A 38-year-old woman with a 10-year history of heavy menstrual bleeding presents with iron-deficiency anemia. Histology of endometrial curettage shows proliferation of endometrial glands with increased mitotic activity. What is the most common cause of endometrial hyperplasia in this patient?

Explanation

## Most Common Cause of Endometrial Hyperplasia **Key Point:** Unopposed estrogen stimulation (estrogen without adequate progesterone) is the most common cause of endometrial hyperplasia, accounting for >90% of cases. ### Pathophysiology of Estrogen-Induced Hyperplasia 1. **Loss of progesterone opposition** → estrogen acts unopposed on endometrial stroma and glands 2. **Increased proliferation** → glandular hyperplasia and increased mitotic activity 3. **Abnormal differentiation** → failure of normal secretory transformation 4. **Increased risk of malignancy** → progression to endometrial cancer if untreated ### Common Causes of Unopposed Estrogen | Cause | Mechanism | Frequency | |-------|-----------|----------| | **Anovulation (PCOS, obesity)** | No corpus luteum → no progesterone | Most common | | **Estrogen replacement without progestin** | Exogenous estrogen unopposed | Common in HRT | | **Granulosa cell tumor** | Estrogen-secreting ovarian tumor | Rare | | **Tamoxifen use** | Partial estrogen agonist on endometrium | Uncommon but important | **Clinical Pearl:** The patient's heavy menstrual bleeding and iron-deficiency anemia are consistent with chronic anovulation leading to unopposed estrogen and endometrial hyperplasia. Anovulation is the most frequent underlying mechanism in reproductive-age women. **High-Yield:** PCOS and obesity are the leading causes of anovulation and unopposed estrogen in India and globally. Endometrial hyperplasia is a precancerous lesion; atypical hyperplasia carries ~30% risk of progression to cancer if untreated. **Mnemonic: PCOS** — Polycystic Ovary Syndrome (most common endocrine cause of anovulation and unopposed estrogen) ### Histologic Features of Hyperplasia - Increased gland-to-stroma ratio - Increased mitotic figures - Crowded glands with minimal intervening stroma - May progress to atypia (nuclear enlargement, irregular membranes) [cite:Robbins 10e Ch 22]