Comparative Antiandrogenic Potency of Spironolactone and Cimetidine: Assessment by the Chicken Cockscomb Topical Bioassay 1

Abstract

Abstract

Spironolactone and cimetidine are effective antiandrogens in vivo, although they differ by five orders of magnitude in affinity for androgen receptors in vitro. To explore this discrepancy, we directly compared the antiandrogenic potency of these two compounds in vivo using the chicken cockscomb topical bioassay. In this assay, the growth of the androgen sensitive cockscomb of immature chicks after stimulation by various doses of androgen (dihydrotestosterone 5, 20, or 100 μg/day sc) is inhibited by antiandrogens in cream vehicle applied topically to the cockscomb itself. At low levels of androgen stimulation (5 μg/day), 0.5% topical cimetidine produced maximal suppression of cockscomb growth, while at high levels of androgen stimulation (100 μg/day), topical cimetidine in concentrations as high as 4% did not suppress cockscomb growth. In contrast, topical spironolactone in concentrations as low as 0.06% produced maximal inhibition of cockscomb growth at all androgen doses. Using an intermediate androgen dose (20 μg/day), the minimally effective antiandrogenic concentration of topical cimetidine was between 0.5 and 1.0%, while that for topical spironolactone was less than 0.001%. We conclude that the chicken cockscomb topical bioassay is a useful method for assessing relative potency of antiandrogens. With this method, spironolactone appears to be at least 500 times as strong an antiandrogen in vivo as cimetidine.