Controversies concerning the safety of estrogen replacement therapy.

Unopposed estrogen replacement is known to cause endometrial carcinoma in a small percentage of postmenopausal women, but the effects on ovarian and breast tissue remain uncertain. The increased risk of endometrial carcinoma seems to be related to both the dosage and duration of unopposed estrogen treatment. Until very recently, the morbidity and costs that result from the need for endometrial biopsy because of abnormal bleeding and from the need for hysterectomy due to hyperplasia have been ignored, but recent data suggest that they are likely to be considerable. Progestogens are known to protect against endometrial hyperstimulation, but the optimal duration of therapy each month and the maximally protective agent and dose remain to be determined. Estrogen replacement therapy may reduce the risk of arterial disease; however, the comparative effects of the various preparations, as well as their respective mechanisms of action, must be subjected to further study.