What is the best course of action for a patient experiencing postmenopausal bleeding (PMB)?

Postmenopausal Bleeding: Urgent Gynecology Referral and Diagnostic Workup

All women with postmenopausal bleeding should be referred urgently to gynecology, as approximately 10% will have endometrial cancer. 1, 2

Immediate Referral Criteria

Refer urgently to gynecology for any episode of bleeding occurring 12 months or more after the last menstrual period. 2 This is non-negotiable regardless of the amount of bleeding or patient risk factors, as endometrial cancer cannot be excluded clinically. 1

Initial Diagnostic Pathway

While awaiting gynecology consultation, the following workup should be initiated:

First-Line Imaging

• Transvaginal ultrasound (TVUS) is the initial diagnostic test of choice to measure endometrial thickness and identify structural abnormalities. 1
• An endometrial thickness ≤4 mm carries a low risk of endometrial cancer (sensitivity 98%), though this does not eliminate the need for referral. 1
• If endometrial thickness is >4 mm, tissue diagnosis becomes mandatory. 1

Tissue Diagnosis

• Office endometrial biopsy is the standard method for obtaining histological diagnosis, with sensitivity of 99.6% for detecting endometrial carcinoma. 1, 3
• However, endometrial biopsy has a 10% false-negative rate, which is a critical pitfall. 1, 3
• If the initial biopsy is negative but bleeding persists or recurs, fractional dilation and curettage (D&C) under anesthesia must be performed. 1, 3

High-Risk Features Requiring Aggressive Evaluation

The following factors increase endometrial cancer risk and mandate thorough investigation: 1

• Age >50 years (>90% of endometrial cancers occur in this age group)
• Obesity (BMI >30)
• Unopposed estrogen exposure
• Tamoxifen use
• Nulliparity
• Diabetes mellitus
• Hypertension
• Lynch syndrome type II (30-60% lifetime risk of endometrial cancer)

Role of Hysteroscopy

Hysteroscopy should be considered when: 1, 3

• Office endometrial biopsy is non-diagnostic or inadequate
• Bleeding persists despite negative initial biopsy
• Focal lesions such as polyps are suspected

Hysteroscopy allows direct visualization and targeted biopsy of suspicious lesions, serving as the final diagnostic step when initial sampling fails. 3

Special Considerations for Tamoxifen Users

Women on tamoxifen require annual gynecologic assessment and must report any vaginal spotting immediately. 1 The increased risk of endometrial adenocarcinoma (2.20 per 1000 women-years versus 0.71 for placebo) makes prompt evaluation essential rather than empiric drug discontinuation. 3

Critical Pitfalls to Avoid

• Never accept a negative or inadequate endometrial biopsy as reassuring in a symptomatic postmenopausal woman, especially those on tamoxifen—the 10% false-negative rate demands escalation to D&C or hysteroscopy for persistent bleeding. 3
• Do not proceed directly to hysterectomy without tissue diagnosis, as this exposes patients to unnecessary surgical risk if pathology is benign. 3
• Do not rely solely on endometrial thickness <4 mm to exclude cancer—clinical judgment and symptom persistence should guide further evaluation. 1

When MRI is Indicated

Consider MRI if: 1

• TVUS cannot adequately evaluate the endometrium due to patient factors (body habitus, uterine position)
• Pathology such as fibroids or adenomyosis obscures visualization
• Uterine sarcoma needs to be ruled out (risk increases with age, up to 10.1 per 1000 in patients 75-79 years)