EVIDENCE FOR DECREASED ANDROGEN 5-ALPHA-REDUCTION IN SKIN AND LIVER OF MEN WITH SEVERE ACNE AFTER 13-CIS-RETINOIC ACID TREATMENT

To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatmen t on androgen metabolism in men with severe nodulocystic acne, eight m en with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 2 4-h urine collections, and skin biopsies obtained before and at the en d of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did in duce significant decreases in serum levels of the 5 alpha-reduced andr ogens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosidur onate (P < 0.04), and 5 alpha-androstan-3 alpha,l7 beta-diol glucosidu ronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metaboli tes 5 alpha-androstan-3 alpha,17 beta-diol and androsterone did not va ry significantly despite a decrease in the excretion of the latter. Mo reover, a marginally significant increase in urinary excretion of etio cholanolone, very similar to the decrease in androsterone excretion, w as observed. The ratio of androsterone to etiocholanolone decreased si gnificantly (P < 0.004) after 13-cis-RA therapy and suggested a metabo lic deviation from the androgen 5 alpha- to 5 beta-reduction pathway i n the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone ( P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it d id induce 1) a highly significant decrease in 5 alpha-dihydrotestoster one formation by skin biopsies; 2) significant decreases in serum 5 al pha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-and rostan-3 alpha,17 beta-diol glucosiduronate; and, finally, 3) deviatio n of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effe ct of 13-cis-RA treatment on severe acne is consistent with the dramat ic decrease in androgen 5 alpha-reduction observed mainly in the skin.