Differential Causes of Postmenopausal Bleeding
Structural Causes
The most critical differential to exclude is endometrial cancer, which accounts for approximately 10% of postmenopausal bleeding cases, with peak incidence between ages 65-75 years. 1, 2
Endometrial Pathology
- Endometrial atrophy is the most common benign cause, accounting for approximately 21% of cases 2, 3
- Endometrial polyps are a frequent structural cause that can be identified on imaging 4, 1
- Endometrial hyperplasia (with or without polyps) represents a precursor lesion to endometrial carcinoma and requires histological diagnosis 4, 2
- Endometrial cancer must be ruled out in all cases, particularly in high-risk patients (age >50, obesity with BMI >30, unopposed estrogen exposure, tamoxifen use, nulliparity, diabetes, hypertension, Lynch syndrome type II) 1
Cervical and Vaginal Causes
- Cervical carcinoma should be assessed during speculum examination 2
- Cervical polyps can be visualized on examination 2
- Vaginal atrophy is a common benign cause related to estrogen deficiency 4, 2
Uterine Myometrial Pathology
- Leiomyomas (fibroids) can cause postmenopausal bleeding, particularly submucosal fibroids 4
- Uterine sarcoma must be excluded even when fibroids are present, as the risk increases with age (up to 10.1 per 1,000 in patients aged 75-79 years) 4, 5
- Adenomyosis can be identified on imaging studies 4
Ovarian Pathology
- Hormone-producing ovarian tumors can stimulate endometrial bleeding 2
Non-Structural Causes
Iatrogenic/Medication-Related
- Hormone replacement therapy (HRT) with estrogen, particularly unopposed estrogen, increases endometrial cancer risk 1, 6
- Tamoxifen use significantly increases endometrial cancer risk and requires mandatory endometrial sampling when bleeding occurs 1, 5
- Anticoagulant therapy can contribute to bleeding 2
Non-Gynecologic Sources
- Hematuria (urinary tract bleeding) should be excluded 2
- Rectal bleeding (gastrointestinal source) must be considered 2
Rare Causes
- Hematologic malignancies such as chronic lymphocytic leukemia with endometrial infiltration have been reported 7
- Trauma-related causes including malunited pelvic fractures causing vaginal wall laceration 8
Critical Risk Stratification
Women with Lynch syndrome type II have a 30-60% lifetime risk of endometrial cancer and require immediate evaluation of any abnormal bleeding. 1, 5
The overall incidence of genital tract malignancies in postmenopausal bleeding is approximately 16%, making thorough evaluation mandatory in all cases. 3