What is the recommended workup for vaginal bleeding after menopause?

Workup for Postmenopausal Vaginal Bleeding

Begin with transvaginal ultrasound (TVUS) to measure endometrial thickness, followed by endometrial biopsy if thickness is ≥5 mm or if bleeding persists despite a thin endometrium. 1, 2

Initial Diagnostic Steps

Transvaginal Ultrasound (First-Line Test)

• TVUS is the recommended first-line imaging modality 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%, making further invasive testing unnecessary if bleeding resolves 1, 2
• If endometrial thickness is ≥5 mm, proceed immediately to endometrial tissue sampling 2
• TVUS is preferred over blind biopsy because it is less invasive, generally painless, has no complications, and may be more sensitive for detecting carcinoma 3

Office Endometrial Biopsy (When Indicated)

• Office endometrial biopsy is the standard method for obtaining tissue when TVUS shows endometrial thickness ≥5 mm 1, 2
• Pipelle or Vabra devices have extremely high sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma 4
• Critical caveat: Office endometrial biopsy carries approximately a 10% false-negative rate, so negative results do not definitively exclude pathology if symptoms persist 1, 2, 4

When Initial Workup is Negative or Non-Diagnostic

Persistent or Recurrent Bleeding

• 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
• Never accept an inadequate or negative endometrial biopsy as reassuring in a symptomatic postmenopausal woman—the 10% false-negative rate mandates further evaluation 4

Hysteroscopy with Directed Biopsy

• Hysteroscopy should be used as the final step in the diagnostic pathway, particularly when initial sampling is inadequate, as it allows direct visualization and targeted biopsy of suspicious lesions such as polyps 2, 4
• Hysteroscopy is especially helpful in evaluating the endometrium for focal lesions in patients with persistent or recurrent undiagnosed bleeding 1, 2

Advanced Imaging (When TVUS is Inadequate)

MRI Indications

• MRI can be considered if TVUS cannot adequately evaluate the endometrium due to patient factors (body habitus, uterine position) or pathology such as fibroids or adenomyosis 1, 2

Saline Infusion Sonography

• Saline infusion sonography (SIS) should be considered when focal lesions are suspected, with high sensitivity (96-100%) and negative predictive value (94-100%) for assessing uterine and endometrial pathology 4
• SIS can distinguish between focal and diffuse endometrial pathology 1

High-Risk Populations Requiring Aggressive Evaluation

Risk Factors Mandating Lower Threshold for Biopsy

• Age >50 years (>90% of endometrial cancers occur in this age group) 1
• Obesity (BMI >30), unopposed estrogen exposure, tamoxifen use, nulliparity, diabetes mellitus, hypertension 1
• Lynch syndrome type II carriers have a 30-60% lifetime risk of endometrial cancer and require annual endometrial biopsy starting at age 30-35 years 4

Tamoxifen Users

• Women on tamoxifen require annual gynecologic assessment and must report any vaginal spotting immediately due to increased endometrial cancer risk 1
• Tamoxifen increases the risk of endometrial adenocarcinoma (2.20 per 1000 women-years vs 0.71 for placebo) and uterine sarcoma (0.17 per 1000 women-years vs 0.0 for placebo) 4
• Do not stop tamoxifen empirically—establish whether endometrial cancer is present first through the diagnostic algorithm above 4

Critical Pitfalls to Avoid

• Do not rely on Pap smear for evaluation of postmenopausal bleeding—it is designed to screen for cervical cancer, not endometrial cancer, and will miss endometrial pathology 2
• Do not use endometrial thickness cutoffs higher than 4-5 mm, as this may miss cases of endometrial cancer 2
• In postmenopausal patients with abnormal bleeding, even in the presence of fibroids, uterine sarcoma and endometrial cancer must be ruled out—the risk of unexpected uterine sarcoma is up to 10.1 per 1,000 in patients 75-79 years of age 1, 2
• Never proceed directly to hysterectomy without tissue diagnosis—this exposes the patient to unnecessary surgical risk if the pathology is benign 4

Diagnostic Algorithm Summary

1. Perform TVUS to measure endometrial thickness 1, 2
2. If ≤4 mm and bleeding resolves: observe with repeat TVUS in 3 months if bleeding recurs 2, 5
3. If ≥5 mm or non-measurable: proceed to office endometrial biopsy 1, 2
4. If biopsy is negative but bleeding persists, or if non-diagnostic: perform D&C under anesthesia 1, 2
5. If symptoms persist despite negative D&C: perform hysteroscopy with directed biopsy 2, 4
6. Consider SIS or MRI if TVUS is inadequate or focal lesions are suspected 1, 4