Androgenic Action of Progestins and Possible Synandrogenic Properties of Antiandrogens Used in Oral Contraceptives

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Abstract
Relative binding affinities (RBA) for the androgen receptor were estimated for levonorgestrel, progesterone, dihydrotestosterone, cyproterone acetate, 17.alpha.-propylmesterolone and 3-keto-desogestrel (13-ethinyl-11-methylene-18,19-dinor-17.alpha.-pregn-4-en-20-yn-17-ol-3-one) which is the biologically active metabolite of desogestrel. Mouse kidney cytosol served as receptor source. Stimulation of mouse kidney .beta.-glucuronidase by s.c. injection of various doses of these compounds was determined. RBA for the androgen receptor of 3-keto-desogestrel was significantly greater (P < 0.02) than that of levonorgestrel, and 3-keto-desogestrel was registered to enhance .beta.-glucuronidase activity more than levonoregestrel at the highest dose level (P < 0.005). Cyproterone acetate in the presence of testosterone exerted synandrogenic action at the lower dose level but suppressed enzyme activity at the higher doses. 17.alpha.-Propylmesterolone which had RBA similar to that noted for cyproterone acetate showed only synandrogenic properties at the dose levels tested. Biological activity of a compound apparently cannot be accurately predicted by receptor assays. Desogestrel and levonorgestrel exhibit similar androgenic properties in this model system. These data correlate with clinical experience on oral contraceptives containing levonorgestrel and desogestrel, respectively, which do not differ from each other in their androgen-related side effects.