What is the initial workup for a postmenopausal woman presenting with bleeding?

Postmenopausal Bleeding Workup

Begin with transvaginal ultrasound (TVUS) as the first-line test to measure endometrial thickness, with an endometrial thickness ≤4 mm having a negative predictive value for cancer of nearly 100%, eliminating the need for further workup if bleeding has resolved. 1, 2, 3

Initial Diagnostic Pathway

First-Line Test: Transvaginal Ultrasound

• TVUS is the recommended initial imaging test to measure endometrial thickness and identify structural abnormalities of the uterus, endometrium, and ovaries. 1, 2, 3
• If endometrial thickness is ≤4 mm and bleeding has stopped, no further evaluation is needed—this threshold has a >99% negative predictive value for endometrial cancer. 1, 4, 5
• If endometrial thickness is ≥5 mm, proceed immediately to endometrial tissue sampling. 2, 5
• TVUS also detects ovarian pathology, including hormone-producing tumors that may cause bleeding. 2, 6

Tissue Diagnosis: Endometrial Biopsy

• Office endometrial biopsy is the standard method for histological assessment when TVUS shows endometrial thickness >4 mm. 1, 2, 3
• This has a sensitivity of 99.6% for detecting endometrial carcinoma, though it carries approximately a 10% false-negative rate. 1, 3
• Do not rely on Pap smear—it screens for cervical cancer, not endometrial pathology, and will miss endometrial cancer. 2, 3

Management of Persistent or Non-Diagnostic Results

When Initial Biopsy is Negative or Inadequate

• If office endometrial biopsy is negative but bleeding persists, or if the biopsy is non-diagnostic, perform fractional dilation and curettage (D&C) under anesthesia. 1, 2, 3
• Hysteroscopy is helpful for evaluating focal lesions such as polyps in patients with persistent or recurrent undiagnosed bleeding. 1, 2, 3
• Saline infusion sonography can distinguish between focal and diffuse endometrial pathology when structural abnormalities are suspected. 1, 2

Alternative Imaging

• MRI can be considered if TVUS cannot adequately evaluate the endometrium due to patient factors (obesity, patient intolerance) or pathology such as large fibroids or adenomyosis. 1, 2

Critical Clinical Considerations

High-Risk Populations Requiring Aggressive Evaluation

• Women on tamoxifen require annual gynecologic assessment and must report any vaginal spotting immediately due to increased endometrial cancer risk. 1, 3
• Women with Lynch syndrome have a 30-60% lifetime endometrial cancer risk and should undergo endometrial biopsy for any abnormal bleeding. 1, 3
• Women on unopposed estrogen therapy (estrogen without progestin in women with a uterus) have significantly increased endometrial cancer risk and require mandatory endometrial sampling when bleeding occurs. 1, 7

Important Pitfalls to Avoid

• Even in the presence of fibroids, uterine sarcoma and endometrial cancer must be ruled out—the risk of unexpected uterine sarcoma reaches 10.1 per 1,000 in patients aged 75-79 years. 1, 2, 3
• Never use endometrial thickness cutoffs higher than 4 mm—this may miss cases of endometrial cancer. 2
• Failing to pursue further evaluation when initial tests are negative but bleeding persists is a critical error. 2

Key Risk Factors to Elicit in History

• Age >50 years (>90% of endometrial cancers occur in this age group). 1
• Obesity (BMI >30), unopposed estrogen exposure, tamoxifen use. 1, 4
• Nulliparity, diabetes mellitus, hypertension. 1
• Lynch syndrome type II (30-60% lifetime risk). 1
• Polycystic ovary syndrome, atypical glandular cells on prior cervical cytology. 4

Physical Examination Essentials

• Perform speculum examination to identify cervical sources of bleeding, assess for atrophic changes, and look for cervical malignancy or polyps. 5
• Perform bimanual pelvic examination to assess for uterine or adnexal masses. 5

Summary Algorithm

1. TVUS first → If ≤4 mm and bleeding stopped, stop workup. 1, 2, 3
2. If >4 mm → Office endometrial biopsy. 1, 2, 3
3. If biopsy negative but bleeding persists or biopsy inadequate → D&C under anesthesia ± hysteroscopy. 1, 2, 3
4. If structural abnormalities suspected → Consider saline infusion sonography or hysteroscopy. 1, 2
5. If TVUS inadequate → Consider MRI. 1, 2