Estrogen hydroxylation--the good and the bad.

Although estradiol itself is primarily responsible for female development, the metabolites are responsible for many of the other positive and negative properties of estrogens. Phase I metabolism of estradiol is exclusively oxidative unlike the other steroid hormones and involves a series of hydroxylations. The specific hydroxylations can be induced or suppressed by endogenous or exogenous compounds that influence the cytochrome enzymes that act on specific sites on the molecule. Modulation of estrogen hydroxylation is essential since some of the other metabolites increase the risk of breast and other hormone-related cancers. The various hydroxylation pathways are discussed as well as the effects of the products of estrogen hydroxylation. The interaction between the human papilloma virus (HPV) and 16alpha-hydroxyestrone is discussed with reference to recurrent respiratory papillomatosis, cervical dysplasia, and cervical cancer. The role of estrogen metabolites in predicting the relative risk for breast cancer is evaluated using prospective and case-control studies. In one pilot study a factor that is a component of body fat is identified to be an inhibitor of estrogen C-2 hydroxylation. The role of environmental toxins like the phthalate esters and how these compounds increase risk for hormonal cancers is examined in a second pilot study.