Pathophysiology and prevalence, alpha blockade and combination therapy of benign prostatic hyperplasia

The pathophysiology of benign prostatic hyperplasia (BPH) is poorly understood. The concept that prostatic enlargement leads to obstruction and lower urinary tract symptoms is an oversimplification. The pathophysiology of lower urinary tract infections in the aging male is likely multifactorial. Randomized clinical trials have consistently demonstrated the safety and effectiveness of alpha(1)-blockers for the treatment of BPH. The primary advantage of the long-acting alpha(1)-blockers such as terazosin, doxazosin and tamsulosin is related to the longer half-lives that allow for once-daily dosing. This has important implications related to compliance and tolerability. The treatment response to alpha(1)-blockers is achieved rapidly, the improvements in symptoms and bladder outlet obstruction are clinically and statistically significant, and the therapeutic response is durable. The development of alpha(1)-subtype selective antagonists may provide the opportunity to further improve the tolerability of alpha-blockade for the treatment of BPH. 5 alpha-Reductase inhibitors represent another medical therapy for the treatment of BPH. The Veterans Administration Cooperative Study on the Medical Management of BPH compared the alpha(1)-blocker terazosin to the 5 alpha-reductase inhibitor finasteride. The study reported that the improvements in symptoms and peak flow rate were equivalent in the placebo and finasteride groups. Finasteride exhibited a measurable improvement only in men with large prostates. Terazosin was effective in men independent of prostate volume. The treatment-related improvement for terazosin was 3-fold greater than finasteride in men with large prostates. In general, combination therapy was no more effective than terazosin alone. This is due to the limited effectiveness of finasteride. A potential indication of combination therapy would be a patient with a large prostate who exhibits a partial response to an alpha(1)-blocker.