Clues to Understanding the Oxidation of Estradiol in Humans

• Published in: Annals of the New York Academy of Sciences 2009-02, Vol.1155 (1), p.242-251
• Main Authors: Lahita, Robert G., Schaefer, Robert A., Bradlow, H. Leon, Kreek, Mary Jeanne
• Format: Article
• Language: English
• Subjects: alterations; alterations in estrogen metabolism; cirrhosis; liver disease
• ISSN: 0077-8923; 1749-6632; 1930-6547
• DOI: 10.1111/j.1749-6632.2009.04359.x

Determination of 2‐ and 16α‐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 16α‐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 16α‐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 16α‐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.