What is the recommended work‑up for a postmenopausal woman (no menstrual periods for at least 12 months) presenting with vaginal bleeding?

Work-Up for Postmenopausal Bleeding

Any postmenopausal woman presenting with vaginal bleeding requires immediate evaluation with transvaginal ultrasound (TVUS) to measure endometrial thickness, followed by endometrial biopsy if the endometrial stripe is ≥4 mm or if bleeding persists despite a thin endometrium. 1, 2, 3

Initial Diagnostic Algorithm

Step 1: History and Physical Examination

• Confirm the bleeding is truly vaginal (not urological or rectal) 4, 5
• Document all medications, particularly hormone replacement therapy (HRT), tamoxifen, and anticoagulants 4, 6
• Identify high-risk features: age >50 years, obesity (BMI >30), unopposed estrogen exposure, tamoxifen use, nulliparity, diabetes mellitus, hypertension, and Lynch syndrome 1, 2, 3
• Perform speculum examination to identify cervical polyps, cervical malignancy, or vaginal atrophy as the bleeding source 4, 5
• Obtain Pap smear to exclude cervical pathology, though this does NOT evaluate endometrial pathology 1, 5

Step 2: Transvaginal Ultrasound (First-Line Imaging)

• TVUS is the initial diagnostic test of choice to measure endometrial thickness and identify structural abnormalities 1, 2, 3
• If endometrial thickness is ≤4 mm: The negative predictive value is >99% for endometrial cancer, and expectant management is acceptable if bleeding has resolved 2, 3, 6
• If endometrial thickness is >4 mm: Proceed immediately to endometrial sampling 1, 2, 3
• If endometrial thickness is not measurable (due to fibroids, adenomyosis, or body habitus): Proceed directly to endometrial sampling 1, 3
• Always evaluate both ovaries during TVUS to exclude hormone-producing ovarian tumors 4, 5

Step 3: Endometrial Sampling (Tissue Diagnosis)

• Office endometrial biopsy using Pipelle or Vabra devices is the standard method with sensitivity of 99.6% and 97.1% respectively for detecting endometrial carcinoma 1, 2
• Critical caveat: Office endometrial biopsy has a 10% false-negative rate 1, 2, 3
• Never accept a negative or inadequate biopsy as reassuring in a symptomatic postmenopausal woman—persistent or recurrent bleeding mandates further evaluation 1, 2, 3

Step 4: When Initial Biopsy is Negative, Non-Diagnostic, or Inadequate

• If bleeding persists despite negative office biopsy: Proceed to fractional dilation and curettage (D&C) under anesthesia 1, 2, 3
• Hysteroscopy with directed biopsy is the final diagnostic step when initial sampling is inadequate, as it allows direct visualization and targeted biopsy of focal lesions such as polyps 1, 3, 7
• Consider saline infusion sonohysterography (SIS) if focal lesions are suspected, with sensitivity of 96-100% for detecting endometrial pathology 1, 5

Special Population Considerations

Tamoxifen Users

• Any vaginal spotting in tamoxifen users requires immediate endometrial sampling due to increased endometrial cancer risk (2.20 per 1,000 women-years vs 0.71 for placebo) 1, 2, 3
• Stopping tamoxifen does not address the diagnostic imperative—you must establish whether endometrial cancer is present before modifying treatment 1
• If initial biopsy is negative but bleeding persists, hysteroscopy is mandatory due to tamoxifen-associated polyps that may be missed on blind sampling 1

Lynch Syndrome Patients

• These women have a 30-60% lifetime risk of endometrial cancer 1, 2, 3
• Annual endometrial biopsy surveillance is recommended starting at age 30-35 years 1, 2

Women on Hormone Replacement Therapy

• Unopposed estrogen significantly increases endometrial cancer risk 3, 6
• Endometrial sampling is mandatory when abnormal bleeding occurs in women with a uterus on estrogen therapy 3

Common Pitfalls to Avoid

• Do NOT rely on Pap smear alone—it screens for cervical cancer, not endometrial pathology 1
• Do NOT accept a thin endometrium (<4 mm) as definitive if bleeding recurs—repeat TVUS and consider endometrial sampling 3, 6, 5
• Do NOT proceed directly to hysterectomy without tissue diagnosis—this exposes patients to unnecessary surgical risk if pathology is benign 1
• Do NOT assume fibroids explain postmenopausal bleeding—endometrial cancer and uterine sarcoma must be ruled out, with sarcoma risk up to 10.1 per 1,000 in women aged 75-79 years 3

Clinical Context

Approximately 10% of postmenopausal women with vaginal bleeding will have endometrial cancer, making tissue diagnosis essential 1, 2, 4. The peak incidence of endometrial carcinoma is between ages 65-75 years, and over 90% of cases present with abnormal uterine bleeding 1, 3. However, most postmenopausal bleeding has a benign cause, including vaginal atrophy, endometrial polyps, cervical polyps, and endometrial hyperplasia 4, 6.