C19and C215β/5αMetabolite Ratios in Subjects Treated with the 5α-Reductase Inhibitor Finasteride: Comparison of Male Pseudohermaphrodites with Inherited 5α-Reductase Deficiency*

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Abstract
Male subjects administered the 5.alpha.-reductase inhibitor finasteride were studied to determine its effect on C19 and C21 5.alpha.-metabolism. Plasma testosterone (T) and 5.alpha.-dihydrotestosterone (DHT) were measured and T/DHT ratios determined at doses of 0.2-80 mg. Urinary etiocholanolone (5.beta.)/androsterone (5.alpha.) ratios and 5.beta./5.alpha. metabolite ratios of cortisol, 11.beta.-hydroxyandrostenedione, and corticosterone were also measured. The steroid profile was compared to male pseudohermaphrodites with inhibited 5.alpha.-reductase deficiency who have a global defect in C19 and C21 5.alpha.-metabolism. The mean plasma DHT levels were decreased at all doses, resulting in elevated T/DHT ratios. The mean urinary etiocholanolone/androsterone, 11.beta.-hydroxyetiocholanolone/11.beta.-hydroxyandrosterone, tetrahydrocortisol/allotetrahydrocortisol, and tetrahydrocorticosterone/allotetrahydrocorticosterone ratios were elevated compared to pretreatment levels and placebo control values. The mean ratios appeared to be dose dependent for plasma T/DHT, urinary etiocholanolone/androsterone tetrahydrocorticosterone/allotetrahydrocorticosterone ratios. The mean 11.beta.-hydroxyetiocholanolone-hydroxyandrosterone ratio was maximally elevated at the lowest doses. The results indicate that finasteride has a broad steroid spectrum inhibiting C19 ad C21 5.alpha.-steroid metabolism and affecting hepatic and peripheral 5.alpha.-metabolism. These results suggest that a single gene codes for a single 5.alpha.-reductase enzyme with affinity for multiple steroid substrates. The steroid profile is strikingly similar to that of male pseudohermaphrodites with inherited 5.alpha.-reductase deficiency.