Who needs an endometrial biopsy for abnormal uterine bleeding (AUB)?

Who Needs Endometrial Biopsy for Abnormal Uterine Bleeding

All women aged ≥45 years with AUB require endometrial biopsy, as do younger women (<45 years) with risk factors for endometrial cancer including obesity, diabetes, hypertension, unopposed estrogen exposure, tamoxifen use, polycystic ovary syndrome, anovulation, nulliparity, or Lynch syndrome. 1

Age-Based Indications

Women ≥45 Years

• Endometrial biopsy is mandatory for all women aged 45 years or older presenting with AUB, regardless of other risk factors 1
• This age threshold reflects the increased prevalence of endometrial cancer and precancerous lesions in this population 1

Women <45 Years

• Endometrial biopsy is indicated when any of the following risk factors are present 1:
  • Long-standing unopposed estrogen exposure 1
  • Polycystic ovary syndrome 1
  • Tamoxifen therapy 1
  • Chronic anovulation 1
  • Nulliparity 1
  • Diabetes mellitus 1
  • Hypertension 1
  • Obesity 1

Postmenopausal Women

• All postmenopausal women with vaginal bleeding require evaluation, as 90% of endometrial cancers present with abnormal bleeding 1
• Transvaginal ultrasound should be performed first; endometrial thickness ≥3-4 mm warrants endometrial biopsy 1
• Endometrial thickness <4 mm has a nearly 100% negative predictive value for cancer 2

Special High-Risk Populations

Lynch Syndrome

• Women with Lynch syndrome (hereditary non-polyposis colorectal cancer) require annual endometrial biopsy screening starting at age 30-35 years 1
• This population has a 30-60% lifetime risk of endometrial cancer 1

Atypical Glandular Cells on Pap Smear

• All women aged ≥35 years with atypical glandular cells (AGC) on cervical cytology require endometrial biopsy as part of initial evaluation 3
• Women <35 years with AGC need endometrial biopsy if they have any risk factors for endometrial cancer or abnormal bleeding 3

Clinical Scenarios Requiring Biopsy

Persistent or Recurrent Bleeding

• Persistent or recurrent undiagnosed bleeding requires endometrial biopsy even if initial biopsy was normal 1
• Office endometrial biopsy has a 10% false-negative rate, necessitating repeat sampling or hysteroscopy with directed biopsy when symptoms persist 1

Failed Medical Management

• Women with AUB who fail medical management should undergo endometrial biopsy before proceeding to surgical options 4

Irregular Menstrual Cycles

• Menstrual cycle irregularity is an independent risk factor for abnormal endometrial histology (14.3% probability) and warrants biopsy regardless of age 5

Diagnostic Approach Algorithm

1. Initial assessment: Obtain transvaginal ultrasound to evaluate endometrial thickness and structural abnormalities 4

2. For postmenopausal women:

   • If endometrial thickness ≥3-4 mm → proceed to endometrial biopsy 1
   • If endometrial thickness <4 mm → biopsy generally not needed unless bleeding persists 2

3. For premenopausal women:

   • Age ≥45 years → endometrial biopsy indicated 1
   • Age <45 years → biopsy if risk factors present (see list above) 1

4. If initial biopsy inadequate or negative but symptoms persist → hysteroscopy with directed biopsy 1

Biopsy Technique and Accuracy

• Office endometrial biopsy using Pipelle or Vabra devices has excellent sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma 1
• Adequate samples are obtained in approximately 86% of cases 6
• When office biopsy is inadequate, non-diagnostic, or negative in a symptomatic patient, fractional D&C under anesthesia must be performed 1
• Hysteroscopy with biopsy provides the highest diagnostic accuracy and should be the final step when initial sampling is inadequate 1

Critical Pitfalls to Avoid

• Never accept an inadequate or negative endometrial biopsy as reassuring in a symptomatic woman with risk factors—persistent bleeding mandates further evaluation 1
• Do not rely solely on age ≥40 years as justification for biopsy in women with regular menstrual cycles and no risk factors 5
• Atrophic endometrium is the most common cause of inadequate samples and requires alternative diagnostic approaches 6
• Never proceed to hysterectomy without tissue diagnosis—this exposes patients to unnecessary surgical risk if pathology is benign 1