Impact of metabolism on the safety of estrogen therapy

Estrogen metabolism has received attention owing to the recognition that oxidative metabolism of these hormones could play a very important role in the initiation and evolution of estrogen-related cancerous processes. This review discusses principal metabolic pathways associated with the molecular constituents found in common hormone formulations. The focus is the formation of catechol estrogens that then oxidize to redox-active and electrophilic quinones, along with potential mechanisms by which these metabolites contribute to oxidative stress and induce damage to essential biological macromolecules. Recent investigations involving specific estrogen metabolites that may offer potential increase of therapeutic safety for estrogen therapy in the future have also been highlighted.