Effects of a new steroidal antiandrogen, TZP-4238 (17 alpha-acetoxy-6-chloro-2-oxa-4, 6-pregnadiene-3, 20-dione), on spontaneously developed canine benign prostatic hyperplasia

Abstract

The effects of the new steroidal antiandrogen, TZP-4238 on spontaneously-developed canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5-9 years old) with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated orally with a placebo, TZP-4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3 mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal ultrasonography before treatment and every 5 weeks during treatment. TZP-4238 produced a regression in spontaneously developed canine BPH, its effects being more potent than those of CMA. TZP-4238 reduced the content of testosterone, dihydrotestosterone (DHT) and androgen receptor in the prostates of these animals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also appeared to reduce 5 alpha-reductase activity by prevention of the androgen action in prostate as described above.