Androgenic action of progestins and possible synandrogenic properties of antiandrogens used in oral contraceptives.

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 biological active metabolite of desogestrel. Mouse kidney cytosol served as receptor source. In addition, stimulation of mouse kidney beta-glucuronidase by subcutaneous injection of various doses of these compounds was determined. RBA for the androgen receptor of 3-keto-desogestrel was significantly greater (p less than 0.02) than that of levonorgestrel, and 3-keto-desogestrel was registered to enhance beta-glucuronidase activity more than levonorgestrel at the highest dose level (p less than 0.005). Furthermore, cyproterone acetate in the presence of testosterone was found to exert synandrogenic action at the lower dose level but suppressed enzyme activity at the higher doses. On the other hand, 17 alpha-propylmesterolone which had RBA similar to the one noted for cyproterone acetate showed only synandrogenic properties at the dose levels tested. The data combine to suggest that biological activity of a compound 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.