What is the appropriate workup for abnormal uterine bleeding?

Workup of Abnormal Uterine Bleeding

Begin with transvaginal ultrasound (TVUS) combined with transabdominal imaging as the first-line diagnostic test, followed by endometrial sampling when indicated based on age, risk factors, and ultrasound findings. 1, 2

Initial Diagnostic Algorithm

Step 1: Pregnancy Exclusion and Laboratory Assessment

• Obtain urine β-hCG in all reproductive-age women before proceeding with further workup 2, 3, 4
• Measure thyroid-stimulating hormone (TSH) and prolactin to assess endocrine causes of ovulatory dysfunction 2, 3
• Order complete blood count with platelets to evaluate for anemia and coagulopathy 4

Step 2: First-Line Imaging with TVUS

• TVUS is the preferred initial imaging modality, rated "usually appropriate" (7-9 appropriateness rating) by the American College of Radiology 1, 2
• Use combined transvaginal and transabdominal approach to fully assess the uterus, especially when enlarged or when TVUS field of view is limited 1, 2
• TVUS effectively distinguishes structural causes (polyps, adenomyosis, leiomyomas, malignancy, hyperplasia) from non-structural causes 2, 3
• In adolescents who have never engaged in vaginal intercourse, use transabdominal ultrasound instead of transvaginal 2, 3

Step 3: Age-Based Endometrial Sampling Criteria

Postmenopausal Women:

• Perform endometrial biopsy when endometrial thickness ≥3-4mm on TVUS 2
• If endometrial thickness <4mm and bleeding persists, repeat TVUS has nearly 100% negative predictive value for cancer 1
• Office endometrial biopsy using Pipelle or Vabra devices achieves 99.6% and 97.1% sensitivity respectively for detecting endometrial carcinoma 2

Premenopausal Women ≥45 Years:

• All women ≥45 years with abnormal uterine bleeding require endometrial sampling regardless of ultrasound findings 2
• This age group experiences increasing anovulatory cycles with unopposed estrogen exposure, markedly raising hyperplasia and carcinoma risk 2

Women <45 Years:

• Perform endometrial biopsy if risk factors present: long-standing unopposed estrogen exposure, polycystic ovary syndrome, tamoxifen therapy, anovulation, nulliparity, diabetes mellitus, hypertension, or obesity 2
• Women with atypical glandular cells (AGC) on cervical cytology require endometrial biopsy: all women ≥35 years, and women <35 years with risk factors or abnormal bleeding 2

Step 4: Advanced Imaging When TVUS Is Inadequate or Inconclusive

Saline Infusion Sonohysterography (SIS):

• Use SIS when focal endometrial lesions are suspected or when standard TVUS inadequately visualizes the endometrium 2
• SIS demonstrates 96-100% sensitivity and 94-100% negative predictive value for detecting endometrial pathology 2, 4
• SIS distinguishes between leiomyomas and endometrial polyps with 97% pooled accuracy 1
• Perform SIS during early proliferative phase (days 4-6) when endometrium is thinnest 2

MRI Pelvis:

• Consider MRI when uterus is incompletely visualized by ultrasound or findings are indeterminate 1
• MRI identifies malignant uterine pathology with 79% sensitivity and 89% specificity for endometrial cancer, and 100% sensitivity and specificity for leiomyosarcomas 1
• Use gadolinium-based IV contrast and include diffusion-weighted sequences 1
• MRI has 78% sensitivity and 93% specificity for diagnosing adenomyosis 1

Step 5: Management of Inadequate or Negative Biopsy Results

Critical pitfall: Office endometrial biopsies have a 10% false-negative rate—never accept a negative or inadequate biopsy as reassuring in a symptomatic patient 2

• When initial biopsy is negative, non-diagnostic, or inadequate and symptoms persist, escalate to hysteroscopy with directed biopsy or fractional D&C under anesthesia 2
• Hysteroscopy provides direct visualization of the endometrium and enables targeted sampling of focal lesions that may be missed by blind techniques 2, 4
• Hysteroscopy has the highest diagnostic accuracy for endometrial cancer and allows simultaneous removal of identified polyps 2

Special High-Risk Populations

Lynch Syndrome:

• Women with Lynch syndrome require annual endometrial biopsy starting at age 30-35 years due to 30-60% lifetime risk of endometrial cancer 2
• Continue annual surveillance even after benign results 2

Tamoxifen Users:

• Tamoxifen increases endometrial cancer risk 4-fold (relative risk 4.0,95% CI 1.70-10.90), with risk rising with higher cumulative dose and longer duration 2
• Never discontinue tamoxifen empirically—establish tissue diagnosis first, as most tamoxifen-associated endometrial cancers present with vaginal spotting as an early symptom 2
• Proceed to hysteroscopy with directed biopsy if initial sampling is inadequate 2

Cardiovascular Disease or Post-SCAD:

• Avoid NSAIDs and tranexamic acid due to MI and thrombosis risk 4
• Levonorgestrel-releasing IUD becomes the preferred treatment option in this population 4

Common Diagnostic Pitfalls to Avoid

• Never rely on Pap smear to evaluate abnormal uterine bleeding—it screens for cervical cancer, not endometrial pathology 2
• TVUS alone cannot provide definitive histologic diagnosis or differentiate between hyperplasia, polyps, and malignancy—it only signals the need for tissue sampling 2
• Do not proceed directly to hysterectomy without tissue diagnosis—this exposes patients to unnecessary surgical risk if pathology is benign 2
• When TVUS cannot adequately visualize the endometrium due to body habitus, uterine position, or interfering pathology (adenomyosis, large fibroids), proceed directly to endometrial sampling rather than relying on the incomplete scan 2
• Endometrial biopsy alone has variable sensitivity for focal lesions—use SIS or hysteroscopy when focal pathology is suspected 4

Doppler Ultrasound Considerations

• Doppler imaging is a standard component of pelvic ultrasound and helps identify vessels within endometrial polyps or cancer 1
• Currently no definitive studies demonstrate whether Doppler can differentiate between benign and malignant endometrial lesions 1
• Doppler evaluation of leiomyomas and adenomyosis cannot definitively differentiate between these entities 1