Postmenopausal Bleeding (PMB): Differential Diagnosis & Approach

Differential Diagnosis

A. Uterine / Endometrial (most common)

B. Cervical

C. Vaginal

D. Vulval

• Vulval intraepithelial neoplasia (VIN), vulval carcinoma, lichen sclerosus with excoriation

E. Non-gynaecological (often misidentified as vaginal bleeding)

F. Systemic / Iatrogenic

• Hormone replacement therapy (HRT): Unscheduled bleeding in first 3 months may be acceptable; after 3 months warrants investigation
• Tamoxifen use: Stimulates endometrium — significantly increases risk of endometrial hyperplasia and carcinoma
• Anticoagulant therapy: Warfarin, DOACs — may unmask underlying pathology
• Coagulopathy: Rare but consider if no structural cause found

Risk Factors for Endometrial Cancer in PMB

Diagnostic Approach

Step 1 — Full History

• Onset, duration, amount, colour of bleeding
• Relationship to coitus (suggests cervical/vaginal source)
• HRT or tamoxifen use
• Smear history, prior gynaecological history
• Family history (Lynch syndrome: endometrial + colorectal cancers)
• Anticoagulant use

Step 2 — Physical Examination

• General: BMI, signs of metabolic syndrome
• Abdominal: Uterine size, adnexal masses, ascites (advanced disease)
• Vulvoscopy / speculum exam: Assess vulva, vagina, cervix for atrophy, polyps, lesions, trauma
• Bimanual exam: Uterine size, mobility, adnexal tenderness/masses

Step 3 — First-Line Investigation: Transvaginal Ultrasound (TVUS)

• Endometrial thickness (ET) threshold:
  • ≤4 mm: Risk of malignancy <1% → reassure (if no structural abnormality or ongoing bleeding)
  • >4 mm or structurally abnormal → proceed to endometrial sampling
• Assess endometrial morphology (homogeneous vs. heterogeneous, fluid in cavity), myometrium, adnexa

Sagittal (a) and axial (b) TVUS views: endometrial stripe measured at 15 mm (normal postmenopausal threshold ≤4 mm). Confirmed endometrial adenocarcinoma.

Step 4 — Endometrial Sampling (Biopsy)

• ET >4 mm on TVUS
• Structurally abnormal or persistently thickened endometrium
• Ongoing / recurrent PMB even with ET ≤4 mm
• On tamoxifen or unopposed oestrogen
• Irregular/unscheduled bleeding on HRT beyond initial 3 months
• Strong risk factors: Lynch syndrome family history, PCOS, obesity

1. Pipelle biopsy (outpatient) — first choice; ~90% sensitivity for endometrial carcinoma
2. Hysteroscopy + directed biopsy — gold standard; mandatory if Pipelle is non-diagnostic or focal lesion suspected (polyp)
3. D&C — largely replaced by hysteroscopy but used when hysteroscopy unavailable

Step 5 — Further Investigations

Summary Algorithm

PMB
  │
  ├─► History + Examination
  │       ├─ Obvious vulval/vaginal/cervical cause on speculum?
  │       │       └─► Treat accordingly (atrophic vaginitis, polyp removal, refer if malignancy suspected)
  │       └─ No obvious cause
  │
  ├─► Transvaginal Ultrasound (TVUS)
  │       ├─ ET ≤4 mm, homogeneous, no structural abnormality
  │       │       └─► Reassure + follow up (if bleeding recurs → hysteroscopy)
  │       └─ ET >4 mm OR heterogeneous / structural abnormality
  │               └─► Endometrial biopsy (Pipelle)
  │                       ├─ Adequate + benign → reassure / treat cause
  │                       ├─ Hyperplasia with atypia / carcinoma → refer oncology/gynae-oncology
  │                       └─ Inadequate / inconclusive → Hysteroscopy + directed biopsy
  │
  └─► If malignancy confirmed → Staging (MRI / CT) → MDT management

Key Points

• Never reassure without investigation — 10% of PMB is endometrial carcinoma
• TVUS ET >4 mm is the standard threshold for proceeding to biopsy in postmenopausal women
• Recurrent PMB with normal TVUS still warrants hysteroscopy — polyps and focal lesions can be missed
• Tamoxifen creates a subendometrial effect that makes TVUS unreliable; direct hysteroscopy/biopsy is preferred
• Lynch syndrome patients require heightened surveillance and counselling for prophylactic surgery
• Atrophic vaginitis/endometrial atrophy is the most common cause, but malignancy must always be excluded first