Endometrial cancer is estrogen-dependent. Which exposure increases risk?

• A. Unopposed estrogen exposure
• B. Progesterone therapy
• C. Androgen therapy
• D. Thyroid hormone therapy

Answer: (A)

Endometrial cancer risk rises when estrogen drives endometrial proliferation without the opposing effects of progesterone. When estrogen exposure is unopposed, the endometrium remains proliferative and is less likely to shed normally, leading to hyperplasia and potential malignant transformation. This explains why factors that increase estrogen without enough progesterone—such as obesity (more peripheral estrogen production), anovulatory states like PCOS, or estrogen therapy without progestin—raise risk. Progesterone, whether from natural cycles or deliberate progestin therapy, counteracts estrogen’s effects by promoting secretory changes and regular shedding, thereby reducing risk. Androgen or thyroid hormone therapies do not have the same impact on endometrial proliferation, so they don’t carry the same risk.