Carrico DJ, Kalinowski SE, et al. Prevalence of pelvic floor dys-
Jha S, Moran P, Greenham H, et al. Sexual function following surgery for function in patients with interstitial cystitis. Urology. 2007;70:168.
urodynamic stress incontinence. Int Urogynecol J Pelvic Floor Dysfunct. Pierce A, Arroyo P, Rogers R, Abed H. Sexual activity in women with fecal
2007;18:845. incontinence. Papers presented at 27th Annual AUGS Scientific Meeting,
Kaplan HS. Disorders of Sexual Desire and Other New Concepts and Tech- October 19–21, 2006. Int Urogynecol J. 2006;17:S396.
niques in Sex Therapy. The New Sex Therapy. vol 2. New York: Bruner/ Rhodes JC, Kjerulff KH, Langenberg PW, Guzinski GM. Hysterectomy and
Meisel U; 1979. sexual functioning. JAMA. 1999;282:1934.
Kingsberg SA. Taking a sexual history. Obstet Gynecol Clin N Am. Rogers RG, Bachmann G, Jumadilova Z, et al. Efficacy of tolterodine on over-
2006;33:535. active bladder symptoms and sexual and emotional quality of life in sexually
Kingsberg SA, Althof SE. Evaluation and treatment of female sexual disorders. active women. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19:1551.
Int Urogynecol J. 2009;20:S33. Rogers RG, Borders N, Leeman L, Albers L. Does spontaneous genital tract
Kingsberg SA, Janata JW. Female sexual disorders: assessment, diagnosis, trauma impact postpartum sexual function? J Midwifery Women’s Health.
and treatment. Urol Clin North Am. 2007;34:497. 2009;54:98.
Kingsberg SA, Reazee RL. Hypoactive sexual desire in women. Menopause. Rogers RG, Coates KW, Kammerer-Doak D, Khalsa S, Qualis C. A short
2013;20:1284. form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Ques-
Klein MC, Gautheir RJ, Robbins JM, et al. Relationship of episiotomy tionnaire (PISQ-12). Int Urogynecol J. 2003;14:164.
to perineal trauma and morbidity, sexual dysfunction, and pelvic floor Rogers RG, Kammerer-Doak DN, Darrow A, et al. Does sexual func-
relaxation. Am J Obstet Gynecol. 1994;171:591. tion change after surgery for stress urinary incontinence and/or pelvic
Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Davidson JM. Effect organ prolapse? A multicenter prospective study. Am J Obstet Gynecol.
of dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction 2006;195:e1.
in postmenopausal women. Menopause. 2009;16:923. Roos AM, Thakar R, Sultan AH, de Leeuw JW, Paulus ATG. The impact of
Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, et al. pelvic floor surgery on female sexual function: a mixed quantitative and
Intravaginal dehydroepiandrosterone (Prasterone), the physiological and qualitative study. BJOG. 2014;121:92.
highly efficient treatment of vaginal atrophy. Menopause. 2009;16:907. Rosen RC, Barsky JL. Normal sexual response in women. Obstet Gynecol
Lamvu G, Robinson B, Zolnoun D, Steege JF. Vaginal apex resection: a Clin North Am. 2006;33:515.
treatment option for vaginal apex pain. Obstet Gynecol. 2004;104:1340. Rosen R, Brown C, Heiman J, Leiblum S, et al. The Female Sexual Function
Latthe P, Latthe M, Say L, Gulmezoglu M, Khan KS. WHO systematic Index (FSFI): a multidimensional self-report instrument for the assess-
review of prevalence of chronic pain: a neglected reproductive health ment of female sexual function. J Sex Marital Ther. 2000;26:191.
morbidity. BMC Public Health. 2006;6:177. Rust J, Derogatis L, Rodenberg C, Koochaki P, Schmitt S, Golombok S.
Laumann E, Paik A, Rosen R. Sexual dysfunction in the United States: Prev- Development and validation of a new screening tool for hypoactive sexual
alence and predictors. JAMA. 1999;281:537. desire disorder: The Brief Profile of Female Sexual Function (B-PSFS).
Leiblum SR, Koochaki PE, Rodenberg CA, Barton IP, Rosen RC. Hypoac- Gynecol Endocrinol. 2007;23:638.
tive sexual desire disorder in postmenopausal women: US results from Rust J, Golombok S. The Golombok-Rust Inventory of Sexual Satisfaction
the Women’s International Study of Health and Sexuality (WISHeS). (GRISS). Br J Clin Psychol. 1985;24:63.
Menopause. 2006;13:46. Salonia A, Giraldi A, Chivers ML, et al. Physiology of women’s sexual
Leif H. Inhibited sexual desire. Med Aspects Hum Sex. 1977;7:94. function: basic knowledge and new findings. J Sex Med. 2010;7:2637.
Levine SB. Sexual Life. New York, NY: Plenum Press; 2004. Sands M, Fisher MA. Women’s endorsement of models of female sexual
Lewicky CE, Valentin C, Saclarides TJ. Sexual function following sphinc- response; the nurses’ sexuality study. J Sex Med. 2007;4:708.
teroplasty for women with third- and fourth-degree perineal tears. Dis Segraves R, Woodard T. Female hypoactive sexual desire disorder. History
Colon Rectum. 2004;47:1650. and current status. J Sex Med. 2006;3:408.
Lue T, Basson R, Rosen R, Guiliano F, Khoury S, Montorsi F. Sexual Dys- Shifren JL, Davis SP, Moreau M, et al. Testosterone patch for the treatment
function in Men and Women. 2nd International Consultation on Sexual of hypoacitve sexual desire disorder in naturally menopausal women:
Dysfunction. Paris, France: Health Publications; 2004. results from the INTIMATE NM1 Study. Menopause. 2006;13:770.
CHAPTER 6  Female Sexual Function and Dysfunction: Assessment and Treatment 95

Shifren JL, Monz BU, Russo PA, et al. Sexual problems and distress in Weber AM, Walters MD, Piedmont MR. Sexual function and vaginal anat-
United States women: prevalence and correlates. Obstet Gynecol. omy in women before and after surgery for pelvic organ prolapse and
2008;12:970. urinary incontinence. Am J Obstet Gynecol. 2000;182:1610.
Signorello LB, Harlow BL, Chekos AK, et al. Postpartum sexual function Weber AM, Walters MD, Schover LR, Mitchinson A. Vaginal anatomy and
and its relationship to perineal trauma: a retrospective study of primiparous sexual function. Obstet Gynecol. 1995;86:946.
women. Am J Obstet Gynecol. 2001;184:881. Wittig K, Santitila P, Alanko K, et al. Female sexual function and its associa-
Sills T, Wunderlich G, Pyke R, et al. The Sexual Interest and Desire Inventory- tions with number of children, pregnancy and relationship satisfaction. J
Female (SIDI-F): item response analyses of data from women diagnosed Sex Marital Ther. 2008;34:89.
with hypoactive sexual desire disorder. J Sex Med. 2005;2:801. World Health Organization. Education and Treatment in Human Sexuality:
Snooks SJ, Swash M, Henry MW, Setchell M. Risk factors in childbirth caus- The Training of Health Professionals. Report of a WHO, meeting. 49 Sheri-
ing damage to the pelvic floor innervation. In J Colorect Dis. 1986;1:20. dan Avenue, Albany, NY: Q Corporation; 2000. 12210.
Symonds T, Boolell M, Quirk F. Development of a questionnaire on sexual Wyman JF, Uebersax JS, McClish D, Fantl JA. Health-related quality of life
quality of life in women. J Sex Marital Ther. 2005;31:385. measures for women with urinary incontinence: the incontinence impact
Tannenbaum C, Corcos J, Assalian P. The relationship between sexual activity questionnaire and the urogenital distress inventory. Continence Program
and urinary incontinence in older women. J Am Geriatr Soc. 2006;54:1220. in Women (CPW) Research Group. Qual Life Res. 1994;3:291.
Trowbridge ER, Morgan D, Trowbridge MJ, DeLancey JO, Fenner DE. Zielinski R, Miller J, Low LK, Sampselle C, DeLancey JO. The relation-
Sexual function, quality of life and severity of anal incontinence after ship between pelvic organ prolapse, genital body image, and sexual health.
sphincteroplasty. Am J Obstet Gynecol. 2006;195:1753. Neurourol Urodyn. 2012;31:1145.
Watersone M, Wolfe C, Hooper R, Bewley S. Postnatal morbidity after
childbirth and severe obstetric morbidity. BJOG. 2003;110:128.
CHAPTER 7

Epidemiology and
Psychosocial Impact
of Female Pelvic
Floor Disorders
Vivian W. Sung
B. Star Hampton

and quality of life and are associated with limitations that


Chapter Outline can negatively impact a woman’s wellness and health. With
the aging population, female pelvic floor disorders are a
Epidemiology significant issue from both an individual and public health
Urinary Incontinence perspective. This chapter reviews the epidemiology, risk
Prevalence factors, and the psychosocial impact of these conditions.
Incidence, Remission, Improvement, and
Progression Urinary Incontinence
Urinary Incontinence during Pregnancy and
In general, urinary incontinence can be characterized by the
Postpartum
presence of specific symptoms, frequency of urine leak-
Costs
age, severity of leakage, degree of bother to the woman,
Pelvic Organ Prolapse and type of incontinence. Prevalence and incidence rates
Prevalence, Incidence, Remission, and Progression can vary widely depending on the definition used, as
Costs well as measurement and survey methods and population
Anal Incontinence differences.
Prevalence, Incidence, and Remission
Prevalence
Anal Incontinence during Pregnancy and
Postpartum Prevalence rates reflect the total number of cases of disease
Costs in the population at a given time. For urinary incontinence,
definitions used in the literature range from using the pres-
Coexisting Pelvic Floor Disorders
ence of leakage (yes/no) to using the frequency of leakage
Future Projections (daily, weekly, monthly, ever) to using symptom bother to
Causes and Prevention of Pelvic Floor Disorders determine prevalence. Therefore, it is important to qualify
Race what specific definition was used when reporting preva-
lence and incidence rates.
Age
A review of 21 studies by Thom et al. (1998) found the
Familial and Genetic Linkage average prevalence of any incontinence for older women
Childbirth was 34%, and 12% for daily incontinence. For middle-aged
Constipation and younger adults, the average prevalence of any inconti-
Obesity nence was slightly lower at 25% in the same study. Nygaard
et al. (2008) analyzed the National Health and Nutrition
Smoking
Examination Survey (NHANES) and used a more strict
Menopause/Hormone Replacement Therapy definition, defining incontinence as “at least weekly leakage
Psychosocial Impact of Pelvic Floor Disorders or monthly leakage more than drops.” Based on this defini-
tion, the authors reported a prevalence of 15.7%. Also using
NHANES data, Markland et al. (2011) reported a preva-
lence of 51% when incontinence was defined as any positive
response. Table 7.1 summarizes the prevalence of urinary
Epidemiology incontinence based on age group and varying definitions.
Female pelvic floor disorders include urinary incontinence, Prevalence rates also vary based on symptom sever-
pelvic organ prolapse, and anal incontinence. These condi- ity. Again using NHANES data, Minassian et al. (2008)
tions can have a significant impact on a woman’s functioning reported that the prevalence of any urinary incontinence in
96
CHAPTER 7  Epidemiology and Psychosocial Impact of Female Pelvic Floor Disorders 97

Table 7.1  Prevalence Rates and Definitions of Urinary Incontinence, by Age Group and Definition
Author Definition Used Prevalence (%)
All Ages
Nygaard et al. (2008) At least weekly leakage or monthly leakage more than drops 15.7
Markland et al. (2011) Any leakage 51.1
Middle Ages
Nygaard et al. (2008) (ages 40-59) At least weekly leakage or monthly leakage more than drops 17.2
Waetjen et al. (2007) (ages 42-52) At least monthly incontinence 46.7
Irwin et al. (2006) (ages 40-59) Any urine loss 13.7
Older Ages
Nygaard et al. (2008) (ages 60 and older) At least weekly leakage or monthly leakage more than drops 23.3-31.7
Irwin et al. (2006) (ages 60 and older) Any urine loss 20

Other improvement, and progression data are more limited.


incontinence Reported 1-year remission rates range from 4.6% to 9.1%
4% (Townsend et al., 2007; Lifford et al., 2008; Komesu et al.,
2009). Improvement rates range from 4.5% to 16% over
Stress
1 year and one study estimated that symptom progression
incontinence rate is 16%.
33%
Urinary Incontinence during Pregnancy
and Postpartum
Stress urinary incontinence is common during pregnancy with
Mixed a prevalence ranging from 40% to 59%. In general, the sever-
incontinence ity may worsen throughout pregnancy. In postpartum women,
50% stress urinary incontinence will resolve in many, and the prev-
alence is estimated to range from 15% to 30% (Milsom et al.,
2009). In longitudinal studies, the cumulative incidence rate
Urge of urinary incontinence is estimated to be approximately 39%
incontinence (Solans-Domenech et al., 2010). Up to 26% of women who
13%
reported urinary incontinence during pregnancy will have
FIGURE 7.1 Prevalence of urinary incontinence based on inconti- persistent leakage in the postpartum period; the majority will
nence type. (Data from Melville JL, Katon W, Delaney K, et al. Urinary have resolution. Of those with persistent leakage, 47% will
incontinence in US women. Arch Intern Med. 2005;165:537.) report moderate to severe symptoms.
Costs
women aged 50 to 59 was 19.9% for “mild” incontinence, The financial burden of urinary incontinence and overac-
16.5% for “moderate” incontinence, and 25% for “severe” tive bladder syndrome is significant and includes direct and
incontinence. Variable prevalence rates were also seen in indirect costs. Direct costs include costs to the patient for
other age groups based on symptoms severity. routine care (absorbent products, laundry), medical visits,
The type of urinary incontinence is also important when and treatments. Indirect costs include loss of productivity
considering the prevalence of the condition (Fig. 7.1). The and costs of paid or unpaid caregivers, which are more dif-
prevalence of stress urinary incontinence ranges from 33% ficult to measure (Table 7.2). Many studies support that the
to 54%, urge urinary incontinence ranges from 12% to 16%, largest cost item associated with urinary incontinence for
and mixed urinary incontinence ranges from 19% to 50% both community-dwelling women as well as those in nurs-
in populations reporting any incontinence. Similar data are ing homes remains routine care and supplies, with only a
available from multiple countries documenting that these minimal proportion of the costs going to evaluation and
conditions are highly prevalent worldwide. treatment. Although most studies evaluate the direct costs
due to accessibility of data, the economic impact of indirect
Incidence, Remission, Improvement, costs should not be underemphasized.
and Progression A study by Wilson et al. (2001) estimated that the annual
Urinary incontinence is a dynamic condition and symptoms direct cost of urinary incontinence for women was $12.4
may wax and wane. Incidence rates reflect the number of billion (2001 U.S. dollars) and the largest cost category
new cases of disease in the population during a specified was routine care (70% of costs), followed by nursing home
period of time. The average one-year incidence ranges from admissions (14%), treatment (9%), complications (6%),
6.9% to 11.1% in the United States in women younger than and diagnosis and evaluation (1%). Medicare spending on
55 years (Townsend et al., 2007; Waetjen et al., 2007). incontinence treatment continues to increase dramatically.
The rate is higher in older women, estimated to be 13.8% For Medicare beneficiaries aged 65 and older, Thom et al.
over 1 year in women 54 to 79 years of age. Remission, (2005) used multiple national databases and reported that
98 PART 2  Basic Science

Table 7.2  Costs of Urinary Incontinence Table 7.3  Prevalence of Pelvic Organ Prolapse
Type of Cost Examples Study Definition of Prolapse Prevalence
Direct Costs Swift et al. Exam only Stage 0 = 24%
Diagnostic and evaluationPhysician consultation and (2005) Stage 1 = 38%
costs evaluation, laboratory, diagnostic Stage 2 = 35%
procedures Stage 3 = 2%
Treatment costs Surgery, medication, pelvic/behav- Hendrix et al. Exam only Any prolapse = 41.1%
ioral therapy (2002) Cystocele = 34.3%
Routine care costs Nursing labor, supplies, laundry Uterine = 14.2%
Rehabilitation costs Nursing, supplies Rectocele = 18.6%
Incontinence consequence Skin breakdowns, urinary tract Handa et al. Exam only Cystocele = 24.6%
costs infections, falls, nursing home/ (2004) Uterine = 3.8%
assisted living care Rectocele = 12.9%
Rortveit et al. Symptoms only 5.70%
Indirect Costs (2007)
Costs of unpaid caregivers Time, loss of work Nygaard et al. Symptoms only 2.90%
Loss of productivity Missed time from work for diagno- (2008)
sis/treatment, missed time from Slieker-ten Symptoms only 11.40%
work due to morbidity Hove et al.
(2009)

the expenditures for inpatient and outpatient medical care of prolapse based on physical examination for various com-
doubled from $128 million in 1992 to $234 million in 1998. partments. These studies did not include patient symptom
They also estimated that 23% of incontinent women missed information. Prevalence estimates based on exam findings
an average of 28.7 h of work due to inpatient and outpatient alone are higher compared to those based on symptom
care associated with urinary incontinence treatment. reports alone.
At the individual level, annual routine costs alone are Data are limited for the incidence and remission of pel-
estimated to be $250 to $900 per woman in 2005 (Subak vic organ prolapse. Based on the WHI data, incidence of
et al., 2008). Direct costs for incontinence management grades 1 to 3 prolapse are estimated to be 9.3/100 women-
increase significantly with greater incontinence frequency. years for cystocele, 5.7/100 women-years for rectocele, and
Subak et al. (2012) evaluated the impact of incontinence 1.5/100 women-years for uterine prolapse. The remission
improvement on incontinence-associated costs and found rates are estimated to be up to 9%, with cystocele having
that the mean cost for an individual decreased by 23% for higher remission rates than rectocele. Prolapse progression
each decrease of seven incontinence episodes per week. ranged from 1.9% for uterine prolapse, to 9.5% for cys-
Because most of the cost associated with incontinence care tocele, and 14% for rectocele. Older, parous women are
is out of pocket, patients assume great financial responsibil- more likely to develop new or progressive prolapse than to
ity in managing this condition. regress. Progression and resolution appear to be dependent
on baseline severity of prolapse.
After pregnancy and delivery, 31% of women have stage
Pelvic Organ Prolapse
II prolapse. After delivery, 14% to 15% of women have pro-
Similar to incontinence, definitions for pelvic organ pro- lapse at or below the hymen and 5% have this after cesarean
lapse are also variable. The International Continence Soci- delivery.
ety (ICS) defines prolapse as the descent of one or more of
the anterior vaginal wall, posterior vaginal wall, and the apex Costs
of the vagina or vault. Most epidemiologic studies define The direct cost of pelvic organ prolapse surgery in 1997 was
prolapse based on either physical examination findings or estimated to be $1012 million based on national average
patient symptom report. Medicare reimbursement. Physician services accounted for
29% and hospitalization accounted for 71% (Subak et al.,
Prevalence, Incidence, Remission, 2001). There are few data on the indirect costs or direct
and Progression patient costs of pelvic organ prolapse.
Most population-based surveys define prolapse based solely
on patient symptoms, commonly defined as an affirmative Anal Incontinence
response to seeing/feeling a vaginal bulge. Using this defini-
tion, the prevalence of prolapse symptoms ranges from 2.9% Prevalence, Incidence, and Remission
to 8% in the United States (Nygaard et al., 2008; R ­ ortveit Anal incontinence includes the involuntary passage of gas,
et al., 2007; Bradley et al., 2005). These studies did not mucus, liquid, or solid stool. The prevalence and epidemi-
include physical examination information. Additional stud- ology of anal incontinence has been poorly documented,
ies from the Women’s Health Initiative (WHI) including and many women are too embarrassed to report the condi-
U.S. women aged 50 to 79 years found the prevalence of tion. Most epidemiologic studies define anal incontinence
any degree of prolapse based on examination alone of grades as any involuntary leakage of stool. Depending on the defi-
1 to 3 prolapse to be 41.1% (Handa et al., 2004; Hendrix nition used, the prevalence of fecal incontinence in U.S.
et al., 2002). Table 7.3 presents the estimated prevalence women ranges from 2.2% to 24%. When defined as any
CHAPTER 7  Epidemiology and Psychosocial Impact of Female Pelvic Floor Disorders 99

leakage in the past year, the prevalence is estimated to be


Future Projections
approximately 24% (Varma et al., 2006). When defined
more frequently as at least monthly leakage, the preva- It is projected that future demands for ambulatory care
lence is estimated to be approximately 9% (Nygaard et al., and surgical treatment for female pelvic floor disorders will
2008). increase. Wu et al. (2009) estimated the increase in num-
Whitehead et al. (2009) estimated the prevalence of dif- ber of women who will be affected by pelvic floor disor-
ferent types and frequencies of fecal incontinence in non- ders through 2050 using NHANES prevalence rates and
institutionalized U.S. women using NHANES data. The U.S. Census Bureau projections. Using these methods, the
overall prevalence of fecal incontinence within the past authors estimated that the number of American women
month was 8.9%, and increased with age from 2.6% in 20 with at least one pelvic floor disorder will increase from
to 29-year-olds to 15.3% in women 70 years and older. The 28.1 million in 2010 to 43.8 million in 2050. During this
most common type of incontinence was with watery/liquid time period, the number of women with urinary inconti-
stool (>20%), followed by hard and normal stool (approxi- nence will increase 55% from 18.3 million to 28.4 million.
mately 9% for both). Fifty-one percent of women reported Fecal incontinence will increase 59% from 10.6 million to
leakage of gas in the past month and 21% reported at least 16.8 million, and the number of women with prolapse will
daily leakage of gas. increase 46% from 3.3 million to 4.9 million. The highest
Data regarding the incidence, regression, and progres- estimated projections for 2050 estimate that 58.2 million
sion of anal incontinence are extremely limited. Markland women will be affected by at least one pelvic floor disorder.
et al. (2010) estimated the incidence and remission of Using estimated surgical rates in national databases and
fecal incontinence in Medicare beneficiaries. Defining fecal population projections from the U.S. Census Bureau from
incontinence as any loss of bowel control during the previ- 2010 to 2050, Wu et al. (2011) project that the total num-
ous year, the incidence rate at four years was approximately ber of women who will undergo stress urinary incontinence
18% in women and the remission rate was 57%. The over- surgery will increase almost 50% from 210,700 in 2010 to
all incidence rate for the development of more severe fecal 310,050 in 2050. Similarly, the total number of women who
incontinence, defined as monthly or greater incontinence, will undergo prolapse surgery will increase from 166,000 in
was 6.3%. 2010 to 245,970 in 2050. These estimates assume that the
rates of surgery will remain unchanged.
Anal Incontinence during Pregnancy
and Postpartum
Causes and Prevention of Pelvic
During pregnancy, up to 10% of women present with
anal incontinence, and the cumulative incidence rate is
Floor Disorders
estimated to be 10.3% (Solans-Domenech et al., 2010). Causes of pelvic floor disorders are multifactorial, and it
Of the women reporting anal incontinence during preg- is difficult to understand the relative importance of each
nancy, 29.7% reported persistent anal incontinence factor for a specific individual or population. However, it
postpartum. is useful to understand the impact of each factor on the
development of pelvic floor disorders to potentially aid in
Costs disease prevention.
Mellgren et al. (1999) reported the average lifetime cost
to be approximately $17,166 per patient for treatment,
Race
follow-up, physician evaluation, and costs for protective
materials in 1996, and average surgical costs were $8555 The role of race as a predisposing risk factor for pelvic floor
per procedure. Sung et al. (2007) estimated the hospital disorders remains unclear. Though some studies report that
cost of inpatient surgery alone for female fecal incontinence white women are at increased risk for stress urinary incon-
to be $6000 per surgical admission in 2003, totaling $24.5 tinence (Thom et al., 2006; Kim et al., 2005; Fenner et al.,
million spent on hospital costs for surgery alone that year. 2008; Sze et al., 2002), symptomatic pelvic organ prolapse
This estimate did not include direct costs of physician ser- (Rortveit et al., 2007; Hendrix et al., 2002; Whitcomb et al.,
vices or any indirect costs. 2009), and fecal incontinence (Markland et al., 2010) this is
not a consistent finding. Thom et al. (2006) specifically eval-
uated urinary incontinence prevalence among major racial
Coexisting Pelvic Floor Disorders
and ethnic groups and found that the prevalence of all types
Pelvic floor disorders often coexist in the same woman. of incontinence was highest in Hispanic women (36%), fol-
In community-dwelling women, 23.7% report symptoms lowed by white (30%), black (25%), and Asian (19%) women.
of one or more pelvic floor disorders. By specific condi- Fenner et al. (2008) also reported that a significantly higher
tion, the co-occurrence of having at least one other pelvic proportion of white women reported stress incontinence
floor disorder is 80% in women with stress incontinence compared to black women (39% versus 25%). However, two
or overactive bladder, 69% with pelvic organ prolapse, and other studies found no difference in pelvic floor disorders
48% with anal incontinence. Fifty-six percent of women among racial/ethnic groups (Nygaard et al., 2008). A large
report both stress incontinence and overactive bladder, epidemiologic study assessing fecal incontinence symptoms
58% report both stress incontinence and anal incontinence, also found no difference by race (Whitehead et al., 2009).
56% report overactive bladder and anal incontinence, and Differences in physiologic makeup may predispose some
29% report pelvic organ prolapse and any incontinence racial and ethnic groups to pelvic floor disorders. MRI mea-
(Lawrence et al., 2008). surements of bony architecture and soft tissue show that
100 PART 2  Basic Science

white women have a wider pelvic inlet, wider outlet, and conducted a longitudinal cohort study following women
shallower anteroposterior outlet than African American for 5 to 10 years from first delivery. When compared with
women (Handa et al., 2008). When compared to white cesarean delivery without labor, spontaneous vaginal birth
women, African American women also demonstrated a 29% was associated with higher odds of stress incontinence (OR
higher average urethral closure pressure during a maximum 2.9 (95% CI, 1.5-5.5)) and prolapse at or beyond the hymen
pelvic muscle contraction (Howard et al., 2000). (OR 5.6 (95% CI, 2.2-14.7)). Operative vaginal deliveries
and perineal lacerations have also been associated with pel-
vic floor disorders. Borello-France et al. (2006) reported
Age
that women with anal sphincter injuries after vaginal deliv-
There is a significant increase in the prevalence of pelvic ery were twice as likely to report postpartum fecal inconti-
floor disorders by age, increasing from 9.7% (95% CI, 7.8%- nence compared to women without sphincter tears.
11.7%) in women aged 20 to 39 years, to 26.5% (95% CI, Regarding potential mechanisms of injury after vaginal
23.0%-29.9%) in women aged 40 to 59 years, to 36.8% (95% delivery, DeLancey et al. (2007) found that women with
CI, 32.0%-41.6%) in women aged 60 to 79 years, to 49.7% prolapse have more frequent defects in the levator ani mus-
(95% CI, 40.3%-59.1%) in women aged 80 years or older cles and generate less vaginal closure force during a maximal
(P < 0.001; Nygaard et al., 2008). For urinary incontinence, contraction than controls. In a study using four-dimensional
the prevalence increases from 17% to 32% for women aged translabial ultrasound and pelvic exam, it was found that
40 to 59 years versus women over 80 years of age. White- women with levator ani avulsion defects had an increased
head et al. (2009) reported that for anal incontinence, the risk of stage II or higher pelvic organ prolapse (Dietz et al.,
prevalence increases from 2.6% at ages 20 to 30 years to 2008). This association was strongest for cystocele (RR 2.3,
15.3% in people aged 70 years or older. 95% CI, 2.0-2.7) and uterine prolapse (RR 4.0, 95% CI,
2.5-6.5).
Familial and Genetic Linkage
Constipation
Epidemiologic evidence suggests that family history of pro-
lapse is a risk factor for disease, and a meta-analysis includ- Constipation and straining associated with constipation has
ing eight studies with over one thousand prolapse patients been associated with pelvic organ prolapse. Indeed, many
showed that women with prolapse are more likely to have providers may counsel patients to avoid constipation and
family members with the same condition when compared related straining at stool to reduce the risk of prolapse.
to controls (Lince et al., 2012). Family based studies have However, whether the association between constipation
shown there is an autosomal dominant inheritance of pelvic and prolapse is causal remains unclear. There are variable
floor disorders. In addition, candidate gene studies, expres- definitions of constipation as well as the use of nonspecific
sion studies, and linkage studies have all been suggestive of definitions for bowel function disorders. In addition, treat-
a genetic contribution to pelvic organ prolapse (Allen-Brady ments of prolapse, including rectocele repair and sacral col-
et al., 2011). popexy, have variable results on improving and/or resolving
Candidate gene studies have focused on collagen and constipation and bowel symptoms.
elastin biosynthesis, extracellular matrix metabolism, and
hormone receptors. For example, it is understood that
Obesity
collagen is one of the main constituents of the connective
tissue in the pelvic floor, with type I collagen being well Increased body mass index (BMI) is a risk factor for pel-
organized, and type III collagen being common in loose vic floor disorders. Many studies have shown that obesity
areolar tissue. In histologic studies, higher levels of type III is a risk factor for urinary incontinence. In addition, sev-
collagen have been found in pelvic floor connective tissue eral studies have shown that both stress and urge inconti-
for women with pelvic organ prolapse (Norton et al., 1992; nence improve when patients lose weight through lifestyle
Moalli et al., 2005). In candidate gene studies, it appears changes and/or bariatric surgery (Greer et al., 2008; Whit-
that gene expression of the gene that encodes the chains of comb et al., 2012). In a clinical trial of women randomized
type III collagen may be variable and therefore put women to an active weight loss program compared to educational
at higher risk for pelvic organ prolapse (Chen et al., 2008). materials, weight loss was associated with improvements in
incontinence episodes among overweight and obese women
(Subak et al., 2009).
Childbirth
A cross-sectional study of postmenopausal women who
Perhaps secondary to increased abdominal pressure and/or enrolled in the WHI Hormone Therapy Clinical Trial found
connective tissue changes, pregnancy itself has been shown an increased risk of prolapse in women with a BMI of 25
to be a risk factor for pelvic floor disorders. However, the or higher (Hendrix et al., 2002). To further understand the
major inciting factor for pelvic floor disorders in parous longitudinal effects of obesity on prolapse, Kudish et al.
women is likely childbirth. Nygaard et al. (2008) reported (2009) performed a secondary analysis of the WHI data to
that the proportion of women reporting at least one pelvic evaluate the relationship between change in weight and pro-
floor disorder increased incrementally with parity: 12.8%, lapse progression/regression in postmenopausal women dur-
18.4%, 24.6%, and 32.4% for 0, 1, 2, and 3 or more deliver- ing a 5-year period. They found being overweight or obese
ies, respectively (P < 0.001). was highly associated with the progression of prolapse when
To further evaluate the association between pelvic compared to women with a healthy BMI. However, weight
floor disorders and mode of delivery, Handa et al. (2012) loss was not associated with prolapse regression.
CHAPTER 7  Epidemiology and Psychosocial Impact of Female Pelvic Floor Disorders 101

With regards to anal incontinence, Richter et al. (2005) Recently, The Cochrane Incontinence Review Group
found prevalence rates to be high among morbidly obese summarized all studies up to June 2012 (Cody et al., 2012).
women compared to the general population. In looking They concluded that urinary incontinence may be improved
at the effect of weight loss surgery on fecal incontinence, with the use of local estrogen treatment, although long-
bariatric surgery in morbidly obese women was associated term effects are unknown. Conversely, systemic hormone
with a decrease in fecal incontinence (solid or liquid stool) replacement therapy using conjugated equine estrogen may
from 19.4% to 9.1% at 6 months and 8.6% at 12 months worsen incontinence. There are too few data to reliably
(P = 0.018; 95% CI, 2.1-19.4%) (Burgio et al., 2007). address other aspects of estrogen therapy, such as estrogen
type and dose, and no direct evidence comparing routes
of administration. The risk of endometrial and breast can-
Smoking
cer after long-term use of systemic estrogen suggests that
Several studies suggest a positive association between smok- treatment should be for limited periods, especially in those
ing and urinary incontinence. A large population-based study, women with an intact uterus.
the Norwegian Epidemiology of Incontinence in the County
of Nord-Trøndelag (EPINCONT) study, investigated the Psychosocial Impact of Pelvic Floor
association between modifiable lifestyle factors such as smok-
ing and urinary incontinence. In this study both former and
Disorders
current smoking was associated with incontinence, limited to
those women who smoked 20 cigarettes a day or who had Our women’s problems have been shoved under the rug
a 15-year pack history, suggesting a dose-response relation- for so many years. And that’s what I did for a long time
ship (Hannestad et al., 2003). The EPINCONT study found too because I was so embarrassed.
that the effect of smoking on incontinence was reduced after Anonymous Patient, 2008
adjusting for coughing and dyspnea; however, there was a per-
sistent effect from smoking not mediated by airway disorders. The societal and personal burdens of pelvic floor dis-
orders and their associated treatments lie in their major
impact on quality of life and functioning. Pelvic floor dis-
Menopause/Hormone Replacement Therapy
orders can have a negative impact on a woman’s physical,
The female genital tract and the lower urinary tract arise social, emotional, and sexual function. Figure 7.2 is an
from the same embryologic origin and thus are both sensi- abbreviated framework of effects of urinary incontinence
tive to the effects of sex hormones. Transition to a hypoes- on a woman’s life. It is likely that anal incontinence and
trogenic state during menopause leads to changes in the pelvic organ prolapse have similar and overlapping effects.
vaginal and urethral mucosa. This could theoretically impact These conditions can interfere with both participation and
the development of incontinence. Sherburn et al. (2001) satisfaction with physical and social activities. Women
reported on a population-based cohort of women who may restrict or completely eliminate activities outside of
experienced menopausal transition and found no associa- the home. At the most severe end, women may become
tion with the development of urinary incontinence. This is increasingly isolated and homebound. Many studies also
consistent with other epidemiologic studies that have not have documented the association between incontinence
found an association between the onset of menopause and and depressive symptoms.
an increase in urinary incontinence. It is possible that the For physical function and activities, many women may
effects of a hypoestrogenic state may not be apparent in the still do the activities, particularly those associated with
first few years. In addition, menopause is associated with responsibility. However, they may limit their extent of par-
age, making it difficult to separate any independent effects ticipation (for example, they may not exercise or participate
of hormonal changes and aging. as long as they would like). Studies have shown that inconti-
Although systemic vaginal estrogen was in the past often nence is a barrier to physical activities (Nygaard et al., 2005)
promoted as beneficial for lower urinary tract symptoms, and that treatment is associated with improvements in both
more recently the role of estrogen has become less clear. physical functioning and physical activity levels (Sung et al.,
In the HERS study, exogenous estrogen and progesterone 2012).
were associated with worsening incontinence (39% ver- In addition to restricting their activities, many women
sus 27%, P = 0.001). This was evident by four months of develop coping and adaptive methods to minimize the
treatment and true for both urge and stress incontinence impact of these conditions (Wren et al., 2006). This may
symptoms (Grady et al., 2001). Similarly, in the WHI, Hen- include extensive preparation prior to certain activities (for
drix et al. (2005) found that exogenous hormone therapy example, voiding multiple times, wearing protection and
increased the risk of all types of urinary incontinence at 1 extra clothes prior to exercise) or other dietary and behav-
year in women who were continent at baseline. They found ioral changes (for example, restricting fluid intake prior to
that the risk was highest for stress incontinence (estrogen certain activities).
and progesterone: RR, 1.87 (95% CI, 1.61-2.18); estrogen Sexual function is also negatively impacted by these con-
alone: RR, 2.15 (95% CI, 1.77-2.62)), followed by mixed ditions. Incontinence and prolapse may be a direct cause
incontinence (estrogen and progesterone: RR, 1.49 (95% of sexual dysfunction due to physical discomfort, or these
CI, 1.10-2.01); estrogen alone: RR, 1.79 (95% CI, 1.26- conditions may cause embarrassment leading to avoidance
2.53)). They also found that menopausal hormone therapy of intimacy and sexual relations. Treatment has been associ-
worsened the severity of incontinence among symptomatic ated with improvements in sexual function, but not all stud-
women after 1 year. ies demonstrate significant improvement.
102 PART 2  Basic Science

Physical activities
(performance)
Physical health Physical function
Participation

Satisfaction
Social function

Social
relationships Social activities
(performance)
Social health Role functioning Participation

Satisfaction
Sexual function

Occupational
function
Embarrassment

Self-reported Emotional distress Depression


health Annoyance

Mental health Cognitive function Preoccupation

Positive
psychological Coping
function

Lifestyle

Daily life function Preparation

Sleep/wake
function

External mediators Quantity, quality of social support, environment

Symptoms Bother
FIGURE 7.2  Conceptual framework for impact of incontinence on a woman’s life. (Adapted from Sung VW, Rogers R, Williams DA, Clark MA.
Content validation of the Patient Reported Outcomes Measurements Information System (PROMIS) framework in women with urinary incontinence.
Neuro Urodyn. 2001;30:503.)

In elderly women, these disorders, particularly urinary Borello-France D, Burgio KL, Richter HE, et al. Fecal and urinary inconti-
or anal incontinence, may lead to such disability and depen- nence in primiparous women. Obstet Gynecol. 2006;108:863.
Bradley CS, Nygaard IE. Vaginal wall descensus and pelvic floor symptoms
dency that caregivers are no longer able to provide the nec- in older women. Obstet Gynecol. 2005;106:759.
essary care. Therefore, incontinence is a major factor leading Bradley CS, Zimmerman MB, Qi Y, Nygaard IE. Natural history of pelvic
to the institutionalization of elderly patients. organ prolapse in postmenopausal women. Obstet Gynecol. 2007;109:
Ultimately, how pelvic floor disorders impact a woman’s 848.
Brown JS, Grady D, Ouslander JG, et al. Prevalence of urinary incontinence
life depends on multiple factors including the severity of and associated risk factors in postmenopausal women. Heart & Estrogen/
symptoms, the individual’s coping mechanisms, and a host Progestin Replacement Study (HERS) Research Group. Obstet Gynecol.
of external mediators. However, it is clear that these condi- 1999;94:66.
tions can have far-reaching effects on a woman’s functioning Brown JS, Seeley DG, Fong J, et al. Urinary incontinence in older women:
and quality of life. who is at risk? Study of Osteoporotic Fractures Research Group. Obstet
Gynecol. 1996;87:715.
Burgio KL, Richter HE, Clements RH, et al. Changes in urinary and fecal
Bibligraphy incontinence symptoms with weight loss surgery in morbidly obese
Allen-Brady K, Cannon-Albright L, Farnham JM, et al. Identification of six women. Obstet Gynecol. 2007;110:1034.
loci associated with pelvic organ prolapse using genome-wide association Cardozo L, Khoury S, Wein AJ, eds. Incontinence: 4th International
analysis. Obstet Gynecol. 2011;118:1345. Consultation on Incontinence. Paris, France: Health Publication Ltd;
Barber MD, Kuchibhatla MN, Pieper CF, Bump RC. Psychometric evalua- 2009:35–112.
tion of 2 comprehensive condition-specific quality of life instruments for Chen HY, Chung YW, Lin WY, Wang JC, Tsai FJ, Tsai CH. Collagen type
women with pelvic floor disorders. Am J Obstet Gynecol. 2001;185:1388. 3 alpha 1 polymorphism and risk of pelvic organ prolapse. Int J Gynaecol
Blandon RE, Bharucha AE, Melton 3rd LJ, et al. Risk factors for pelvic floor Obstet. 2008;103:55.
repair after hysterectomy. Obstet Gynecol. 2009;113:601. Chiaffarino F, Chatenoud L, Dindelli M, et al. Reproductive factors, family
Bø K. Urinary incontinence, pelvic floor dysfunction, exercise and sport. history, occupation and risk of urogenital prolapse. Eur J Obstet Gynecol
Sports Med. 2004;34:451. Reprod Biol. 1999;82:63.
CHAPTER 7  Epidemiology and Psychosocial Impact of Female Pelvic Floor Disorders 103

Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen Markland AD, Goode PS, Burgio KL, et al. Incidence and risk factors for
therapy for urinary incontinence in post-menopausal women. Cochrane fecal incontinence in black and white older adults: a population-based
Database Syst Rev. October 17, 2012;10:CD001405. study. J Am Geriatr Soc. 2010;58:1341.
DeLancey JO, Morgan DM, Fenner DE, et al. Comparison of levator ani Markland AD, Richter HE, Fwu C, Eggers P, Kusek JW. Prevalence and
muscle defects and function in women with and without pelvic organ trends of urinary incontinence in adults in the United States, 2001 to
prolapse. Obstet Gynecol. 2007;109:295. 2008. J Urol. 2011;186:589.
Dietz HP, Simpson JM. Levator trauma is associated with pelvic organ pro- McLennan MT, Harris JK, Kariuki B, et al. Family history as a risk fac-
lapse. BJOG. 2008;115:979. tor for pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct.
Fenner DE, Trowbridge ER, Patel DA, et al. Establishing the prevalence 2008;19:1063.
of incontinence study: racial differences in women’s patterns of urinary Mellgren A, Jensen LL, Zetterstrom JP, Wong WD, Hofmeister JH, Lowry
incontinence. J Urol. 2008;179:1455. AC. Long-term cost of fecal incontinence secondary to obstetric injuries.
Grady D, Brown JS, Vittinghoff E, Applegate W, Varner E, Snyder T, HERS Dis Colon Rectum. 1999;42:857.
Research Group. Postmenopausal hormones and incontinence: the heart Melville JL, Katon W, Delaney K, et al. Urinary incontinence in US women.
and estrogen/progestin replacement study. Obstet Gynecol. 2001;97:116. Arch Intern Med. 2005;165:537.
Greer WJ, Richter HE, Bartolucci AA, et al. Obesity and pelvic floor disor- Milsom I, Altman D, Lapitan MC, Nelson R, Sillen U, Thom DH. Epidemi-
ders: a systematic review. Obstet Gynecol. 2008;112:341. ology of urinary (UI) and faecal (FI) incontinence and pelvic organ pro-
Handa VL, Blomquist JL, Knoepp LR, Hoskey KA, McDermott KC, Muñoz lapse (POP). In: Abrams P, Milsom I, eds. Lower Urinary Tract Symptoms
A. Pelvic floor disorders 5–10 years after vaginal or Cesarean childbirth. in Women. Curr Opin Urol; ;19; 2009:337.
Obstet Gynecol. 2011;118:777. Minassian VA, Stewart WF, Wood GC. Urinary incontinence in women:
Handa VL, Blomquist JL, McDermott KC, Friedman S, Muñoz A. Pelvic variation in prevalence estimates and risk factors. Obstet Gynecol.
floor disorders after vaginal birth: effect of episiotomy, perineal lacera- 2008;111:324.
tion, and operative birth. Obstet Gynecol. 2012;119:233. Moalli PA, Jones Ivy S, Meyn LA, Zyczynski HM. Risk factors associated
Handa VL, Garrett E, Hendrix S, Gold E, Robbins J. Progression and remis- with pelvic floor disorders in women undergoing surgical repair. Obstet
sion of pelvic organ prolapse: a longitudinal study of menopausal women. Gynecol. 2003;101:869.
Am J Obstet Gynecol. 2004;190:27. Moalli PA, Shand SH, Zyczynski HM, Gordy SC, Meyn LA. Remodeling
Handa VL, Lockhart ME, Fielding JR, et al. Racial differences in pelvic of vaginal connective tissue in patients with prolapse. Obstet Gynecol.
anatomy by magnetic resonance imaging. Obstet Gynecol. 2008;111:914. 2005;106:953.
Hannestad YS, Rortveit G, Daltveit AK. Are smoking and other lifestyle Norton P, Allen-Brady K, Cannon-Albright L. Significant linkage evidence
factors associated with female urinary incontinence? The Norwegian of a predisposition gene for pelvic floor disorders on chromosome 9.
EPINCONT study. BJOG. 2003;110:247. J Pelvic Med Surg. 2008;14:219.
Hendrix SL, Clark A, Nygaard I, et al. Pelvic organ prolapse in the Norton P, Boyd C, Deak S. Abnormal collagen ratios in women with genito-
Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol. urinary prolapse. Neurourol Urodyn. 1992;11:2.
2002;186:1160. Nygaard I, Barber MD, Burgio KL, et al. Prevalence of symptomatic pelvic
Hendrix SL, Cochrane BB, Nygaard IE, et al. Effects of estrogen with and floor disorders in US women. JAMA. 2008;300:1311.
without progestin on urinary incontinence. JAMA. 2005;293:935. Nygaard I, Girts T, Fultz NH, Kinchen K, Pohl G, Sternfeld B. Is uri-
Howard D, Delancey JO, Tunn R, et al. Racial differences in the structure nary incontinence a barrier to exercise in women? Obstet Gynecol.
and function of the stress urinary continence mechanism. Obstet Gynecol. 2005;106:307.
2000;95:713. Richter HE, Burgio KL, Brubaker L, et al. Factors associated with inconti-
Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence nence frequency in a surgical cohort of stress incontinent women. Am J
estimates of lower urinary tract symptoms, overactive bladder, urinary Obstet Gynecol. 2005;193:2088.
incontinence and bladder outlet obstruction. BJU Int. 2011;108:1132. Richter HE, Burgio KL, Clements RH, et al. Urinary and anal incontinence
Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary in morbidly obese women considering weight loss surgery. Obstet Gyne-
incontinence, overactive bladder, and other lower urinary tract symptoms col. 2005;106:1272.
in five countries: results of the EPIC study. Eur Urol. 2006;50:1306; Robinson D, Cardozo L. Estrogens and the lower urinary tract. Neurourol
discussion Urodyn. 2011;30:754.
Irwin DE, Mungapen L, Milsom I, Kopp Z, Reeves P, Kelleher C. The eco- Rogers RG, Kammerer-Doak D, Villarreal A, Coates K, Qualls C. A new
nomic impact of overactive bladder syndrome in six western countries. instrument to measure sexual function in women with urinary inconti-
BJU Int. 2009;103:202. nence or pelvic organ prolapse. Am J Obstet Gynecol. 2001;184:552.
Jelovsek JE, Walters MD, Paraiso MF, Barber MD. Functional bowel disor- Rortveit G, Brown JS, Thom DH, et al. Symptomatic pelvic organ prolapse:
ders and pelvic organ prolapse: a case-control study. Female Pelvic Med prevalence and risk factors in a population-based, racially diverse cohort.
Reconstr Surg. 2010;16:209. Obstet Gynecol. 2007;109:1396.
Kim S, Harvey MA, Johnston S. Review of the epidemiology and patho- Schaffer JI, Wai CY, Boreham MK. Etiology of pelvic organ prolapse. Clin
physiology of pelvic floor dysfunction: do racial differences matter? Obstet Gynecol. 2005;48:639–647.
J Obstet Gynaecol Can. 2005;27:251. Sherburn M, Guthrie JR, Dudley EC, et al. Is incontinence associated with
Komesu YM, Rogers RG, Schrader RM, Lewis CM. Incidence and remission menopause? Obstet Gynecol. 2001;98:628.
of urinary incontinence in a community-based population of women ≥50 Shumaker SA, Wyman JF, Uebersax JS, McClish D, Fantl JA. Health-related
years. Urogynecol J Pelvic Floor Dysfunct. 2009;20:581. quality of life measures for women with urinary incontinence: the inconti-
Kruger JA, Dietz HP, Murphy BA. Pelvic floor function in elite nulliparous nence impact questionnaire and the urogenital distress inventory. Continence
athletes. Ultrasound Obstet Gynecol. 2007;30:81. Program in Women (CPW) Research Group. Qual Life Res. 1994;3:291.
Kudish BI, Iglesia CB, Sokol RJ, et al. Effect of weight change on natural Slieker-ten Hove MC, Pool-Goudzwaard AL, Eijkemans MJ, Steegers-
history of pelvic organ prolapse. Obstet Gynecol. 2009;113:81. Theunissen RP, Burger CW, Vierhout ME. Pelvic floor muscle function in
Lawrence JM, Lukacz ES, Nager CW, Hsu JW, Luber KM. Prevalence and a general female population in relation with age and parity and the rela-
co-occurrence of pelvic floor disorders in community-dwelling women. tion between voluntary and involuntary contractions of the pelvic floor
Obstet Gynecol. 2008;111:678. musculature. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20:1497.
Lifford KL, Townsend MK, Curhan GC, Resnick NM, Grodstein F. The Snooks SJ, Barnes PR, Swash M, et al. Damage to the innervation of the
epidemiology of urinary incontinence in older women: incidence, progres- pelvic floor musculature in chronic constipation. Gastroenterology.
sion, and remission. J Am Geriatr Soc. 2008;56:1191. 1985;89:977.
Lince SL, van Kempen LC, Vierhout ME, Kluivers KB. A systematic review Solans-Domenech M, Sanchez E, Espuna-Pons M. Urinary and anal incon-
of clinical studies on hereditary factors in pelvic organ prolapse. Int Uro- tinence during pregnancy and postpartum: incidence, severity, and risk
gynecol J. 2012;23:1327. factors. Obstet Gynecol. 2010;115:618.
Liu X, Zhao Y, Pawlyk B, Damaser M, Li T. Failure of elastic fiber homeo- Spence-Jones C, Kamm MA, Henry MM, et al. Bowel dysfunction: a patho-
stasis leads to pelvic floor disorders. Am J Pathol. 2006;168:519. genic factor in uterovaginal prolapse and urinary stress incontinence.
Lubowski DZ, Swash M, Nicholls RJ, et al. Increase in pudendal BJOG. 1994;101:147.
nerve ­ terminal motor latency with defaecation straining. Br J Surg. Steers WD, Lee KS. Depression and incontinence. World J Urol.
1988;75:1095. 2001;19:351.
104 PART 2  Basic Science

Subak LL, Brubaker L, Chai TC, et al. High costs of urinary incontinence Townsend MK, Danforth KN, Lifford KL, et al. Incidence and remission
among women electing surgery to treat stress incontinence. Obstet Gyne- of urinary incontinence in middle-aged women. Am J Obstet Gynecol.
col. 2008;111:899. 2007;197:167e1.
Subak LL, Marinilli Pinto A, Wing RR, et al. Decrease in urinary inconti- Townsend MK, Danforth KN, Rosner B, et al. Physical activity and incident
nence management costs in women enrolled in a clinical trial of weight urinary incontinence in middle-aged women. J Urol. 2008;179:1012.
loss to treat urinary incontinence. Obstet Gynecol. 2012;120:277. Varma MG, Brown JS, Creasman JM, et al. Fecal incontinence in females
Subak LL, Waetjen LE, van den Eeden S, Thom DH, Vittinghoff E, Brown older than aged 40 years: who is at risk? Dis Colon Rectum. 2006;49:841.
JS. Cost of pelvic organ prolapse surgery in the United States. Obstet Waetjen LE, Liao S, Johnson WO, et al. Factors associated with prevalent
Gynecol. 2001;98:646. and incident urinary incontinence in a cohort of midlife women: a longi-
Subak LL, Wing R, West DS, PRIDE Investigators, et al. Weight loss to treat tudinal analysis of data: study of women’s health across the nation. Am J
urinary incontinence in overweight and obese women. N Engl J Med. Epidemiol. 2007;165:309.
2009;360:481. Weber AM, Walters MD, Ballard LA, et al. Posterior vaginal prolapse and
Sung VW, Kassis N, Raker CA. Improvements in physical activity and func- bowel function. Am J Obstet Gynecol. 1998;179:1446.
tioning after undergoing midurethral sling procedure for urinary inconti- Whitcomb EL, Horgan S, Donohue MC, Lukacz ES. Impact of surgi-
nence. Obstet Gynecol. 2012;120:573. cally induced weight loss on pelvic floor disorders. Int Urogynecol J.
Sung VW, Rogers ML, Myers DL, Akbari HM, Clark MA. National trends 2012;23:1111.
and costs of surgical treatment for female fecal incontinence. Am J Obstet Whitcomb EL, Rortveit G, Brown JS, et al. Racial differences in pelvic organ
Gynecol. 2007;197:652e1. prolapse. Obstet Gynecol. 2009;114:1271.
Sung VW, Rogers R, Williams DA, Clark MA. Content validation of the Whitehead WE, Borrud L, Goode PS, Pelvic Floor Disorders Network, et al.
Patient-Reported Outcomes Measurement Information System (PRO- Fecal incontinence in US adults: epidemiology and risk factors. Gastroen-
MIS) framework in women with urinary incontinence. Neurourol terology. 2009;137:512.e1–512.e2.
­Urodyn. 2011;30:503. Wilson L, Brown JS, Shin GP, Luc KO, Subak LL. Annual direct cost of
Sung VW, West DS, Hernandez AL, Wheeler TL, Myers DL, Subak LL. urinary incontinence. Obstet Gynecol. 2001;98:398.
Association between urinary incontinence and depressive symptoms in Woodman PJ, Swift SE, O’Boyle AL, et al. Prevalence of severe pelvic
overweight and obese women. AJOG. 2009;200:557e1. organ prolapse in relation to job description and socioeconomic status: a
Swift SE, Tate SB, Nicholas J. Correlation of symptoms with degree of pel- multicenter cross-sectional study. Int Urogynecol J Pelvic Floor Dysfunct.
vic organ support in a general population of women: what is pelvic organ 2006;17:340.
prolapse?. Am J Obstet Gynecol. 2003;189:372; discussion Wren PA, Janz NK, Brubaker L, et al. Development of the Measure of Adap-
Swift S, Woodman P, O’Boyle A, et al. Pelvic Organ Support Study tations for Pelvic Symptoms (MAPS): the importance of incorporating
(POSST): the distribution, clinical definition, and epidemiologic condi- the female patient’s voice. Appl Res Qual Life. 2006;1:239.
tion of pelvic organ support defects. Am J Obstet Gynecol. 2005;192:795. Wu JM, Hundley AF, Fulton RG, Myers ER. Forecasting the prevalence
Sze EH, Jones WP, Ferguson JL, et al. Prevalence of urinary incontinence of pelvic floor disorders in U.S. women: 2010–2050. Obstet Gynecol.
symptoms among black, white, and Hispanic women. Obstet Gynecol. 2009;114:1278.
2002;99:572. Wu JM, Kawasaki A, Hundley AF, Dieter AA, Myers ER, Sung VW. Predict-
Thom DH, Brown JS. Reproductive and hormonal risk factors for urinary ing the number of women who will undergo incontinence and prolapse
incontinence in later life: a review of the clinical and epidemiologic litera- surgery, 2010 to 2050. Am J Obstet Gynecol. 2011;205:230.e1–230.e5.
ture. J Am Geriatr Soc. 1998;46:1411. Wu JM, Visco AG, Grass EA, et al. Comprehensive analysis of LAMC1
Thom DH, van den Eeden SK, Ragins AI, et al. Differences in prevalence of genetic variants in advanced pelvic organ prolapse. Am J Obstet Gynecol.
urinary incontinence by race/ethnicity. J Urol. 2006;175:259. 2012;206:447.e1–447.e6.
Thom DH, Nygaard IE, Calhoun EA. Urologic diseases in America project:
urinary incontinence in women-national trends in hospitalizations, office
visits, treatment and economic impact. J Urol. 2005;173:1295.
CHAPTER 8

Description and
Classification of
Lower Urinary
Tract Dysfunction
and Pelvic Organ
Prolapse
Mark D. Walters
Cecile A. Unger

Classification Systems of Lower Urinary Chapter Outline


Tract Dysfunction
The purpose of any classification system is to facilitate Classification Systems of Lower Urinary Tract
understanding of the etiology and pathophysiology of dis- Dysfunction
ease, to help establish and standardize treatment and International Continence Society Classification
research guidelines, and to avoid confusion among those Filling and Storage Phase
who are concerned with the problem. A number of clas- Voiding Phase
sification systems for voiding disorders and stress urinary
Functional Classification
incontinence have been developed. These classifications
have been based on various symptoms, as well as anatomic, Differential Diagnosis of Urinary Incontinence
radiographic, and urodynamic findings. The advantages, Description and Staging of Pelvic Organ
disadvantages, and applicability of the various classification Prolapse
systems of voiding dysfunction were described by Wein and
Barrett (1988). This chapter reviews two practical systems Classification System of Complications Related
for the classification of voiding dysfunction in women. In to Insertion of Vaginal Prostheses and Grafts
addition, the differential diagnosis of urinary incontinence
in women is discussed utilizing updated terminology from
the International Continence Society (ICS). Last, the ICS
classification system of vaginal prostheses and graft com- between a woman’s symptoms, signs, and relevant diagnos-
plications is presented. It is hoped that the nomenclature tic investigations. For example, stress urinary incontinence is
used in these classification systems will become more the complaint of involuntary loss of urine with increases in
widely understood and used and that further research will intra-abdominal pressures from physical exertion, laughing,
be aimed at defining their clinical applicability. sneezing, and coughing, whereas urodynamic stress incon-
tinence is a diagnosis by symptoms, signs, and urodynamic
testing and involves the finding of involuntary leakage with
International Continence Society
increases in intra-abdominal pressure during filling cystom-
Classification
etry in the absence of detrusor contractions. One must
In 1973, the ICS established a committee for the stan- understand these subtle differences in the definitions of
dardization of terminology of lower urinary tract function. incontinence when diagnosing and classifying patients. The
Five of the first six reports from this committee were pub- following is a summary of the ICS Committee’s most recent
lished. These reports were revised, extended, and collated findings.
in a monograph published in 1988 (see Appendix A). The The lower urinary tract is composed of the bladder and
definitions were updated and revised by the Standardiza- urethra, which work together as a functional unit to promote
tion Subcommittee of the ICS in 2002 and again in 2010 storage and emptying of urine. Symptoms, signs, urodynamic
(see Appendix B). Each report highlights the importance of observations, and conditions are separate categories with
basing diagnoses for pelvic floor disorders on the correlation unique but overlapping terminologies. Although a complete
105
106 PART 2  Basic Science

Abnormalities of storage and voiding phases


Box 8.1  The International Continence
Society Classification of Lower Urinary Tract
Storage phase Voiding phase
Dysfunction
Bladder
I. Storage phase
A. Bladder function during storage Normal Detrusor relaxation Detrusor contraction
1. Detrusor activity
a. Normal Abnormal Detrusor overactivity Detrusor underactivity
b. Overactive or acontractility
2. Bladder sensation
a. Normal Urethra
b. Increased (oversensitivity)
Normal Urethral sphincter Urethral sphincter
c. Reduced
contraction relaxation
d. Absent
e. Nonspecific bladder sensations Abnormal Sphincter incompetence Urethral obstruction,
f. Bladder pain (SUI or ISD) dysfunctional voiding,
g. Urgency detrusor sphincter
3. Bladder capacity dyssynergia
4. Bladder compliance
B. Urethral function during storage FIGURE 8.1  Abnormalities of storage and voiding phases. SUI, stress
1. Normal urinary incontinence; ISD, intrinsic sphincter deficiency.
2. Incompetent
3. Urethral relaxation (instability)
II. Voiding phase
Urethral function during storage can be assessed clini-
A. Detrusor function during voiding cally (direct observation of urine loss with cough or Valsalva
1. Normal maneuver), urodynamically (urethral closure pressure pro-
2. Abnormal filometry and leak point pressure measurements), or radio-
a. Underactive graphically (cystourethrography with or without video). The
b. Acontractile urethral closure mechanism may be competent or incom-
B. Urethral function during voiding petent. An incompetent urethral closure mechanism is one
1. Normal that allows leakage of urine during activities that may raise
2. Abnormal intra-abdominal pressures in the absence of a detrusor con-
a. Bladder outlet obstruction
traction. Involuntary leakage during filling cystometry may
b. Dysfunctional voiding
c. Detrusor sphincter dyssynergia
occur during increased abdominal pressure, in the absence
of a detrusor contraction (urodynamic stress incontinence),
or as a result of urethral relaxation in the presence of raised
abdominal pressure or detrusor overactivity (urethral relax-
urodynamic investigation is not necessary for all symptom- ation incontinence). The definition and significance of the
atic patients, some clinical or urodynamic assessment of the latter condition await additional data.
filling and voiding phases is essential for each patient. It is Urinary incontinence is the complaint of any involun-
useful to examine bladder and urethral activity separately tary (urethral or extraurethral) leakage of urine. Urinary
in each phase. If urodynamic studies are performed, results incontinence is a symptom, a sign, and a condition. Urinary
should clearly reflect the patient’s signs and symptoms. incontinence as a symptom means that the patient states she
has involuntary urine loss. Types of incontinence symptoms
Filling and Storage Phase include stress incontinence, urgency incontinence, mixed
The ICS classification of abnormalities of the storage and incontinence, nocturnal enuresis, situational incontinence,
voiding phases is outlined in Box 8.1 and diagrammed in and continuous incontinence. In each specific circumstance,
Figure 8.1. Cystometry measures the pressure–volume urinary incontinence should be described further by speci-
relationship of the bladder during filling and storage and fying relevant factors, such as type, frequency, severity,
assesses bladder function in terms of bladder sensation, precipitating factors, social impact, effect on hygiene and
detrusor activity, bladder capacity, and bladder compliance. quality of life, the measures used to contain leakage, and
Detrusor activity may be normal or overactive. Overactive whether or not the individual seeks or desires help because
detrusor function is characterized by involuntary detrusor con- of urinary incontinence. The sign of stress incontinence
tractions during filling. They may be spontaneous or provoked denotes the observation of urine loss from the external ure-
and cannot be suppressed completely. Overactive detrusor thral meatus synchronously with physical exertion such as a
function in the absence of a known neurologic abnormality cough or Valsalva maneuver. Because symptoms and signs of
is called idiopathic detrusor overactivity; overactivity caused urinary incontinence can be misleading, accurate diagnosis
by disturbance of the nervous system control mechanisms often requires urodynamic investigation in addition to care-
is called neurogenic detrusor overactivity. These conditions ful history and physical examination.
often are associated with the symptom of urinary urgency.
Urgency, with or without urge incontinence, usually with fre- Voiding Phase
quency and nocturia in the absence of urinary tract infection During the voiding phase, the detrusor muscle may be nor-
or obvious pathology, is described as the overactive bladder mal, underactive, or acontractile. Normal voiding usually is
syndrome, urge syndrome, or urgency-frequency syndrome. achieved by an initial voluntary reduction in intraurethral
CHAPTER 8  Description and Classification of Lower Urinary Tract Dysfunction and Pelvic Organ Prolapse 107

pressure (urethral relaxation) followed by a continuous


Box 8.2  Expanded Functional Classification
detrusor contraction that leads to complete bladder empty-
ing within a normal time span and in the absence of obstruc- OUTLET DYSFUNCTION
tion. Detrusor underactivity during micturition implies that
UNDERACTIVE OUTLET (REDUCED URETHRAL RESISTANCE)
the detrusor contraction is of inadequate strength or dura-
tion to effect bladder emptying within a normal time span. Stress urinary incontinence*
Anatomic support defects
An acontractile detrusor is one that cannot be demonstrated
Intrinsic sphincter deficiency (ISD)
to contract during urodynamic studies, resulting in incom- Combination of anatomic support defects and ISD
plete bladder emptying. Pelvic floor underactivity (failure to inhibit the detrusor)
During voiding, urethral function may be normal or
abnormal. Abnormal urethral function may be due to either OVERACTIVE OUTLET (INCREASED URETHRAL RESISTANCE)
uncoordinated or involuntary urethral contractions, urethral Frequency-urgency, urinary retention, and overflow
stricture, or obstruction from an anatomic abnormality, incontinence*
such as severe pelvic organ prolapse or changes after a stress Anatomic obstruction
 Surgical
incontinence procedure.
 Congenital
Simultaneous measurement of intravesical or detrusor  Inflammatory
pressure and urine flow is necessary to determine whether  Neoplastic
the patient’s voiding is obstructed. In general, high detrusor  Traumatic
pressures with low flow rates suggest an obstructive prob- Functional obstruction
lem, whereas low detrusor pressures with low flow rates   Failure of urethra to relax
imply that the problem is one of detrusor underactivity   Neurogenic—detrusor-sphincter dyssynergia
or acontractility. Simultaneous external urethral sphincter  Behavioral
electromyography is necessary to determine whether an Combination of anatomic and functional obstruction
obstructive voiding pattern is secondary to urethral overac- Pelvic floor overactivity
tivity or mechanical obstruction. BLADDER DYSFUNCTION
DETRUSOR OVERACTIVITY
Functional Classification Urge-frequency, urgency urinary incontinence*
Involuntary detrusor contractions
Wein (1981) classified voiding dysfunction on a func-  Idiopathic
tional basis, describing the dysfunction simply in terms   Neurogenic—detrusor-sphincter dyssynergia
of whether the deficit is primarily one of the bladder Decreased bladder compliance
(detrusor) or bladder outlet (sphincter) during the filling  Fibrosis
and storage phase or the voiding and emptying phase. The  Inflammatory
expanded functional classification, with relevant symp-   Immune response
toms and pathophysiology as suggested by Staskin and  Neurogenic
Combination of involuntary detrusor contractions and decreased
Wein (2010), is shown in Box 8.2. This classification sys-
bladder compliance
tem takes into account pelvic floor activity in addition to
bladder and sphincter function. Classification of neurologic UNDERACTIVE DETRUSOR
voiding dysfunction also has been adapted into a functional Urinary retention*
classification system by Staskin and Wein (2010) and is Peripheral neuropathy
useful for the diagnosis and management of patients with  Congenital
primary neurologic disorders.  Trauma
A reasonably accurate urodynamic description is required  Neoplastic
 Diabetes
for proper use of a functional system for a given voiding
 Metabolic
problem, but an exact diagnosis is not required for treat- Detrusor myopathy
ment. Several deficits can be present in the same patient,  Fibrosis
and all of them must be recognized to properly use this clas-  Inflammatory
sification system.  Obstruction
Pharmacologic
Differential Diagnosis of Urinary  Antimuscarinics
  Muscle relaxants
Incontinence Pelvic floor overactivity
Among women complaining of urinary incontinence, the
Modified from Staskin DR, Wein AJ. Classification of lower urinary tract dysfunc-
differential diagnosis includes genitourinary and nongenito- tion in the female patient. In: Cardozo L, Staskin DR, eds. Textbook of Female
urinary conditions (Box 8.3). As mentioned, genitourinary Urology and Urogynecology. 3rd ed. London: Informa Healthcare; 2010.
disorders include problems of bladder filling and storage, as *Presenting symptoms
well as extraurethral disorders such as fistula and congenital
abnormalities. Nongenitourinary conditions that cause uri- The most common urine storage disorder in women is
nary incontinence generally are functional conditions that urodynamic stress incontinence. Bladder filling disorders
occur simultaneously with normal or abnormal urethral and caused by overactive detrusor function resulting in urgency
bladder function. These conditions are most common in urinary incontinence are the second most common cause of
elderly women. urinary incontinence. Underactive or acontractile detrusor
108 PART 2  Basic Science

Stress Detrusor overactivity


Box 8.3  Differential Diagnosis of Urinary incontinence and other
Incontinence in Women
100
GENITOURINARY ETIOLOGY
FILLING/STORAGE DISORDERS

incontinent women
80
Urodynamic stress incontinence

Percent of
Detrusor overactivity (idiopathic)
60
Detrusor overactivity (neurogenic)
Mixed types
40
FISTULA
Vesical 20
Ureteral
Urethral 0
CONGENITAL Healthy Ambulatory Institutionalized
Ectopic ureter adult elderly elderly
Epispadias FIGURE 8.2  Estimated likelihood of conditions causing incontinence
NONGENITOURINARY ETIOLOGY in women in various age categories.
Functional
 Neurologic
 Cognitive
women, occurring in 30% to 60% of cases. In a urodynamic
 Psychologic study of elderly community-dwelling women with inconti-
  Physical impairment nence, however, Diokno et al. (1988) reported a prevalence
Environmental of detrusor abnormalities of only 12%, probably reflecting a
Pharmacologic healthier group of women. Institutionalized elderly women
Metabolic who are incontinent have detrusor overactivity (with or with-
out impaired bladder contractility) in 38% to 60% of cases and
urodynamic stress incontinence in only 16% to 21% of cases.
function may result in voiding dysfunction or urinary incon-
tinence. The ICS no longer recommends the term “overflow Description and Staging of Pelvic
incontinence,” but, if it is used, a precise definition and any
associated pathophysiology, such as reduced urethral func-
Organ Prolapse
tion, or detrusor overactivity and low bladder compliance, Pelvic organ prolapse refers to descent of one or more of the
should be stated. Voiding disorders with incontinence in anterior vaginal wall, posterior vaginal wall, the uterus (cer-
women usually are associated with diabetes, neurologic dis- vix), or the apex of the vagina (cuff scar after hysterectomy).
eases, severe genital prolapse, or postsurgical obstruction. As with voiding dysfunction, a systematic description and
Functional incontinence is associated with cognitive, psy- classification of pelvic organ prolapse are useful to document
chologic, or physical impairments that make it difficult to and communicate the severity of the problem, establish
reach the toilet or interfere with appropriate toileting. With treatment guidelines, and improve the quality of research by
these conditions, continent women may not have enough time standardizing definitions. Two general classification systems
to avoid an accident. Functional causes also may act synergisti- are in use, although it is recommended that the ICS termi-
cally with other urinary problems. For example, women with nology be used routinely by clinicians and researchers.
manageable detrusor overactivity may become incontinent if For many years, the severity of pelvic organ prolapse has
another disease or physical problem keeps them from reaching been described using criteria modified from Beecham (1980)
the toilet. Physical conditions that may cause functional incon- and Baden et al. (1968). This grading system is simple to
tinence include joint abnormalities, arthritic pain, or muscu- use; it is widely understood among gynecologic surgeons and
lar weakness. An unfamiliar setting, lack of convenient toilet has been found to have reasonable interobserver variability
facilities, or other environmental factors can aggravate this for all segments of the vagina and for uterine support. The
condition. Dementia, psychologic difficulties, and repressed most dependent position of the pelvic organs during maxi-
or hostile behavior may be related to incontinence, especially mum straining or standing is used and graded as normal, or
in the institutionalized elderly. Finally, iatrogenic factors, such first, second, and third degree. First-degree prolapse is used
as pharmacotherapy, can cause or aggravate incontinence. for vaginal segments that descend halfway (but not to) the
The relative likelihood of each condition causing inconti- hymen; second-degree prolapse is used for descent to the
nence varies with the age and health of the individual (Fig. hymen; and third-degree prolapse is used for descent beyond
8.2). Among ambulatory incontinent women, the most com- the hymen. Classification of posterior vaginal wall prolapse
mon condition is urodynamic stress incontinence, which can be aided by performing a rectovaginal examination.
represents 50% to 70% of cases. Detrusor abnormalities and In 1996, Bump et al. described the ICS standardization
mixed forms (usually stress incontinence and detrusor overac- of terminology of female pelvic organ prolapse, with the
tivity) account for 20% to 40% of incontinence cases. Among most recent ICS revision published in 2010. The Pelvic
elderly, noninstitutionalized incontinent women evaluated in Organ Prolapse Quantification (POPQ) system is applied
referral centers, urodynamic stress incontinence is found less during physical examination of the external genitalia and
often (30% to 46%), and detrusor abnormalities and mixed vaginal canal and describes the topographic positions of
disorders are more common than in younger ambulatory six vaginal sites. It has been used among clinicians and
CHAPTER 8  Description and Classification of Lower Urinary Tract Dysfunction and Pelvic Organ Prolapse 109

researchers as a standard method of describing degree of


prolapse severity. Segments of the lower reproductive tract
replace the terms cystocele, enterocele, rectocele, and ure-
throvesical junction because these terms imply an unreal-
istic certainty as to the structures on the other side of the
vaginal bulge, particularly in women who have had previ-
ous prolapse surgery. Because most gynecologists continue
to use these terms to describe pelvic organ prolapse, they
remain incorporated in the ICS system. With the bladder
empty, the examiner sees and describes the maximum pro-
trusion noted by the patient during her daily activities. The
hymen remains the fixed point of reference for prolapse
description. The details of the examination, including cri-
teria for the endpoint of the examination and full devel-
opment of the prolapse, should be specified. Suggested
criteria for demonstration of maximum prolapse include
one or all of the following: protrusion of the vaginal wall
becomes tight during straining by the patient; traction on
the prolapse causes no further descent; the subject con- FIGURE 8.3  Six sites (points Aa, Ba, C, D, Bp, and Ap), genital hiatus
firms that the size of the prolapse and the extent of the (gh), perineal body (pb), and total vaginal length (tvl) used for pelvic
protrusion seen by the examiner are as extensive as the organ support quantitation.
most severe protrusion she has had (a small handheld mir-
ror to visualize the protrusion may be helpful); and a stand- a positive value equal to the position of the cuff in
ing or straining examination confirms that the full extent women with total posthysterectomy vaginal eversion.
of the prolapse was observed in the other positions used. Two points are on the superior vagina. These points rep-
Details about the patient position, types of vaginal specula resent the most proximal locations of the normally posi-
or retractors, the type and intensity of straining used to tioned lower reproductive tract and describe uterine or
develop the prolapse maximally, and the fullness of the cervical and vaginal vault (cuff scar) prolapse.
bladder should be reported. Point C: A point that represents either the most distal
The POPQ system is a series of site-specific measure- (i.e., most dependent) edge of the cervix or the lead-
ments of the woman’s pelvic organ support. It can be ing edge of the vaginal cuff (hysterectomy scar) after
learned easily and taught by means of a video tutorial. Pro- total hysterectomy.
lapse in each segment is evaluated and measured relative Point D: A point that represents the location of the posterior
to the hymen (not introitus), which is a fixed anatomic fornix in a woman who still has a cervix. It represents a
landmark that can be identified consistently and precisely. level of uterosacral ligament attachment to the proximal
The anatomic position of the six defined points for mea- posterior cervix. It is included as a point of measurement
surement should be centimeters above or proximal to the to differentiate suspensory failure of the uterosacral car-
hymen (negative number) or centimeters below or distal to dinal ligament complex from cervical elongation. Point
the hymen (positive number), with the plane of the hymen D is omitted in the absence of the cervix.
being defined as zero. For example, a cervix that protrudes Two points are located on the posterior vaginal wall. Pos-
3 cm distal to the hymen should be described as +3 cm. terior vaginal wall descent often is due to rectal protrusion
Six points (two on the anterior vaginal wall, two in the into the vagina (rectocele) with higher stage prolapse usu-
superior vagina, and two on the posterior vaginal wall) are ally involving prolapse of the vaginal vault or an enterocele.
located with reference to the plane of the hymen (Fig. 8.3). Analogous to anterior prolapse, posterior prolapse should be
Descent of the anterior vaginal wall is most commonly a discussed in terms of segments of the vaginal wall rather than
result of bladder prolapse (cystocele), whereas higher stage the organs that lie behind it. Thus, the term posterior vaginal
anterior wall prolapse may be a result of uterine or vaginal wall prolapse is preferable to rectocele or enterocele unless the
vault descent or an anterior enterocele in patients with prior organs involved are identified by ancillary tests. If small bowel
prolapse surgery. Although the terms cystocele and enterocele appears to be present in the rectovaginal space, the examiner
continue to be used by most gynecologists, anterior vaginal should comment on this fact and clearly describe the basis
wall prolapse remains the preferred terminology. There are for this clinical impression (e.g., by observation of peristaltic
two anterior sites: activity in the distended posterior vagina or palpation of loops
Point Aa: A point located in the midline of the anterior of small bowel between an examining finger in the rectum
vaginal wall 3 cm proximal to the external urethral and one in the vagina). In such cases, a “pulsion” addendum
meatus, corresponding to the proximal location of the to the point Bp position may be noted (e.g., Bp equals +5
urethrovesical crease. By definition, the range of posi- [pulsion]; see following text for further discussion).
tion of point Aa relative to the hymen is −3 to +3 cm. Point Ap: A point located in the midline of the posterior
Point Ba: A point that represents the most distal (i.e., vaginal wall 3 cm proximal to the hymen. By defini-
most dependent) position of any part of the upper tion, the range of position point Ap relative to the
anterior vaginal wall from the vaginal cuff or anterior hymen is −3 to +3 cm.
vaginal fornix to point Aa. By definition, point Ba is Point Bp: A point that represents the most distal (i.e.,
at −3 cm in the absence of prolapse and would have most dependent) position of any part of the upper
110 PART 2  Basic Science

posterior vaginal wall from the vaginal cuff or poste- −3, −3, 9, 2, 2 for points Aa, Ba, C, D, Bp, Ap, total vagi-
rior vaginal fornix to point Ap. By definition, point Bp nal length, genital hiatus, and perineal body, respectively).
is at −3 cm in the absence of prolapse and would have Alternatively, a 3 × 3 grid can be used to concisely organize
a positive value equal to the position of the cuff in a the measurements, as shown in Figure 8.4, or a line dia-
woman with total posthysterectomy vaginal eversion. gram of a configuration can be drawn, as shown in Figures
Other landmarks include the genital hiatus, which is 8.5 and 8.6. Figure 8.5 is a grid and line diagram contrast-
measured from the middle of the external urethral meatus ing measurements that indicate normal support to those of
to the posterior midline hymen. The perineal body is mea- posthysterectomy vaginal eversion. Figure 8.6 is a grid and
sured from the posterior margin of the genital hiatus to the line diagram representing predominant anterior and poste-
midanal opening. The total vaginal length is the greatest rior vaginal wall prolapse with partial vault descent.
depth of the vagina in centimeters when point C or D is The profile for quantifying prolapse provides a precise
reduced to its full normal position. The points and measure- description of anatomy for individual patients. An ordinal
ments are presented in Figure 8.3. staging system of pelvic organ prolapse is suggested using
The positions of points Aa, Ba, Ap, Bp, C, and (if appli- these measurements and can be useful for the description
cable) D with reference to the hymen are measured and of populations and for research comparisons. Stages are
recorded. Positions are expressed as centimeters above or assigned according to the most severe portion of the pro-
proximal to the hymen (negative number) or centimeters lapse when the full extent of the protrusion has been dem-
below or distal to the hymen (positive number), with the onstrated. For a stage to be assigned to an individual subject,
plane of the hymen defined as 0. Measurements may be it is essential that her quantitative description be completed
recorded as a simple line of numbers (e.g., −3, −3, −7, −9, first. The five stages of pelvic organ support (0-IV) are
described in Box 8.4.
Ancillary techniques for describing pelvic organ prolapse
include performance of a digital rectal examination while
the patient is straining; digital assessment of the contents of
the rectovaginal septum during examination to differentiate
between a “traction” enterocele (the posterior cul-de-sac
is pulled down by the prolapsing cervix or vaginal cuff but
is not distended by intestines) and a “pulsion” enterocele
(the intestinal contents of the enterocele distend the rectal-­
vaginal septum and produce a protruding mass); cotton
swab testing for the measurement of urethral axis mobility
(Q-Tip® test); measurement of perineal descent; measure-
ment of the transverse diameter of the genital hiatus or of
the protruding prolapse; measurement of vaginal volume;
description and measurement of rectal prolapse; and exami-
nation techniques differentiating between various types
FIGURE 8.4  Three-by-three grid for recording quantitative descrip-
of defects (e.g., central versus paravaginal defects of the
tion of pelvic organ support. (From Bump RC, Mattiasson A, Bo K, et al. anterior vaginal wall). Cystoscopy and imaging can be use-
The standardization of terminology of female pelvic organ prolapse and ful in describing pelvic organ prolapse. Imaging procedures
pelvic floor dysfunction. Am J Obstet Gynecol. 1996;175:10.) include ultrasonography, contrast radiography, computed

FIGURE 8.5  A, Grid and line diagram of com-


plete eversion of vagina. Most distal point of
anterior wall (point Ba), vaginal cuff scar (point
C), and most distal point of the posterior wall
(point Bp) are all at same position (+8) and
points Aa and Ap are maximally distal (both
at +3). Because total vaginal length equals
maximum protrusion, this is stage IV prolapse.
B, Normal support. Points Aa and Ba and points
Ap and Bp are all −3 because there is no anterior
or posterior wall descent. Lowest point of the
cervix is 8 cm above hymen (−8) and posterior
fornix is 2 cm above this (−10). Vaginal length
is 10 cm, and genital hiatus and perineal body
measure 2 and 3 cm, respectively. This repre-
sents stage 0 support. (From Bump RC, Mattiasson
A, Bo K, et al. The standardization of terminology
of female pelvic organ prolapse and pelvic floor
A B dysfunction. Am J Obstet Gynecol. 1996;175:10.)
CHAPTER 8  Description and Classification of Lower Urinary Tract Dysfunction and Pelvic Organ Prolapse 111

tomography, and magnetic resonance imaging. Intraopera-


Box 8.4  Stages of Pelvic Organ Prolapse
tive evaluation of pelvic support defects is not standard of
care and is not recommended. Stage 0 No prolapse is demonstrated. Points Aa, Ap, Ba,
Precise characterization of pelvic floor muscle strength and Bp are all at –3 cm and either point C or D is
and the description of functional symptoms are important. between –tvl (total vaginal length) cm and –(tvl –
The reader is referred to the ICS committee document for 2) cm (i.e., the quantitation value for point C or D
further details (Haylen et al., 2010). is ≤ –(tvl – 2) cm). Figure 8.5B represents stage 0.
Stage I The criteria for stage 0 are not met, but the most
distal portion of the prolapse is > 1 cm above the
level of the hymen (i.e. its quantitation value is
Classification System of Complications < −1 cm).
Related to Insertion of Vaginal Stage II The most distal portion of the prolapse is ≤ 1 cm
Prostheses and Grafts proximal to or distal to the plane of the hymen
(i.e., its quantitation value is ≥ −1 cm but ≤ +1 cm).
The use of synthetic mesh for treatment of pelvic organ Stage III The most distal portion of the prolapse is > 1 cm
prolapse has been shown to reduce objective and subjective below the plane of the hymen but protrudes
recurrence when compared with native tissue repairs; how- no further than 2 cm less than the total vaginal
ever, a higher risk of complications is associated with the use length in centimeters (i.e. its quantitation value
is > +1 cm but < +(tvl – 2) cm). Figure 8.6A,
of mesh. In July 2011, the U.S. Food and Drug Administra-
­represents stage III Ba and Fig. 8.6B, represents
tion issued an update on the original 2008 public health noti-
stage III Bp prolapse.
fication that identified surgical mesh for transvaginal repair Stage IV Essentially, complete eversion of the total length
of pelvic organ prolapse as an “area of continuing serious of the lower genital tract is demonstrated. The
concern.” Both the American Congress of Obstetricians and distal portion of the prolapse protrudes to at least
Gynecologists (ACOG) and the American Urogynecologic (tvl – 2) cm (i.e., its quantitation value is ≥ +(tvl
Society (AUGS) have recognized the importance of these – 2) cm). In most instances, the leading edge of
concerns and have emphasized the need for a thorough dis- stage IV prolapse is the cervix or vaginal cuff scar.
cussion of potential risks before consenting patients for pro- Figure 8.5A, represents stage IV C prolapse.
cedures involving the placement of transvaginal mesh. With
From Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology
the ongoing use of mesh in pelvic reconstructive surgery, the of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet
number of patients seeking care for mesh-related complica- Gynecol. 1996;175:10.
tions has increased. Common complications include mesh
erosion, chronic pelvic pain, dyspareunia, infection, intraop-
erative bladder perforations, infection, and fistula formation.

A B
FIGURE 8.6  A, Grid and line diagram of predominant anterior support defect. Leading point of prolapse is upper anterior vaginal wall, point
Ba (+6). There is significant elongation of bulging anterior wall. Point Aa is maximally distal (+3) and vaginal cuff scar is 2 cm above hymen
(C = −2). Cuff scar has undergone 4 cm of descent because it would be at −6 (total vaginal length) if it were perfectly supported. In this
example, total vaginal length is not maximum depth of vagina with elongated anterior vaginal wall maximally reduced but rather depth of
vagina at cuff with point C reduced to its normal full extent, as specified in text. This represents stage III Ba prolapse. B, Predominant posterior
support defect. Leading point of prolapse is upper posterior vaginal wall, point Bp (+5). Point Ap is 2 cm distal to hymen (+2) and vaginal cuff
scar is 6 cm above hymen (−6). Cuff has undergone only 2 cm of descent because it would be at −8 (total vaginal length) if it were perfectly
supported. This represents stage III Bp prolapse. (From Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology of female pelvic
organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol. 1996;175:10.)
112 PART 2  Basic Science

In response to this, an International Urogynecological Asso- Abrams P, Blaivas JG, Stanton SL, et al. The standardization of terminology
ciation (IUGA)/ICS joint report on the terminology and classi- of lower tract function. Scand J Urol Nephrol. 1988;114(suppl):5.
Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower
fication of complications arising from the insertion of prostheses urinary tract function: report from the Standardization Sub-committee of the
and grafts in female pelvic floor surgery was published by Hay- International Continence Society. Am J Obstet Gynecol. 2002;187:116.
len et al. (2011). The complete classification system is included Bates P, Bradley WE, Glen E, et al. First report on the standardization of ter-
in Appendix D. There are three components to the classifica- minology of lower urinary tract function. Urinary incontinence. Procedures
related to the evaluation of urine storage: cystometry, urethral closure
tion system– category, time, and site and each complication pressure profile, units of measurement. Br J Urol. 1976;48:39. Eur Urol.
is reported using these three identifiers. Each complication is 1976;2:274; Scand J Urol Nephrol. 1976;11:193; Urol Int. 1976;32:81.
placed in a category “C”, which is composed of a class and divi- Bates P, Bradley WE, Glen E, et al. Second report on the standardization
sion. Each class is based on site and extent of the complica- of terminology of lower urinary tract function. Procedures related to
tion at that site: (1), vaginal without epithelial separation; (2), the evaluation of micturition: flow rate, pressure measurement, sym-
bols. Acta Urol Jpn. 1977;27:1563; Br J Urol. 1977;49:207; Scand J Urol
vaginal exposure less than or equal to 1 cm in size; (3), vaginal Nephrol. 1977;11:197.
exposure or extrusion greater than or equal to 1 cm in size; (4), Bates P, Bradley WE, Glen E, et al. Third report on the standardization of
urinary tract; (5), rectal or bowel; (6), skin or musculoskeletal; terminology of lower urinary tract function. Procedures related to the
(7), patient compromise. Each class is then further divided evaluation of micturition: pressure flow relationships, residual urine. Br J
Urol. 1980;52:348; Eur Urol. 1980;6:170; Acta Urol Jpn. 1980;27:1566;
(A, asymptomatic; B, symptomatic; C, infection; D, abscess). Scand J Urol Nephrol. 1980;12:191.
A subclassification of each category also exists to describe the Bates P, Bradley WE, Glen E, et al. Fourth report on the standardization of
presence of pain as a result of the complication (a, no pain; b, terminology of lower urinary tract function. Terminology related to neu-
provoked pain during examination; c, pain during intercourse; romuscular dysfunction of lower urinary tract. Br J Urol. 1981;52:333;
d, pain during physical activities; e, spontaneous pain). Time Urology. 1981;17:618; Scand J Urol Nephrol. 1981;15:169; Acta Urol
Jpn. 1981;27:1568.
“T” is reported as the time that the complication is clinically Bent AE, Richardson DA, Ostergard DR. Diagnosis of lower urinary tract dis-
diagnosed and incorporates four possible time periods (1, intra- orders in postmenopausal patients. Am J Obstet Gynecol. 1983;145:218.
operative; 2, 48 h to 2 months; 3, 2 months to 12 months; 4, Blaivas JG. Classification of stress urinary incontinence. Neurourol Urodyn.
>12 months). Site “S” describes where the prostheses or graft 1983;2:103.
Blaivas JG, Olsson CA. Stress incontinence: classification and surgical
complication is noted (1, vaginal area of suture line; 2, vaginal approach. J Urol. 1988;139:727.
away from area of suture line; 3, nonintrabdominal trocar pas- Castleton CM, Duffin HM, Asher MJ. Clinical and urodynamic studies in
sage; 4, other skin or musculoskeletal; 5, intrabdominal). 100 elderly incontinent patients. BMJ. 1981;282:1103.
A complete classification code for any complication Diokno AC, Brown MB, Brock BM, et al. Clinical and cystometric charac-
includes all three components. An example of a complete teristics of continent and incontinent non-institutionalized elderly. J Urol.
1988;140:567.
code is the following: 2Bc/T3/S2, suggesting that the compli- Haylen BT, de Ridder D, Freeman RM, et al. An International Urogyneco-
cation is a vaginal mesh exposure less than or equal to 1 cm in logical Association (IUGA)/International Continence Society (ICS) joint
size, which the patient is symptomatic from, with pain during report on the terminology for female pelvic floor dysfunction. Neurourol
intercourse, diagnosed between 2 and 12 months from the Urodyn. 2010;29:4.
McGuire EJ, Lytton B, Pepe V, et al. Stress urinary incontinence. Am J
index surgery, and found in the vagina away from the area of Obstet Gynecol. 1976;47:255.
the suture line. Multiple as well as early and late complica- Ouslander J, Staskin D, Raz S, et al. Clinical versus urodynamic diagnosis in
tions are reported separately. If there is progression of any an incontinent female geriatric population. J Urol. 1987;37:68.
complication over time, the highest and final category is used. Quigley GJ, Harper AC. The epidemiology of urethral–vesical dysfunction
The IUGA/ICS classification system for vaginal prosthe- in the female patient. Am J Obstet Gynecol. 1985;151:220.
Resnick NM, Yalla SV, Laurino E. The pathophysiology of urinary inconti-
ses and graft complications is much more comprehensive and nence among institutionalized elderly persons. N Engl J Med. 1989;320:1.
specific than any other surgical complication classification Staskin DR, Wein AJ. Classification of lower urinary tract dysfunction in
system currently in use. The classification system has been the female patient. In: Cardozo L, Staskin DR, eds. Textbook of Female
criticized for being too complex, however, with categories Urology and Urogynecology. 3rd ed. London: Informa Healthcare; 2010.
Wein AJ. Classification of neurogenic voiding dysfunction. J Urol.
that are too broad with unclear definitions, leading to poor 1981;125:605.
inter-rater reliability among providers. Additionally, the clas- Wein AJ. Pathophysiology and categorization of voiding dysfunction. In:
sification system does not lend to gradation of severity of a Walsh PC, Retik AB, Vaughan ED, et al., eds. Campbell’s Urology. 7th ed.
complication, which some critics assert is important when Philadelphia: WB Saunders; 1998.
choosing a management plan for treatment and when relay- Wein AJ, Barrett DM. Voiding Function and Dysfunction. Chicago: Mosby;
1988.
ing information about a disease process. The classification Williams ME, Pannill FC. Urinary incontinence in the elderly. Ann Intern
system currently is not used in the same routine fashion as Med. 1982;97:895.
the systems that are currently in place for pelvic organ pro- Classification of Pelvic Organ Prolapse
lapse and urinary incontinence. However, with the rate of Baden WF, Walker T. Fundamentals, symptoms, and classification. In:
patients seeking care for mesh-related complications on the Baden WF, Walker T, eds. Surgical Repair of Vaginal Defects. Philadel-
rise, it is likely that this classification system will continue to phia: JB Lippincott; 1992.
evolve until it is easy to use with good interobserver reliabil- Baden WF, Walker T, Lindsey JH. The vaginal profile. Tex Med. 1968;64:56.
ity so that it may one day become part of routine practice. Beecham CT. Classification of vaginal relaxation. Am J Obstet Gynecol.
1980;136:957.
Bibliography Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology of
female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet
Classification of Urinary Incontinence Gynecol. 1996;75:10.
Abrams P, Blaivas JG, Stanton SL, et al. Sixth report on the standardiza- Hall AF, Theofrastous JP, Cundiff GW, et al. Interobserver and intrao-
tion of terminology of lower urinary tract function. Procedures related bserver reliability of the proposed International Continence Society,
to neurophysiological investigations: electromyography, nerve conduction Society of Gynecologic Surgeons, and American Urogynecology Society
studies, reflex latencies, evoked potentials and sensory testing. World J pelvic organ prolapse classification system. Am J Obstet Gynecol. 1996;
Urol. 1986;4(2); Scand J Urol Nephrol. 1986;20:161. 175:467.
CHAPTER 8  Description and Classification of Lower Urinary Tract Dysfunction and Pelvic Organ Prolapse 113

Kobak WH, Rosenberger K, Walters MD. Interobserver variation in the Nguyen JN, Burchette RJ. Outcome after anterior vaginal prolapse repair: a
assessment of pelvic organ prolapse. Int Urogynecol J. 1996;7:121. randomized controlled trial. Obstet Gynecol. 2008;111:891.
Porges RF. A practical system of diagnosis and classification of pelvic relax- Ridgeway B, Walters MD, Paraiso M, et al. Early experience with mesh
ations. Surg Gynecol Obstet. 1963;117:769. excision for adverse outcomes after transvaginal mesh placement using
Steele A, Mallipeddi P, Welgoss J, et al. Teaching the pelvic organ prolapse prolapse kits. Am J Obstet Gynecol. 2008;199. 703.e1.
quantitation system. Am J Obstet Gynecol. 1998;179:1458. Tunitsky E, Abbott S, Barber MD. Interrater reliability of the International
Continence Society and International Urogynecological Association
Classification of Complications Related to Vaginal Prostheses and
(ICS/IUGA) classification system for mesh-related complications. Am J
Grafts
Obstet Gynecol. 2012;206. 422.e1.
Diwadkar GB, Barber MD, Feiner B, et al. Complication and reopera- US Food and Drug Administration. FDA Public Health Notification: Seri-
tion rates after apical vaginal prolapse surgical repair. Obstet Gynecol. ous Complications Associated with Transvaginal Placement of Surgical
2009;113:367. Mesh in Repair of Pelvic Organ Prolapse and Stress Urinary Inconti-
Haylen BT, Freeman RM, Swift SE, et al. An International Urogynecological nence; ­October 20, 2008. Available at: http://www.fda.gov/MedicalDe
Association (IUGA)/International Continence Society (ICS) joint termi- vices/Safety/AlertsandNotices/PublicHealthNotifications/UCM061976.
nology and classification of the complications related directly to the inser- Accessed 07.11.10.
tion of prostheses (meshes, implants, tapes) and grafts in female pelvic US Food and Drug Administration. FDA Safety Communication: Update on
floor surgery. Neurourol Urodyn. 2011;30:2. Serious Complications Associated with Transvaginal Placement of Surgical
Hiltunen R, Nieminen K, Takala T, et al. Low-weight polypropylene mesh Mesh in Repair of Pelvic Organ Prolapse; July 13, 2011. Available at: htt
for anterior vaginal wall prolapse: a randomized controlled trial. Obstet p://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.
Gynecol. 2007;110(2 Pt 2):455. htm. Accessed 07.07.13.
Maher C, Feiner B, Baessler K, Schmid C. Surgical management of
pelvic organ prolapse in women. Cochrane Database Syst Rev.
2013;4:CD004014.
CHAPTER 9

Evaluation
of Urinary
Incontinence
and Pelvic
Organ Prolapse:
History, Physical
Examination, and
Office Tests
Mark D. Walters

Urinary incontinence can be a symptom of which patients


complain, a sign demonstrated on examination, or a con- Chapter Outline
dition (i.e., diagnosis) that can be confirmed by definitive
studies. When a woman complains of urinary incontinence, History and Physical Examination
appropriate evaluation includes exploring the nature of her History of Urinary Incontinence
symptoms and looking for physical findings. The history and Urinary Diary
physical examination are the first and most important steps
History of POP
in the evaluation. A preliminary diagnosis can be made with
simple office and laboratory tests, with initial therapy based Gynecologic Examination
on these findings. If complex conditions are present, if the Neurologic Examination
patient does not improve after initial therapy, or if surgery is Techniques for Measuring Urethral Mobility
being considered, definitive, specialized studies are usually Radiologic Assessment
necessary. Ultrasonography
Pelvic organ prolapse (POP) is a heterogeneous condi- Q-Tip Test
tion in which weaknesses of the pelvic floor musculature
and connective tissue result in descent or bulging of pelvic Perineal Pad Tests
organs into the vaginal canal. In more severe cases, prolapse Diagnostic Tests
can protrude through the vaginal introitus and beyond the
Laboratory
hymenal ring. In anterior vaginal wall prolapse, the bladder
and urethra may potentially protrude into the vaginal canal Radiologic
(cystocele). Patients may have uterine prolapse or, after Evaluation of Bladder Filling and Voiding
hysterectomy, the vaginal cuff may herniate resulting in api- Making the Incontinence Diagnosis
cal vaginal prolapse. The rectum, small bowel, and sigmoid
colon also may herniate in posterior vaginal wall prolapse, Diagnostic Accuracy of Office Evaluations
resulting in rectoceles, enteroceles, and sigmoidoceles, Indications for Urodynamic Tests and
respectively. That said, terminologies such as “cystocele” Cystoscopy
and “rectocele,” although commonly used in clinical prac-
tice, are perhaps less precise because they imply an unrealis-
tic certainty as to the specific organs behind the vaginal wall
at the time of physical examination. most clinicians can recognize the extremes of normal sup-
Definitions of prolapse as a clinical condition or disease port versus severe prolapse, most cannot objectively state
are based on measured severity or staging by Pelvic Organ at what point vaginal laxity become pathologic and require
Prolapse Quantification (POPQ; see Chapter 8) examina- intervention. There are limited data concerning the normal
tion and by assessment of relevant symptoms. Although distribution of POP in the population and the correlations
117
118 PART 3 Evaluation

between symptoms and physical findings. In a study of 497


Box 9.1  Helpful Questions in the Evaluation
women, Swift (2000) demonstrated that the distribution
of Female Urinary Incontinence
of prolapse in a population exhibited a bell-shaped curve,
with the majority of women having Stage I or II prolapse by 1. Do you leak urine when you cough, sneeze, or laugh?
the POPQ classification system and only 3% having Stage 2. Do you ever have such an uncomfortably strong need to
III prolapse. This signifies that, at baseline, a majority of urinate that if you don’t reach the toilet you will leak?
women, especially those who have borne children, have 3. If “yes” to question 2, do you ever leak before you reach
some degree of pelvic relaxation. However, these women the toilet?
are generally asymptomatic and will only develop symptoms 4. How many times during the day do you urinate?
5. How many times do you void during the night after going
as their prolapse increases in severity, especially as it pro-
to bed?
trudes to the hymen and beyond (Swift et al., 2005; Swift 6. Have you wet the bed in the past year?
and Barber 2010). Therefore, even if prolapse is found on 7. Do you develop an urgent need to urinate when you are
physical examination, it may not be clinically relevant and nervous, under stress, or in a hurry?
may not require intervention if the patient is asymptomatic. 8. Do you ever leak during or after sexual intercourse?
Swift and Barber (2010) proposed that POP, the disease, 9. How often do you leak?
be defined as the descent of one or more of the anterior 10. Do you find it necessary to wear a pad because of your
vaginal wall, posterior vaginal wall, the uterus (cervix), or leaking?
the apex of the vagina beyond the hymen on straining exam- 11. Have you had bladder, urine, or kidney infections?
ination (the sign of POP) associated with feeling or seeing 12. Are you troubled by pain or discomfort when you urinate?
13. Have you had blood in your urine?
a bulge from the vagina during daily activities (the symp-
14. Do you find it hard to begin urinating?
tom of POP). Patients with descent beyond the hymen who 15. Do you have a slow urinary stream or have to strain to pass
do not have bulge symptoms would be classified as having your urine?
asymptomatic POP and those with bulge symptoms should 16. After you urinate, do you have dribbling or a feeling that
be classified as having symptomatic POP. your bladder is still full?

History and Physical Examination


Table 9.1  Medications that Can Affect Lower
History of Urinary Incontinence Urinary Tract Functions
Early in the interview, one should elicit a description of the Type of Medication Lower Urinary Tract Effects
patient’s main complaint, including duration and frequency.
Diuretics Polyuria, frequency, urgency
A clear understanding of the severity of the problem or Caffeine Frequency, urgency
disability and its effect on quality of life should be sought. Alcohol Sedation, impaired mobility,
Assessment of mobility and living environment is especially diuresis
important in certain patients. Questions should be asked Narcotic analgesics Urinary retention, fecal impaction,
about access to toilets or toilet substitutes and about social sedation, delirium
Anticholinergic agents Urinary retention, voiding difficulty
factors such as living arrangements, social contacts, and Antihistamines Anticholinergic actions, sedation
caregiver involvement. Psychotropic agents
Box 9.1 lists questions that are helpful in evaluating  Antidepressants Anticholinergic actions, sedation
incontinence in women. The first question is designed to  Antipsychotics Anticholinergic actions, sedation
 Sedatives/hypnotics Sedation, muscle relaxation,
elicit the symptom of stress incontinence (i.e., urine loss confusion
with events that increase intraabdominal pressure). The Alpha-adrenergic blockers Stress incontinence
symptom of stress incontinence is usually (but not always) Alpha-adrenergic agonists Urinary retention, voiding difficulty
associated with the diagnosis of urodynamic stress incon- Calcium-channel blockers Urinary retention, voiding difficulty
tinence. Questions 2 through 9 help elicit the symptoms
associated with detrusor overactivity. The symptom of urge
incontinence is present if the patient answers question 3 noted because chronic severe constipation has been associ-
affirmatively. Frequency (questions 4 and 5), bedwetting ated with voiding difficulties, urgency, stress incontinence,
(question 6), leaking with intercourse (question 8), and a increased bladder capacity, and POP. A history of hysterec-
sense of urgency (questions 2 and 7) are all associated with tomy, vaginal repair, pelvic cancer and/or radiotherapy, or
detrusor overactivity. Questions 9 and 10 help to define the surgery for incontinence should alert the physician to the
severity of the problem. Questions 11 through 13 screen possibility of prior surgical trauma to the lower urinary tract.
for urinary tract infection and neoplasia, and questions A complete list of the patient’s medications (including
14 through 16 are designed to elicit symptoms of voiding nonprescription medications) should be sought to deter-
dysfunction. mine whether individual drugs might influence the function
After the urologic history, thorough medical, surgical, of the bladder or urethra, leading to urinary incontinence
gynecologic, neurologic, and obstetric histories should be or voiding difficulties. A list of drugs that commonly affect
obtained. Certain medical and neurologic conditions, such lower urinary tract function is shown in Table 9.1. In these
as diabetes, stroke, and lumbar disk disease, may cause cases, altering drug dosage or changing to a drug with similar
urinary incontinence. Furthermore, strong coughing associ- therapeutic effectiveness but with fewer lower urinary tract
ated with chronic pulmonary disease can markedly worsen side effects, will often improve or “cure” the offending uri-
symptoms of stress incontinence. A bowel history should be nary tract symptom.
CHAPTER 9  Evaluation of Urinary Incontinence and Pelvic Organ Prolapse: History, Physical Examination, and Office Tests 119

FIGURE 9.1 Prevalence of pro-


lapse symptoms per POPQ group.
The percentage of patients who
report urinary splinting, digital
assistance, and vaginal bulge for
each relevant POPQ measure-
ments. Bars represent 95% con-
fidence intervals. (Modified from
Tan JS, Lukacz ES, Menefee SA,
et al. Predictive value of prolapse
symptoms: a large database study.
Int Urogynecol J. 2005;16:203.)

Urinary Diary
Vaginal prolapse in any compartment—anterior, apical,
Patient histories regarding frequency and severity of uri- or posterior—can manifest as vaginal fullness, pain and/or
nary symptoms are often inaccurate and misleading. Uri- protruding mass. In a study by Tan et al. (2005), the feeling
nary diaries are more reliable and require the patient to of “a bulge or that something is falling outside the vagina”
record volume and frequency of fluid intake and of voiding, had a positive predictive value of 81% for POP; the lack of
usually for a one- to seven-day period. A three-day diary this symptom had a negative predictive value of 76% for
seems to be as accurate as a seven-day diary to document predicting prolapse at or past the hymen. Not surprisingly,
symptoms, and compliance is improved. Episodes of uri- increased degree of prolapse, especially beyond the hymen,
nary incontinence and associated events or symptoms such is associated with increased pelvic discomfort and visualiza-
as coughing, urgency, and pad use are noted. The number tion of a protrusion. The presence of vaginal bulge symp-
of times voided each night and any episodes of bedwet- toms is a highly specific (but not sensitive) symptom for
ting are recorded the next morning. The maximum voided predicting the presence of prolapse beyond the hymen on
volume also provides a relatively accurate estimate of blad- a straining examination (specificity 99% to 100%) (Bradley
der capacity. The physician should review the frequency/ and Nygaard, 2005; Barber et al., 2006). The association
volume charts with the patient and corroborate or modify of POPQ measures on examination with three commonly
the initial diagnostic impression. If excessive frequency and related symptoms—urinary splinting, digital assistance with
volume of fluid intake are noted, restriction of excessive defecation, and vaginal bulge—is shown in Figure 9.1.
oral fluid intake (combined with scheduled voiding) may Stress urinary incontinence and voiding difficulties can
improve symptoms of stress and urge incontinence by keep- occur in association with anterior and apical vaginal prolapse.
ing the bladder volume below the threshold at which uri- However, women with advanced degrees of prolapse may
nary leaking results. not have overt symptoms of stress incontinence because the
Urinary diaries are a useful and accepted research method prolapse may cause a mechanical obstruction of the urethra,
to measure the severity of incontinence and as an outcome thereby preventing urinary leakage. Instead, these women
measure after interventions. This is reviewed in Chapter 44. may require vaginal pressure or manual replacement of the
prolapse to accomplish voiding. They are therefore at risk
for incomplete bladder emptying and recurrent or persistent
History of POP
urinary tract infections and for the development of de novo
Patients with POP may present with symptoms directly stress incontinence after the prolapse is repaired. Patients
related to the prolapse such as vaginal bulge, pressure, and who require digital assistance to void in general have more
discomfort as well as a plethora of associated symptoms advanced degrees of prolapse. In addition to difficulty void-
relating to voiding, defecatory, and sexual dysfunction. The ing, other urinary symptoms such as urgency, frequency,
severity of the prolapse is not necessarily associated with and urge incontinence are found in women with prolapse.
increased visceral symptomatology. However, it is not clear whether the severity of prolapse is
120 PART 3 Evaluation

directly associated with more irritative voiding symptoms that suggests a urethral diverticulum, carcinoma, or inflam-
or bladder pain. matory condition of the urethra. The integrity of the peri-
POP, especially in the apical and posterior compartments, neal body is evaluated and the extent of all prolapsed parts
can be (but are not always) associated with defecatory dys- are assessed. A retractor, Sims speculum, or the posterior
function, such as pain with defecation, the need for manual blade of a bivalve speculum can be used to depress the pos-
assistance with defecation, and anal incontinence of flatus, terior vagina to aid in visualizing the anterior vagina, and vice
liquid, or solid stool. These patients often have outlet-type versa for the posterior vagina. Because most patients with
constipation secondary to the trapping of stool within the prolapse are postmenopausal, the vaginal mucosa should be
rectal hernia necessitating the need for splinting or apply- examined for atrophy and thinning because this may affect
ing manual pressure in the vagina, rectum, or perineum to management. Healthy, estrogenized tissue, without signifi-
reduce the prolapse aiding in defecation. Although defeca- cant evidence of prolapse, will be well perfused and have
tory dysfunction remains an area that is least understood rugation and physiologic moisture. Atrophic vaginal tissue
in patients with prolapse, clinical and radiographic studies consistent with hypoestrogenemia appears pale, thin, with-
have shown that the severity of prolapse is not strongly cor- out rugation, and can be friable; this finding suggests that
related with increased symptomatology. the urethral mucosa is also atrophic.
Although the relationship between sexual function and After the resting vaginal examination, the patient is
POP is not clearly defined, questions regarding sexual dys- instructed to perform the Valsalva maneuver or to cough
function must be included in the evaluation of any patients vigorously. During this maneuver, the order of descent of
with prolapse. Patients may report symptoms of dyspareu- the pelvic organs is noted, as is the relationship of the pelvic
nia, decreased libido and orgasm, and increased embarrass- organs at the peak of increased intraabdominal pressure. The
ment with altered anatomy that affects body image. Some presence and severity of anterior vaginal relaxation, includ-
studies have reported that prolapse adversely affected ing cystocele and proximal urethral detachment and mobility,
sexual functioning with subsequent improvement in sexual or anterior vaginal scarring, are estimated. Associated pelvic
function after repair of prolapse (Barber et al., 2002; R
­ ogers support abnormalities, such as rectocele, enterocele, and
et al., 2001; Weber et al., 2000). However, Burrows et al. uterovaginal prolapse, are noted. The amount or severity of
(2004) showed little correlation between the extent of pro- prolapse in each vaginal segment should be measured, staged
lapse and sexual dysfunction. Evaluating sexual function and recorded according to POPQ guidelines noted in Chap-
may be especially difficult in this patient population as the ter 8. A rectovaginal examination is recommended to fully
hindrances to sexual function may include factors other than evaluate prolapse of the posterior vaginal wall and perineal
prolapse, such as partner limitations and functional deficits. body. Digital assessment of bowel contents in the rectovagi-
Symptoms of incontinence and prolapse and their impact nal septum during straining examination can help to diagnose
on the woman can be measured or quantified using a num- an enterocele. Other clinical observations and tests to help
ber of easy-to-use and validated questionnaires measuring delineate prolapse include: cotton swab testing for the mea-
symptom severity, quality of life, and sexual function. These surement of urethral axis mobility (Q-tip test); measurement
outcome measures can be useful in clinical practice and in of perineal descent; measurement of the transverse diameter
research; they are reviewed in detail in Chapter 44. of the genital hiatus or of the protruding prolapse; measure-
ment of vaginal volume; description and measurement of
posterior prolapse; and examination techniques differenti-
Gynecologic Examination
ating between various types of defects (e.g., central versus
General, gynecologic, and lower neurologic examinations paravaginal defects of the anterior vaginal wall). Inspection
should be performed on every woman with incontinence should also be made of the anal sphincter because fecal
and/or prolapse. The pelvic examination is of primary incontinence is often associated with posterior vaginal sup-
importance. A bimanual examination is performed to rule port defects. Grossly, women with a torn external sphincter
out coexistent gynecologic pathology, which can occur in up may have scarring or a “dove-tail” sign on the perineal body.
to two-thirds of patients. The rectal examination further Anterior vaginal wall descent usually represents bladder
evaluates for pelvic pathology and fecal impaction, the lat- descent with or without concomitant urethral hypermobility.
ter of which may be associated with voiding difficulties and However, in 1.6% of women with anterior vaginal prolapse, an
incontinence in elderly women. Urinary incontinence has anterior enterocele can mimic a cystocele on physical exami-
been shown to improve or resolve after the removal of fecal nation. Furthermore, lateral paravaginal defects, identified as
impactions in institutionalized geriatric patients. detachment of the lateral vaginal sulci, may be distinguished
The physical examination for incontinence and prolapse from central defects, seen as a midline protrusion with pres-
should be conducted with the patient in dorsal lithotomy ervation of the lateral sulci, by using a curved forceps placed
position, as for a routine pelvic examination. If physical in the anterolateral vaginal sulci directed toward the ischial
findings do not correspond to symptoms or if the maximum spine. Bulging of the anterior vaginal wall in the midline
extent of the prolapse cannot be confirmed, the woman can between the forceps blades implies a midline defect; blunting
be reexamined in the standing position. or descent of the vaginal fornices on either side with straining
Initially, the external genitalia are inspected, and if no dis- suggest lateral paravaginal defects. However, researchers have
placement is apparent, the labia are gently spread to expose shown that the physical examination technique to detect
the vestibule and hymen. Vaginal discharge can mimic paravaginal defects is not particularly reliable or accurate. In
incontinence, so evidence of this problem should be sought a study by Barber et al. (1999) of 117 women with prolapse,
and, if present, treated. Palpation of the anterior vaginal the sensitivity of clinical examination to detect paravaginal
wall and urethra may elicit urethral discharge or tenderness defects was good (92%), yet the specificity was poor (52%).
CHAPTER 9  Evaluation of Urinary Incontinence and Pelvic Organ Prolapse: History, Physical Examination, and Office Tests 121

Despite a high prevalence of paravaginal defects, the positive muscle strength, (2) anal sphincter resting tone, (3) voluntary
predictive value was only 61%. Less than two-thirds of women anal contraction, and (4) perineal sensation. This simple screen-
believed to have a paravaginal defect on physical examination ing examination can be performed quickly and easily as part of
were confirmed to possess the same at surgery. Another study the gynecologic examination. When abnormalities are noted, or
by Whiteside et al. (2004) demonstrated poor reproducibility when an individual is suspected of having neurologic dysfunc-
of clinical examination to detect anterior vaginal wall defects. tion, a comprehensive neurologic examination with particular
Thus the clinical value of determining the location of midline, emphasis on the lumbosacral nerve roots should be performed.
apical and lateral paravaginal defects remains unknown. This comprehensive evaluation should be performed before
In regard to posterior prolapse, clinical examinations do any neurophysiologic testing, because any such testing should
not always accurately differentiate between rectoceles and only be interpreted in the context of the patient’s history and
enteroceles. Some investigators thus have advocated per- physical examination findings.
forming imaging studies to further delineate the exact nature Mental status is determined by noting the patient’s level
of the posterior wall prolapse. Traditionally, most clinicians of consciousness, orientation, memory, speech, and com-
believe they are able to detect the presence or absence of prehension. Disorders associated with mental status aberra-
these defects without anatomically localizing them. How- tions that may result in changes in bowel or bladder function
ever, little is known regarding the accuracy or utility of include senile and presenile dementia, brain tumors, stroke,
clinical examinations in evaluating the anatomic locations of Parkinson’s disease, and normal pressure hydrocephalus.
prolapsed small or large bowel or of specific defects in the Evaluation of the sensory and motor systems may iden-
rectovaginal space. Burrows et al. (2003) found that clinical tify an occult neurologic lesion or can help determine the
examinations often did not accurately predict the specific level of a known lesion. Common diseases associated with
location of defects in the rectovaginal septum that were sensory and motor abnormalities that can produce urologic
subsequently found intraoperatively. Clinical findings corre- disturbances include Parkinson’s disease, multiple sclerosis,
sponded with intraoperative observations in 59% of patients cerebrovascular disease, infections, and tumors. Sacral seg-
and differed in 41%; sensitivities and positive predicative ments 2 through 4, which contain the important neurons
values of clinical examinations were less than 40% for all pos- controlling micturition, are particularly important (Fig. 9.2).
terior defects. However, what remains unclear is the clinical Sensory function is evaluated by testing the lumbosacral
consequence of not detecting these defects preoperatively. dermatomes for the ability to sense light touch, pinprick,
As noted previously, the POPQ classification should and temperature. The sensory dermatomes of interest
be done on all women with prolapse. This descriptive sys-
tem contains a series of site-specific measurements of the
woman’s pelvic organ support. The measurements can be
obtained quickly in both experienced and nonexperienced
hands. It can be easily learned and taught by means of a
brief video tutorial. Prolapse in each segment is evaluated
and measured relative to the hymen (not introitus), which
is a fixed anatomic landmark that can be identified consis-
tently and precisely. The anatomic position of the six defined
points for measurement should be centimeters above or
proximal to the hymen (negative number) or centimeters
below or distal to the hymen (positive number), with the
plane of the hymen being defined as zero. For example, a
cervix that protrudes 3 cm distal to (beyond) the hymen
should be described as +3 cm. Studies have demonstrated
excellent interexaminer and intraexaminer reliability when
using the POPQ system to quantify prolapse. The POPQ
system does not take into account lateral defects and peri-
neal body prolapse, but these can be added in descriptive
terms. POPQ measurements can also help predict or aid in
the diagnosis of voiding dysfunction (Chae et al., 2014) and
levator hiatus ballooning (Gerges et al., 2013). Despite its
limitations, POPQ system is currently the classification sys-
tem used in most research studies and National Institutes of
Health trials, and is gaining popularity in clinical practice.

Neurologic Examination
Urinary (and fecal) incontinence may be the presenting
symptom(s) of neurologic disease. The screening neurologic
examination should evaluate mental status, sensory and motor FIGURE 9.2 Sensory dermatomes of the lower extremities and
function of both lower extremities, and include a screening perineum. Shaded area represents sacral segments 2, 3, and 4.
lumbosacral neurologic examination. The screening lumbosa- (Modified from Boileau Grant JC. Grant’s Atlas of Anatomy. 6th ed.
cral examination should include assessments of: (1) pelvic floor Baltimore: Williams & Wilkins; 1972.)
122 PART 3 Evaluation

include the perineum and perianal skin (pudendal n., S2-4), tone suggests disruption of the internal anal sphincter
mons pubis and upper aspect of labia majora (ilioinguinal and/or an injury to its sympathetic innervation (i.e., pel-
n., L1-2), front of the knees (L3-4), and sole of the foot vic plexus injury). The patient then should be asked to
(S1). Dermatome maps are useful for characterizing sen- maximally squeeze her anal sphincter. The presence of a
sory deficits, although it is important to remember that strong voluntary anal sphincter contraction indicates intact
there can be considerable overlap between dermatomes. pudendal innervation and external anal sphincter. Unlike
To test motor function, the patient extends and flexes the pelvic muscle strength, there is no widely accepted vali-
hip, knee, and ankle and inverts and everts the foot. The dated scale for quantifying anal squeeze strength. Kaushal
strength and tone of the levator ani muscle and external and Goldner (1991) used a 0 to 3+ scale and found that it
anal sphincter are estimated digitally. The strength of pelvic had a high correlation with maximum squeeze pressure as
floor musculature is assessed by palpating the levator ani measured by anal manometry. Weidner et al. (2000) used a
muscle complex in the posterior vaginal wall approximately modified version of the pelvic muscle rating scale to quan-
2 to 4 cm cephalad to the hymen. The patient is then asked tify anal squeeze strength. Absence or decrease of both
to squeeze around the examiner’s fingers. Weakness in this anal sphincter tone and voluntary contraction suggests a
muscle can be a result of neurologic deficits or direct trauma possible sacral or peripheral nerve lesion. Preservation of
during childbirth. Skeletal muscle strength is graded on a resting tone in the absence of a voluntary contraction sug-
scale from 0 to 5 (see Table 9.2). Position sense and vibra- gests a suprasacral lesion.
tion should be assessed, but need only be evaluated in the
distal extremities. The patellar, ankle, and plantar reflex
Techniques for Measuring Urethral Mobility
responses are tested.
Visceral sensation of the bladder and rectum can be Examination of the anterior vaginal wall is inaccurate in pre-
assessed with cystometry and anal manometry, respectively. dicting the amount of urethral mobility. It is difficult with
Loss of perineal sensation in a patient with bowel or bladder physical examination to differentiate between cystocele and
dysfunction, particularly if acute, should always alert the rotational descent of the urethra and the two often coexist.
examiner to a potentially serious neurologic problem. Neu- Measuring urethral mobility aids in the diagnosis of urody-
rophysiologic testing and/or radiologic evaluation should be namic stress incontinence and in planning treatment for this
performed to assess for conus medullaris or cauda equina condition (bladder neck suspension or sling versus urethral
syndrome. injection of bulking agents).
Two reflexes may help in the examination of sacral reflex Although pelvic examination alone is generally consid-
activity. In the anal reflex, stroking the skin adjacent to the ered to be unreliable in predicting urethral mobility, Noblett
anus causes reflex contraction of the external anal sphinc- et al. (2005) showed that essentially all of the women with
ter muscle. The bulbocavernosus reflex involves contraction Stage II to IV prolapse by POPQ had Q-tip angle greater
of the bulbocavernosus and ischiocavernosus muscles in than 30°. Thus perhaps measures of urethral mobility would
response to tapping or squeezing of the clitoris. Unfortu- only be useful in women with Stage 0 or I prolapse or in
nately, these reflexes can be difficult to evaluate clinically those with prior surgical repairs or other interventions. Sev-
and are not always present, even in neurologically intact eral tests are available for estimating the amount of urethral
women. mobility in women.
Both the resting tone and voluntary contraction of the
anal sphincter should be assessed. The examiner should Radiologic Assessment
first inspect the anus, looking for scarring or a gaping Lateral cystourethrography in the resting and straining view
sphincter. Women with disruption of the external anal can identify mobility or fixation of the bladder neck, fun-
sphincter may have gross abnormalities of the perineal neling of the bladder neck and proximal urethra, and degree
body with a “dove-tail” sign in the area of the disrupted of cystocele. The voiding component can identify a urethral
sphincter. A digital rectal examination should be per- diverticulum, fistula, mass, obstruction, or vesicoureteral
formed, noting the resistance to entry of the examining reflux. Videocystourethrography allows a dynamic assess-
finger. Fifty percent to 85% of overall resting anal tone is ment of the anatomy and function of the bladder base and
generated by the internal anal sphincter. Loss of resting urethra during retrograde filling with contrast material and
during voiding. It is most helpful in sorting out causes of
complex incontinence problems. However, it is invasive,
Table 9.2  Grading Scales for Muscle Strength expensive, and not widely available. For these reasons, other
methods are usually used to measure urethral mobility in
Score Limb Muscles Levator Ani
incontinent women.
0/5 No movement No contraction
1/5 Trace of contraction Flicker, barely perceptible Ultrasonography
2/5 Active movement when Loose hold, 1-2 s
gravity eliminated
Ultrasonography is an alternative method of evaluating ure-
3/5 Active movement against Firmer hold, 1-2 s throvesical anatomy and is described in detail in Chapter
gravity only 13. Vaginal ultrasonography accurately displays descent of
4/5 Active movement against Good squeeze, 3-4 s, the urethrovesical junction, opening of the bladder neck,
resistance, but not pulls fingers in and up and detrusor contractions. This technique is a noninvasive
normal loosely
5/5 Normal strength Stronger squeeze, 3-4 s, and accurate method of evaluating the position and mobil-
pulls in and up snugly ity of the urethrovesical junction and proximal urethra in
incontinent women.
CHAPTER 9  Evaluation of Urinary Incontinence and Pelvic Organ Prolapse: History, Physical Examination, and Office Tests 123

Q-Tip Test The total weight of urine lost during the test period is taken
Placement of a cotton swab in the urethra to the level of to be equal to the gain in weight of the collecting device(s).
the vesical neck and measurement of the axis change with In interpreting the results of the test, it should be remem-
straining can be used to demonstrate urethral mobility. To bered that a weight gain of up to 1 g may be due to weighing
perform the Q-tip test, a sterile, lubricated cotton-tipped errors, sweating, or vaginal discharge.
applicator is inserted transurethrally into the bladder, Two critical variables determine the sensitivity of pad
then withdrawn slowly until definite resistance is felt, weighing: the amount of fluid in the bladder during exercise
indicating that the cotton tip is at the bladder neck. This and the type of activity used to generate increased intraab-
is best accomplished with the patient in the supine lithot- dominal pressure. Lose et al. (1986) found that pad weight
omy position during a pelvic examination. The resting correlated significantly with the fluid load on the bladder
angle of the applicator stick in relation to the horizontal (i.e., the initial volume plus diuresis). Pad weighing has
is measured with a goniometer or protractor. The patient acceptable test-retest reliability and is easy to perform in
is then asked to cough and perform a Valsalva maneuver, a clinical setting. However, it has low sensitivity and poor
and the maximum straining angle from the horizontal correlation between pad gain and videographic assessment
is measured. Results are not affected by the amount of of incontinence severity. These shortcomings have limited
urine in the bladder. Care should be taken to ensure that acceptance of pad weighing as a routine part of the evalua-
the cotton tip is not in the bladder or at the mid-urethra tion of incontinence.
because this results in a falsely low measurement of ure- Phenazopyridine hydrochloride (Pyridium) is sometimes
thral mobility. used to aid clinicians in differentiating urinary continence
Although maximum straining angle measurements from incontinence in women with disturbing vaginal wet-
greater than 30° are generally considered to be abnormal, ness (“Pyridium pad test”). Patients are given Pyridium tab-
few data are available to differentiate normal from abnor- lets and instructed to wear a sanitary pad for a given time.
mal measurements. Urethral mobility in continent women The pad is then removed and examined. Red-orange staining
is related to age, parity, and support defects of the ante- is taken as evidence that urine loss has occurred. Although
rior vaginal wall, and “urethral hypermobility” is common this test may occasionally be useful, Wall et al. (1990) dem-
in asymptomatic women. Women with urodynamic stress onstrated that although all incontinent women had pad
incontinence have higher maximum straining Q-tip angles, staining, 52% of healthy continent women also had staining,
although there wide overlap in measurements between the reflecting a high rate of false-positive tests.
continent and incontinent women. In general, arbitrary cut-
off values around 30° are too low to define “normal” ure-
thral mobility for parous women, and this test is no longer Diagnostic Tests
considered useful in helping with diagnosis or treatment of
Laboratory
incontinence.
Few laboratory tests are necessary for the evaluation of
incontinence and prolapse. A clean midstream or catheter-
Perineal Pad Tests ized urine sample should be obtained for dipstick urinalysis.
Perineal pad weighing may be used when one wants to docu- Urine culture and sensitivity should be obtained when the
ment objectively the presence and amount of urine loss. The dipstick test indicates infection. Acute cystitis can pres-
test should approximate activities in daily life and should ent with multiple irritative symptoms, such as dysuria,
evaluate as long a period as possible, yet be practical. A 1-h frequency, urgency, incontinence, and voiding difficulty. In
period of testing is recommended and can be extended for these cases, treatment of the infection usually eradicates
additional 1-h periods if the result of the first test is not the symptoms. However, bacteriuria is often asymptomatic,
considered representative of the symptoms by either the especially in the elderly. Boscia et al. (1986) demonstrated
patient or the physician. Alternatively, the test can be per- that no differences in urinary symptoms were found when
formed after filling the bladder to a defined volume or at elderly bacteriuric subjects were compared with themselves
home over a 24-h period. when they were nonbacteriuric. In view of these conflicting
The total amount of urine lost during the test period is data, it seems reasonable to examine the urine for infection
determined by weighing a collecting device such as an absor- in all incontinent patients and, if bacteriuria is found, to pre-
bent pad. The pad should be worn inside waterproof under- scribe appropriate antibiotics and reevaluate the patient in
pants or should have a waterproof backing. Care should several weeks.
be taken to use a collecting device of adequate capacity. Blood testing (blood urea nitrogen, creatinine, glucose,
Immediately before the test begins, the collecting device and calcium) is recommended if compromised renal func-
is weighed to the nearest gram. A typical test schedule tion is suspected or if polyuria (in the absence of diuretics)
is started without the patient voiding and with drinking is present. Urine cytology is not recommended in the rou-
approximately 500 mL of fluid. A period of walking, cough- tine evaluation of the incontinent patient or in the initial
ing, exercise, and hand-washing is done. At the end of the evaluation of microscopic hematuria (three to five red blood
1-h test, the collecting device is removed and weighed. If cells per high-powered field on microscopic examination).
the test is regarded as representative, the patient voids and Cytology may be useful, however, in patients with persistent
the volume is recorded; if not, the test is repeated for an microhematuria after a negative workup or with risk factors
additional hour. for carcinoma in situ (e.g., irritative voiding symptoms, cur-
If the collecting device becomes saturated or filled dur- rent or past tobacco use, chemical exposures) (Davis et al.,
ing the test, it should be removed, weighed, and replaced. 2012; Lambert 2013).
124 PART 3 Evaluation

of pelvic soft tissue. Some surgeons use this modality to


Radiologic
help decide whether an abdominal or vaginal prolapse repair
After a careful history and physical examination, few diag- is most appropriate. However, the clinical utility of this
nostic tests are needed to further evaluate patients with costly imaging modality in routine practice is debatable as
POP if there is no concomitant voiding or defecatory dys- it has not yet been shown to alter clinical decision-making.
function. Although hydronephrosis does occur in a small
proportion of women with prolapse, even if identified, it
Evaluation of Bladder Filling and Voiding
usually does not change management in the women for
whom surgical repair is planned. Therefore, routine imaging The office evaluation of incontinence should involve some
of the kidneys and ureters is not necessary. assessment of voiding, detrusor function during filling, and
As discussed in previous sections, preoperative clinical competency of the urethral sphincteric mechanism. During
assessments of specific support defects involved in prolapse the assessment, one should try to determine the specific cir-
often do not correspond to subsequent intraoperative find- cumstances leading to the involuntary loss of urine. If pos-
ings. Therefore, some investigators have advocated using sible, such circumstances should be reproduced and directly
imaging procedures such as ultrasonography, contrast radi- observed during clinical evaluation. The examination is most
ography, and magnetic resonance imaging (MRI) to further easily initiated with the patient’s bladder comfortably full.
describe the exact nature of pelvic support or other defects The patient is allowed to void as normally as possible in pri-
before attempting surgical repairs. For example, some prac- vate. The time to void and the amount of urine voided are
titioners have used contrast ultrasonography to evaluate recorded. The patient then returns to the examination room
for paravaginal defects by placing a water filled condom in and the volume of residual urine is noted by transurethral
the vaginal canal to better delineate the paravaginal spaces catheterization. If a sterile urine sample has not yet been
(Ostrzenski et al., 1997). Vaginal grafts, meshes, and slings obtained for analysis, it can be obtained at this time. A 50-mL
are easily seen on perineal ultrasound. Others have used syringe without its piston or bulb is attached to the catheter
MRI to better characterize the soft tissue and viscera of the and held above the bladder. The patient is then asked to sit
pelvis. However, currently there is a lack of standardized or stand and the bladder is filled by gravity by pouring 50-mL
radiologic criteria for diagnosing POP. Therefore, the clinical aliquots of sterile water into the syringe (Fig. 9.3). The
utility of imaging studies remains unknown; they are cur- patient’s first bladder sensation and maximum bladder capac-
rently mostly used for research purposes. ity are noted. The water level in the syringe should be closely
Patients with prolapse who are without symptoms of observed during filling, as any rise in the column of water can
defecatory dysfunction generally do not warrant ancillary be secondary to a detrusor contraction. Unintended increases
bowel testing. For example, although defecating proctog- in intraabdominal pressure by the patient should be avoided.
raphy can provide additional information regarding rectal The catheter is then removed and the patient is asked
emptying, Siproudhis et al. (1993) demonstrated that it is to cough in a standing position. Loss of small amounts of
no more sensitive at detecting rectoceles compared with urine in spurts simultaneous with the coughs strongly sug-
physical examination alone. However, patients with con- gests a diagnosis of urodynamic stress incontinence. Pro-
comitant defecatory dysfunction or motility disorders do longed loss of urine, leaking 5 to 10 s after coughing, or
merit further evaluation. no urine loss with provocation indicates that other causes
In patients with defecatory dysfunction, it is necessary to
differentiate between those with colonic motility disorders
versus those with pelvic outlet symptoms. Useful ancillary
tests include anoscopy and proctosigmoidoscopy to evaluate
for prolapsing hemorrhoids and