Are estradiol metabolites involved in gynaecological carcinogenesis?

Abstract

AbstractCertain estradiol metabolites are biologically active, sometimes several times more potent than their parent substance. Highly sophisticated laboratory methods allow us to understand oestrogenic effects as a net effect of the corresponding metabolite pattern. Currently, research is focused on the anticancerogenic effects of 2-hydroxyestrone and particularly 2-methoxyestradiol, as well as the possible carcinogenic properties of 4-hydroxyoestrogens and 16α-hydroxyestrone. The clinical relevance of these activities, demonstrated in in-vitro and animal experiments, remains unclear – it is proven, however, that the metabolite production can be altered in certain malignancies such as endometrial-, breast- and cervical carcinoma. Clinical studies, including our studies, have demonstrated a negative correlation between the ratio of 2-hydroxyestrone to 16α-hydroxyestrone and breast cancer risk. However, the design and interpretation of such studies should consider factors influencing metabolic pattern such as diet, physical activity, smoking, as well as internal diseases and certain drugs.