On the Mechanism of the Anti-androgenic Effect of Medroxyprogesterone Acetate*

Administration of medroxyprogesterone acetate (MPA) to castrated male rats inhibited the testosterone mediated growth of prostate and seminal vesicle. MPA, however, failed to increase the activity of testosterone A-ring reductase in the prostate in contrast to its marked inductive effect on the liver enzyme. MPA treatment caused a diminished uptake of radioactivity by the prostate and seminal vesicle in vivo after a single injection of 3H-testosterone, as well as, a lower plasma level of the labeled hormone. However, in vitro incubation of prostatic tissue derived from MPA treated rats with 3H-testosterone showed no local interference with the uptake of radioactivity. It appears, that the anti-androgenic effect of MPA can be explained on the basis of induction of hepatic testosterone reductase activity which in turn increases the catabolism of the hormone, leading to its lower plasma concentration and consequently to a lower target tissue uptake of testosterone. (Endocrinology 93: 417, 1973)