Inhibition of skin 5 alpha-reductase by oral contraceptive progestins in vitro

Androgenic disorders of female skin such as hirsutism, acne and alopecia an etiologically caused by androgen excess. Skin 5 alpha-reductase activity i s a major factor influencing the manifestation of endogenous androgen exces s in women. Oral contraceptives have proven useful for the treatment of and rogen disorders of the skin. The mechanisms of action by which oral contrac eptives correct skin androgen levels may include inhibition of 5 alpha-redu ctase and androgen receptor activity. We investigated the inhibitory effect of oral contraceptive progestins and ethinyl estradiol on skin 5 alpha-red uctase and their influence on androgen receptor activity and affinity, usin g three different in vitro assay systems. It was shown that norgestimate bl ocked 5 alpha-reductase activity with an IC50 value of 10 mu M, followed by levonorgestrel (IC50 52 mu M), dienogest (IC50 55 mu M), cyproterone aceta te (IC50 87 mu M) and gestodene (IC50 98 mu M). To determine the full andro genic potential of the progestins, androgen receptor binding affinities and activation potentials were determined. The progestins norgestimate and die nogest in particular combined 5 alpha-reductase inhibition with minimal and rogenic potential. These data demonstrate that the progestins norgestimate and dienogest might help in the treatment of clinical hyperandrogeny in wom en.