The development of benign prostatic hyperplasia (BPH) requires aging and testicular androgens; BPH does not develop in patients castrated prior to puberty. Therefore, androgen withdrawal therapy aimed at alleviating or preventing the progression of BPH is rational. Androgen ablation leads to partial involution of the hyperplastic gland, but improvement in urinary flow rate and symptoms occur in a minority of patients. More selective androgen blockade with the 5-alpha reductase inhibitor, finasteride, achieves a significant decrease in intra-prostatic dihydrotestosterone (DHT) with minimal toxicity, but mean prostate volume reduction is limited to 20%. Significant clinical improvement occurs in only one-third of men treated with 5mg of finasteride daily for one year. To date, the probability of clinical improvement has not correlated with initial prostatic volume, serum prostate specific antigen levels, or other clinical parameters. More detailed knowledge of baseline prostatic physiology and potential heterogeneity is needed than current BPH clinical trials provide.
The specific aims of the current proposal are to: 1) determine if finasteride produces a sustained or progressive decrease in prostate volume, urodynamic obstruction, and symptom score, while increasing uroflow rate compared to placebo, 2) determine what baseline clinical, histologic, or biochemical studies predict treatment response, and 3) determine what baseline clinical, histologic, or biochemical studies predict the natural history of BPH (placebo group). This four year study will randomize patients to placebo or 5mg of finasteride daily. In addition to classic clinical endpoints, prostatic biopsies will be analyzed for stromaepithelial cell ratios, T and DHT concentrations, and 5-alpha reductase isozyme expression, The initial pilot phase will focus on study design and the feasibility of tissue analyzes which require invasive procedures.
