Effect of anti-androgen (TZP-4238) on steroid-induced canine prostatic hyperplasia. Light and electron microscopic investigations.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced canine prostatic hyperplasia was studied by light and electron microscopy. Male beagle dogs (1-2 years old) were divided into four experimental groups. Group 1 consisted of intact controls. The other animals were castrated. The castrated animals were treated for 25 weeks with 1) 5 alpha-androstane-3 alpha, 17 beta-diol (A-diol) plus 17 beta-estradiol (E2) (Group 2), 2) A-diol plus E2 + TZP-4238 0.5 mg/kg (Group 3) and 3) A-diol plus E2 + chlormadinone acetate (CMA) 2.5 mg/kg (Group 4). TZP-4238 and CMA were administered orally for 21 weeks after 4 weeks treatment with A-diol plus E2. In group 2, glandular hyperplasia of the prostate was clearly noted. In contrast, combined treatment with TZP-4238 (Group 3) or CMA (Group 4) produced marked atrophy of the glandular epithelium. Loss of secretory and metabolic activities was confirmed by ultrastructural investigations. Our data indicate that TZP-4238 is a potent anti-androgen for the prevention of canine prostatic hyperplasia in the steroid-induced benign prostatic hyperplasia (BPH) model.