What are the differential diagnoses for a postmenopausal woman presenting with bleeding?

Differential Diagnosis for Postmenopausal Bleeding

The differential diagnosis for postmenopausal bleeding must prioritize endometrial cancer first, as it accounts for approximately 10% of cases and requires urgent exclusion in all patients. 1, 2, 3, 4

Malignant Causes (Must Rule Out First)

Endometrial Adenocarcinoma

• Present in approximately 10% of postmenopausal bleeding cases 1, 2, 3
• Abnormal uterine bleeding occurs in 90% of endometrial cancer presentations 1
• Peak incidence between 65-75 years of age 3
• Risk factors include: obesity, unopposed estrogen exposure, tamoxifen use, polycystic ovary syndrome, diabetes mellitus, hypertension, nulliparity, and Lynch syndrome 1, 5
• In approximately 75% of cases, disease is confined to the uterus at diagnosis, making early detection critical 6

Cervical Carcinoma

• Must be evaluated during speculum examination 3
• Can present with postmenopausal bleeding 3

Uterine Sarcoma

• Rare but serious cause, particularly in women with known fibroids 6
• Risk increases with age: 2.94 per 1,000 women undergoing surgery for presumed fibroids, rising to 10.1 per 1,000 in women aged 75-79 years 6
• Cannot be reliably distinguished from benign fibroids on imaging alone 6

Hormone-Producing Ovarian Tumors

• Can cause endometrial stimulation leading to bleeding 3

Benign Causes (After Malignancy Excluded)

Atrophic Vaginitis/Endometritis

• Most common benign cause, accounting for approximately 21% of cases 2, 3, 4
• Results from estrogen deficiency after menopause 3, 4

Endometrial Hyperplasia

• May be a precursor to endometrial cancer 7
• Associated with unopposed estrogen exposure 1, 7
• Requires tissue diagnosis to distinguish from malignancy 1

Endometrial or Cervical Polyps

• Common structural cause of bleeding 3
• Best visualized with sonohysterography or hysteroscopy 1, 6
• Require directed biopsy as blind sampling may miss focal lesions 1, 6

Submucous Leiomyomas (Fibroids)

• Typically shrink after menopause due to decreased estrogen 6
• Any postmenopausal bleeding with fibroids requires ruling out malignancy first 6

Hormone Replacement Therapy Effects

• Unopposed or inadequate progestational protection increases endometrial cancer risk 1, 7
• Estrogen-alone therapy increases risk of endometrial cancer 2- to 12-fold compared to non-users 7

Rare/Unusual Causes

Hematological Malignancies

• Chronic lymphocytic leukemia with endometrial infiltration has been reported 8
• Should be considered when standard workup is negative 8

Non-Gynecologic Sources

• Hematuria (urinary tract bleeding) 3
• Rectal bleeding (gastrointestinal source) 3
• Must be excluded during initial evaluation 3

Critical Clinical Pitfalls

Never assume benign pathology without tissue diagnosis—endometrial cancer is present in 10% of cases and requires urgent exclusion. 1, 2, 3

• Do not accept stable fibroid size as reassurance; uterine sarcoma cannot be distinguished from benign fibroids without tissue sampling 6
• Office endometrial biopsy has a 10% false-negative rate; persistent bleeding after negative biopsy mandates hysteroscopy with directed biopsy or fractional D&C 1, 6
• Do not skip endometrial evaluation in women on tamoxifen—they have increased risk of both endometrial adenocarcinoma and uterine sarcoma 1
• Women with Lynch syndrome have 30-60% lifetime risk of endometrial cancer and require annual surveillance starting at age 30-35 years 1