A 56-year-old woman has estrogen-only HRT and is aware that this can increase the incidence of certain cancers. By approximately how many times does the risk of endometrial cancer increase after 10 years of estrogen-only HRT?

• A. 9-fold
• B. 2-fold
• C. 1.5-fold
• D. 4-fold

Answer: (A)

Estrogen-only HRT increases endometrial cancer risk because estrogen stimulates the lining of the uterus without the balancing effect of progesterone. This endometrial proliferation is not just immediate; the longer the uterus is exposed to unopposed estrogen, the greater the chance that abnormal cells accumulate and progress toward cancer. The risk rises with the duration of therapy, and after about 10 years it’s estimated to be roughly nine times higher than in women who haven’t used estrogen alone. This heightened risk applies to women with an intact uterus; in women who have had a hysterectomy, endometrial cancer risk from estrogen alone is not increased. To reduce this risk in women who still have a uterus, adding a progestin is recommended to oppose estrogen’s effect on the endometrium.