Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate.

Flutamide is approximately 2-fold more potent than cyproterone acetate in reversing the stimulatory effect of dihydrotestosterone (DHT) on ventral prostate weight. Even at the highest dose of cyproterone acetate, prostate weight remains 40% above control while flutamide completely reverses the stimulatory action of DHT, thus suggesting some partial androgenic activity of cyproterone acetate. Megestrol acetate, on the other hand, is devoid of any antiandrogenic activity and it even increases the stimulatory effect of DHT on prostate weight. While flutamide completely reverses the inhibitory effect of DHT on plasma LH levels in castrated animals, cyproterone acetate reverses the value of this parameter by only 30% while megestrol acetate further inhibits plasma LH levels at all the doses used. Both cyproterone acetate and megestrol acetate inhibit adrenal weight to approximately 25% of control, thus indicating their glucocorticoid activity. As direct measure of androgenic activity, cyproterone acetate and megestrol acetate increased prostate weight in castrated animals by 60 and 100%, respectively (P less than 0.01) while flutamide had no effect. The present data show that cyproterone acetate and megestrol acetate, in addition to their well-known progestational and glucocorticoid action, have intrinsic androgenic activity. Since it is the only compound having pure antiandrogenic activity, flutamide provides the best scientific arguments for its successful use for the treatment of androgen-sensitive diseases.