A perspective on the role of estrogen in hormone-induced prostate carcinogenesis

Androgens are thought to cause prostate cancer, but the precise mechanisms by which they do so are unclear. Data, mostly from animal studies, suggest that for androgens to cause prostate cancer they must be aromatized to estrogen and act in concert with these estrogen metabolites. Androgen-receptor mediated activity of androgens and estrogen receptor-mediated effects of estrogen metabolites are likely to be necessary, but estrogen genotoxicity appears to be a probable critical factor as well. Only when all these mechanisms are active, may prostate carcinogenesis result. Convincing proof-of-concept studies are needed to definitively test this concept which, if proven, may lead to clinically feasible chemoprevention approaches interfering with these mechanisms.

► Prostate cancer is likely caused by androgens in concert with estradiol and estrogen metabolites.
► Androgen-receptor mediated activity of androgens is critically involved prostate carcinogenesis.
► Estrogen receptor-mediated estradiol effects and genotoxicity of estrogen metabolites are likely both necessary for prostate carcinogenesis.