ABSTRACT
It has been recognized for many years that an aberration of endogenous estrogen may have an impact upon the endometrium. The association of feminizing ovarian tumors and endometrial cancer is well documented in the literature. Over a quarter of a century ago, studies appeared which suggested an increased incidence of endometrial cancer in patients who used unopposed exogenous estrogen. Although publications noted risk ratios (RRs) into the teens, most were much less than that, and a recent meta-analysis of 29 observational studies noted an RR of 2.3 (95% confidence interval (CI) 2.1-2.5)1. In cases in which unopposed estrogen, either endogenous or exogenous, has been associated with endometrial cancer, the malignancy is usually well differentiated and superficially invasive without extrauterine disease. These individuals have an excellent survival prognosis. Studies have indicated that adenocarcinoma in patients with a history of estrogen replacement therapy (ERT) is associated with just as good survival, if not better, than that of cohorts on ERT but without cancer and much better than that of patients not on ERT and without cancer. It is also well recognized that the combination of estrogen and progestogen decreases the risk of endometrial cancer back to, if not below, the normal incidence of the disease. This is particularly true if the progestin is given for 1214 days cyclically or as continuous therapy along with the estrogen.
