Androgenic disorders of female skin such as hirsutism, acne and alopecia are etiologically caused by androgen excess. Skin 5α-reductase activity is a major factor influencing the manifestation of endogenous androgen excess in women. Oral contraceptives have proven useful for the treatment of androgen disorders of the skin. The mechanisms of action by which oral contraceptives correct skin androgen levels may include inhibition of 5α-reductase and androgen receptor activity. We investigated the inhibitory effect of oral contraceptive progestins and ethinyl estradiol on skin 5α-reductase and their influence on androgen receptor activity and affinity, using three different in vitro assay systems. It was shown that norgestimate blocked 5α-reductase activity with an IC₅₀ value of 10 μM, followed by levonorgestrel (IC₅₀ 52 μM), dienogest (IC₅₀ 55 μM), cyproterone acetate (IC₅₀ 87 μM) and gestodene (IC₅₀ 98 μM). To determine the full androgenic potential of the progestins, androgen receptor binding affinities and activation potentials were determined. The progestins norgestimate and dienogest in particular combined 5α-reductase inhibition with minimal androgenic potential. These data demonstrate that the progestins norgestimate and dienogest might help in the treatment of clinical hyperandrogeny in women.