The relationship of exogenous estrogens to cancer risk

Much attention has focused on the relationship of exogenous estrogens to cancer risk. The present review examines the available data according to specific disease associations. Well established is an increased risk of endometrial cancer following estrogen use, the elevations ranging from 2- to 8-fold. Although the reality of this association has been questioned, relationships with specific measures of use (e.g. duration, dose, currency of use) as well as with disease status (e.g. stage, grade) are supportive of causality. Less well established is the relationship of estrogen use to risk of breast cancer, although several studies have shown slight elevations in risk for long term users. Discrepant findings, however, exist in terms of subgroups that are at excess risk, notably with respect to ovarian status, although there is some consistency with regard to an interaction between estrogen use and benign breast disease on subsequent breast cancer. The relationship of estrogen use to ovarian cancer has not been well studied, but a clear link has been established between diethylstilbestrol exposure in utero and vaginal adenocarcinomas. In addition, there is some evidence that estrogen use may elevate the risk of several non-gynecologic cancers, including cancers of the thyroid, gallbladder and colon, and melanoma; further exploration of these associations is warranted.