Metabolism of Epitestosterone in Man1

Abstract

Production rates of epitestosterone (17a-hydroxy-4-androsten-3-one) measured in 4 normal men by the urinary isotope dilution technique averaged 220 [mu]g/day. This was 3% of the simultaneously determined testosterone production rate of 6. 8 mg/day. Administration of human chorionic gonadotropin and of corticotropin increased epitestosterone production by 21 and 29%, respectively. The daily excretion of epitestosterone in the normal men was 1/3 to 1/2 that of testosterone. In 3 patients with endocrine abnormalities epitestosterone excretion was elevated and it was 5 times greater than testosterone in 2 of them. Metabolites were sought following an intravenous dose of 6. 7 mg labeled epitestosterone. Recovery of radio-activity in raw urine for the 2 days following averaged 92%. Approximately 50% of the injected radioactivity was recovered in all neutral extract fractions, mostly as glucuronides. Unchanged epitestosterone glucuronide accounted for almost half of the extracted radioactivity, etiocholanolone plus androsterone represented only about 2%, while 2 transformation products, probably 5[beta]-androstane-3[alpha], 17[alpha]-diol and 5-androstane-3[alpha] , 17[alpha]-diol, accounted for about 5%. The sulfate fraction yielded 2. 5% of the total epitestosterone recovered. Since both oxidation of the 17[alpha] -OH group and reduction of the a , [beta]-unsaturated 3-ketone occur only to a limited extent, epitestosterone is poorly metabolized in man. Plasma testosterone is not a precursor or urinary epitestosterone, and epitestosterone is not metabolized to either 16-androsten-3[alpha]-ol or to testosterone.