Breast cancer: are estrogen metabolites carcinogenic?

Certain estrogen metabolites can act as carcinogens in in vitro and animal experiments. The clinical relevance remains unclear. However, in the presence of factors that could influence estradiol metabolism, such as smoking or genetic polymorphisms, it seems prudent to prefer transdermal therapy to minimize the production of possible toxic metabolites. In addition, various defense mechanisms operate in the physiologic human body that prevent the formation of possible toxic intermediate products of estradiol metabolism, especially during oxidative stress. Only under rare special conditions is it conceivable that the human body cannot react sufficiently.