C19 and C21 5 beta/5 alpha metabolite ratios in subjects treated with the 5 alpha-reductase inhibitor finasteride: comparison of male pseudohermaphrodites with inherited 5 alpha-reductase deficiency

• Published in: The journal of clinical endocrinology and metabolism Vol. 70; no. 3; p. 777
• Main Authors: Imperato-McGinley, J, Shackleton, C, Orlic, S, Stoner, E
• Format: Journal Article
• Language: English
• Published: United States 01.03.1990
• Subjects: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - blood; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - deficiency; 5-alpha Reductase Inhibitors; Aged; Androstenedione - analogs & derivatives; Androstenedione - metabolism; Androstenes - therapeutic use; Androsterone - urine; Azasteroids - therapeutic use; Corticosterone - metabolism; Dihydrotestosterone - metabolism; Disorders of Sex Development - blood; Disorders of Sex Development - enzymology; Disorders of Sex Development - urine; Etiocholanolone - urine; Finasteride; Gas Chromatography-Mass Spectrometry; Humans; Hydrocortisone - metabolism; Liver - drug effects; Liver - enzymology; Luteinizing Hormone - metabolism; Male; Middle Aged; Prostatic Hyperplasia - blood; Prostatic Hyperplasia - drug therapy; Prostatic Hyperplasia - urine; Radioimmunoassay; Randomized Controlled Trials as Topic; Steroids, Heterocyclic - therapeutic use; Testosterone - metabolism
• ISSN: 0021-972X
• DOI: 10.1210/jcem-70-3-777

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 inherited 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 and 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.