A prospective randomized trial evaluating tissue effects of finasteride therapy in benign prostatic hyperplasia

Finasteride is widely used for the treatment of benign prostatic hyperplasi a (BPH). Its therapeutic efficacy is believed to be mediated through select ive inhibition of prostatic 5 alpha-reductase (type II). This prospective, controlled, randomized study examines various relationships between changes in tissue 5 alpha-reductase isozyme activity, epithelial proliferative ind ex and morphology in men with BPH treated with finasteride for 6 months, an d correlates these with clinical response. Thirty-one patients presenting with symptomatic bladder outflow obstruction were prospectively randomized to receive either finasteride or placebo (2: 1) for 24 weeks. Of these, 27 men aged 55-80y (median 69y) completed the st udy, including 18 patients on treatment. Symptom score determination, urofl ow and prostate volume were assessed at baseline and end of study. Prostati c tissue was obtained by ultrasound-guided needle biopsy at baseline and by transurethral resection (TURP) at end of study for biochemical and morphom etric analysis. Epithelial proliferation was examined quantitatively in the resected tissue using MIB-1 antibody to Ki-67 and counting the percentage of positively staining cells. Type II 5 alpha-reductase activity was strongly inhibited by finasteride in resected BPH tissue, with over 100-fold decrease in V-max (P = 0.001), whe reas the type I isozyme was inhibited 5-fold (P= 0.005). Selective inhibiti on of type II 5 alpha-reductase was demonstrated in all treated patients. N o significant difference in epithelial proliferation was observed between t he finasteride and placebo groups. Epithelial proliferation was, however, g reater in prostatic tissue with histological manifestation of inflammation (2.02% vs 0.89%, P= 0.001). Positive correlation between the total epitheli al volume and the ratio of transition zone volume/total prostate volume was observed in the placebo group (r = 0.834), whereas there was no such corre lation in men taking finasteride (r = - 0.300), consistent with a reduction in epithelial content in the treatment group. Improvement in uroflow and r eduction in prostatic volume in patients treated with finasteride did not r each statistical significance. This study shows that finasteride causes inhibition of 5 alpha-reductase ac tivity in human BPH tissue with selectivity for the type II isozyme. In spi te of this, no significant effects in epithelial proliferation or tissue mo rphology were demonstrated. The presence of inflammation was, however, asso ciated with significantly greater proliferative activity. The power of this study was limited by the small number of recruited patients, and a larger study would be required for further investigation of morphological changes induced by finasteride in BPH tissue and their biochemical basis.