Are estrogens carcinogens?

Unopposed estrogens increase the risk of developing endometrial cancer. A relationship between estrogen exposure and the risk for breast cancer is very probable, an association of long-term estrogen substitution and ovarian cancer risk has been postulated recently. Estrogens have been considered as typical tumor promotors. Due to their estrogen-receptor-mediated mitogenic activity, these steroids were supposed to increase the statistical probability of spontaneous mutations. Recent experimental findings, however, suggest that estrogen metabolites, in particular 4-hydroxyes trogens are capable of inducing DNA-damage and transforming mutations.The clinical relevance of these genotoxic properties remains to be established. First molecular-epidemiologic studies suggest that some women might produce relevant amounts of mutagenic estrogen metabolites, increasing their risk for breast-, endometrial- or ovarian cancer. These findings might result in novel preventive strategies. The present data do not justify to abandon hormone replacement therapy. It seems to be wise, however, to restrict hormone replacement therapy to symptomatic women with a clear indication and according to the actual trend to limit it temporarily.