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Subject: Bleeding, Abnormal Uterine: Postmenopausal and Menopausal Transition
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Absence of menstruation for 1 year
Due to physiologic decline in ovulatory function (1)
Menopausal transition (MT)
Commonly referred to as "perimenopause"
Begins with onset of cycle irregularity
Ends at 1 year from last menstruation (1)
Postmenopausal abnormal uterine bleeding (AUB)
Uterine bleeding that occurs >1 year after last menstruation or unscheduled bleeding for women taking hormone replacement therapy (HRT) (2,3).
Women taking HRT may have abnormal bleeding for several months after initiation of therapy (4). Bleeding that recurs after long bleeding-free period should be considered abnormal and prompt further investigation (5).
AUB during MT
May be defined by increase in volume or frequency of bleeding, midcycle bleeding, postcoital bleeding
Average length MT is 4 years (1).
Mean age of menopause in developed countries is 51.4 years of age (1).
Premature ovarian failure is defined as onset of menopause <40 years of age.
Incidence of postmenopausal AUB is as high as 10%, with majority of cases occurring shortly after menopause (2).
AUB accounts for nearly 20% of outpatient office visits for gynecologic reasons (6).
Postmenopausal AUB is caused by endometrial cancer in 10–15% cases. More commonly caused by endometrial polyps or atrophy (2).
Incidence of endometrial cancer among women, aged 40–50 years, ranges from 13.6 to 24 cases per 100,000 women-years (1).
Peak incidence of endometrial cancer is between 65 and 75 years of age.
Premature ovarian failure
Infections: pelvic inflammatory disease (PID), endometritis
Pregnancy, ectopic pregnancy, or miscarriage
Time since menopause
Early menarche and/or late menopause
Previous endometrial hyperplasia or polyps
Hereditary nonpolyposis colorectal cancer
Screening for endometrial cancer by transvaginal ultrasound (TVUS) is not recommended for asymptomatic women (7)[A].
Women undergoing HRT with estrogen should also be treated with progesterone to reduce risk of endometrial hyperplasia (8)[A].
Date of last menstruation
Volume of menstrual bleeding
Presence of midcycle bleeding
History of abnormal cervical lesions
Sexual activity and contraception use
Medication history—particularly anticoagulants, selective serotonin reuptake inhibitors (SSRIs), antipsychotics, corticosteroids, hormone replacement, tamoxifen, and herbal supplement (especially gingko, ginseng, soy) (6)
Family history—age of menopause onset; bleeding disorders; and cervical, endometrial, or ovarian cancers
Pelvic speculum exam—assess for cervical and vaginal lesions.
Bimanual exam—assess for uterine enlargement, adnexal masses, and cervical motion tenderness.
Abdominal exam—assess for masses.
Uterine source bleeding
See list of possible etiologies
Cervical source bleeding
Cervical dysplasia or neoplasia
Vaginal source bleeding
Urine or serum hCG
Must exclude pregnancy, especially during MT as intermittent ovulation may occur (1)
Thyroid function tests (1,6)
Serum prolactin level
Complete blood count (CBC)
Pap smear, if indicated
Testing for infection if clinically indicated: gonorrhea, chlamydia, Trichomonas, yeast, bacterial vaginosis
Endometrial thickness <3 mm provides 98% sensitivity for ruling out endometrial cancer, although some recommend a cutoff of <4–5 mm (9)[B].
Stripe >4 mm in postmenopause should prompt further evaluation.
Saline infusion sonohysterography
Better able to define intrauterine pathology compared to TVUS alone
Less invasive than hysteroscopy
More invasive than TVUS
Lacks ability to perform targeted biopsy or removal of suspected lesions as with hysteroscopy
May risk dissemination of neoplastic cell, therefore should not be performed if abnormal cytology present on endometrial biopsy (EMB) (3).
Indicated for all women >45 years of age with AUB if not using TVUS triage strategy
Indicated for MT women <45 years of age with AUB if additional risk factors for endometrial cancer. Uterine stripe measurement generally not useful.
Advantages: simple in-office procedure
Disadvantages: can miss up to 18% focal lesions (3)
Advantages: allows targeted biopsy at time of procedure has greater sensitivity and specificity over TVUS for diagnosis of uterine polyps and greater sensitivity for diagnosis of submural fibroids
Disadvantages: more invasive procedure, increased pain of procedure, and possible anesthesia risk if unavailable in outpatient setting (10,11)
Dilation and curettage
Less commonly performed with increased availability and tolerance of endometrial sampling biopsy and hysteroscopy for targeted biopsy (2)
Endometrial cancer, atypia, and hyperplasia must be ruled out prior to proceeding with treatment. Recommendations for reasonable exclusion of likelihood of endometrial cancer vary, with some using a cutpoint of <3–4 mm on TVUS if the endometrium is thin and homogeneous and most conservative recommending at least TVUS and endometrial sampling. Following this strategy, if
Negative cytology on endometrial biopsy
<3 mm endometrial stripe on TVUS or sonohysterography
And if above criteria are met, may proceed with
Contraceptive hormone therapy
Other treatments as indicated for specific diagnoses if identified on workup such as atrophic vaginitis or genital infection
If above criteria cannot be met, or patient has persistent AUB:
Further investigation is indicated for additional workup and treatment.
Referral to gynecology for surgical procedures, such as removal of endometrial polyps or fibroids, endometrial ablation, or hysterectomy
For patients in MT, not indicated in postmenopausal (see surgical options)
Bleeding at this time is likely anovulatory due to paucity of progesterone in the second half of the cycle, leading to unopposed estrogen. Raises the concern for endometrial hyperplasia, which must be ruled out prior to hormonal therapy.
Goal of therapy is to stabilize the endometrium with progesterone. This also regulates the cycle and minimizes other associated menopausal symptoms if present. No real consensus in the literature on best therapy out of choices listed below or length of therapy (6–12 months prior to discontinuing is reasonable) (6).
Progestin-only oral therapy (for cycle control only, no contraceptive coverage)
Medroxyprogesterone acetate 10 mg PO daily for 14 days each month
Start on cycle day 14, taken for 14 days to cover second half of theoretical cycle (then 14 days off, 14 days on, etc.)
Megestrol acetate 40 mg PO daily
Norethindrone acetate 2.5–10 mg PO daily times 5–10 days each cycle
Start on cycle day 14–21 taken during second half of theoretical cycle
Depot medroxyprogesterone acetate 150
Levonorgestrel intrauterine device (IUD)
Combined hormonal contraceptives
≤35 μg ethinyl estradiol plus progesterone agent
If no contraindications to estrogen use
Oral, transdermal, and vaginal ring preparations available (6)[C]
Nonhormonal options to reduce heavy AUB
Ibuprofen 600–1,200 mg PO daily, taken for first 5 days after bleeding onset
Naproxen 550–1,100 mg PO daily, taken for first 5 days after bleeding onset
Comparable to hormonal therapies
Caution in patients with gastrointestinal (GI) disease
Tranexamic acid, 1,300 mg PO taken three times daily for first 5 days of cycle, beginning with bleeding onset
Caution in patients with risk factors for thromboembolic disease
May be more effective than NSAIDs or luteal phase progestins (6,12)
For all medications listed above, consider patient’s individual risk for thromboembolic disease.
Abnormal endometrial sampling biopsy
Indication for hysteroscopy or dilation and curettage, to further evaluate and biopsy suspected focal lesions
Removal of endometrial polyps/fibroids
Patient preference or indication for hysterectomy
Polypectomy or myomectomy
Can reduce 75–100% of symptomatic bleeding
Endometrial polyps more likely to represent premalignant or malignant lesions in women >60 years of age with postmenopausal AUB.
Uterine artery embolization
Indicated if premalignant or malignant lesions are identified during workup of AUB
May be preferred by patient for severe anemia-associated heavy menstrual losses in MT or postmenopausal bleeding, multiple or large fibroids, recurrent abdominal pain, uterine prolapse, or recurring bleeding after other procedures attempted
Routine well woman care
Should be followed by gynecologic oncology if indicated for premalignant or malignant diagnosis and treatment
Consider referral to reproductive endocrinology for complicated menopausal symptom management.
AUB in MT typically improves on its own with onset of menopause.
If endometrial cancer is found, prognosis depends on the extent of the disease at the time of diagnosis. Most cases when diagnosed early have a 5-year survival rate of >96% (3).
626.9 Unspecified disorders of menstruation and other abnormal bleeding from female genital tract
627.1 Postmenopausal bleeding
627.0 Premenopausal menorrhagia
626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract
N93.9 Abnormal uterine and vaginal bleeding, unspecified
N95.0 Postmenopausal bleeding
N92.4 Excessive bleeding in the premenopausal period
N93.8 Other specified abnormal uterine and vaginal bleeding
312984006 Abnormal uterine bleeding unrelated to menstrual cycle (disorder)
76742009 Postmenopausal bleeding (finding)
88424000 Premenopausal menorrhagia (finding)
19155002 Dysfunctional uterine bleeding (finding)
Endometrial cancer must be reasonably ruled out in patients with AUB in MT or menopause.
Medical management should be first line for patients in MT, once endometrial cancer and hyperplasia ruled out. Surgical options should be reserved for persistent symptoms or postmenopausal patients.
AUB in MT is likely anovulatory and would benefit from progesterone in the luteal phase of theoretical menstrual cycle.