Aromatase inhibition in the dog. II. Effect on growth, function, and pathology of the prostate.

To evaluate the role of aromatase inhibitors in the treatment of benign prostatic hyperplasia (BPH), the effects of a potent, oral, nonsteroidal aromatase inhibitor [4-(5,6,7,8-tetrahydroimidazo[1,5a]pyridin-5yl)benzonitrile; CGS-16949A, CIBA-GEIGY] on canine BPH have been studied. Twelve mature beagles with enlarged prostates were divided into two groups of similar age, prostatic size, and prostatic histology. Dogs were given either CGS-16949A at a dosage of 2.5 mg./kg./day p.o. (n = 6) or an oral placebo (n = 6) for 25 weeks. Treatment with aromatase inhibitor had no significant effect on prostatic weight nor on total DNA content when compared to controls (p greater than 0.1). Semen volume did not change with treatment, and prostatic tissue concentrations of testosterone, dihydrotestosterone (DHT), and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) were similar for the treated and control beagles (p greater than 0.1). Protein concentration in the ejaculate, however, was significantly greater for the dogs receiving CGS-16949A (p less than 0.01). Histologically, there was no difference in the incidence or type of BPH between the two treatment groups. Beagles treated with aromatase inhibitor, however, did have a more severe inflammatory infiltrate of the prostatic parenchyma than the control dogs (p less than 0.01). The mean serum testosterone concentration for the beagles treated with aromatase inhibitor was 10 times greater than that for the control animals (p less than 0.01). The endocrine effect of this aromatase inhibitor in the male canine is presented in the preceding paper. Taken together, these results suggest that inhibition of endogenous aromatase activity is not an effective treatment for spontaneous BPH in the intact canine.