To investigate the effect of
13-cis-retinoic acid (13-cis-RA) treatment on
androgen metabolism in men with severe nodulocystic
acne, eight men 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, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal
androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced
androgens:
5 alpha-dihydrotestosterone (P < 0.02),
androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha, 17 beta-diol and
androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of
etiocholanolone, very similar to the decrease in
androsterone excretion, was observed. The ratio of
androsterone to
etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA
therapy and suggested a metabolic deviation from the
androgen 5 alpha- to 5 beta-reduction pathway in 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 did induce 1) a highly significant decrease in
5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum
5 alpha-dihydrotestosterone,
androsterone glucosiduronate, and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver
androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe
acne is consistent with the dramatic decrease in
androgen 5 alpha-reduction observed mainly in the skin.