Abnormal Uterine Bleeding

BLOODY HELL
Abnormal Uterine Bleeding

(AUB)
Dr. Christiane Kuntz
MD CCFP FCFP
Annual Scientific Assembly
Nov. 29, 2013
Faculty/Presenter Disclosure
• Faculty: Dr. Christiane Kuntz
• Program: 51st Annual Scientific Assembly
• Relationships with commercial interests:

– Grants/Research Support: none
– Speakers Bureau/Honoraria: see next slides
– Consulting Fees: none
– Other: none
Disclosure of Commercial
Support
• This program has received no financial support through any
commercial organization.
• This program has received no in-kind support from any
commercial organization.
• Potential for conflict(s) of interest:

– Bayer/Berlex are makers of Mirena which will be discussed in this
session; the company has provided unrestricted educational
grants to fund the Benign Uterine Conditions project sponsored by
the OCFP.
Mitigating Potential Bias
• The speaker has no direct involvement with
Bayer/Berlex in terms of financial support; the OCFP
administers the BUC program through an
unrestricted educational grant.
Objectives
 Define AUB in pre-, peri- and post-
menopausal women
 Explore the etiology and pathophysiology
of AUB
 Review assessment tools
 Discuss treatment options
 Apply learning pearls through clinical
cases
Normal Menstrual Physiology
 average cycle 28-35 d, with approximately
14-21 d in follicular phase and 14 d in
luteal phase (relatively constant)
 relatively little cycle variability ages 20-40
 cycle varies 5-7 y after menarche and for
10 y before menopause
 cycle often shortens as women approach
menopause
 follicular phase begins with the onset of
menstrual flow and ends on the day
before the luteinizing hormone (LH) surge
 luteal phase begins on the day of the LH
surge and ends at the onset of the next
menstrual period
Hormonal Changes during
Normal Menstrual Cycle

Abbreviations
 Estradiol (E)
 Progesterone (P)
 Gonadotropin-releasing hormone (GnRH)
 Follicle-stimulating hormone (FSH)
 Luteinizing hormone (LH)
 Transvaginal Ultrasound (TVUS)
 Early follicular phase:
 low E & P levels
 release from the negative feedback effects of E,
P, and probably luteal phase inhibin A results in
late follicular phase increase in GnRH pulse
frequency and subsequent increase in FSH
 small increase in FSH secretion appears to be
required for the recruitment of the subsequent
group of developing follicles, one of which will
become dominant and ultimately ovulatory follicle
during that cycle
 rapid increase in LH pulse frequency at this time
 Early follicular phase:
 TVUS has demonstrated that ovary is quiescent
except for occasionally visible resolving corpus
luteum from the previous cycle
 The endometrium is relatively indistinct during
menses and then becomes a thin line once
menses is complete
 normal to see small follicles of 3 to 8 mm in
diameter at this time
 Mid-follicular phase:
 Increase in FSH secretion causes follicle growth
and E production
 Ovarian follicle granulosa cells hypertrophy and
divide, producing increasing E via FSH
stimulation of aromatase and then inhibin A
 Increase in E production feeds back negatively
on the hypothalamus and pituitary, resulting in
suppression of mean serum FSH and LH
concentrations as well as the LH pulse amplitude
 Mid-follicular phase:
 In comparison, the GnRH pulse generator
speeds up slightly to a mean LH pulse
frequency of about one per hour (vs. one
per 90 minutes in early follicular phase)
 GnRH stimulation is presumably due to
release of negative feedback effects of P
from the previous luteal phase
Mid-follicular phase:
 Within about 7 d from the onset of
menses, several 9 to 10 mm antral follicles
are visible on TVUS
 increasing E results in thickening
endometrium, with increase in number of
glands and development of "triple stripe"
pattern on TVUS
 Late follicular phase:
 E and inhibin A levels increase daily during the
week before ovulation due to release from the
growing follicle
 Serum FSH and LH concentrations decrease at
this time due to negative feedback effects of E
 As dominant follicle selected and grows, FSH
induces LH receptors in the ovary and increases
ovarian secretion of intrauterine growth factors
such as insulin-like growth factor-I (IGF-I)
 Endometrium thickens further
 Mid-cycle surge and ovulation:
 E continues to rise until peak approximately 1 d
before ovulation
 Mid-cycle surge represents a switch from
negative feedback control of LH secretion by
ovarian hormones (such as E & P) to sudden
positive feedback effect, resulting in 10X
increase in LH and smaller rise in FSH
 other ovarian factors contribute to the LH surge
besides E & P (poorly understood)
 Ovulation:
 LH surge initiates substantial changes in the ovary
 Oocyte in dominant follicle completes its first meiotic
division
 Local secretion of plasminogen activator and other
cytokines required for ovulation increased
 Oocyte is released from the follicle at the surface of the
ovary approximately 36 hours after LH surge
 Oocyte travels down fallopian tube to the uterine cavity
 Close relation of follicular rupture and oocyte release to
the LH surge and as a result, measurements of serum or
urine LH can be used to estimate the time of ovulation in
women
 Ovulation:
 Even before oocyte released, granulosa cells surrounding
it begin to luteinize and produce progesterone
 Progesterone acts rapidly to slow pulse generator so that
LH pulses become less frequent by the termination of
surge
 Gradually increasing serum P has a profound impact on
the endometrial lining initiating cessation of mitoses and
"organization" of the glands
 Change can be detected on US relatively soon after
ovulation: the "triple stripe" image is lost and the EE
becomes more uniformly bright
 Mid- to late luteal phase:
 Rising P concentrations leads to progressive slowing of
LH pulses down to one pulse every four hours
 Pulses of P occur soon after these slow LH pulses
 As a result, there can be significant excursions in serum
P concentrations during the luteal phase
 Inhibin A is also produced by the corpus luteum, and
serum concentrations of inhibin A peak in the mid-luteal
phase
 Inhibin B secretion is virtually absent and serum leptins
are highest during luteal phase
 Late luteal phase:
 Gradual decrease in LH secretion results in
gradual fall in P & E production by the corpus
luteum in absence of a fertilized oocyte
 If oocyte becomes fertilized, it implants in the
endometrium several days after ovulation
 early embryo begins to make chorionic
gonadotropin, which maintains the corpus
luteum and P production
 Late luteal phase:
 decline in E & P release from resolving corpus luteum
results sequentially in loss of endometrial blood supply,
endometrial sloughing, and onset of menses about 14
days after the LH surge
 Menses is relatively imprecise marker of hormonal
events in the menstrual cycle, since there is considerable
inter-individual variability in relationship between the
onset of endometrial sloughing and fall in serum
hormone concentrations during luteal phase
 In response to falling corpus luteum steroid production,
the hypothalamic-pituitary axis is released from negative
feedback and FSH levels rise, thereby beginning next
cycle.
Premenopausal Women
Definition
 Any variation from the normal menstrual cycle,
including changes in regularity and frequency of
menses, in duration of flow, or in amount of
blood loss
 Subdivided based on volume of menstruation,
regularity, frequency, duration, chronicity, and
timing related to reproductive status
 Bleeding not related to menses may be further
characterized as well
Premenopausal Women
 Ovulatory AUB
Categories
 usually regular
 often associated with premenstrual symptoms and
dysmenorrhea
 Anovulatory AUB
 more common near menarche and the perimenopause
 often irregular, heavy, and prolonged flow
 more likely to be associated with endometrial
hyperplasia and cancer
Abnormal Genital Bleeding
Premenopausal Women
Differential Diagnosis
 Anatomic categorisation:
 Uterus – pregnancy, menorrhagia,
anovulatory – periods of transition in
reproductive life including adolescence
and perimenopause; PCO, endocrine,
other; fibroid, polyp, adenomyosis,
structural abnormalities; Ca; FB; infections
like endometritis/PID; bleeding disorders;
meds; ruptured ovarian cyst
Premenopausal Women
 Anatomic categorisation contd.:
 Cervix – polyps, cervicitis, ectropian, Ca, pelvic
floor laxity
 Vagina – vaginitis, trauma, Ca, fistulas, benign
neoplasms, cysts, radiation changes, FB, atrophy
 Vulva – infection, benign growths, Ca, trauma
 ***Neighbouring structures – bowel, urethra,
bladder, systemic disease involving skin in
region eg. Crohn’s, lichen sclerosis
Premenopausal Women

In adolescent within the first 1.5-2 years following
menarche, the AUB may be caused by an immature HPO
axis***
 Other Endocrine Causes:
 PCOS, CAH, hyperprolactinemia, Cushings, thyroid
dysfunction, pituitary tumors
 Meds: see list
 Infections: vulva, vagina, cervix etc.
 Bleeding disorders
 Systemic disorders eg. DM, renal failure, SLE, Ca
 Structural lesions eg. fibroids, polyps
 Other Causes: FB, trauma
Premenopausal Women
 Systemic: SOB, History
dizziness – consider anemia; Sx of
hypothyroidism, hyperprolactinemia, coagulation
disorders, polycystic ovary syndrome, adrenal or
hypothalamic disorders
 GU Sx: vaginal discharge, change in odor, pelvic
pain/pressure
 Sexual Hx: contraception, pregnancy risk, STDs,
cervical screening
 Reproductive Hx: family planning, infertility
 Social Hx: impact on QOL including sexual function
Medications causing AUB
 Anticoagulants
 Antidepressants (selective serotonin reuptake
inhibitors and tricyclics)
 Hormonal contraceptives
 Tamoxifen
 Antipsychotics (first generation and risperidone)
 Corticosteroids
 Herbs: ginseng, chasteberry, danshen
Premenopausal Women
History
 PMH: hormonally dependent tumours,
thromboembolic disease, or cardiovascular
problems – affects Rx choices
 FH: inherited coagulation disorders,
PCOS, endometrial or colon cancer
Premenopausal Women
Physical Exam
 Vital signs
 Weight/BMI
 Thyroid exam
 Skin exam (pallor, bruising, striae, hirsutism, petechiae)
 Abdominal exam (mass, hepatosplenomegaly)
 GU: inspection: vulva, vagina, cervix, anus, and
urethra; Bimanual examination of uterus and adnexal
structures; Pap smear, cervical cultures if risk for
sexually transmitted infection
 Rectal examination if bleeding from rectum suspected or
risk of concomitant pathology
AUB Management
Premenopausal Women
SOGC Guidelines May 2013
 Investigations:
 CBC
 Pregnancy test (urine or serum) if any chance of
pregnancy
 TSH if there is other evidence of thyroid disease
 Coagulopathy tests if FH of coagulopathy or if
woman has had AUB since menarche
 FSH – measure twice 1 month apart; irregular
bleeding could herald POI (my suggestion)
AUB Management
Premenopausal Women
 Imaging:
 Transvaginal US (TVUS) is first line
 Saline infusion sonogram (SIS) and
diagnostic hysteroscopy to be used for Dx
of intrauterine abnormalities such as
submucosal fibroids or polyps or
abnormally structured uterus
AUB Management
Premenopausal Women
 TVUS endometrial thickness in pre-

menopausal woman:
 Follicular phase: as thin as 4 mm

 Luteal phase: up to 16 mm
AUB Management
Premenopausal Women
 Imaging:
 MRI rarely used to assess the endometrium in
patients who have menorrhagia
 may be helpful to map exact location of fibroids
in planning surgery and prior to therapeutic
embolization for fibroids
 may also be useful in assessing the
endometrium when transvaginal ultrasound or
instrumentation of the uterus (i.e. congenital
anomalies) cannot be performed.
FIBROIDS
 Benign smooth muscle tumors of uterus
 If asymptomatic do not require treatment
 Symptoms: pain/pressure, bowel and bladder
dysfunction, AUB/anemia & infertility
 Physical exam and ultrasound
 Must SAMPLE ENDOMETRIUM if AUB and
risk factors for cancer present.
AUB Management
Premenopausal Women
 Tissue sampling:
 Endometrial biopsy (Bx) should be
considered in bleeding women over age
40 or in those with bleeding not
responsive to medical therapy, as well as
in younger women with risk factors for
endometrial cancer.
AUB Management
Risk Factors for Endometrial Ca
 Fam. Hx endometrial or colon Ca (HNPCC)
 Age > 40
 Diabetes type II
 PCOS/Anovulatory cycles
 Obesity (BMI > 30 kg/m2)
 Nulliparity
 Tamoxifen
AUB Management
Pre-menopausal Women
 Indications:
 Pre-menopausal
 Any persistent change in menstrual cycle, frequency,
duration, or flow
 Breakthrough bleeding
 ***The average age for women with endometrial

cancer is 61 years, but 5% to 30% of cases occur
in premenopausal women (SOGC May 2013)
AUB Management
Endometrial Biopsy
 Purpose is to evaluate the endometrial lining for:
 Cancer
 Pre-cancerous tissue (hyperplasia)
 Normal endometrial growth
 Infertility: luteal phase defect
 Small tube inserted through the os

 Office procedure
AUB Management
Endometrial Biopsy
 Sensitivity to detect abnormalities 81-96 %
 Comparable to D&C; may be better
 Less reliable than hysteroscopy
 Adequate sample obtained > 85%

 OHIP billing: Z770 & E542
AUB Management
Premenopausal Women
 Tissue sampling:
 Office endometrial Bx should replace D&C
as initial assessment of endometrium
 Focal lesions of endometrium requiring Bx
should be managed through hysteroscopy-
guided evaluation
AUB Management
Interpreting Endometrial Biopsy
 Normal
 Symptoms resolve→follow
 Symptoms persist→TVUS
 Unable to perform/inadequate sample
 Repeat
 TVUS
AUB Management
Interpreting Endometrial Biopsy
 Hyperplasia without atypia
 Provera 10mg od/ Prometrium 200 mg po/pv for
30 days or cyclic 12-14 days x 3- 6 months
 Repeat biopsy 3- 6 months
 Hyperplasia with atypia, cancer→refer
AUB Management
Medications for AUB
 NSAIDS
 Tranexamic acid (Cyklokapron)
 OCP (combined)
 Mirena
 Progestins (oral, IM)
 GNrH agonist
 Danazol
AUB Management
Premenopausal Women
 Treatment:
 Non-hormonal options such as NSAIDs
and antifibrinolytics (tranexamic acid or
Cyklokapron) can be used effectively to
treat heavy menstrual bleeding that is
mainly cyclic or predictable in timing
AUB Management
Medications for AUB
 Cyclokapron:
 Synthetic derivative of lysine (amino acid)
 Antifibrinolytic effect through reversible blockade
on production of plasminogen
 Coagulation/dysmenorrhea not affected
 s/e: nausea, leg cramps in 30%
 Dose: 2-3 tabs (500 mg) tid prn - start Rx at
onset of bleeding for heaviest days
 Cost: $1/tab generic; $1.50 trade name
 **Calendar BMJ 1970;24:214-6
AUB Management
Premenopausal Women
 Treatment:
 Combined oral contraceptive pills, depot
medroxyprogesterone acetate, and
levonorgestrel-releasing intrauterine
systems significantly reduce menstrual
bleeding and should be used to treat
women with abnormal uterine bleeding
who desire effective contraception
AUB Management
Premenopausal Women
 Treatment:
 ****In premenopausal women who have
regular periods, cyclic luteal-phase
progestins do not effectively reduce blood
loss and therefore should not be used as a
specific treatment for heavy menstrual
bleeding
AUB Management
Medications for AUB
 Danazol:
 Synthetic steroid with mild androgenic properties
 Inhibits steroid production in the ovary
 80% reduction in menstrual blood loss
 20% of patients develop amenorrhea; 70 % of
women develop oligomenorrhea
 s/e – none in 50%; 20% report minor concerns
like weight gain 2-6 lbs.
 Dose: 100-200 mg od for three months
AUB Management
Medications for AUB
 GnRH agonists:
 induce reversible hypoestrogenic state –
like “temporary menopause”
 Decrease fibroids and uterine volume by
40-60% (reverses within months of
stopping Rx) which decreases blood flow
 s/e: hot flashes; decreased bone density
 **Friedman Obs Gyne 1991;77:720-5.
AUB Management
Medications for AUB
 GnRH agonists:
 Leuprolide (Lupron) depot given IM 7.5
mg q monthly or 11.25 mg q 3 months for
6-12 months – duration of Rx based on
individual woman
 Add back therapy – progestin +/- estradiol
transdermal preferred – patch/gel
AUB Management
Premenopausal Women
 Treatment:
 Danazol and gonadotropin-releasing hormone
(GnRH) agonists to be used when other medical
or surgical treatments have failed or are
contraindicated
 women receiving GnRH agonist for longer than 6
months should be prescribed add-back hormone
therapy if not already initiated with GnRH
agonist commencement
AUB Management
Premenopausal Women
 Treatment:
 Progestin intrauterine system (ie. Mirena)
has outcomes similar to endometrial
ablation for women with heavy menstrual
bleeding and thus may be considered prior
to surgical intervention
Progestin Intrauterine System
(Mirena)
 Indication initially: contraception
 Also used for:
 AUB
 Endometriosis
 Fibroids
 Endometrial Hyperplasia
(Mirena)
 Breakthrough bleeding up to 6 months
 followed by amenorrhea in 70 % by one year
 Mild cramps upon insertion
 Possible progesterone side effects from
systemic absorption in first few weeks
 Expulsion, perforation rate (1/1000)
(Mirena)
 T-shaped device which releases 20 ug/day of
levonorgestrel locally in the uterine cavity
 Inserted in the office, similar to regular IUD
 Lasts 5 years
 $400 + script fee ($11.99 at SDM Sept. 2013)
 Device covered on ODB
 OHIP billing: G378 & E430
(Mirena)
 Insert early in cycle (days 4-8) to reduce
spotting/bleeding
 Consider priming with OCP x 1-2 months if
severe menorrhagia
 Warn patient about potential side-effects to
improve compliance
 Ovulation will continue normally in most ♀
(Mirena)
 Immediately effective as contraceptive, and
immediately reversible
 May get free replacement if dropped,
expulsed, or causing pain
 No need to remove if endometritis; treat with
Mirena in-situ
 May do PAP, SIS, and endo biopsy with
Mirena in-situ
AUB Management
Premenopausal Women
 Treatment:
 With the exception of NSAIDs, same
medical agents used to treat heavy
menstrual bleeding among women with
normal coagulation can effectively be used
in the setting of inherited bleeding
disorders
AUB Management
Premenopausal Women
 Treatment:
 Acute heavy menstrual bleeding should be
managed promptly and systematically to
minimize patient morbidity and the need
for blood transfusion using high-dose
estrogen and tranexamic acid
 Consider possible bleeding disorder in
recently menarchal adolescents
AUB Management
Premenopausal Women
Surgery
 D&C: out of favor; bleeding decreased for
a couple of months after procedure and
then returns to pre-treatment levels
 Endometrial ablation: usual outcome
markedly decreased menstrual flow rather
than amenorrhea
 Hysterectomy
AUB Management
Premenopausal Women
Surgery
 Endometrial Ablation:
 surgical destruction of the endometrium
 Resectoscopic ablation performed under
hysteroscopic guidance, using resectoscopic
instruments to ablate or resect the endometrium
 Non-resectoscopic ablation performed with a
disposable device which is inserted into the
uterine cavity and delivers energy to uniformly
destroy the uterine lining
AUB Management
Premenopausal Women
Surgery
 Designed for women who have completed
their families
 Contraception still required for those who
are sexually active
 Pre-op: biopsy needed to rule out Ca and
hyperplasia
 Post-op: cramping and vaginal discharge
AUB Management
Premenopausal Women
Surgery
 Presence of submucosal fibroids make
procedure less effective; may need to be
removed prior to ablation
 Endometrial preparation using GnRH
agonists recommended prior to ablation
(using either resectoscope or non-
resectoscope procedure)
AUB Management
Premenopausal Women
Surgery
 Resectoscope vs. Non-resectoscope
endometrial ablation:
 Equal efficacy and patient satisfaction
 Resectoscopic ablation - regional or
general anesthesia
 Non-resectoscopic uses local, regional, or
general anesthesia
AUB Management
Premenopausal Women
Surgery
 Resectoscopic endometrial ablation
 Cons: more frequent use of general anesthesia,
longer duration, increased risk of surgical
complications like fluid overload
 Pros: less costly per procedure; optimal for
women with acute flexion or version of the
uterus that does not allow a non-resectoscopic
ablation device to reach the uterine fundus;
better for women undergoing repeat procedure
AUB Management
Premenopausal Women
Surgery
 Hysterectomy (minimally invasive):
 option in women who desire definitive
therapy and who are willing to accept the
risk of perioperative complications
AUB Management
Premenopausal Women
Surgery
 Endometrial ablation vs. hysterectomy:
 ablation less costly, lower complication
rates of bleeding and infection (sexual
effects?), less recovery time post-op
 At 2 yrs. post-op patient satisfaction
favored hysterectomy (79 vs. 71%) but at
4 yrs. basically the same
Postmenopausal Women (PMW)
 Postmenopausal bleeding (PMB) refers to
any uterine bleeding in a menopausal
woman (other than that expected with
progestin withdrawal in cyclic combined
postmenopausal hormone therapy)
 Unexpected vaginal bleeding in PMW must
be investigated
 Vaginal bleeding occurs in 4-11% of PMW
 In PMW with vaginal bleeding, the risk of
uterine Ca is 7.3% if the endometrial
thickness or echo (EE) is >5 mm and
<0.07% if EE is thin < or = 5 mm**
 As age increases the risk for endometrial
Ca for each EE measurement increases
 **Smith-Bridman Ultrasound Obstet
Gynecol 2004;24(5):558
Causes of AUB
Postmenopausal Women
 Atrophy** 59%
 Endometrial Polyp 12%
 Endometrial Hyperplasia 10%
 Endometrial Cancer 10%
 Hormonal effect 7%
 Cervical Cancer <1%
 Other 2%
Source: Karlsson et al 1995
AUB Management
Endometrial Biopsy
 Indications in PMW:
 Vaginal bleeding > 12 months after last period
 Bleeding > 6-12 months after initiating HT

AUB Management
PMW
 If AUB occurs, evaluate endometrium and
uterine cavity as well as the genital tract and
external genitalia
 Either endometrial Bx, TVUS or both can be done to

initially assess the endometrium
 Can base choice of first investigation upon patient
preference, physician comfort with procedure, US
availability
 If TVUS done as initial investigation,
endometrial cancer can reasonably be
excluded in postmenopausal women with
a thin (<5 mm), homogeneous
endometrium.
AUB Management
Endometrial Biopsy
 Endometrial tissue sampling required if:
 Endometrial thickness > 4 mm
 Endometrium heterogeneous or irregular in

thickness within various areas of the cavity
 Endometrium not adequately examined
 PMW bleeds persistently

AUB Management
PMW
 Once endometrial Ca excluded no need for
further treatment of bleeding
 Endometrial ablation not recommended
for PMW – can be difficult to assess for Ca
after procedure

Abnormal Uterine Bleeding - Presentation

Caricato da

Informazioni sul documento

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Abnormal Uterine Bleeding - Presentation

Caricato da

Copyright:

Formati disponibili

BLOODY HELL

• Relationships with commercial interests:

• Potential for conflict(s) of interest:

 TVUS endometrial thickness in pre-

 Follicular phase: as thin as 4 mm

 ***The average age for women with endometrial

 Small tube inserted through the os

 Adequate sample obtained > 85%

 Vaginal bleeding > 12 months after last period

 Bleeding > 6-12 months after initiating HT

 Either endometrial Bx, TVUS or both can be done to

 Endometrial thickness > 4 mm

 Endometrium heterogeneous or irregular in

 Endometrium not adequately examined

 PMW bleeds persistently

Potrebbero piacerti anche