Abnormal Uterine Bleeding: Postmenopausal and Menopausal Transition
- Menopausal transition (MT)
- Commonly referred to as “perimenopause”
- Begins with onset of cycle irregularity
- Ends at 1 year from last menstruation
- Absence of menstruation for 1 year
- Due to physiologic decline in ovulatory function
- Abnormal uterine bleeding (AUB) during MT
- May be defined by increase in volume or frequency of bleeding, midcycle bleeding, postcoital bleeding
- Postmenopausal AUB
- Uterine bleeding that occurs >1 year after last menstruation or unscheduled bleeding for women taking hormone replacement therapy (HRT) (1,2)
- Women taking HRT may have irregular bleeding for several months after initiation of therapy. Bleeding that recurs after a long bleed-free period should be considered abnormal and prompt further investigation.
- Average length of MT is 4 years (3).
- Mean age of menopause in developed countries is 51.4 years of age (3).
- 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 (1).
- AUB is most commonly caused by endometrial polyps or atrophy (1).
- Prevalence of endometrial cancer among postmenopausal women is 0.7% but increases with additional risk factors (2). Among with postmenopausal AUB, risk of endometrial cancer is significantly higher, approximately 9% (4).
- Peak incidence of endometrial cancer is between 65 and 75 years of age.
Etiology and Pathophysiology
- Pregnancy, ectopic pregnancy, or miscarriage
- Endometrial polyps
- Endometrial hyperplasia/cancer
- Premature ovarian failure
- Ovarian cancer
- Infections: pelvic inflammatory disease (PID), endometritis
- Thyroid dysfunction
- Pituitary dysfunction
For endometrial cancer:
- Time since menopause
- Obesity (body mass index [BMI] >25)
- Type 2 diabetes
- Early menarche and/or late menopause
- Polycystic ovarian syndrome
- Estrogen therapy
- Tamoxifen therapy
- Previous endometrial hyperplasia or polyps
- Hereditary nonpolyposis colorectal cancer
- There are no recommended screening tests for endometrial cancer (4,5)[A].
- Women undergoing HRT with estrogen should also be treated with progesterone to reduce risk of endometrial hyperplasia (4,5)[A]. Progesterone is generally considered not to be necessary for women using vaginal cream to treat local vaginal symptoms.
- Use of combined oral contraceptives, depot medroxyprogesterone acetate, or the levonorgestrel intrauterine device (IUD) are protective factors against developing endometrial cancer (5).
- Date of last menstruation
- Bleeding patterns
- Menses length/frequency
- Volume of menstrual bleeding
- Presence of midcycle bleeding
- Postcoital 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 Ginkgo biloba, ginseng, soy)
- Smoking history
- History of colon cancer/last colon cancer screening
- Family history—age of menopause onset; bleeding disorders; colon, 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 polyps
- Cervical dysplasia or neoplasia
- Vaginal source bleeding
- Vaginal cancer
Diagnostic Tests & InterpretationInitial Tests (lab, imaging)
- Initial tests:
- Urine or serum hCG
- Must exclude pregnancy, especially during MT as intermittent ovulation may occur
- Thyroid function tests
- Follicle-stimulating hormone (FSH)
- Serum prolactin level
- Complete blood count (CBC)
- Consider coagulopathy.
- Pap smear, if indicated
- Test for infection if clinically indicated: gonorrhea, chlamydia, Trichomonas, yeast, bacterial vaginosis.
- Postmenopausal endometrial thickness (ET) <4 mm does not require endometrial sampling unless bleeding is persistent or recurrent, whereas ET >4 mm in should prompt further evaluation (5)[B].
- ET <3 mm provides 98% sensitivity for ruling out endometrial cancer, with 35% specificity.
- ET <5 mm provides 90% sensitivity for ruling out endometrial cancer, with 54% specificity.
- ET is not useful in premenopausal women (5)[C].
- 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 (2)
- Endometrial sampling
- 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 with risk factors for endometrial cancer
- Advantages: simple in-office procedure
- Disadvantages: can miss up to 18% focal lesions (2)
- Advantages: allows targeted biopsy at the time of procedure; greater sensitivity and specificity over TVUS for diagnosis of uterine polyps; greater sensitivity over TVUS for diagnosis of submural fibroids
- Disadvantages: more invasive procedure; increased pain of procedure; possible anesthesia risk if unavailable in outpatient setting
- Dilation and curettage
- Less commonly performed due to increased availability and tolerance of endometrial sampling biopsy and hysteroscopy for targeted biopsy (1)
- Endometrial cancer, atypia, and hyperplasia must be ruled out prior to proceeding with treatment. Recommendations vary for reasonable exclusion of possible endometrial cancer; most using a cut point between 3 and 5 mm on TVUS if the endometrium is thin and homogeneous. Some are more conservative, recommending at least:
- Negative cytology on endometrial biopsy
- <3 mm endometrial stripe on TVUS or sonohysterography
- If above criteria are met, may proceed with:
- Watchful waiting
- Combined contraceptive hormone therapy
- Progestin-only 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 as indicated, 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 can also help regulate the cycle and minimize 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 to 12 months prior to discontinuing is reasonable) (6)[C]
- Progestin-only oral therapy (for symptom 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 to 10.0 mg PO daily times 5 to 10 days each cycle
- Start on cycle day 14 to 21 taken during second half of theoretical cycle.
- Depot medroxyprogesterone acetate 150 mg every 1 to 3 months
- Levonorgestrel 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
- Tranexamic acid 1,300 mg PO taken 3 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 nonsteroidal anti-inflammatory drugs (NSAIDs) or luteal phase progestins
- NSAIDs (6)
- Ibuprofen 600 to 1,200 mg PO daily, taken for first 5 days after bleeding onset
- Naproxen 550 to 1,100 mg PO daily, taken for first 5 days after bleeding onset
- Comparable to hormonal therapies
Consider patient’s individual risk for thromboembolic disease, breast cancer, and gastrointestinal bleeding.
Issues For Referral
- Abnormal endometrial sampling results
- Indication for hysteroscopy or dilation and curettage, to further evaluate and biopsy suspected focal lesions
- Removal of endometrial polyps/fibroids
- Uncertain diagnosis
- 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
- Endometrial ablation
- 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 >95% (2,4). 5-year survival estimates of later stage endometrial cancers ranges from 16% to 45% (4).
- N92.4 Excessive bleeding in the premenopausal period
- N93.9 Abnormal uterine and vaginal bleeding, unspecified
- N95.0 Postmenopausal bleeding
- 626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract
- 626.9 Unspecified disorders of menstruation and other abnormal bleeding from female genital tract
- 627.0 Premenopausal menorrhagia
- 627.1 Postmenopausal bleeding
- 19155002 Dysfunctional uterine bleeding (finding)
- 312984006 Abnormal uterine bleeding unrelated to menstrual cycle (disorder)
- 76742009 Postmenopausal bleeding (finding)
- 88424000 Premenopausal menorrhagia (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 are 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.
Catherine A. Gill, MD, FAAFP
- Breijer MC, Timmermans A, van Doorn HC, et al. Diagnostic strategies for postmenopausal bleeding. Obstet Gynecol Int. 2010;2010:850812. [PMID:20169169]
- Null DB, Weiland CM, Camlibel AR. Postmenopausal bleeding-first steps in the workup. J Fam Pract. 2012;61(10):597–604. [PMID:23106061]
- Committee on Practice Bulletins—Gynecology. Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013;122(1):176–185. [PMID:23787936]
- Clarke MA, Long BJ, Del Mar Morillo A, et al. Association of endometrial cancer risk with postmenopausal bleeding in women: a systematic review and meta-analysis. JAMA Intern Med. 2018;178(9):1210–1222. [PMID:30083701]
- Committee on Practice Bulletins—Gynecology. Practice bulletin no. 149: endometrial cancer. Obstet Gynecol. 2015;125(4):1006–1026. [PMID:25798986]
- Sweet MG, Schmidt-Dalton TA, Weiss PM, et al. Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2012;85(1):35–43. [PMID:22230306]
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