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

The effects of the new steroidal antiandrogen, TZP-4238 on spontaneous ly developed canine prostatic hyperplasia (BPH) were studied in compar ison with those of chlormadinone acetate (CMA), a steroidal antiandrog en used for the treatment of BPH and prostatic cancer in Japan. Aged b eagle dogs (5-9 years old) with spontaneously developed BPH (mean pros tate 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. Prost ate volume was measured by transrectal ultrasonography before treatmen t and every 5 weeks during treatment. TZP-4238 produced a regression i n spontaneously developed canine BPH, its effects being more potent th an those of CMA. TZP-4238 reduced the content of testosterone, dihydro testosterone (DHT) and androgen receptor in the prostates of these ani mals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also appeared to reduce 5 alpha-reductase activity by prevention of the an drogen action in prostate as described above. (C) 1995 Wiley-Liss, Inc .