What is the most common cause of postmenopausal (after menopause) bleeding?

Most Common Cause of Postmenopausal Bleeding

Endometrial atrophy is the most common cause of postmenopausal bleeding, although endometrial cancer is the most serious etiology that must be ruled out in all cases. 1, 2

Etiology of Postmenopausal Bleeding

Postmenopausal bleeding (PMB) has several potential causes, with varying frequencies:

1. Atrophic vaginitis/endometritis - Most common cause 2
2. Endometrial polyps
3. Endometrial hyperplasia
4. Endometrial cancer - Occurs in approximately 10% of PMB cases 2
5. Exogenous hormone therapy - Including unopposed estrogen 3
6. Submucosal leiomyomas (fibroids)
7. Less common causes:
   • Cervical cancer
   • Trauma to vaginal tissue 4
   • Hematologic malignancies (rare) 5, 6

Clinical Significance

While atrophic changes represent the most common etiology, the critical concern with any postmenopausal bleeding is the possibility of endometrial cancer. The American College of Radiology guidelines emphasize that "endometrial cancer is the most serious etiology and is thus the main focus of the evaluation of the workup of AUB in the postmenopausal population" 1.

Endometrial cancer is the most common gynecologic malignancy in developed countries 1, with 90% of cases presenting with abnormal uterine bleeding as the initial symptom 1, 7. Early detection through prompt evaluation of PMB typically leads to diagnosis at early stages when prognosis is excellent 2.

Diagnostic Approach

The diagnostic algorithm for postmenopausal bleeding should follow these steps:

1. First-line evaluation: Transvaginal ultrasound (TVUS) to measure endometrial thickness 1, 7, 8

   • Endometrial thickness ≤4 mm has high negative predictive value for malignancy
   • Endometrial thickness >4 mm requires further evaluation

2. Second-line evaluation: Endometrial sampling/biopsy 7, 8

   • Pipelle or Vabra devices have high sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma 7
   • Office-based sampling has largely replaced hospital-based dilation and curettage (D&C)

3. Additional evaluation if needed: Hysteroscopy 7

   • Particularly useful when focal pathology is suspected
   • Allows for direct visualization and targeted biopsy

Risk Factors for Endometrial Cancer

Risk factors that increase suspicion for malignancy in a woman with PMB include:

• Obesity (BMI >30) - increases risk 3-4 fold 7
• Diabetes mellitus 7
• Hypertension 7
• History of unopposed estrogen exposure 7, 3
• Nulliparity 7
• Lynch syndrome (30-60% lifetime risk) 7

Important Clinical Considerations

• All women with postmenopausal bleeding require evaluation to exclude malignancy, regardless of risk factors
• Unopposed estrogen therapy significantly increases endometrial cancer risk, as noted in FDA warnings 3
• The FDA label for estradiol specifically warns: "Estrogens increase the chances of getting cancer of the uterus. Report any unusual vaginal bleeding right away while you are taking estrogens." 3
• Transvaginal ultrasound is preferred over transabdominal due to superior resolution and visualization 1
• In cases where ultrasound cannot adequately visualize the endometrium (due to patient factors or uterine pathology), MRI may be considered 1

By following this systematic approach to evaluation, clinicians can efficiently identify the cause of postmenopausal bleeding while ensuring that no cases of endometrial cancer are missed.