Review Saw Palmetto Extracts for Treatment of Benign Prostatic Hyperplasia A Systematic Review Timothy J. Wilt, MD, MPH; Areef Ishani, MD; Gerold Stark, MD; Roderick MacDonald, MS; Joseph Lau, MD; Cynthia Mulrow, MD, MS Objective.—To conduct a systematic review and, where possible, quantitative SYMPTOMATIC BENIGN prostatic meta-analysis of the existing evidence regarding the therapeutic efficacy and safety hyperplasia (BPH) is one of the most of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign commonmedicalconditionsinoldermen. prostatic hyperplasia (BPH). As many as 40% of men aged 70 years or Data Sources.—Studies were identified through the search of MEDLINE (1966- older have lower urinary tract symp- toms consistent with BPH.1 Treatment 1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials goals in the vast majority of men are to and review articles, and contact with relevant authors and drug companies. relieve irritative (urgency, frequency, Study Selection.—Randomized trials were included if participants had symp- and nocturia) and obstructive (weak tomatic BPH, the intervention was a preparation of S repens alone or in combina- stream,hesitancy,intermittency,andin- tion with other phytotherapeutic agents, a control group received placebo or other complete emptying) symptoms. In the pharmacological therapies for BPH, and the treatment duration was at least 30 United States, treatment of BPH ex- days. ceeds $2 billion in costs, accounts for 1.7 Data Extraction.—Two investigators for each article (T.J.W., A.I., G.S., and million physician office visits,2 and re- R.M.) independently extracted key data on design features, subject characteristics, sults in more than 300 000 prostatecto- 3 therapy allocation, and outcomes of the studies. mies annually. Treatment options in- clude lifestyle modification, device and Data Synthesis.—A total of 18 randomized controlled trials involving 2939 men surgical therapies, and pharmaceutical met inclusion criteria and were analyzed. Many studies did not report results in a and phytotherapeutic preparations.4,5 method that permitted meta-analysis. Treatment allocation concealment was ad- Phytotherapy or the use of plant ex- equate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks tracts for treating BPH symptoms was (range, 4-48 weeks). As compared with men receiving placebo, men treated with first described in Egypt in the 15th cen- S repens had decreased urinary tract symptom scores (weighted mean difference tury BC. Currently, phytotherapy is com- [WMD], −1.41 points [scale range, 0-19] [95% confidence interval (CI), −2.52 to mon in Europe and is increasing in the −0.30] [n = 1 study]), nocturia (WMD, −0.76 times per evening [95% CI, −1.22 to western hemisphere. The sale of all bo- −0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; tanical medications in the United States risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine is $1.5 billion per year and the use of phy- totherapies increased nearly 70% among flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men re- US adults in the past year.6,7 Phytothera- ceiving finasteride, men treated with S repens had similar improvements in urinary peutic agents represent nearly half the tract symptom scores (WMD, 0.37 International Prostate Symptom Score points medications dispensed for treatment of [scale range, 0-35] [95% CI, −0.45 to 1.19] [n = 2 studies]) and peak urine flow BPH in Italy, compared with 5% for a- (WMD, −0.74 mL/s [95% CI, −1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with fi- From the Department of Veterans Affairs Coordinat- , ing Center of the Cochrane Collaborative Review Group nasteride (4.9%) than with S repens (1.1%; P .001). Withdrawal rates in men as- in Prostatic Diseases and Urologic Malignancies and signed to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively. Minneapolis/Veterans Integrated Service Network 13 Conclusions.—The existing literature on S repens for treatment of BPH is lim- Center for Chronic Diseases Outcomes Research, Min- neapolis Veterans Affairs Medical Center, Minneapolis, ited in terms of the short duration of studies and variability in study design, use of Minn (Drs Wilt, Ishani, and Stark and Mr MacDonald); phytotherapeutic preparations, and reports of outcomes. However, the evidence New England Medical Center, Boston, Mass (Dr Lau); and the Department of Veterans Affairs San Antonio suggests that S repens improves urologic symptoms and flow measures. Com- Cochrane Center, San Antonio, Tex (Dr Mulrow). pared with finasteride, S repens produces similar improvement in urinary tract The authors have no commercial, proprietary, or financial interest in the products or companies in this symptoms and urinary flow and was associated with fewer adverse treatment article. events. Further research is needed using standardized preparations of S repens to Reprints: Timothy J. Wilt, MD, MPH, Minneapolis Vet- erans Affairs Medical Center (111-0), 1 Veterans Dr, Min- determine its long-term effectiveness and ability to prevent BPH complications. neapolis, MN 55417 (e-mail: wilt.timothy@minneapolis JAMA. 1998;280:1604-1609 .va.gov). 1604 JAMA, November 11, 1998—Vol 280, No. 18 Palmetto Extracts for Benign Prostatic Hyperplasia—Wilt et al ©1998 American Medical Association. All rights reserved. Downloaded From: by a University of Kansas HQ User on 01/04/2019 blockers and 5% for 5 a-reductase inhibi- mally sensitive search strategy for trials ences and their 95% confidence intervals tors.8 In Germany and Austria, phyto- from the Cochrane Collaboration with (CIs) were calculated using RevMan 3.0 therapy is the first-line treatment for the medical subject headings prostatic software.18 For categorical variables mild-to-moderate lower urinary tract hyperplasia, phytosterols, plant ex- weighted risk ratios (RRs) and 95% CIs symptomsandrepresentsmorethan90% tracts,sitosterols,Serenoarepens,orSa- were calculated.19 For continuous mea- of all drugs prescribed for the treatment bal serrulata, including all subhead- surements, a difference between treat- of BPH.9 In the United States, phyto- ings.16 EMBASE, (1974-July 1997), ment means and its correlated SE of the therapies for BPH are readily available Phytodok (Munich, Germany), and the difference were calculated using the as nonprescription dietary supplements. Cochrane Library, including the data- methods of Lau19 and Laird and Mo- Most of these compounds are unlicensed base of the Cochrane Prostatic Diseases steller.20 Because studies did not report and often promoted to “maintain a and Urologic Malignancies Group and the SE of the difference between the healthy prostate” and as a natural and the Cochrane Field for Complementary means (S repens and control), analyses harmless treatment of BPH symptoms. Medicine, were searched in a similar were carried out for 3 different assumed There are about 30 phytotherapeutic fashion. Reference lists of all identified values of correlation (0.25, 0.50, 0.75). compounds used for the treatment of trials and previous reviews were This approach was taken to test the sen- BPH.10 The most widely used is the ex- searched for additional trials. Expert sitivity of the results to this unknown tract of the dried ripe fruit from the relevant trialists and pharmaceutical parameter. Because there were no sta- American dwarf saw palmetto plant Sere- companies were asked to identify addi- tistically significant differences in the noa repens (also known by its botanical tional published or unpublished trials. outcomes, according to the different cor- name Sabal serrulata). Berries from saw There were no language restrictions. relation coefficients, we used SEMs cal- palmetto were first used by the Ameri- culated with a correlation coefficient of can Indians in Florida in the early 1700s Data Extraction and Study Appraisal 0.50. x2 Tests were used for analysis of to treat testicular atrophy, erectile dys- Study characteristics, demographic in- bivariate comparisons. To assess the function, and prostate gland swelling or formation,enrollmentcriteria,therapyal- percentage of patients having improve- inflammation.10 The medicinal value of location, adverse effects, outcomes and ment in urologic symptoms, a modified S repens for relief of prostate gland swell- numbers, and reasons for dropouts were intention-to-treat analysis was per- ing has been reported in medical litera- extracted independently by 2 reviewers. formed(ie,menwhodroppedoutorwere ture since the 1800s. The mechanism of Missing information was sought from au- losttofollow-upwereconsideredtohave action of S repens is not known but may thors and/or sponsors. Extracted data had worsening symptoms).21 The de- include alteration of cholesterol metabo- were reviewed by the principal reviewer nominator for the modified intention-to- lism,11 antiestrogenic, antiandrogenic, and discrepancies resolved by discussion. treat analysis included the number ran- and anti-inflammatory effects,12-14 and The main outcome was the efficacy of domized to treatment at baseline, and a decrease in available sex hormone– S repens vs placebo or active control in the numerator included the number binding globulin.15 Although S repens has improving urologic symptom scale completing the trial and showing im- been evaluated in several randomized tri-