In VivoStudies on Progesterone Metabolism by Human Skin

The metabolism of radioactive progesterone administered simultaneously intravenously and percutaneously has been studied in 4 normal subjects and 1 patient with testicular feminization syndrome. The relative contribution to urinary 5β- and 5α-pregnan-3α,20α-diol (pregnanediol and allopregnanediol) of labeled progesterone, according to its mode of administration, was determined. In normal subjects, the yield of pregnanediol originating from an intravenous dose of progesterone was 8 times higher than that of allopregnanediol. By contrast, when progesterone was administered percutaneously, the recovery of labeled allopregnanediol in urine was greater than that of pregnanediol. These data indicate that in normal subjects progesterone might be 5α-hydrogenated to a greater extent in the skin. In addition, the metabolism of progesterone administered either intravenously or percutaneously was similar in men and women; it was unchanged throughout the menstrual cycle and by estrogen treatment of men. In the patient with testicular feminization syndrome, the contribution of radioactive progesterone administered percutaneously to urinary pregnanediol was comparable to that observed in normal men. The fact that, in the skin of patients with feminizing testes, progesterone but not testosterone undergoes normal 5α-reduction deserves attention.