## Risk Factors for Endometrial Cancer ### Established Risk Factors (Estrogen-Related) **Key Point:** Endometrial cancer is predominantly an estrogen-driven malignancy. The majority of cases (80%) are associated with unopposed estrogen exposure. | Risk Factor | Mechanism | Relative Risk | | --- | --- | --- | | Unopposed estrogen (HRT) | Direct endometrial proliferation | 2–10× | | Obesity | Peripheral aromatization of androgens to estrogen | 2–5× | | Nulliparity | Lack of progesterone-protective cycles | 2–3× | | PCOS | Chronic anovulation, unopposed estrogen | 2–3× | | Tamoxifen (breast cancer) | Partial agonist on endometrium | 2–3× | | Diabetes mellitus | Hyperinsulinemia, estrogen excess | 1.5–2× | ### Why Prolonged Oral Contraceptive Use is PROTECTIVE **High-Yield:** Oral contraceptives (OCPs) contain progestins that suppress endometrial proliferation and are **protective** against endometrial cancer. Long-term OCP use reduces risk by ~40% and the benefit persists for years after discontinuation. **Clinical Pearl:** This is a classic exam trap — students often confuse OCPs with unopposed hormone replacement therapy. OCPs contain both estrogen and progestin; the progestin provides endometrial protection. **Warning:** Do NOT confuse: - **Unopposed estrogen** (HRT without progestin) → **increases** risk - **Estrogen + progestin** (OCPs, combined HRT) → **decreases or neutral** risk ### Other Protective/Neutral Factors - Multiparity (protective) - Prolonged lactation (protective) - Smoking (slight protective effect, likely confounding) ## Summary All options except prolonged OCP use are established risk factors. OCPs are protective and are not a risk factor for endometrial cancer.
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