THE METABOLISM OF 17α-HYDROXYPROGESTERONE AND ITS RELATION TO CONGENITAL ADRENAL HYPERPLASIA*

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Abstract
17α-Hydroxyprogesterone was administered orally to 4 patients, including 1 adult with congenital adrenal hyperplasia. Chromatographic analysis of the urinary metabolites obtained after enzymatic hydrolysis yielded four pregnanctriol isomers, three 17-hydroxypregnanolone isomers, androsterone, epiandrosteronc, etiocholanolone, androstanedione, etiocholanedione and two C19O3 compounds (11-hydroxyandrosterone and 11-ketoetiocholanolone). It is concluded that the metabolism of l7α-hroxyprogesterone proceeds by way of full reduction of the Δ4-3-keto group, followed by reduction of the C20-ketone group and finally by cleavage of the side-chain. Considerable individual variation was observed with respect to the proportion of C21 and C19 compounds excreted and also with respect to the proportions of the individual isomers of the C21 compounds. The metabolites of 17α-hydroxyprogestcrone do not appear to account for the masculinization seen in congenital adrenal hyperplasia; this and the disproportionately high excretion of androsterone in this disorder are highly suggestive of an associated overproduction of adrenal androgens, presumably dehydroisoandrosterone, Δ4-androstenedione and 11-oxygenated Δ4-androstenedione.