The role of hormones in the etiology and prevention of endometrial cancer.

Unopposed estrogens, both exogenous and endogenous, increase the risk of endometrial cancer although the magnitude of the association between estrogen replacement therapy and adenocarcinoma has been exaggerated by the epidemiologic case-control studies. Not all postmenopausal women need estrogen replacement therapy since some produce sufficient endogenous estrogens to remain asymptomatic and prevent atrophic vaginitis, osteoporosis and atherosclerosis. However, within this group may be those at risk for endometrial cancer, so they need to be identified and treated with cyclic progestogens. Sequential oral contraceptives did not protect young women from adenocarcinoma of the endometrium because of too little progestogen for too short a duration in view of the relatively high dosage of estrogen. However, combination birth control pills significantly decrease the risk for endometrial carcinoma. Endometrial hyperplasia is a precancerous lesion in some women and can be effectively reversed with 10-13 days of progestogen monthly in at least 98% of patients. The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma. It should be administered to all postmenopausal women with an intact uterus. This includes asymptomatic women, patients receiving estrogen replacement therapy and women being evaluated for hormone therapy. If there is a positive response to the progestogen challenge, as manifested by withdrawal bleeding, then the progestogen should be continued for 13 days each month for as long as withdrawal bleeding results. If there is no response then the progestogen challenge test should be repeated at each annual examination. Universal use of the progestogen challenge test should prevent nearly all endometrial cancers.