Clues to understanding the oxidation of estradiol in humans: effects of acute infectious hepatitis, autoimmune hepatitis, and chronic liver disease.

Determination of 2- and 16alpha-hydroxylation of estradiol in patients with a variety of liver disorders using a dynamic method of quantitating the extent of hydroxylation revealed specific and characteristic differences in the metabolic response. Patients with acute or silent variants of hepatitis B had estrogen metabolite patterns that were indistinguishable from those found in the control subjects. Female patients with autoimmune hepatitis (formerly known as lupoid hepatitis), however, showed a moderate significant decrease (P < 0.01) in 2-hydroxylation as compared with normal controls (mean 16.3 +/- 1.9 vs. 33.9 +/- 2.5), with no significant change in 16alpha-hydroxylation. Male and female subjects with chronic alcoholic cirrhosis were almost devoid of 2-hydroxylation (mean 2.9 +/- 0.5, P < 0.01), but did show a significant increase in 16alpha-hydroxylation (P < 0.01). The results, therefore, show that the alterations in patterns of biological oxidation are highly specific and do not reflect a general inability to metabolize estrogens in the cirrhotic patient. However, the results also suggest the possibility that a substantial fraction of 16alpha-hydroxylation may occur elsewhere in the body at sites other than in the liver, explaining why this biotransformation pathway is elevated, while the reaction at C-2 is almost absent in the alcoholic cirrhotic subjects.