Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia

The effects of the new steroidal antiandrogen TZP‐4238 on hormone‐induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One‐ to 2‐year‐old beagle dogs were castrated and administered 75 mg/week of androstanediol (A‐diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP‐4238, 0.1 mg/kg/day of TZP‐4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A‐diol plus E2. Treatment with 0.5 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP‐4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/ kg/day of TZP‐4238 decreased 5α‐reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP‐4238 and CMA were effective in inhibiting the growth of hormone‐induced canine BPH, and TZP‐4238 was at least 5 times more potent than CMA. TZP‐4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen‐AR complex. TZP‐4238 decreased 5α‐reductase activity by prevention of the androgen action described above.