What is the appropriate management for a postmenopausal woman presenting with postmenopausal bleeding (PMB)?

Management of Postmenopausal Bleeding

All postmenopausal women presenting with vaginal bleeding require urgent evaluation to exclude endometrial cancer, which is present in approximately 10% of cases, with transvaginal ultrasound (TVUS) as the first-line diagnostic test followed by endometrial tissue sampling when indicated. 1, 2

Initial Diagnostic Approach

First-Line Imaging

• Transvaginal ultrasound should be performed immediately to measure endometrial thickness and identify structural abnormalities of the uterus, endometrium, and ovaries 1, 2
• An endometrial thickness ≤4 mm has a negative predictive value for cancer of nearly 100% and allows for expectant management 1, 2
• If endometrial thickness is ≥5 mm, proceed directly to endometrial tissue sampling 1

Endometrial Tissue Sampling

• Office endometrial biopsy is the standard method for obtaining tissue for histological assessment, with sensitivity of 99.6% for detecting endometrial carcinoma 1, 3
• However, office endometrial biopsy carries a false-negative rate of approximately 10%, which is a critical pitfall 1, 3, 2
• Pipelle or Vabra devices are the preferred sampling methods with high diagnostic accuracy 3

Management Algorithm for Persistent or Negative Initial Workup

When Initial Biopsy is Negative or Non-Diagnostic

• If office endometrial biopsy is negative but bleeding persists, or if the biopsy is non-diagnostic, fractional dilation and curettage (D&C) under anesthesia must be performed 1, 3, 2
• Never accept a negative endometrial biopsy as reassuring in a symptomatic postmenopausal woman—the 10% false-negative rate mandates further evaluation 3

Role of Hysteroscopy

• Hysteroscopy should be used as the final step in the diagnostic pathway, particularly when structural abnormalities such as polyps are suspected or when initial sampling is inadequate 1, 3, 2
• Hysteroscopy allows direct visualization of the endometrium and targeted biopsy of suspicious lesions 3
• This has the highest diagnostic accuracy for endometrial cancer 3

Alternative Imaging

• MRI can be considered if TVUS cannot adequately evaluate the endometrium due to patient body habitus, uterine position, or pathology such as fibroids or adenomyosis 1, 2
• Saline infusion sonography has 96-100% sensitivity and 94-100% negative predictive value for assessing endometrial pathology and can distinguish between focal lesions (polyps, submucous fibroids) and diffuse endometrial thickening 3

Critical Considerations in Specific Populations

Malignancy Risk Stratification

• In postmenopausal patients with abnormal uterine bleeding, even in the presence of fibroids, uterine sarcoma and endometrial cancer must be ruled out before any treatment 4, 1, 2
• The risk of unexpected uterine sarcoma increases dramatically with age, reaching 10.1 per 1,000 in patients 75-79 years of age 4, 1, 2
• Continued fibroid growth or bleeding after menopause should raise suspicion for uterine sarcoma 4

Tamoxifen Users

• Postmenopausal women taking selective estrogen receptor modulators (SERMs) like tamoxifen have increased risk of endometrial cancer (2.20 per 1,000 women-years versus 0.71 for placebo) 1, 2
• Any vaginal spotting or bleeding in tamoxifen users requires immediate endometrial evaluation—stopping tamoxifen does not address the diagnostic imperative 3, 2
• Hysteroscopy with directed biopsy is particularly important in this population due to tamoxifen-induced endometrial changes that can obscure pathology 3

High-Risk Genetic Syndromes

• Women with Lynch syndrome have a 30-60% lifetime risk of endometrial cancer and require annual endometrial biopsy screening starting at age 30-35 years 3, 2
• Universal tumor testing for Lynch syndrome is recommended for all patients diagnosed with endometrial cancer 2

Common Pitfalls to Avoid

• Never rely on Pap smear for evaluation of postmenopausal bleeding—it is designed to screen for cervical cancer, not endometrial pathology, and will miss endometrial cancer 1, 3
• Do not use endometrial thickness cutoffs higher than 4 mm, as this may miss cases of endometrial cancer 1
• Never proceed directly to hysterectomy without establishing a tissue diagnosis—this exposes patients to unnecessary surgical risk if the pathology is benign 3
• Do not accept inadequate or non-diagnostic biopsy results as reassuring in symptomatic patients 3

Benign Etiologies (After Malignancy Excluded)

While endometrial cancer must be excluded first, the most common causes of postmenopausal bleeding are benign 1, 5, 6:

• Atrophic vaginitis or endometritis (most common benign cause) 5, 6
• Endometrial polyps 1
• Endometrial hyperplasia 1
• Cervical polyps 1
• Hormone-producing ovarian tumors 1