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

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Abstract
The effects of the new steroidal antiandrogen, TZP‐4238 on spontaneouslydeveloped 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 5α‐reductase activity by prevention of the androgen action in prostate as described above.