Which of the following is a risk factor for endometrial cancer?

• A. Unopposed estrogen exposure
• B. Regular exercise
• C. Progestin-containing therapy
• D. Oophorectomy

Answer: (A)

Unopposed estrogen exposure increases endometrial cancer risk because estrogen drives endometrial proliferation and, without progesterone to oppose and shed the proliferating lining, the endometrium can undergo hyperplasia with a higher chance of malignant transformation. Estrogen can be unopposed in several situations: obesity increases peripheral conversion of androgens to estrogen, anovulatory cycles (as in PCOS) mean there’s no progesterone production, and estrogen replacement therapy without a progestin component adds estrogen without opposition. In contrast, factors that reduce risk include regular exercise and therapies containing progestin, which counteract estrogen’s effects, and oophorectomy, which lowers estrogen production. So the key risk factor is unopposed estrogen exposure.