Reversible Reproduction of the Abnormal Cortisol Metabolite Pattern of Cirrhosis by Administration of Norethandrolone

ABSTRACT Administration of norethandrolone (17-ethyl-19-nortestosterone), 60 mg daily p.o., to 2 subjects with normal liver function, reversibly altered the previously normal cortisol metabolite pattern (studied after iv tracer doses of 4-14C-cortisol) to one resembling that reported in cirrhosis. Conversion to tetrahydrocortisone was decreased by half, conversion to cortolone (20α) was increased 3-fold, and there was increased formation of Reichstein's substances U and epi-U. The decreased glucuronic acid conjugation of cortisol metabolites observed in cirrhosis was not reproduced by norethandrolone. Norethandrolone also produced 2 changes of cortisol metabolism not found in cirrhosis: increase in the ratio of 11-hydroxy to 11-keto metabolites, and decrease in cortisol production. These changes were fully developed within 2 weeks, and regressed completely within 2–3 months after stopping the steroid. This observation provides an approach to studying mechanisms of abnormal cortisol metabolism in cirrhosis...