The NEW ENGLAND JOURNAL Of MEDICINE prostatic hyperplasia.often as an alterna- a residual yolume of more than 250 ml after void tive to pharmaceutica ing);had a history of prostate cancer,surgery for ey conduct 1 percent of th enign prosta more than 2.0mg per deciliter (177 umol per liter) The herb is widely used in Europe,where half of had a prostate-specific antigen (PSA)level of more than 4.0 ng per deciliter;were using medications extracts to rugs. ugmost prio severe co small improvements in the symptoms of benign pate if they had sto ped taking an apha-blocker prostatic hyperplasia or in urinary flow rates at least one month before randomization or discon se studies are limited by the smal 2 standar nd the ed to lack of information from participants concerning one-month,single-blind,placebo runin period and how effectively the placebo was blinded. were excluded if their rate of adherence was less widely accepted outcome m asures and a ma than 75 percent,as measured by a capsule count double-blind trial to determine the efficacy of 时the6 Eligible patients were randomly assigned to re- aw palmetto extract,160 mg twice dai aring placebo in s oft br METHODS it had been used in the vast maiority of prior clin PARTICIPANTS ical trials.An advisory committee chartered by the Natio Center fo omple fCalifor ctea a c lect the the Kaiser Foundation Research Institute,Oak be used in this trial.a proprietary cabon dioxide land,California.The stud ly took place between July 2001 and May 200 tmctgpyhdelsAinasofgelhatincapsue furni by extrac 9 ne s who had moderate-to-sever of bnign prostatic hyperplasia,as defined by a phy of samples of the extract revealed that it con- score on the Am aed 2. per nt tota al fatty acids just befo a f less thap 15 t ana vere recruited from the san francisco extract contained 90.7 percent total fatty acids Affairs Medical Cer and 0.33 percent total sterols.Placebo capsules ing com -400 itte posters,ande and a h radio advertisements.all potential participants placebo with the appearance of saw palmetto. ve phone interview Patients v advised to take the study me criteria. en who pa a sit.Pang all clinic visit:those who declined or did not ap eight visits to the study clinic over a neriod of 1d at the clinic were classified as having declined to months,including 12 months of post-random- participate.Men were ineligible if they were at ization follow-up. 558 N ENGLJ MED 354:6 WWW.NEJM.ORG FEBRUARY 9.2006 Downloaded from n without permissionThe new england journal o f medicine 558 n engl j med 354;6 www.nejm.org february 9, 2006 Extracts of the saw palmetto berry are widely used for the treatment of benign prostatic hyperplasia, often as an alterna￾tive to pharmaceutical agents. In a national sur￾vey conducted in 2002, 1.1 percent of the adult population in the United States, or approximately 2.5 million adults, reported using saw palmetto.1 The herb is widely used in Europe, where half of German urologists prefer prescribing plant-based extracts to synthetic drugs.2 Although most prior randomized trials of saw palmetto have reported small improvements in the symptoms of benign prostatic hyperplasia or in urinary flow rates, these studies are limited by the small numbers of subjects enrolled, their short duration, their fail￾ure to use standard outcome measures, and the lack of information from participants concerning how effectively the placebo was blinded.3-20 Using widely accepted outcome measures and a matched placebo capsule, we conducted a randomized, double-blind trial to determine the efficacy of saw palmetto for the treatment of benign pros￾tatic hyperplasia. Methods Participants The study protocol and all procedures were ap￾proved by the committee on human research at the University of California, San Francisco, and the Kaiser Foundation Research Institute, Oak￾land, California. The study took place between July 2001 and May 2004. All participants provid￾ed written informed consent. Men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia, as defined by a score on the American Urological Association Symptom Index (AUASI) of at least 8 and a peak urinary flow rate of less than 15 ml per second, were recruited from the San Francisco Veterans Affairs Medical Center, Kaiser Permanente North￾ern California, and the surrounding community by direct mailings to patients, letters to primary care providers, posters, and newspaper and local radio advertisements. All potential participants were screened by means of a telephone interview to identify exclusion criteria. Men who passed the screening interview were asked to come for a clinic visit; those who declined or did not appear at the clinic were classified as having declined to participate. Men were ineligible if they were at high risk for urinary retention (defined by a peak urinary flow rate of less than 4 ml per second or a residual volume of more than 250 ml after void￾ing); had a history of prostate cancer, surgery for benign prostatic hyperplasia, urethral stricture, or neurogenic bladder; had a creatinine level of more than 2.0 mg per deciliter (177 μmol per liter); had a prostate-specific antigen (PSA) level of more than 4.0 ng per deciliter; were using medications known to affect urination; or had a severe con￾comitant disease. Patients were eligible to partici￾pate if they had stopped taking an alpha-blocker at least one month before randomization or discon￾tinued taking saw palmetto or a 5α-reductase in￾hibitor six months before randomization. All po￾tentially eligible participants were assigned to a one-month, single-blind, placebo run-in period and were excluded if their rate of adherence was less than 75 percent, as measured by a capsule count. Intervention Eligible patients were randomly assigned to re￾ceive a saw palmetto extract, 160 mg twice daily, or a similar-appearing placebo in soft brown gela￾tin capsules. This regimen was selected because it had been used in the vast majority of prior clin￾ical trials.21 An advisory committee chartered by the National Center for Complementary and Alter￾native Medicine (NCCAM) conducted a competi￾tive process to select the saw palmetto product to be used in this trial, a proprietary carbon dioxide extract from Indena USA in a soft gelatin capsule furnished by Rexall-Sundown. The extract was manufactured in one batch to optimize product consistency. High-performance gas chromatogra￾phy of samples of the extract revealed that it con￾tained 92.1 percent total fatty acids just before the initiation of the study; a subsequent analysis at the midpoint of the study revealed that the extract contained 90.7 percent total fatty acids and 0.33 percent total sterols. Placebo capsules contained polyethylene glycol-400, a bitter-tasting liquid with an oily appearance and no free fatty acids, and a brown coloring agent to produce a placebo with the appearance of saw palmetto. Patients were advised to take the study medica￾tion twice a day with meals and to bring all un￾used capsules to each study visit. Patients made eight visits to the study clinic over a period of 14 months, including 12 months of post-random￾ization follow-up. The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2006 Massachusetts Medical Society. All rights reserved