There is evidence to suggest that diet, ethnicity and medications could have clinically significant effects on plasma concentrations of estradiol during ERT. One hypothesis is that these effects may be due to variability in the cytochrome P450 enzymes responsible for the oxidative metabolism of estradiol. Estradiol, the most potent endogenous estrogen, is metabolized by a series of oxidative transformations to much less potent metabolites. The most important of these oxidations, is C-2 hydroxylation is performed by both CYP1A2 and CYP3A which are present in the liver. CYP3A is also present in the intestine. These P450 enzymes are responsible for the metabolism of endogenous steroids, a large number of medications, detoxification of poisons and activation of carcinogens. Dietary manipulations, such as high and low salt diets and grapefruit juice have been shown to affect the activity of CYP3A w/altered concentrations and clinical effects for other drugs metabolized by the P450 system. SPECIFIC HYPOTHESES: Switching an individual from a low salt to a high salt diet will result in a significant lowering of their estradiol concentration and, conversely, switching from a high to a low salt diet will result in a significant elevation of their estradiol concentration.
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