PROGRESSION OF BPH ON MEDICAL THERAPY

Benign prostatic hyperplasia (BPH) is the most common affliction of men over the age of 50. Traditionally associated symptoms are felt to be secondary to bladder outlet obstruction, dynamic tone of the smooth muscle of the prostate or inherent bladder dysfunction. A host of alternative therapeutic options have been described in the literature over the past 5 years. However, these studies have focused on the relative efficacy and side effect profile of these therapies. There have been few long term studies of the natural history of BPH progression in those who are either treated or in those who are followed by watchful waiting. Moreover, the natural history of BPH in various age and ethnic groups have been poorly characterized. Finally, to date, there have been no long term studies of the association between bladder function, prostatic obstruction, prostate size, symptoms and therapy employed. This full scale, 7 year trial, will provide enormous insight into the progression of prostate enlargement and symptoms in both an untreated population and one treated with medication. This is of particular importance because efficacy of medical therapy can be truly determined only with an understanding of the untreated natural history of BPH. The effects of pharmacologic reduction in the size of the prostate utilizing the 5alpha reductase inhibitor, finasteride, and/or physiologic reduction of urethral outlet resistance using the alpha1 receptor antagonist, doxazosin, on symptoms, voiding parameters and reversibility of bladder dysfunction will be assessed. Four treatment groups will be studied, l) placebo, 2) 5 mg of finasteride (PROSCAR), 3) 8 mg of doxazosin (CARDURA) and, 4) 5 mg finasteride and 8 mg of doxazosin. Progression of disease will be measured by either a rise in baseline AUA Symptom Score of 4 points, development of urinary retention, incontinence or recurrent urinary tract infections or a rise in baseline serum creatinine of 50%. Through this full scale BPH trial, we hope to ascertain: A) the optimal temporal intervention in the treatment of BPH, B) whether reduction in the size of the prostate result in true regression of the disease process? C) a priori prostate tissue characteristics which predict severity of disease or preferential response to medical therapy, D) whether specific ethnic groups manifest various forms of BPH resulting in different rates of progression and differential response to therapy? and, E) whether concomitant prostate conditions such as cancer or prostatitis are effected by pharmacologic intervention for BPH?