When should I consider an endometrial biopsy?

When to Consider Endometrial Biopsy

Perform endometrial biopsy immediately for any postmenopausal bleeding, and in premenopausal women aged ≥35 years with abnormal uterine bleeding plus risk factors for endometrial cancer. 1, 2, 3

Postmenopausal Women

Absolute Indications

• Any postmenopausal bleeding requires immediate endometrial biopsy to rule out endometrial cancer, as 90% of endometrial cancer cases present with abnormal uterine bleeding. 1, 3
• Proceed with biopsy when transvaginal ultrasound shows endometrial thickness ≥3-4mm, though biopsy should not be delayed if bleeding is present regardless of ultrasound findings. 1
• Never accept a negative or inadequate biopsy as reassuring in a symptomatic postmenopausal woman—the false-negative rate is approximately 10%, requiring escalation to fractional D&C or hysteroscopy if bleeding persists. 1, 3

Special Populations

• Women on tamoxifen therapy with any vaginal spotting require immediate biopsy, as tamoxifen increases endometrial cancer risk (2.20 per 1000 women-years versus 0.71 for placebo). 1
• Do not stop tamoxifen before establishing tissue diagnosis—you must determine whether cancer is present before modifying treatment. 1

Premenopausal Women

Age-Based Thresholds

• All women aged ≥35 years with atypical glandular cells (AGC) on cervical cytology require endometrial biopsy as part of initial evaluation. 1
• Women <35 years with AGC need biopsy only if they have risk factors for endometrial cancer or abnormal bleeding. 1

Risk Factor-Driven Indications

Perform endometrial biopsy in premenopausal women with abnormal uterine bleeding who have any of these risk factors: 1, 2

• Long-standing unopposed estrogen exposure
• Polycystic ovary syndrome (PCOS)
• Chronic anovulation
• Obesity
• Diabetes mellitus
• Hypertension
• Nulliparity
• Tamoxifen therapy

Bleeding Pattern Considerations

• Intermenstrual bleeding carries higher cancer risk (0.52%) compared to heavy menstrual bleeding alone (0.11%), making biopsy more urgent with intermenstrual patterns. 4
• Persistent bleeding unresponsive to medical management warrants biopsy even without other risk factors. 2
• The overall risk of endometrial cancer in premenopausal women with abnormal bleeding is low (0.33%), but rises substantially with risk factors present. 4

Genetic High-Risk Populations

• Women with Lynch syndrome require endometrial biopsy screening every 1-2 years starting at age 30-35 years, due to their 30-60% lifetime risk of endometrial cancer. 1, 2, 3
• Continue annual surveillance even with benign results, as these patients remain at persistently elevated risk. 1

Diagnostic Algorithm

Initial Approach

• Start with transvaginal ultrasound in premenopausal women to assess endometrial thickness and structural abnormalities, but proceed directly to biopsy if risk factors are present. 1
• In postmenopausal women, biopsy should not be delayed for imaging—tissue diagnosis is the priority. 3

When Initial Biopsy is Negative or Inadequate

• Office endometrial biopsy has a 10% false-negative rate—if symptoms persist despite benign results, escalate to fractional D&C under anesthesia or hysteroscopy with directed biopsy. 1, 5
• Hysteroscopy provides the highest diagnostic accuracy and allows direct visualization with targeted sampling of focal lesions like polyps. 1
• Blind sampling may miss focal pathology, making hysteroscopy essential for persistent symptoms after negative biopsy. 5

Technical Considerations

• Pipelle or Vabra devices have extremely high sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma in postmenopausal women. 1
• Inadequate samples occur more commonly in postmenopausal women due to endometrial atrophy, requiring alternative sampling methods. 6
• Pregnancy is the only absolute contraindication to endometrial biopsy. 5

Common Pitfalls to Avoid

• Never perform routine surveillance biopsies in asymptomatic average-risk women—there is no evidence that screening reduces mortality from endometrial cancer in the general population. 1
• Do not accept inadequate tissue sampling as a final result in symptomatic patients—pursue definitive diagnosis with D&C or hysteroscopy. 1
• Do not neglect family history assessment, as hereditary cancer syndromes dramatically alter screening recommendations. 2
• Avoid proceeding to hysterectomy without tissue diagnosis, as this exposes patients to unnecessary surgical risk if pathology is benign. 1