Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are very common findings in aging men and present a considerable health care burden both in terms of morbidity as well as health care resource utilization. Aside from the standard therapy transurethral resection of the prostate (TURP), minimally invasive surgical therapies (MIST) have been developed over the past decade, which are utilized to varying degrees. In addition, three classes of medications are currently being utilized for the treatment of LUTS and BPH: alpha adrenergic receptor blocker, 5 alpha reductase inhibitors (5 ARI), and phytotherapeutic agents. The use of alpha blocker is supported by RCTs of up to 12 mo duration and open label extension trials up to 60 mo duration. Use of the 5 ARI is supported by RCTs of up to 48 mo duration and open label extension trials up to 72 mo. duration. Of the many different phytotherapeutic preparations available, few have been studied in randomized placebo-controlled trials usually 6 mo or shorter in duration. The most commonly used preparation is saw palmetto extract, which has undergone the most extensive testing including randomized trials of up to 12 mo duration in direct comparison to an alpha blocker, however, not against placebo. Given the widespread use of these over the counter preparation data regarding the relative safety and efficacy of the most commonly used compounds are urgently needed. The purpose of the consortium is to develop and carry out a relevant clinical trial involving these compounds. A randomized, placebo-controlled trial of saw pametto extract and pygeum africanum with a 4 to 6 yrs follow-up period is proposed enrolling approx 3,000 patients at the participating centers with the following objectives: Determine the efficacy.of saw palmetto and pygeum africanum compared with placebo in preventing the progression of LUTS and BPH defined (1) as a twice validated increase in the AUA Symptom Index by four or more points from baseline, (2) as the development of either spontaneous or precipitated acute urinary retention (AUR), (3) as the need for MIST or surgical therapy for BPH with or without a preceding episode of AUR, (4) as the development of renal insufficiency ( due to BPH), recurrent urinary tract infection (UTI) (due to BPH), or incontinence. (5) Determine the efficacy of saw palmetto and pygeum africanum compared with placebo in terms of improving the AUA SI, other humanistic questionnaires, sexual functioning, global subjective assessment and maximum urinary flow rate from baseline to end of study. (7) Determine whether baseline parameters are able to predict response to the different therapies administered. (8) Determine whether saw palmetto or pygeum africanum compared to placebo induce measurable changes in prostate volume, transition zone volume, serum PSA and other serum or tissue based biomarkers of BPH.
