Benign Prostatic Hyperplasia:

Optimizing Management in the

Primary Care Setting

Educational Partner:
Asante Communications, LLC

June 23, 2012

Jacob Javits Convention CenterNew York, New York

Session 2: Benign Prostatic Hyperplasia:

Optimizing Management in the Primary Care Setting
Learning Objectives
1.
2.
3.
4.
5.

Conduct an initial and ongoing assessment of patients with benign prostatic hyperplasia (BPH), addressing lower
urinary tract symptoms (LUTS), coexisting disorders, and patient quality of life and function.
Evaluate the risk of BPH disease progression and complications.
Teach patients with BPH-LUTS practical self-management approaches and behavioral modifications to slow disease
progression.
Evaluate the clinical profiles and utility of 5- reductase inhibitors (5-ARIs),
-1 adrenergic receptor blockers, and phosphodiesterase-5 (PDE-5) inhibitors for patients with BPH-LUTS with and
without erectile dysfunction (ED).
Tailor monotherapy and multidrug regimens for patients with BPH-LUTS based in part on signs and symptoms, prior
medication history, ED and other common comorbidities, risk of disease progression, and patient goals.

Faculty

Martin M. Miner, MD, FAAFP

Clinical Associate Professor of Family Medicine and Urology
The Warren Alpert Medical School of Brown University
Co-Director, Mens Health Center
Chief of Family and Community Medicine
Miriam Hospital
Providence, Rhode Island
Dr Miner is clinical associate professor of family medicine and urology at the Warren Alpert Medical School of Brown
University in Providence, Rhode Island. Within the Lifespan/Brown University system, he is developing a multidisciplinary
mens health center. He is also chief of family and community medicine and co-director of the Mens Health Center at The
Miriam Hospital in Providence.
Dr Miner received his medical degree from the University of Cincinnati College of Medicine in Ohio, and completed his
residency at Brown University. He is a member of the American Academy of Family Physicians, Massachusetts Academy of
Family Physicians, and American Urological Association. In addition, Dr Miner is a fellow of the Sexual Medicine Society of
North America (SMSNA), Inc., and a member of the SMSNA board of directors. He is also a member of the International
Society for the Study of Womens Sexual Health and the steering committee for the International Society of Mens Health.
Dr Miner is active in several research studies on mens health. He has published extensively in the areas of erectile
dysfunction and cardiovascular disease, benign prostatic hyperplasia and lower urinary tract symptoms, and male sexuality
and hormone replacement therapy. He is the author/coauthor of numerous articles in such journals as Cleveland Clinic Journal
of Medicine, The Journal of Sexual Medicine, Mayo Clinic Proceedings, and American Journal of Medicine. He also serves on several
editorial boards.
Matt T. Rosenberg, MD
Medical Director
Mid-Michigan Health Centers
Chief, Department of Family Medicine
Foote Health System
Jackson, Michigan
Matt T. Rosenberg, MD, earned his medical degree at the University of California, Irvine. He trained in general surgery at
the University of California, Irvine, and in urologic surgery at the Brigham and Womens Hospital in Boston before
changing fields to general practice. Dr Rosenberg now practices in Jackson, Michigan, and serves as medical director of MidMichigan Health Centers. He is also actively on the staff of the Foote Health System, where he served as chief of the
department of family medicine from 2002 to 2006.
Dr Rosenberg has a special interest in the medical management of urologic diseases and has authored and coauthored
articles appearing in Urology, the Journal of Urology, BJU International, and other peer-reviewed journals. He has presented his
original research at many national meetings, including those of the National Institutes of Health, the American Urological

Session 2

Association, the Sexual Medicine Society of North America, and the European Society for Sexual Medicine. He is a reviewer
for several national and international journals and was recently selected to be the section editor of urology for the
International Journal of Clinical Practice.
Dr Rosenberg was honored as the most recent recipient of the Continence Care Champion award by the National
Association For Continence (NAFC). This nationwide award is bestowed by the NAFC board of directors to a healthcare
provider who has distinguished himself in research, clinical practice, and education with accomplishments meaningful to
continence care.
In the summer of 2006, Dr Rosenberg was featured in a PBS documentary on interstitial cystitis as part of the Healthy Body,
Healthy Mind series, which focused on some of his research findings in this clinical area.

Faculty Financial Disclosure Statements

The presenting faculty reports the following:

Martin M. Miner, MD, serves as a consultant for Abbott Laboratories and receives research grants from Auxilium
Pharmaceuticals, Inc.
Matt T. Rosenberg, MD, serves as a consultant for Astellas Pharma US, Inc.; Eli Lilly and Company; Ferring
Pharmaceuticals Inc.; Horizon Pharma; and Pfizer Inc. He is on the speakers bureau for Astellas Pharma US, Inc.; Forest
Laboratories, Inc.; Horizon Pharma; Ortho-McNeil-Janssen Pharmaceuticals, Inc; and Pfizer Inc.

Education Partner Financial Disclosure Statement

The content collaborators at Asante Communications, LLC, have reported the following:
Christopher S. Ontiveros, PhD, Group Scientific Supervisor, has no financial relationships to disclose.

Suggested Reading List

Gacci M, Eardley I, Giuliano F, et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract
symptoms due to benign prostatic hyperplasia. Eur Urol. 2011;60(4):809-825.
McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia.
J Urol. 2011;185(5):1793-1803.
Naslund MJ, Gilsenan AW, Midkiff KD, Bown A, Wolford ET, Wang J. Prevalence of lower urinary tract symptoms and
prostate enlargement in the primary care setting. Int J Clin Pract. 2007;61(9):1437-1445.
Rosenberg MT, Miner MM, Riley PA, Staskin DR. STEP: simplified treatment of the enlarged prostate. Int J Clin Pract.
2010;64(4):488-496.
Rosenberg MT, Staskin DR, Kaplan SA, MacDiarmid SA, Newman DK, Ohl DA. A practical guide to the evaluation and
treatment of male lower urinary tract symptoms in the primary care setting. Int J Clin Pract. 2007;61(9):1535-1546.

Session 2

Pharmacotherapeutic Agents in this Program

Generic

Trade

Alfuzosin
Doxazosin
Dutasteride
Finasteride

Uroxatral
Cardura, Cardura XL
Avodart
Propecia, Proscar
Fortamet, Glucophage, Glucophage XR,
Glumetza, Riomet
Actos
Revatio, Viagra
Rapaflo
Adcirca, Cialis
Flomax
Hytrin
Levitra, Staxyn

Metformin
Pioglitazone hydrochloride
Sildenafil
Silodosin
Tadalafil
Tamsulosin
Terazosin
Vardenafil

Benign Prostatic
Hyperplasia
Optimizing Management in
the Primary Care Setting

XL, extended release; XR, extended release.

Faculty

Educational Objectives
Upon completion of this CME initiative, participants should be better
prepared to:

Matt T. Rosenberg, MD
Medical Director
Mid-Michigan Health Centers
Chief, Department of Family Medicine
Foote Health System
Jackson, Michigan

1. Conduct an initial and ongoing assessment of patients with benign prostatic

hyperplasia (BPH), addressing lower urinary tract symptoms (LUTS),
coexisting disorders, and patient quality of life and function
2. Evaluate the risk of BPH disease progression and complications
3. Teach patients with BPH-LUTS practical self-management approaches and
behavioral modifications to slow disease progression
4. Evaluate the clinical profiles and utility of 5- reductase inhibitors (5-ARIs),
-1 adrenergic receptor blockers, and phosphodiesterase-5 (PDE-5) inhibitors
for patients with BPH-LUTS with and without erectile dysfunction (ED)
5. Tailor monotherapy and multidrug regimens for patients with BPH-LUTS
based in part on signs and symptoms, prior medication history, ED and other
common comorbidities, risk of disease progression, and patient goals

Martin M. Miner, MD
Clinical Associate Professor Family
Medicine and Urology
The Warren Alpert Medical School of
Brown University
Co-Director, Mens Health Center
Chief of Family and Community Medicine
Miriam Hospital
Providence, Rhode Island

Pre-Activity Evaluation
In men with LUTS, frequency and nocturia are usually
associated with bladder problems whereas hesitancy and
poor flow are usually associated with prostate problems.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

Alfuzosin and tamsulosin monotherapy reduce the risk of

BPH-LUTS disease progression.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

Physical activity reduces the risk of BPH-LUTS.

1.
2.
3.
4.
5.

1.
2.
3.
4.
5.

Phosphodiesterase-5 inhibitor monotherapy reduces

BPH-LUTS and ED.
1.
2.
3.
4.
5.

I currently obtain serum PSA measurements in patients with

LUTS.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

Tamsulosin monotherapy reduces BPH-LUTS and ED in

patients with both conditions.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

Compared to either drug alone, combination therapy with

tamsulosin and dutasteride is significantly more effective at
reducing clinical progression of BPH-LUTS.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

Pre-Activity Evaluation

1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

I currently recommend self-management approaches to my

patients who have BPH-LUTS.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Pre-Activity Evaluation

I currently consider combination pharmacotherapy for my

patients with BPH-LUTS.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Establishing BPH-LUTS
as a Clinical Construct

Assessment and Diagnosis in Primary Care

Matt T. Rosenberg, MD
Medical Director
Mid-Michigan Health Centers
Chief, Department of Family Medicine
Foote Health System
Jackson, Michigan

Prostate Function

BPH Is a Histologic Construct

Normal Function

Progressive disease associated with stromal-glandular hyperplasia

within the prostate

Does not grow (enlarge) into the urethra

allowing unobstructed urinary flow
Contributes to continence mechanism
Produces fluid for seminal emission

100

Prevalence, %

80

Abnormal Function
Obstruction of urinary flow
Sphincteric damage/usually surgical
(stress incontinence)

Baron, 1941
Harbitz, 1972
Karube, 1961
Franks, 1954
Moore, 1943
Holund, 1980
Pradhan, 1975
Fang-Lui, 1991
Swyer, 1944

60

40
20

Normal Prostate

0
20-29 30-39 40-49 50-59 60-69 70-79 80-89

Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds.
Campbell-Walsh Urology. 9th ed. Philadelphia, PA: WB Saunders/Elsevier; 2007:1973-1985.

Bladder Function

Filling, Storage, and Voiding

Normal function
Storage capacity (300 400 mL)
Adequate low pressure urinary storage (bladder)
Adequate outlet resistance (sphincter)

Empty to completion (minimal residual)

Adequate bladder contraction
Absence of outlet obstruction

Abnormal function
Voiding frequently small amounts
Uncontrollable urge (urgency) to empty
with frequency

Age, y

Roehrborn CG. Int J Impot Res. 2008;20(suppl 3):s11-s18.

Overactive Bladder
Syndrome that includes urinary urgency (intense, sudden
desire to void) with or without incontinence, urinary
frequency, and nocturia
Present without any pathologic or metabolic disorders that
might otherwise result in symptoms
Etiology is heterogeneous and may result from abnormal
signaling, a sensory amplification (afferent), or increased
motor output (efferent)

Incomplete emptying
Hesitancy, poor stream, feeling of incomplete emptying

Poor function = failure to store or empty

Lukacz ES, et al. Int J Clin Pract. 2011;65(10):1026-1036; Wein AJ. Pathophysiology and categorization of
voiding dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds. Campbell-Walsh Urology. 9th ed. Philadelphia, PA:
WB Saunders/Elsevier; 2007:1973-1985.

Abrams P, et al. Neurol Urodyn. 2002;21(2):167-178; Ouslander JG. N Engl J Med. 2004;350(8):786-799;
Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.

Male Lower Urinary Tract Symptoms

BPH-LUTS vs OAB

Storage (bladder/OAB)
Urgency
Frequency
Nocturia
Urge incontinence
Stress incontinence
Mixed incontinence
Overflow incontinence

Voiding (prostate/BPH-LUTS)
Hesitancy
Poor flow/weak stream
Intermittency
Straining to void
Terminal dribble
Prolonged urination
Urinary retention

Prevalence and Bother of Urinary

Symptoms in BPH-LUTS
Bothersomeness

Frequency

Bladder Pain
Urge Incontinence
Straining
Post-mict. Dribbling
Frequency
Nocturia
Urgency
Incomplete Emptying
Hesitancy
Intermittency
Reduced Stream
Terminal Dribbling

Many patients exhibit both OAB and BPH-LUTS

OAB, overactive bladder.

Lukacz ES, et al. Int J Clin Pract. 2011;65(10):1026-1036; Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546;
Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds.
Campbell-Walsh Urology. 9th ed. Philadelphia, PA: WB Saunders/Elsevier; 2007:1973-1985.

10

20

30

Post-mict, post-micturition.
Peters TJ, et al. J Urol. 1997;157(3):885-889.

BPH, LUTS, EP, and BOO

40

50

60

70

80

Common Comorbidities
Erectile or Other
Sexual Dysfunction

All Men >40 y

36

Hypertension

53

High Cholesterol

45

Heart Disease/Heart Failure

EP

Histologic
BPH

18

General Pain/Inflammation

11

Digestive Tract Disorder

21

Diabetes

BOO

17

Depression/Anxiety/
Sleep Disorder

16

Arthritis

20

Allergies/Cold/Flu/Congestion

LUTS

Incidence, %

22.3

14.9

15.3
12.4

13.2
10.3

10

7.5

Reduced NO
cGMP signaling

Increased RhoA
ROCK signaling

FUNCTIONAL
CONSEQUENCES AT
TISSUE LEVEL
(corpora cavernosa,
prostate, urethra, and
bladder functional
alterations)

0
50-59 Years

n=10,636 sexually active men within the last 4 weeks.

McVary KT, et al. BJU Int. 2006;97(suppl 2):23-28.

60-69 Years

50

60

70-79 Years

Autonomic
hyperactivity

Pelvic
atherosclerosis

Reduced function of nerves

and endothelium
Altered smooth muscle
relaxation or contractility

BPH-LUTS
ED

Arterial insufficiency, reduced

blood flow, and hypoxia-related
tissue damage

Chronic inflammation
Normal ED

40

BPH-LUTS and ED

18.3
15.8

30

Common Pathophysiologic Mechanisms

21.1
19.2

20

Roehrborn CG, et al. BJU Int. 2007;100(4):813-819.

No
Mild
Moderate
Severe

18.9

10

BPH-LUTS Registry Patients, %

Erectile Function Declines

With LUTS Severity

20

15
0

BOO, bladder outlet obstruction; EP, enlarged prostate; LUTS, lower urinary tract symptoms.
Emberton M, et al. Int J Clin Pract. 2008;62(7):1076-1086; Roehrborn CG. Rev Urol. 2005;7(suppl 9):S3-S14;
Roehrborn CG. Med Clin N Am. 2011;95(1):87-100.

30

100

BPH-LUTS

Complex Interrelationship

Severe ED

90

BPH-LUTS Patients, %

Steroid hormone unbalance

Comorbidities
Hypertension, Metabolic Syndrome, Diabetes, etc.
cGMP, cyclic guanosine monophosphate; NO, nitric oxide; ROCK, Rho-associated protein kinase.
Gacci M, et al. Eur Urol. 2011;60(4):809-825.

Dennis

LUTS Evaluation

Presentation to PCP

Unlikely OAB/BPH/SI

Focused HPE

Treat or Refer

UA/PSA Blood Sugar

Likely OAB/BPH/SI
No

Desires
Treatment

Im going to the bathroom more

frequently and afraid that my
diabetes is getting worse.

Watchful
Waiting

Yes
Provisional BPH
Provisional
OAB/SI

Treat for BPH

Effective

Continue
Medication

Effective

Continue
Medication

Ineffective

Assess and
Treat OAB/SI
Ineffective

Refer
HPE, history and physical exam; PSA, prostate-specific antigen; SI, stress incontinence; UA, urinalysis.
Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.

LUTS Evaluation

Focused Physical Exam

Abdominal palpation for tenderness, masses, or
bladder distension
Neurologic evaluation to assess general mental status,
ambulatory status, and motor function
Genitalia exam including the meatus and testes
Digital rectal exam (DRE) to evaluate rectal tone, prostate
size, consistency, nodules, or pain

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546; Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

Medications Can Cause or

Exacerbate BPH-LUTS
Medication
Sedatives
Alcohol, caffeine, diuretics
Anticholinergics
-Agonists
-Blockers
Calcium-channel blockers
Angiotensin-converting
enzyme
First-generation
antihistamines
Cholinesterase inhibitors
Opioids

LUTS-Related Effect
Confusion, secondary incontinences
Diuresis
Impaired contractility, voiding difficulty, overflow incontinence
Increased outlet resistance, voiding difficulty
Decreased urethral closure, stress incontinence
Reduce bladder smooth muscle contractility
Induce cough, stress urinary incontinence
Increase outlet resistance
Precipitate urge incontinence
Constipation

DeBeau CE. J Urol. 2006;175(3, pt 2):S11-S15; Gill SS, et al. Arch Intern Med. 2005;165(7):808-813; Lavelle JP, et al.
Am J Med. 2006;119(3, suppl 1):37-40; Newman DK. Nurse Pract. 2009;34(12):33-45;
Wyman JF, et al. Int J Clin Pract. 2009;63(8):1177-1191.

Voiding Diary

Evaluation of Frequency and Volumes

Differentiates between
behavioral and LUTS
pathology
Alerts the patients to
modifiable
habits/opportunities
Monitors treatment
progress and efficacy

Wyman JF, et al. Int J Clin Pract. 2009;63(8):1177-1191.

Relationship Between
PSA and Prostate Size
DRE tends to
underestimate prostate
size in larger prostates
PSA is more accurate than
a DRE when estimating
prostate size
PSA 1.5 ng/mL suggests
a prostate volume >30 mL

Age

65

75

60

Prostate Volume, mL

PCP, primary care physician.

70
65
60
55
50

55
50
45
40
35
30
1

Serum PSA, ng/mL

Bosch J, et al. Eur Urol. 2004;46(6):753-759; Roehrborn C, et al. Urology. 1999;53(3):581-589;

Roehrborn CG. Int J Impot Res. 2008;20(suppl 3):s19-s26.

Dennis

Differential Diagnosis of LUTS

Bladder cancer
Prostate cancer
Prostatitis
Bladder stones
Interstitial cystitis
Radiation cystitis
Urinary tract infection
Diabetes mellitus

Patient Evaluation

Parkinsons disease
Primary bladder neck
hypertrophy
Congestive heart failure
Lumbosacral disc disease
Multiple sclerosis
Nocturnal polyuria

Symptom onset may provide a clue to the etiology

Personal history
Medical history
Diagnosed 6 years earlier with type 2
diabetes controlled with medication
and diet
Metformin ER: 1000 mg daily
Pioglitazone hydrochloride: 30 mg daily

No prior UTI or trauma to genitourinary

tract

Laboratory tests
Fasting serum glucose: 98 mg/dL
Serum HbA1c: 6%
Urinalysis: clear, no growth with
midstream specimen culture
PSA: 1.7 ng/mL
Creatinine*: 1 mg/dL

Patient Interview

Not at
All

Less Than
One Time
in Five

Less Than
Half the
Time

About
Half the
Time

More Than
Half the
Time

Almost Always

1. Over the past month, how often have you had a

sensation of not emptying your bladder
completely after you finished urinating?

2. Over the past month, how often have you had to

urinate again less than 2 hours after you
finished urinating?

3. Over the past month, how often have you found

you stopped and started again several times
while urinating?

4. Over the past month, how often have you found

it difficult to postpone urination?

5. Over the past month, how often have you had a

weak urinary stream?

6. Over the past month, how often have you had to

push or strain to begin urination?

7. Over the past month, how many times did you

typically get up to urinate from the time you went
to bed until the time you got up in the morning?

Never

1 time

2 times

3 times

4 times

5 times

18

HR: 87 bpm
BP: 138/85 mm Hg
Height: 5 11; Weight: 235 lbs
BMI: 32.8 (obese)
Abdominal exam: unremarkable
Neurologic exam: unremarkable
Genital exam: unremarkable
DRE: 50 mL, smooth, nontender

Dennis

AUA Symptom Index

Total for Urinary Symptoms:

*Not uniformly recommended as part of laboratory evaluation in patients with possible LUTS; however, this test
provides information about the status of renal function.
BP, blood pressure; BMI, body mass index; bpm, beats per minute; HR, heart rate; UTI, urinary tract infection.
Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.

Urinary Symptoms

Physical exam

62 years old
Married 35 years

Are patient-administered questionnaires practical

during an often time-constrained primary care visit?
In your practice, how do you determine the severity
of the patients symptoms?

Mild: 0-7; Moderate: 8-19; Severe: 20-35

AUA, American Urological Association.
Adapted from Barry M, et al. J Urol. 1992;148(5):1549-1557.

Risk of BPH Progression

Worsening of symptoms
Deterioration of urinary flow rate
Increase in prostate volume
Outcomes such as AUR and need for surgery
Renal insufficiency
Recurrent urinary tract infection

Natural History of Disease Progression

Age

55 yrs

60 yrs

65 yrs

70 yrs

PV
PSA

30 mL
1.5 ng/mL

>40 mL

>50 mL

>61 mL

A 55-year-old man with a 30 mL prostate volume, PSA=1.5 ng/mL, and

BPH-LUTS can expect a doubling of prostate size over the next 15 years
AUR, acute urinary retention.
Emberton M, et al. Int J Clin Pract. 2008;62(7):1076-1086.

PV, prostate volume.

Roehrborn C, et al. J Urol. 2000;163(1):13-20.

AUR/BPH-Related Surgery Rates

Increase With Increasing Baseline PSA
PLESS Placebo 4-Year Data

30

Cumulative Incidence, %

25
20
15

Either
Surgery

10
5

AUR

Risk Evaluation of BPH-LUTS Progression

Baseline Factors as Predictors

Five risk factors

1. Total prostate volume 31 mL
2. PSA 1.6 ng/mL
3. Age 62
Not usually evaluated by the PCP
4. Qmax <10.6 mL/s
5. PVR 39 mL

0
>0.0 >0.5 >1.0 >1.5 >2.0 >2.5 >3.0 >3.5 >4.0 >4.5 >5.0 >5.5 >6.0 >6.5 >7.0 >7.5 >8.0

Baseline PSA, ng/mL

PLESS, Proscar Long-Term Efficacy and Safety Study.

Roehrborn CG. Int J Impot Res. 2008;20(suppl 3):S19-S26; Roehrborn CG, et al. Urology. 1999;53(3):473-480.

LUTS and Indications for Referral

Suspicion of neurologic cause of symptoms

History of recurrent UTI or other infection
Findings or suspicion of urinary retention
Abnormal prostate exam (nodules)
Microscopic or gross hematuria
History of genitourinary trauma
Prior genitourinary surgery
Uncertain diagnosis
Meatal stenosis
Elevated PSA
Pelvic pain

Treatment choice does not hinge on Qmax and PVR

PVR, post-void residual; Qmax, maximum flow rate.
Crawford ED, et al. Urology. 2006;175(4):1422-1427.

Conclusions
BPH is a histologic construct; BPH-LUTS is a clinical
construct
BPH-LUTS is often comorbid with other disorders (eg, ED)
BPH-LUTS is a progressive disease
Assessment of BPH-LUTS is based primarily on a focused
physical exam and history, laboratory tests, and evaluation
of symptom bother

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546; Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

Formulating an Approach to
Initial and Ongoing
Management of BPH-LUTS in
Primary Care
Martin M. Miner, MD
Clinical Associate Professor Family Medicine and Urology
The Warren Alpert Medical School of Brown University
Co-Director, Mens Health Center
Chief of Family and Community Medicine
Miriam Hospital
Providence, Rhode Island

Treatment Now Can Be Empiric

No identifiable etiology
No reversible causes
Bother?
No, watchful waiting
Yes, treatment
Weak flow think prostate
Poor voiding volumes think bladder

Rosenberg MT. Curr Urol Rep. 2008;9(6):428-432.

4 Years of Watchful Waiting in

Mild BPH-LUTS
Clinical Progression

100

Worse IPSS

Same IPSS

Self-Management and Behavioral

Modification for BPH-LUTS

Better IPSS

Successful self-management is facilitated by

enhancing problem-solving and goal-setting skills,
and developing interventions that promote
behavioral change

84
75

Patients, %

80
65

60

60
40
20

20

13

17
9

11

10

Education and reassurance

Fluid management
Caffeine and alcohol regulation
Medication adjustment
Toilet and bladder training

12 Months

24 Months

36 Months

48 Months

87% of men with mild symptoms had symptom worsening, while 13% had
reduced or stabilized symptoms
N=397 men who presented with mild LUTS suggestive of BOO (IPSS score <8). IPSS, International Prostate Symptom Score.
American Urological Association (AUA) defines BOO as the generic term for all forms of obstruction to the bladder outlet (eg, urethral
stricture). AUA Clinical Practice Guidelines. Benign Prostatic Hyperplasia. Chapter 1: Guideline on the Management of Benign Prostatic
Hyperplasia (BPH). http://www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines/main-reports/bphmanagement/chap_1_GuidelineManagementof(BPH).pdf; Djavan B, et al. Urology. 2004;64(6):1144-1148.

100
80

Treatment
failure

SC

SM

60
40

20

20

IPSS Score

Subjects, %

Self-Management Significantly Reduces

Treatment Failure and LUTS
15
10

BPH Impact
Index

SC

SM

0
3 months

6 months

Moderate

Vigorous

Meigs et al, 2001

6 months

AUA QoL

12 months

SC

SM

Lacey et al, 2001

Del Maso et al, 2006
Rohrmann et al, 2005
Hong et al, 2006

3 months

6 months

12 months

Rohrmann et al, 2006

Combined

12 months

Source
Gann et al, 1995

4
2

Moderate and Vigorous Physical Activity

Reduces the Risk of BPH and LUTS
Platz et al, 1998

3 months

12 months

AUA-QoL Score

BII Score

6 months

4
2

SM

0
3 months

SC

IPSS

Newman S, et al. Lancet. 2004;364(9444):1523-1537; Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496;
Yap T, Emberton M. Curr Opin Urol. 2010;20(1):20-27.

BII, BPH Impact Index; IPSS, international prostate symptom score; QoL, quality of life; SC, standard care;
SM, self-management.
*P<0.05 vs SC; N= 140 men >40 with LUTS (n=67 for SC; n=73 for SM); SC began with watchful waiting. Escalation to
medical treatment and surgery was left to the discretion of the clinician and patient. The SM group included SC as well
as 3 small group sessions comprising education, lifestyle advice, and training in problem solving and goal setting.
Brown CT, et al. BMJ. 2007;334(7583):25.

Dennis

P=0.006
2.0
0.74
95% CI, 0.60-0.92

0.18

Odds Ratio

0.74
95% CI, 0.59-0.92

3.1

Odds Ratio

Physical activity was divided into low, moderate, and vigorous levels corresponding to intensity categories
within the individual studies.
Parsons JK, Kashefi C. Eur Urol. 2008;53(6):1228-1235.

Medical Management of BPH-LUTSED

Diagnosed with BPH-LUTS

What nonpharmacologic treatment
recommendations could you provide if the patient
prefers not to take medication?
Does his AUA Symptom Index score of 18
(moderate severity) influence your recommended
treatment approach?
Would your treatment recommendation change if his
score indicated mild symptoms or severe symptoms?

P=0.005
0.9

Predominant
Bladder Outlet
Obstruction

Small Gland and/or

Low PSA*
-Blocker

Larger Gland and/or

Higher PSA
-Blocker +
5-Reductase
Inhibitor

PDE5 Inhibitor?

*PSA

<1.5 ng/mL; PSA >1.5 ng/mL.

BOO, bladder outlet obstruction; PDE5, phosphodiesterase 5. American Urological Association (AUA) defines BOO as
the generic term for all forms of obstruction to the bladder outlet (eg, urethral stricture).
Abrams P, et al. J Urol. 2009;181(4):1779-1787; AUA Clinical Practice Guidelines. Benign Prostatic Hyperplasia.
Chapter 1: Guideline on the Management of Benign Prostatic Hyperplasia (BPH).
http://www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines/mainreports/bphmanagement/chap_1_GuidelineManagementof(BPH).pdf; McVary KT, et al. J Urol. 2011;185(5):1793-1803.

-Adrenergic Receptor Antagonists

-Adrenergic Receptor Antagonists

ALTESSSymptoms vs Symptom Progression

1-Blocker

1-Receptor Selectivity

Side Effects*

Doxazosin

1A=1D=1B

Dizziness, dyspnea, edema, fatigue, somnolence

Terazosin

1A=1D=1B

Asthenia, dizziness, postural hypotension

Alfuzosin

1A=1D=1B

Dizziness, upper respiratory tract infection

Tamsulosin

1A=1D>1B

Abnormal ejaculation, asthenia, back pain, dizziness,

increased cough, infection, rhinitis, sinusitis, somnolence

Silodosin

1A>1D>1B

Retrograde ejaculation

*Adverse

20

16.8
11.7

Allows for immediate symptom relief from the -blocker while

facilitating prostate reduction from the 5-reductase inhibitor.

P=0.82

Symptom Progression

-Blockers reduce symptoms but not the risk

of AUR or BPH-related surgery
ALTESS, Alfuzosin Long-Term Efficacy and Safety Study; AUR, acute urinary retention; OD, once daily.
Roehrborn CG, et al. BJU Int. 2006;97(4):734-741.

Combination Therapy

25

Finasteride (P=0.002)

15

Doxazosin (P<0.001)

10

Finasteride+Doxazosin (P<0.001)

0
3.0

3.5

4.0

4.5

5.0

5.5

Years

Doxazosin or finasteride monotherapy and the two drugs in combination reduce the
risk of overall clinical progression of BPH
Combination therapy is significantly more effective at reducing clinical progression
than either drug alone
MTOPS, Medical Therapy of Prostatic Symptoms.
Progression was defined by an increase of 4 points vs baseline in the AUA Symptom Index score, acute urinary
retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection.
McConnell JD, et al. N Engl J Med. 2003;349(25):2387-2398.

Incidence, %

Cumulative Incidence of
Progression, %

Placebo

2.5

Type II

5 weeks

<1 day

Half-life
Serum DHT

~95% reduction

~70% reduction

Intraprostatic
DHT

~98% reduction

68%-85% reduction

PSA

~50% reduction

Prostate volume

~25% reduction
Reduced libido,
impotence

Abnormal ejaculation,
decreased ejaculate
volume, impotence,
reduced libido

CombAT Study

20

2.0

Finasteride

Type I and II

RRR=65.8%
(54.7%, 74.1%)

25

1.5

Dutasteride
5-Reductase
specificity

Combination Therapy

MTOPS Study

1.0

BPH-Related Surgery

*Adverse effects present in 2% of treated vs non-treated subjects.

DHT, dihydrotestosterone.
Avodart package insert. 2012; Azzouni F, et al. Adv Urol. 2012:530121; Gravas S, Oelke M. World J Urol.
2010;28(1):9-15; Proscar package insert. 2012; Roehrborn CG. Int J Impot Res. 2008;20(suppl 3):S11-S18;
Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

*PSA <1.5 ng/mL; PSA >1.5 ng/mL.

Crawford ED, et al. Urology. 2006;175(4):1422-1427; Kaplan S. Urology. 2009;73:2417;
Roehrborn CG, et al. Eur Urol. 2009;55(2):461-471.

0.5

AUR

Adverse events*

5.1

PDE5 Inhibitor?

Larger Gland and/or

Higher PSA
-Blocker +
5-Reductase
Inhibitor

6.5
2.1

1.8

Blocks conversion of testosterone to

DHT, shrinking the prostate and
preventing further growth
Improves flow and bothersome
symptoms similar to -blockers but
may take 3-6 months

Predominant
Bladder Outlet
Obstruction

0.0

P=0.18

10

5-Reductase Inhibitors Regulate

Prostate Growth and BPH Development

Rationale for Combination Therapy

Small Gland and/or

Low PSA*
-Blocker

Alfuzosin 10 mg OD (n=749)

P=0.0013

15

effects present in 2% of treated vs non-treated subjects.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019668s021lbl.pdf de La Rosette J, et al. J Urol. 2002;167(4):1734-1739

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020579s027lbl.pdf; Hatano A, et al. Br J Pharmacol. 1994;113(3):723728; http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019057s022lbl.pdf; Lepor H. Rev Urol. 2011;13(1):20-33;
McConnell J, et al. N Engl J Med. 2003;349(25):2387-2398; Schwinn DA, Michelotti GA. BJU Int.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022206s006lbl.pdf; 2000;85(suppl 2):6-11;
http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021287s016lbl.pdf; Yoo TK, Cho HJ. Korean J Urol. 2012;53:139-148.

Placebo (n=757)

25

Cumulative Incidence, %

Relieve BOO by inhibiting 1-adrenergicmediated contraction and relaxing smooth

muscle contraction of the urethra and bladder
Symptomatic relief usually occurs within the first week of treatment
Potential side effects are decreased with uroselective agents

20
15

RRR=44.1%
(33.6%, 53.0%)

RRR=19.6%
(-10.9%, 41.7%)

RRR=31.2%
(17.7%, 42.5%)
21.5
17.8

Combination (n=1610)
Dutasteride (n=1623)
Tamsulosin (n=1611)

11.9

12.6

n=191

n=203

10
5
0

4.2

n=67

5.2

n=84

AUR or BPH-Related Surgery

n=289

n=347

BPH Clinical Progression

Dutasteride and tamsulosin combination therapy significantly reduced the relative

risk of AUR or BPH-related surgery compared with tamsulosin monotherapy
Combination therapy significantly reduced the relative risk of BPH clinical
progression and symptom deterioration compared with both monotherapies
CombAT, Combination of Avodart and Tamsulosin; RRR, reduction in relative risk.
Roehrborn CG. Eur Urol. 2010;57(1):123-131.

Phosphodiesterase 5 Inhibitor Therapy

Phosphodiesterase 5 Inhibitors

Potential Overlapping Role in BPH-LUTS and ED

Alters signaling pathways (eg, NO/cGMP and smooth

muscle relaxation)
Modulates ANS overactivity and afferent nerve activity from
bladder and prostate
Increases pelvic blood perfusion reducing lower urinary tract
chronic ischemia
Reduces inflammation

PDE5 Inhibitor
Sildenafil

Erectile dysfunction

Tadalafil

Erectile dysfunction
Signs and symptoms of BPH
Erectile dysfunction and the
signs and symptoms of BPH

Back pain, dyspepsia, flushing,

headache, limb pain, myalgia,
nasal congestion

Erectile dysfunction

Dyspepsia, flushing, headache,

rhinitis, sinusitis

Vardenafil

Vardenafil at 8 Weeks Reduces

Symptoms in BPH-LUTSED

Management of Patient With ED and BPH-LUTS

Common Clinical Questionnaires

Erectile function
Orgasmic function
Sexual desire
Intercourse satisfaction
Overall satisfaction

Clinical interpretation of IIEF score

Clinical interpretation of IPSS

Mildly symptomatic: 0-7
Moderately symptomatic: 8-19
Severely symptomatic: 20-35

Severe dysfunction, 0-6

Moderate dysfunction, 7-12
Mild to moderate dysfunction, 13-18
Mild dysfunction, 19-24
No dysfunction, 25-30

20
15.9

15.9
13.2

13.4

10

Baseline

12 Weeks

IPSS Score,
Mean Change From Baseline

IIEF-EF Score, Mean

20

-3.00

20
16.8

16.8

15

13.2

11.0
10

0
Baseline

8 Weeks

Baseline

8 Weeks

vs placebo;
vs placebo. EF, erectile function.
Vardenafil is not FDA approved for the treatment of BPH-LUTS.
Increasing IIEF-EF denotes improvement in erectile function; Decreasing IPSS denotes reduced LUTS.
Stief CG, et al. Eur Urol. 2008;53(6):1236-1244.

P=0.0013

64 Weeks Tadalafil Reduces

Symptoms in BPH-LUTSED
6

Sildenafil (n=179)

0.00
23.5*

17.4

-1.9

-6.00
-6.3*

IIEF-EF Score,
Mean Change From Baseline*

Placebo (n=162)

15.9

10

Sildenafil at 12 Weeks Reduces

Symptoms in BPH-LUTS+ED
Placebo (n=170)
Sildenafil (n=181)

Placebo (n=110)
Vardenafil (n=105)

23.4*

*P=0.0001

Barry MJ, et al. J Urol. 1992;148(5):1549-1557; Rosen RC, et al. Urology. 1997;49(6):822-830.

30

25

Vardenafil (n=105)

IPSS Score, Least Square Mean

Placebo (n=110)

30

5.9

Men without ED (n=132)

20
4

2
1.1

*P<0.0001 vs placebo.
Sildenafil is not FDA approved for the treatment of BPH-LUTS.
Increasing IIEF-EF denotes improvement in erectile function; Decreasing IPSS denotes reduced LUTS.
McVary KT, et al. J Urol. 2007;177(3):1071-1077.

18.1 17.8
13.8 14.0

15

12.7 13.2

10

0
Week 0-64

-9.00

Men with ED (n=295)

25

IPSS Score, Mean

Incomplete emptying
Frequency
Intermittency
Urgency
Weak stream
Straining
Nocturia
Quality of life

International Index of Erectile Function

(IIEF) score assesses

IIEF-EF Score, Least Square Mean

Adverse Events*
Abnormal vision, diarrhea,
dyspepsia, flushing, headache,
nasal congestion

*Adverse effects present in 2% of treated vs non-treated subjects.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf;
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020895s036lbl.pdf;
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021400s013lbl.pdf

ANS, autonomic nervous system; cGMP, cyclic guanosine monophosphate; NO, nitric oxide.
Andersson KE, et al. Neurourol Urodyn. 2011;30(3):292-301.

International Prostate Symptom Score

(IPSS) assesses

Indication

Week 12-64

Baseline

12 Weeks

64 Weeks

*N=219

sexually active men with ED.

Increasing IIEF-EF denotes improvement in erectile function; Decreasing IPSS denotes reduced LUTS.
Donatucci CF, et al. BJU Int. 2011;107(7):1110-1116.

10

Tadalafil and Tamsulosin Monotherapy

PDE5 Inhibitors + -Blockers

5
4

IPSS Score,
LS Mean Change From Baseline

IIEF-EF Score,
LS Mean Change From Baseline

BPH-LUTS and ED

3
2
1
0
-1
Tadalafil 5 mg

Tamsulosin 0.4 mg

BPH-LUTS, ED, and Flow Rate

Source

Placebo
Tadalafil 5 mg
Tamsulosin 0.4 mg

-1
-2

-2

Liguori et al, 2009

-5

-6

Tuncel et al, 2009

0 1

Gacci et al, 2012

Overall

12/EP
-blocker
+ PDE5 inhibitor

Duration of Treatment, Weeks

-blocker
alone

-blocker
+ PDE5 inhibitor

Conclusions

What pharmacologic treatment would you

recommend for Dennis BPH-LUTS?
How would you restructure therapy if Dennis
diabetes remains well controlled and his LUTS
persist at a 3-month follow-up appointment?
Would a comorbid diagnosis of ED influence your
treatment choice?

In men with LUTS, frequency and nocturia are usually

associated with bladder problems whereas hesitancy and
poor flow are usually associated with prostate problems.

-blocker
+ PDE5 inhibitor

PDE5 inhibitors included in the meta-analyses are sildenafil, tadalafil, vardenafil, and UK-369003; -blockers
included in the meta-analyses are alfuzosin and tamsulosin.
Gacci M, et al. Eur Urol. 2012;61(5):994-1003.

Dennis

Post-Activity Evaluation

-blocker
alone

Compared with monotherapy, -blocker + PDE5 inhibitor combination

therapy results in greater IPSS, IIEF, and Qmax improvement

*P<0.001 vs baseline; P<0.05 vs placebo.

IIEF-EF, International Index of Erectile Function-Erectile Function Domain; LS, least square.
Oelke M, et al. Eur Urol. 2012;61(5):917-925.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Qmax
Mean Differences

0 2 4 6 8 10 12

-2

Bechara et al, 2008

-4

Tadalafil or tamsulosin monotherapy similarly reduced BPH-LUTS

Tadalafil reduced erectile dysfunction

1.
2.
3.
4.
5.

IIEF Score
Mean Differences

-4

Kaplan et al, 2007

-3

-7

IPSS Score
Mean Differences
-6

Behavioral modifications and pharmacotherapy comprise

potential treatment approaches for BPH-LUTS
Treatment regimens are based in part on signs and
symptoms, medication history, comorbidities, risk of disease
progression, and patient preferences
Combination therapy with an -blocker and 5-reductase
inhibitor is significantly more effective at reducing clinical
progression than either drug alone
PDE5 inhibitors are a newly available pharmacotherapy to
reduce LUTS and ED

Post-Activity Evaluation

Alfuzosin and tamsulosin monotherapy reduce the risk of

BPH-LUTS disease progression.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

11

Post-Activity Evaluation

Physical activity reduces the risk of BPH-LUTS.

1.
2.
3.
4.
5.

1.
2.
3.
4.
5.

Phosphodiesterase-5 inhibitor monotherapy reduces

BPH-LUTS and ED.
1.
2.
3.
4.
5.

I now plan to obtain serum PSA measurements in patients

with LUTS.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Post-Activity Evaluation

Tamsulosin monotherapy reduces BPH-LUTS and ED in

patients with both conditions.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Post-Activity Evaluation

Compared to either drug alone, combination therapy with

tamsulosin and dutasteride is significantly more effective at
reducing clinical progression of BPH-LUTS.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Post-Activity Evaluation

Post-Activity Evaluation

1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Post-Activity Evaluation

I now plan to recommend self-management approaches to

my patients who have BPH-LUTS.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

12

Post-Activity Evaluation
I now plan to consider combination pharmacotherapy for my
patients with BPH-LUTS.
1.
2.
3.
4.
5.

Strongly Disagree
Disagree
Neutral
Agree
Strongly agree

Audience
Question & Answer Session

13