Abstract

PIP: Estrogen has been used to induce a wide variety of tumors in various animal species but only the rabbit is reported to reliably develop endometrial carcinoma. Variables associated in humans with an increase susceptibility to endometrial adenocarcinoma include aging, obesity, liver diseases, polycystic ovary disease, and ovarian tumors. In women estrogen induces mitotic activity in the endometrium and promotes the proliferation of the endometrium. Current concern that estrogen replacement therapy in postmenopausal women may be associated with increased risk of endometrial adenocarcinoma is based on: 1) reports of increased incidence of the disease, and 2) epidemiologic studies associating estrogen administration with an increased risk of endometrial carcinoma. The author draws the following conclusions based on the existing data: 1) there is likely a small but significant increase in the risk of development of endometrial adenocarcinoma among menopausal women on estrogen replacement therapy; 2) the increase in risk appears to be greatest for women who do not have any of the constitutional stigmas that would ordinarily place them at higher risk for adenocarcinoma; 3) risk increases with increasing duration of therapy, probably following a latent period of undetermined duration; 4) risk increases with increasing dose of estrogen; 5) progestin administration likely affords some protection against the risk, but the potential risks of administering the hormonal equivalent of a combination oral contraceptive periodically to elderly women have yet to be examined carefully; and 6) careful surveillance of patient populations on estrogen replacement therapy may limit the risk of adenocarcinoma associated with estrogens to early, highly curable lesions. It is incorrect to assume that estrogen actually causes carcinoma of the endometrium; it more likely induces a precancerous hyperplastic state in a dose-related fashion and only certain individuals ultimately develop invasive carcinoma.