Cassidenti D L, Paulson R J, Serafini P, Stanczyk F Z, Lobo R A
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.
Obstet Gynecol. 1991 Jul;78(1):103-7.
Skin 5 alpha-reductase activity is the major factor influencing the manifestation of androgen excess. Although oral contraceptives have been useful for the treatment of androgen excess, little is known of the independent effects of the various progestins and estrogens on inhibition of skin 5 alpha-reductase activity. We incubated minces of normal genital and pubic skin with physiologic concentrations of 3H-testosterone to assess 5 alpha-reductase activity by its conversion to 3H-dihydrotestosterone. In separate experiments, 5 alpha-reductase activity was assessed before and after the addition of progesterone, medroxyprogesterone acetate, levonorgestrel, norethindrone, 17 beta-estradiol, and ethinyl estradiol. Progesterone, levonorgestrel, and norethindrone demonstrated 97 +/- 5.3%, 47.9 +/- 6.3%, and 59 +/- 4.6% inhibition, respectively, of genital skin 5 alpha-reductase activity at 10(-4) mol/L (P less than .01). Medroxyprogesterone acetate, however, failed to affect 5 alpha-reductase activity at similar doses. Estradiol exhibited 40.8 +/- 14.2% inhibition at 10(-4) mol/L (P less than .01), whereas ethinyl estradiol at concentrations from 10(-8) to 10(-4) mol/L failed to inhibit 5 alpha-reductase activity. We conclude that progesterone and the 19-nor-derivatives inhibit 5 alpha-reductase activity at high doses, whereas medroxyprogesterone acetate does not. Therefore, the 19-nor-progestin component may expand the usefulness of oral contraceptives in the treatment of hirsutism by an inhibitory action on skin 5 alpha-reductase activity.
皮肤5α-还原酶活性是影响雄激素过多表现的主要因素。虽然口服避孕药对治疗雄激素过多有用，但对于各种孕激素和雌激素对抑制皮肤5α-还原酶活性的独立作用了解甚少。我们用生理浓度的3H-睾酮孵育正常生殖器和耻骨皮肤的碎块，通过其转化为3H-双氢睾酮来评估5α-还原酶活性。在单独的实验中，在添加孕酮、醋酸甲羟孕酮、左炔诺孕酮、炔诺酮、17β-雌二醇和乙炔雌二醇之前和之后评估5α-还原酶活性。在10(-4)mol/L时，孕酮、左炔诺孕酮和炔诺酮分别对生殖器皮肤5α-还原酶活性有97±5.3%、47.9±6.3%和59±4.6%的抑制作用（P<0.01）。然而，醋酸甲羟孕酮在类似剂量下未能影响5α-还原酶活性。雌二醇在10(-4)mol/L时有40.8±14.2%的抑制作用（P<0.01），而乙炔雌二醇在浓度从10(-8)到10(-4)mol/L时未能抑制5α-还原酶活性。我们得出结论，孕酮和19-去甲衍生物在高剂量时抑制5α-还原酶活性，而醋酸甲羟孕酮则不然。因此，19-去甲孕激素成分可能通过对皮肤5α-还原酶活性的抑制作用扩大口服避孕药在治疗多毛症中的用途。
