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.
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.
Cornell University Medical College, New York, New York 10021.
J
J
Imperato-McGinley
C
C
Shackleton
S
S
Orlic
E
E
Stoner
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000097:blood / Q000172:deficiency; D058891:5-alpha Reductase Inhibitors; D000368:Aged; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism; D000736:Androstenes / Q000627:therapeutic use*; D000738:Androsterone / Q000652:urine; D001378:Azasteroids / Q000627:therapeutic use*; D003345:Corticosterone / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000378:metabolism; D012734:Disorders of Sex Development / Q000097:blood / Q000201:enzymology* / Q000652:urine; D005043:Etiocholanolone / Q000652:urine; D018120:Finasteride; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D011863:Radioimmunoassay; D016032:Randomized Controlled Trials as Topic; D013260:Steroids, Heterocyclic / Q000627:therapeutic use*; D013739:Testosterone / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; C003582:11-hydroxyandrostenedione; D018120:Finasteride; D007986:Luteinizing Hormone; D005043:Etiocholanolone; D000738:Androsterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D003345:Corticosterone; D006854:Hydrocortisone