Effectiveness of antiandrogens in the rat

In order to determine the relative effectiveness of several antiandrogens, megace (megestrol acetate), flutamide and RU23908 were administered in optimal doses (20 mg./kg., 10 mg./kg. and 20 mg./kg.) subcutaneously daily to adult male Sprague-Dawley rats for 14 and 28 days and their effects on ventral prostate, seminal vesicles, and serum testosterone were determined. To avoid the possibility that these agents might also work through inhibition of testosterone production, all the treated animals were castrated and then implanted with a testosterone-filled silastic pellet to maintain a constant exogenous source of the androgen. A castrate placebo-treated group, an implanted placebo-treated group, and an intact placebo-treated group served as controls. The mechanisms and sites of action of the antiandrogens were thus limited to the target organs. Serum testosterone levels were equivalent at all time periods for all groups except the castrate controls which were significantly lower. The ventral prostates of the flutamide and RU23908 groups were similar and reduced 75% and 85% at 14 and 28 days respectively; the group receiving megace experienced prostatic regression of 49% and 65% which was significantly less of a reduction than that of the flutamide or RU23908 group. Results for seminal vesicle weights indicated similar trends. The administration of both steroidal (megace) and nonsteroidal (flutamide and RU23908) antiandrogens yielded a significant reduction of androgen dependent tissue weights relative to the intact control group and the implanted placebo group but still not as great a reduction as the effect produced by castration. In the rat, castration remains the optimal means of inducing regression of androgen dependent tissues.