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Bleeding, Abnormal Uterine: Postmenopausal and Menopausal Transition

Nanette Santoro MD
Matthew Lederman MD
Basics
Description
MT:
o Previously referred to as perimenopause
o

Reproductive aging nomenclature defined by STRAW (Stages of


Reproductive Aging Workshop) and applies to healthy, normally
menstruating, nonsmoking women without anatomic abnormalities and
a BMI between 1830 kg/m2. Comprised of 7 stages from -5 to +2.
Perimenopause includes the MT and 12 months after the final
menstrual period (FMP).

-5 to -3: Mid reproductive life

-2 to -1: Menopausal transition. Begins with first skipped


menses (or >7 day variation in cycle length):
-2 (early stage): Menses at least once every 3 months
-1 (late stage): 311 months amenorrhea

0 (menopause): 12 months after FMP


+1 to +2 (postmenopause):

+1 (early stage): 1st 5 years after FMP

+2 (late stage): Through remainder of life

Postmenopausal abnormal uterine bleeding (AUB):


o

Bleeding occurring >1 year after FMP

Age-Related Factors
Median age of onset MT = 47.5 years
Median length of MT = 4 years

Median age of menopause = 51.4 years

Premature ovarian failure: Prolonged hypergonadotropic amenorrhea


occurring >2 standard deviations below the mean for the reference population:
o

Generally accepted as <40 for premature and <45 for early


menopause

Epidemiology
AUB accounts for up to 20% of office visits and frequently seen in MT.
<10% of cases of postmenopausal bleeding are due to endometrial cancer.
Risk Factors

Factors affecting timing of natural MT:


o Earlier transition: Current smoking, lower SES, heart disease,
separated/widowed/divorced, unemployed
o

Later transition: Multiparity, prior use of OCPs, Japanese ethnicity

See risk factors for cervicitis, endometrial hyperplasia/carcinoma, cervical


carcinoma, fibroids, cervical lesions, and atrophic vaginitis/endometritis
o

In general, anatomic abnormalities increase with age.

Endometrial polyps: Estrogen exposure, Tamoxifen

Fibroids

Genetics
Primary determining factor influencing age of menopause
Pathophysiology
MT:
o Shorter menstrual cycles 2o shorter follicular-phase in ovulatory cycles
alternating with variable-length anovulatory cycles:

Cycles may get 37 days shorter

Bleeding may decrease and get lighter as menopause nears,


BUT

Anovulatory cycles lack progesterone stabilization and cause increased


endometrial vascularity without adequate stromal support, leading to
endometrial fragility and occasional heavy bleeding.

Increased risk of hyperplasia and neoplasia with unopposed estrogen


stimulation

Postmenopausal AUB:
o

Usually related to hypoestrogenic state but depends on specific


etiology; always rule out hyperplasia or carcinoma.

Diagnosis
Signs and Symptoms
History
Important to distinguish between a normal MT and a pathologic cause.
Changes in bleeding patterns:
o

May be physiologic not requiring investigation

Prolonged bleeding >10 days or intermenstrual bleeding requires


workup

Postcoital bleeding

Pregnancy still possible until >12 months amenorrhea

Vaginal atrophy/pruritus/dyspareunia

Family history of gynecologic malignancies, breast cancer, or colon cancer

Review of Systems
Hot flashes:
o Prevalence of 57% in late perimenopause and 49% in early menopause

Sleep disturbances

Symptoms of thyroid dysfunction (possible etiology for AUB in MT)

Symptoms of anemia

Urethritis/Cystitis

Changes in bowel function

Physical Exam
Vital signs:
o Tachycardia or postural hypotension (if suspicious of anemia)

Abdominal exam to rule out masses or ascites

Pelvic exam assessing for:

Size of uterus

Uterine/Cervical masses or abnormalities

Vaginal atrophy

Evidence of thyroid disease (See Thyroid Disease.)

Rectal exam

Tests

ACOG recommends assessment of endometrium if >35 years with


anovulatory bleeding or <35 years if chronic anovulation, bleeding refractory
to medical management, or risk factors for endometrial hyperplasia such as
diabetes, obesity, or HTN
EMB or EMBx (Pipelle):
o

May miss focal lesions in up to 18% of cases

Pap smear

+/- cervical cultures

Labs

CBC
TFTs

+/- early follicular phase FSH/Estradiol

+/- HCG

Imaging
Clinician comfort and skill will direct workup.
Menopausal transition AUB; use Goldstein's clinical algorithm:
o

TVS on cycle day (CD) 46 may be useful as triage tool:

EE 45 mm (bilayer) generally excludes pathology. No


further workup necessary

+/- EMBx because rare case reports of endometrial cancer even


when EE 4

EE >5 mm (bilayer) or not adequately visualized: HSN performed on


CD 510 when bleeding has ceased:

If EE 3 mm (monolayer) with no focal abnormalities, no


further workup needed

If EE >3 mm and symmetrical (monolayer), EMBx performed

If EE >3 mm and asymmetrical (monolayer) or if focal


abnormality, D&C/hysteroscopy

Postmenopausal bleeding:
o

TVS with EE 4 mm: No further workup usually required

If EE >4 mm, EMBx required

HSN option if TVS is suggestive of polyp or myoma; may also use in


combination with EMBx in initial evaluation

Differential Diagnosis
Infection
Cervicitis/Chronic endometritis
Hematologic
Unlikely: Acquired von Willebrand disease
Metabolic/Endocrine
Unlikely postmenopause unless hormone treatment used
MT:
o

Anovulation is most likely etiology:

Diagnosis of exclusion termed dysfunctional uterine bleeding


(DUB)

Rule out thyroid dysfunction

Tumor/Malignancy
Endometrial hyperplasia:
o Simple vs. complex

Endometrial carcinoma:
o

+/- atypia

Incidence increases with age

Cervical carcinoma

P.15
Trauma
Unlikely in this age group; rule out with history
Drugs
Hormonal therapy:
o Breakthrough bleeding usually resolves after 612 months in
postmenopausal women:

Consider endometrial evaluation if >6 months or patient


anxiety

Tamoxifen:
o

Increased risk of endometrial proliferation, hyperplasia, polyps, or


carcinoma:

Endometrial assessment is required if AUB

Other/Miscellaneous
Pregnancy
Anatomic:
o

Uterine fibroids

Cervical/Endometrial polyps

Adenomyosis (MT)

Atrophy:

Most common etiology (postmenopausal)

Urethral caruncle (postmenopausal)

Management
Treatment depends on specific diagnosis
Medication (Drugs)
DUB: Goal is to restore the stabilizing effect of luteal progesterone and
prevent hyperplasia:
o Low dose monophasic OCPs:

Assess contraindications and risks

Oral progestin 1014 days q12 months:

Does not provide contraceptive benefit

Provera 10 mg daily, or Prometrium 200 mg daily, or Aygestin


2.510 mg/d

Levonorgestrel-IUD (Mirena):

20 g levonorgestrel released daily; 80% reduction of bleeding


after 3 months:

Provides contraception

Combination hormonal therapy:

NSAIDs

Endometrial hyperplasia:
o

Medical vs. surgical treatment depends on presence of atypia

No reliable contraceptive benefit

If no atypia, daily OCPs (perimenopausal) or cyclical Provera


1020 mg/d for 10 days for a duration of 6 months with repeat
EMBx every 3 months

Atrophic vaginitis:
o

Oral or transdermal hormonal therapy

Vaginal low-dose estrogen (e.g., Estring every 3 months or Vagifem


daily for 2 weeks then twice weekly)

Systemic absorption possible; consider intermittent progestin or


endometrial surveillance if >6 months of treatment

Surgery
Anovulation:
o Endometrial ablation:

More cost-effective than hysterectomy, less invasive, decreased


morbidity, and quicker recovery

1:10 women will still have hysterectomy within 5 years 2o


treatment failure.

Uterine artery embolization:

Alternative treatment if medical comorbidities

Endometrial polyp: Hysteroscopic resection

Cervical polyp: Office polypectomy

Uterine fibroids:

Hysteroscopic resection if submucosal

Hysterectomy

Uterine artery embolization:

Alternative treatment if medical comorbidities

Endometrial hyperplasia: Hysterectomy vs. high-dose progestin (less desirable


option in this age group) if atypia present

Endometrial carcinoma: Hysterectomy +/- surgical staging

Cervical carcinoma: Treatment depends on stage

Followup
Depends on specific diagnosis
Hysteroscopy may be needed for persistent bleeding even if workup is
negative.
Disposition
Issues for Referral
May require referral to gynecological oncologist if carcinoma present or to
reproductive endocrinologist for management of menopause
Prognosis
Depends on specific diagnosis
DUB eventually remits with menopause.

Endometrial polyps:
o

Present in 13% of women with AUB in MT:

Rarely associated with malignancy

Endometrial hyperplasia:
o

Progression to carcinoma:

Simple hyperplasia without atypia: 1%

Complex hyperplasia without atypia: 3%

Simple hyperplasia with atypia: 8%

Complex hyperplasia with atypia: 29%

Patient Monitoring
Depends on specific diagnosis and treatment
Yearly office visit recommended unless change in bleeding pattern
Bibliography
Gold EB, et al. Relation of demographic and lifestyle factors to symptoms in a multiracial/ethnic population of women 4055 years of age. Am J Epidemiol.
2002;152:463473.

Goldstein SR, et al. Ultrasonography-based triage for perimenopausal patients with


abnormal uterine bleeding. Am J Obstet Gynecol. 1997;177:102108.
Kurman RJ, et al. The behavior of endometrial hyperplasia: A long term study of
untreated hyperplasia in 170 patients. Cancer. 1985;56:403412.
Langer RD, et al. Transvaginal ultrasonography compared with endometrial biopsy
for the detection of endometrial disease. N Engl J Med. 1997;337:17921798.
McKinlay SM, et al. The normal menopausal transition. Maturitas. 1992;14:103115.
Milson I, et al. A comparison of flurbiprofen, tranexamic acid, and levonorgestrelreleasing intrauterine contraceptive device in the treatment of idiopathic menorrhagia.
Am J Obstet Gynecol. 1991;164:879883.
O'Connor H, et al. Endometrial resection for the treatment of menorrhagia. N Engl J
Med. 1996;335:151156.
Practice Bulletin. ACOG. Management of Anovulatory Bleeding. 2006;14:623630.
Soules MR, et al. Stages of Reproductive Aging Workshop (STRAW). J Women
Health Gender-Based Med. 2001:10:843848.
Miscellaneous
See Menopause and Menopausal Symptoms.
Synonym(s)
Dysfunctional uterine bleeding
Clinical Pearls
Postmenopausal bleeding is cancer until proven otherwise.
Abbreviations
CDCycle day
DUBDysfunctional uterine bleeding
EEEndometrial echo
EMBxEndometrial biopsy
FMPFinal menstrual period
FSHFollicle-stimulating hormone
HCGHuman chorionic gonadotropin
HSNHysterosonogram
HTNHypertension
IUDIntrauterine device
MTMenopausal transition
OCPOral contraceptive pill
SESSocioeconomic status
TFTThyroid function tests
TVSTransvaginal sonogram
Codes
ICD9-CM
627.0 Perimenopausal bleeding
627.1 Postmenopausal bleeding
628.8 DUB
Patient Teaching
Educate patients about normal bleeding patterns during MT and in response to
HT.
Report to physician any change in bleeding patterns after initial diagnosis
established or if breakthrough bleeding >6 months on postmenopausal HT.
Prevention
Goal is to prevent missing detectable early gynecologic malignancy
Recommend yearly gynecologic exam