Serenoa repens for benign prostatic hyperplasia

Article (PDF Available)inCochrane database of systematic reviews (Online) 2(2):CD001423 · April 2009with217 Reads
DOI: 10.1002/14651858.CD001423.pub2 · Source: PubMed
Abstract
Benign prostatic hyperplasia (BPH) is the nonmalignant enlargement of the prostate gland that is caused by an increase in volume of epithelial (top layer of tissue that line cavities and surfaces of the body) and stromal (connective tissue) cells. This increase in cells can, over time, create fairly large, discrete nodules in the periurethral region of the prostate, and in turn can restrict the urethral canal causing partial or complete blockage. The use of plants and herbs (phytotherapy) for the treatment of lower urinary tract symptoms associated with BPH is common and has been growing steadily in most Western countries. The extract of the berry of the American saw palmetto, or dwarf palm plant, Serenoa repens (SR), which is also known by its botanical name of Sabal serrulatum, is one of several phytotherapeutic agents available for the treatment of BPH. The update of this review included 32 randomized controlled trials involving 5666 men. Compared with placebo, Serenoa repens, at double and triple the usual dose, provides no improvement for nocturia, peak urine flow, and symptom scores for men with benign prostatic hyperplasia.
Serenoa repens for benign prostatic hyperplasia (Review)
Wilt T, Ishani A, MacDonald R
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1
http://www.thecochranelibrary.com
Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
29DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Serenoa repens versus placebo, Outcome 1 Symptom Score (points). . . . . . . . 30
Analysis 1.2. Comparison 1 Serenoa repens versus placebo, Outcome 2 IPSS total score, mean change (0-no sx to 35-severe
sx). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Analysis 1.3. Comparison 1 Serenoa repens versus placebo, Outcome 3 Patient self -rating for improved symptoms (# men
rating very good to good). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Analysis 1.4. Comparison 1 Serenoa repens versus placebo, Outcome 4 Physician-assessed improvement of symptoms. 32
Analysis 1.5. Comparison 1 Serenoa repens versus placebo, Outcome 5 Nocturia (times/ evening). . . . . . . . 32
Analysis 1.6. Comparison 1 Serenoa repens versus placebo, Outcome 6 Qmax (mL/s). . . . . . . . . . . . 33
Analysis 1.7. Comparison 1 Serenoa repens versus placebo, Outcome 7 Mean urine flow (ml/s). . . . . . . . . 34
Analysis 1.8. Comparison 1 Serenoa repens versus placebo, Outcome 8 Residual volume (mL). . . . . . . . . 34
Analysis 1.9. Comparison 1 Serenoa repens versus placebo, Outcome 9 Prostate size (cc). . . . . . . . . . . 35
Analysis 1.10. Comparison 1 Serenoa repens versus placebo, Outcome 10 Study withdrawals. . . . . . . . . 35
Analysis 2.1. Comparison 2 Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride, Outcome 1 IPSS total score,
mean change. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis 2.2. Comparison 2 Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride, Outcome 2 Nocturia
(times/evening). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis 2.3. Comparison 2 Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride, Outcome 3 Qmax (mL/sec). 37
Analysis 2.4. Comparison 2 Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride, Outcome 4 Mean urine flow
(mL/sec). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis 2.5. Comparison 2 Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride, Outcome 5 Residual volume
(mL). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Analysis 2.6. Comparison 2 Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride, Outcome 6 Prostate size (cc). 38
Analysis 3.1. Comparison 3 Serenoa repens versus Pygeum africanum, Outcome 1 Nocturia (times/evening). . . . 39
Analysis 4.1. Comparison 4 Serenoa repens/Sabal urtica (PRO 160/120) versus placebo, Outcome 1 IPSS total score, mean
change. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Analysis 4.2. Comparison 4 Serenoa repens/Sabal urtica (PRO 160/120) versus placebo, Outcome 2 Qmax (mL/s). . 40
Analysis 5.1. Comparison 5 Serenoa repens versus gestonorone caproate, Outcome 1 Qmax (mL/s). . . . . . . 40
40WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iSerenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Serenoa repens for benign prostatic hyperplasia
Timothy Wilt
1
, Areef Ishani
2
, Roderick MacDonald
1
1
General Internal Medicine (111-0), VAMC, Minneapolis, USA.
2
Department of Medicine (111), VA Medical Center, Minneapolis,
USA
Contact address: James Tacklind, AHR&Q Center for Chronic Disease Outcomes Research, Minneapolis Veterans Hospital, 1 Veterans
Drive, Minneapolis, MN, 55417, USA.
james.tacklind@med.va.gov. (Editorial group: Cochrane Prostatic Diseases and Urologic
Cancers Group.)
Cochrane Database of Systematic Reviews, Issue 1, 2009 (Status in this issue: Unchanged)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD001423
This version first published online: 22 July 2002 in Issue 3, 2002.
Last assessed as up-to-date: 29 January 2002. (Help document -
Dates and Statuses explained)
This record should be cited as: Wilt T, Ishani A, MacDonald R. Serenoa repens for benign prostatic hyper plasia. Cochrane Database
of Systematic Reviews 2002, Issue 3. Art. No.: CD001423. DOI: 10.1002/14651858.CD001423.
A B S T R A C T
Background
Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, can lead to obstructive and irritative lower urinary
tract symptoms (LUTS). The pharmacologic use of plants and herbs (ph ytotherapy) f or the treatment of LUTS associated with BPH
has been growing steadily. The extract of the American saw palmetto, or dwarf palm plant, Serenoa repens (also known by its botanical
name of Sabal serrulatum), is one of the several phytotherapeutic agents available for the treatment of BPH.
Objectives
This systematic review aimed to assess the effects of Serenoa repens in the treatment of LUTS consistent with BPH.
Search strategy
Tr ials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by
checking bibliographies, and by contacting manufacturers and researchers.
Selection criteria
Tr ials were e ligible if the y (1) randomized men with BPH to receive preparations of Serenoa repens (alone or in combination) in
comparison with placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms,
or urodynamic measurements. Eligibility was assessed by at least two independent observers.
Data coll ection and analysis
Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form.
The main outcome measure for comparing the effectiveness of Serenoa repens with placebo or other BPH medications was the change
in urologic symptom-scale scores. Secondary outcomes included changes in nocturia and urodynamic measures. The main outcome
measure for side effects was the number of men reporting side effects.
Main results
In this update 3 new trials involving 230 additional men ( 7.8%) have been included.
Three thousand one hundred thirty-nine men from 21 randomized trials lasting to 48 weeks were assessed. E ighteen trials were double
blinded and treatment allocation concealment was adequate in 11 studies. Compared with placebo, Serenoa repens improved urinary
1Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
symptom scores, symptoms, and flow measures. The weighted mean difference (WMD) for the IPSS total score (range 0 to 35) was -
0.77 (95% CI -2.88 to 1.34, n = 2 studies). The WMD for the urinary symptom score was -1.41 points (scale range 0 to 19), (95% CI -
2.52 to -0.30, n = 1 study), and the risk ratio (RR) for self-rated improvement was 1.76 (95% CI 1.21 to 2.56, n = 6 studies). The WMD
for nocturia was -0.76 times per evening (95% CI -1.21 to -0.31, n = 10 studies). The WMD for peak urine flow (Qmax) was 1.40
mL/s (95% CI 0.32 to 2.48, n = 10 studies). Compared with finasteride, Serenoa repens/Sabal urtica produced similar improvements
in the IPSS urinary symptom score (WMD 0.37, 95% CI -0.45 to 1.19, n = 2 studies) and peak urine flow (WMD -0.74 mL/s, 95%
CI -1.66 to 0.18, n = 2 studies). Adverse effects due to Serenoa repens were mild and infrequent. Withdrawal rates in men assigned to
placebo, Serenoa repens or finasteride were 7%, 9% and 11%, respectively.
Authors conclusions
The evidence suggests that Serenoa repens provides mild to moderate improvement in urinary symptoms and flow measures. Serenoa
repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse
treatment events. The long-term effectiveness, safety and ability to prevent BPH complications are not known. The results of this
update are in agreement with our initial review.
P L A I N L A N G U A G E S U M M A R Y
Serenoa repens, an herbal medicine, provides mild to moderate improvement in urinary s ymptoms and flow measures for men
with enlarged prostate glands (benign prostatic hyperplasia).
An e nl arged prostate gland, benign prostatic hyperplasia (BPH), can interfere with urination, increasing the frequency and urge, or
cause problems emptying the bladder. Surgery and drugs can be used to try to treat BPH. However, using herbal medicines to try to
relieve BPH symptoms is common. Serenoa repens is a popular herbal medicine for BPH. The review found that Serenoa repens was well
tolerated, providing mild to moderate improvement in urinary symptoms and flow measures. These improvements were comparable
to those seen in men taking a prescription drug, finasteride, for BPH. Research into long-term effects of Serenoa repens is needed.
2Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
B A C K G R O U N D
Benign prostatic hyperplasia (BPH) is a nonmalignant enlarge-
ment of the prostate. Symptoms related to BPH are one of the
most common problems in older men. Histological evidence of
BPH is found in more than 40% of men in their fifties and nearl y
90% of men in their eighties (
Berry 1984). Histologic evidence of
prevalence can be misleading because it does not translate to clin-
ical disease. Although absolute prevalence rates diff er widely in a
plethora of multinational, logitudinal, population-based studies,
there are strikingly consistent, age-related increases that parallel
Berry’s (
Berry 1984) reporting in his biopsy and cadaver study. The
majority of men over the age of 60 are considered to have urinary
symptoms attributable to BPH. In the United States treatment
of BPH accounts for approximately 1.7 million physician office
visits (
Guess 1992), and results in more than 300,000 prostate-
ctomies annually (
McConnell 1994). The treatment goal in the
vast majority of patients with BPH is to relieve the bothersome
obstructive (weak urinary stream, hesitancy, intermittency, incom-
plete bladder emptying, terminal urine dribbling and abdominal
straining) and irritative (urinary frequency, urgency and nocturia)
symptoms (Caine 1987).
Several strategies have been utilized to reduce the symptoms of
BPH (
Oesterling 1995). The standard treatment, especially for
men with severe symptoms or complications resulting from pro-
static obstruction, has been transurethral surgical resection of the
prostate (TURP). Less invasive approaches to relieve symptoms
have included transurethral incision of the prostate, laser prosta-
tectomy, prostatic stents, and microwave therapy. Pharmacologic
therapies such as 5-alpha reductase inhibitors and alpha-adrener-
gic drugs have also been shown to reduce symptoms. It is believed
that these agents decrease resistance to urinary flow by either de -
creasing prostatic size or the smooth muscle tone of the prostate
and bladder neck.
The use of plants and herbs for medicinal purposes (phytotherapy)
including treatment of BPH symptoms has been growing steadily
in most countries. Phytotherapeutic agents represent nearly half
of the medications dispensed for BPH in Italy, compared with 5%
for alpha blockers and 5% for 5-alpha reductase inhibitors (
Di
Silverio 1993
). In Ger many and Austria, phytotherapy is th e first-
line treatment for mild to moderate urinary obstructive symp-
toms and represents > 90% of all drugs prescribed for the treat-
ment of BPH (
Buck 1996). In the United States their use has
also markedly increased, they are readily available as nonprescrip-
tion dietary supplements and are often recommended in natural
health food stores or books for self treatment of BPH symptoms.
A recent survey demonstrated that one third of men choosing
nonsurgical therapy for benign prostatic hyperplasia were utiliz-
ing herbal preparations alone or in combination with prescription
medications (
Bales 1999).
There are about 30 phytotherapeutic compounds available for the
treatment of BPH. The most widely used of the plant pharmaceu-
ticals is the extract of the American saw palmetto or dwarf palm
plant, Serenoa repens (also known by its botanical name of Sabal
serrulatum). Wh ile the mechanism by which Serenoa repens works
is unknown many in vitro studies have been conducted. Some of
the proposed mechanisms of action include alteration in choles-
terol metabolism (Christensen 1990), antiestrogenic and antian-
drogenic eff ects (Dreikorn 1989; Marwick 1995), anti-inflamma-
tory effects (
McGuire 1987) and a decrease in available sex hor-
mone-binding globulin (
Di Silverio 1993). Despite wide-spread
use, the clinical efficacy of Serenoa repens to improve BPH symp-
toms and urodynamic measures remains unclear. We conducted
and updated a systematic review, first published in 1998, to eval-
uate the efficacy and adverse events of Serenoa repens in men with
lower urinary tract symptoms consistent with benign prostatic h y-
perplasia.
O B J E C T I V E S
The main outcome was the efficacy of Serenoa repens versus placebo
or active control in improving urologic symptom scale scores or
global report of urinary symptoms (improved versus stable or wors-
ened). Secondary outcomes included changes in nocturia, peak
and mean urine flow, residual urine volume, prostate size and side
effects associated with the use of Serenoa repens.
M E T H O D S
Criteria for considering studies for this review
Types of studies
Randomized controlled clinical trials.
Types of participants
Men with lower urinary tract symptoms consistent with benign
prostatic hyperplasia.
Types of interventions
Comparisonof preparations of Serenoa repens with placebo or med-
ical therapies for BPH with a treatment duration of at least 30
days.
Types of outcome measures
Urologic symptom scores (Boyarsky, American Urologic Associ-
ation Symptom Index (AUASI), and the International Prostate
Symptom Score (IPSS)); Urodynamic me asures, defined as change
in peak urine flow (PUF), mean urine flow (MUF), and residual
urine volume; changes in prostate size (measured in cc); nocturia
(times/per evening); and overall physician/patient health assess-
ment.
Search methods for identification of studies
3Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
We searched MEDLINE from 1966 to 2002 by crossing an op-
timally sensitive search strategy for trials from the Cochrane Col-
laboration with the MeSH headings prostatic hyperplasia,” and
phytosterols,” “plant extracts,” sitosterols,” “Serenoa repens or
“Sabal serrulata including all subheadings (Dickersin 1994). EM-
BASE (1974 to July 1997) Phytodok, Munich Germany, and
the Cochrane Library, including the database of the Cochrane
Prostatic Diseases and Urologic Malignancies Group and the
Cochrane Field for Complementary Medicine were searched in a
similar fashion. Reference lists of all identified trials and previous
reviews were searched for additional trials. Expert relevant trialists
were asked to identify additional published or unpublished trials.
There were no language restrictions.
Data c ollection and analysis
Eligibility:
At least two reviewers independently decided on eligibility.
Extraction:
Study characteristics were assessed and data extraction was per-
formed independently by two reviewers. Missing or additional in-
formation was sought from authors/sponsors. Extracted data was
reviewed by the principal reviewer and discrepancies resolved by
discussion.
Assessment of methodological quality:
As a measure of overall methodologic study quality we assessed
the quality of concealment of treatment allocation according to a
scale developed by
Schulz 1995 assigning 1 to poorest quality and
3 to best quality: 1 = trials in which concealment was inadequate
(e.g. such as al ternation or reference to case record numbers or
to dates of birth); 2 = trials in which the authors either did not
report an allocation concealment approach at all or reporte d an
approach that did not fall into one of the other categories; and 3
= trials deemed to have taken adequate measures to conceal allo-
cation (e.g. central randomization; numbered or coded bottles or
containers; drugs prepared by the pharmacy; serially numbered,
opaque, sealed envelopes etc. that contained elements convincing
of concealment). Additionally, we assessed whether study partici-
pants and investigators were blinded to the treatment provided.
Summarizing results of primary studies:
Outcomes:
We assessed the mean urologic symptom score, nocturia (# times),
peak and mean urine flow (mL/s), residual urine volume (mL),
and prostate size (cc). The number and percent of men reporting
specific side effects and/or withdrawing from the study were also
evaluated.
Meta-analysis:
For the primary analysis (of the stated primary and secondary out-
comes) all trials including Serenoa repens in mono-preparations
and in combination were analyzed separately (Serenoa repens ver-
sus placebo or versus active controls). Summary effe ct estimates
were done using a random effects model to allow for heterogene-
ity between studies. For continuous measurements, a difference
between treatment means and its correlated standard error of the
difference were calculated using the methods of Laird and Lau (
Laird 1990; Lau 1996). Because studies did not report the stan-
dard error of the difference between the means (Serenoa repens and
control), analyses were carried out for 3 different assumed values
of correlation (0.25, 0.50, 0.75). This approach was taken in or-
der to test the sensitivity of the results to this unknown param-
eter. Because there were no statistically significant differences in
the outcomes according to the different correlation coefficients
we utilized standard errors of the mean calculated with a correla-
tion coefficient of 0.50. To assess the percentage of patients hav-
ing improvement in urologic symptoms a modified intention-to-
treat (ITT) analysis was performed (i.e. men who dropped out
or were l ost to follow up were considered to have had worsening
symptoms) (
Lavori 1992). The denominator for the modified ITT
analysis included the number randomized to treatment at baseline
and the numerator included the number completing the trial and
showing improvement.
R E S U L T S
Description of studies
See:
Characteristics of included studies; Characteristics of excluded
studies
.
The updated se arch strategy identified 5 new trials, 3 included
(
Bauer 1999; Marks 2000; Gerber 2001), and two excluded (
Gerber 1998; Sökeland 2000).
The combined search strategies identified 29 reports of trials; 21
met inclusion criteria. Reasons for exclusion included: duration
unknown or less than 30 days (
Comar 1986; Grasso 1995 ); no
clinical outcomes (examining enzyme or tissue effects (
Di Silverio
1992
; Strauch 1994; Weisser 1997); no indication of random-
ization (
Adriazola Semino 1992), no control group (open-label
study) (
Gerber 1998), and dual publication (Sökeland 2000). A
total of 3139 participants were randomized in the 21 trials (1408
in trials of Serenoa repens alone or in combination versus placebo,
1701 in trials of Serenoa repens alone or in combination versus
active control, and 30 in a therapeutic bioequivalence study). The
mean age of enrollees was 65.0 years and ranged from 40 to 88.
The mean study duration was 13 weeks (range 4 to 48 weeks).
The percentage of men who dropped out or were lost to follow up
was 10% (n = 319) and ranged from 0% to 18%.
The mean baseline values for urologic symptoms, nocturia, peak
urine flow and residual urine volume did not differ by treatment
group and included: urologic symptom scale score (International
Prostate Symptom Scale - IPSS) in two studies with active control =
14.4 +/- 5.9 points (scale range = 0 to 35; moderate BPHsymptoms
= 8 to 19); urologic symptom scale score in one study with placebo
= 7.0 +/- 2.8 points (scale range = 0 to 19, based on an addition of
4Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
subscores for six variables: pollakiuria, nocturia, dysuria, hesitancy,
urgency and perineal heaviness); nocturia = 2.5 +/- 1.5 times per
night; peak urine flow11.2+/- 3.9 mL/s; and residual urine volume
= 55.8 +/- 41.5 mL. Baseline values (+/- SD) for me an urine flow
(5.7 +/- 2.1 mL/s) and prostate volume (43.9 +/- 21.6 cc) also
did not differ by treatment group. These results indicate that on
average, men had urinary symptoms and flow measures consistent
with moderate BPH.
Risk of bias in included studies
Treatment allocation concealment was adequate in 11 studies
(52%) and 18 studies (86%) were double blinded (
Boccafoschi
1983; Emili 1983; Mandressi 1983; Champault 1984; Cukier
1985
; Tasca 1985; Reece Smith 1986; Gabric 1987; Carbin
1990
; Mattei 1990; Descotes 1995; Lobelenz 1992; Carraro 1996;
Metzker 1996; Braeckman 1997; Sökeland 1997; Bauer 1999;
Gerber 2001).
Main comparisons in the remaining studies were: Serenoa repens
alone versus placebo (
Boccafoschi 1983; Emili 1983; Champault
1984
; Cukier 1985; Tasca 1985; Reece Smith 1986; Mattei 1990;
Descotes 1995; Lobelenz 1992; Braeckman 1997; Bauer 1999;
Gerber 2001). Serenoa repens in combination with other phy-
totherapeutic agents versus placebo (
Gabric 1987; Carbin 1990;
Metzker 1996; Bauer 1999); Serenoa repens alone versus active
control (Pannunzio 1986; Carraro 1996); Serenoa repens versus
another phytotherapeutic agent and versus placebo (
Mandressi
1983
); Serenoa repens in combination with other phytotherapeutic
agents versus active control (
Sökeland 1997); and Serenoa repens
orally versus a rectal suppository form of Serenoa repens, a thera-
peutic bioequivalence study (
Roveda 1994).
Effects of interventions
Urinary symptoms:
Symptom scale score results were reported in 13 studies (
Mandressi
1983
; Champault 1984; Reece Smith 1986; Gabric 1987; Carbin
1990
; Descotes 1995; Carraro 1996; Metzker 1996; Braeckman
1997; Sökeland 1997; Bauer 1999; Marks 2000; Gerber 2001).
The weighted mean difference for urinary symptom scale scores
for Serenoa repens versus placebo was -1.41 points (scale range = 0
to 19) (28% absolute improvement vs. placebo) (95% CI -2.52 to -
0.30) (
Braeckman 1997). The weighted mean difference for me an
change from baseline for the IPSS relative to placebo was -2.20
points (12% absolute improvement vs. placebo) (95% CI -4.40 to
0.30) (
Gerber 2001). Versus finasteride, the weighted mean dif-
ference was 0.37 IPSS points (scale range = 0 to 35) (37% absolute
improvement from baseline for Serenoa repens versus 40% abso-
lute improvement from baseline for finasteride) (95% CI -0.45 to
1.19) (Carraro 1996; Sökeland 1997). The weighted mean differ-
ence f or the combination preparation Sabal-Urtica versus placebo
was -3.50 IPSS points (scale range = 0 to 35) (17% absolute im-
provement vs. placebo) (95% CI -6.75 to -0.25) (
Metzker 1996).
Participants and their physicians were both more likely to report
improvement in symptoms in men treated with Serenoa repens
than with placebo. The weighted risk ratio (RR) for participant
self rating of improvement in urinary symptoms for Serenoa repens
versus placebo was 1.76 (95% CI 1.21 to 2.54) (Mandressi 1983;
Champault 1984; Carbin 1990; Descotes 1995; Metzker 1996;
Braeckman 1997). The weighted RR for physician rating of im-
proved urologic symptoms for Serenoa repens versus placebo was
1.72 (95% CI 1.11 to 2.66) (
Champault 1984; Descotes 1995;
Braeckman 1997).
Nocturia:
Nocturia results were reported in 12 studies (
Boccafoschi 1983;
Emili 1983; Mandressi 1983; Champault 1984; Cukier 1985;
Tasca 1985; Pannunzio 1986; Reece Smith 1986; Carbin 1990;
Mattei 1990; Descotes 1995; Carraro 1996). Serenoa repens re-
duced nocturia 25% (absolute difference) compared with placebo.
It was comparable to finasteride and Pygeum africanum. The
weighted mean difference for nocturia was -0.76 times per evening
versus placebo (95% CI -1.21 to -0.32) (
Boccafoschi 1983; Emili
1983
; Mandressi 1983; Champault 1984; Cukier 1985; Tasca
1985
; Reece Smith 1986; Carbin 1990; Mattei 1990; Descotes
1995
). Versus finasteride, the weighted mean difference was -0.05
(95% CI -0.49 to 0.39) (
Carraro 1996) and -0.20 (95% CI -1.69
to 1.29) versus Pygeum africanum (Mandressi 1983).
Urinary flow measures and prostate size:
Serenoa repens was superior to pl acebo and comparable to finas-
teride in improving peak and mean urine flow rates and resid-
ual urine volume. Peak urine flow was reported in 16 studies (
Boccafoschi 1983; Emili 1983; Champault 1984; Tasca 1985;
Pannunzio 1986; Reece Smith 1986; Gabric 1987; Lobelenz 1992;
Descotes 1995; Carraro 1996; Metzker 1996; Braeckman 1997;
Sökeland 1997; Bauer 1999; Marks 2000; Gerber 2001). The
weighted mean differences for peak urine flow were 1.86 mL/s
(95% CI 0.60 to 3.12) versus placebo (
Boccafoschi 1983; Emili
1983
; Champault 1984; Tasca 1985; Reece Smith 1986; Gabric
1987; Descotes 1995; Braeckman 1997; Gerber 2001) and -0.74
mL/s versus finasteride (95% CI -1.66 to 0.18) (
Carraro 1996;
Sökeland 1997), 2.0 mL/s versus gestonorone caproate (95% CI
1.36 to 2.64) (
Pannunzio 1986) and 1.6 mL/s for Sabal-Urtica
versus placebo (95% CI -1.67 to 4.87) (
Metzker 1996).
Mean urine flow was reported in nine studies (
Boccafoschi 1983;
Emili 1983; Champault 1984; Tasca 1985; Reece Smith 1986;
Carbin 1990; Lobelenz 1992; Carraro 1996; Braeckman 1997;
Bauer 1999). The weighted mean differences for mean urine flow
were 2.22 mL/s (95% CI 1.17 to 3.27) (
Emili 1983; Champault
1984
; Carbin 1990; Braeckman 1997) and -0.40 mL/s versus fi-
nasteride (95% CI -0.95 to 0.15) (
Carraro 1996).
Twelve studies provided information related to residual volume (
Boccafoschi 1983; Emili 1983; Champault 1984; Cukier 1985;
Reece Smith 1986; Gabric 1987 ; Carbin 1990; Mattei 1990;
Lobelenz 1992; Metzker 1996; Braeckman 1997; Sökeland 1997).
The weighted mean difference for residual volume was -22.95
5Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
mL/s (95% CI -42.33 to -3.56) versus placebo (Emili 1983;
Champault 1984; Gabric 1987; Carbin 1990; Mattei 1990;
Braeckman 1997), 5.70 mL/s versus finasteride (95% CI -5.42 to
16.82) (
Sökeland 1997).
Serenoa repens did not reduce prostate size; the weighted mean
differences for prostate size were -2.14 cc (95% CI -10.92 to 6.65)
(
Mattei 1990; Braeckman 1997) versus pl acebo and 4.80 cc (95%
CI 1.42 to 8.18) versus finasteride (
Carraro 1996).
Adverse effects:
Adverse effects due to Serenoa repens were generally mild and com-
parable to placebo. Withdrawal rates were: Serenoa repens 8.9%;
Placebo 7.1% and Finasteride 9.0% (P = 0.17 for Serenoa repens
versus placebo and P = 1.0 versus finasteride). Specific adverse
events were reported in 11 trials. Impotence was reporte d in 1.1%
of men on Serenoa repens, 0.7% placebo and 4.9% finasteride (P
= 0.58 f or Serenoa repens verus placebo and P < 0.001 versus fi-
nasteride). Gastrointestinal side effects were reported in 1.3% of
men on Serenoa repens, 0.9% placebo and 1.5% finasteride (P >
0.5 versus placebo and finasteride.)
D I S C U S S I O N
The available data indicate that Serenoa repens (alone or in combi-
nation with other phytotherapeutic agents) provides mild to mod-
erate improvement in urinary symptoms and flow measures. Our
results were similar to a meta-analysis (n = 11 RCTs) of the Serenoa
repens compound Permixon, which also found improvement in
peak flow rate and nocturia (
Boyle 2000). The results of this up-
date do not differ from previous findings and add additional data
from 3 placebo-controlled RCTs involving 230 men. Men taking
Serenoa repens were nearly twice as likely to report improvement
in symptoms than men taking pl acebo. When compared to finas-
teride, Serenoa repens provided similar responses in urologic symp-
toms and flow measures and was associated with a lower rate of
impotence.
Participant baseline characteristics regarding age, prostate volume,
peak urine flow and symptom scale scores were similar to previous
trials and meta-analyses involving pharmacologic management of
BPH (
Boyle 1996; Chapple 1996; Roehrborn 1996; McConnell
1998
). Therefore, our results are generalizable. They did not sub-
stantially change when we restricted our analysis to studies th at
had adequate treatment allocation concealment (level 3) or were
double blinded. The treatment effect size with regard to symptom
scale scores, peak and mean urinary flow, nocturia and residual
volume are similar to effects reported with other pharmacologic
agents (
Boyle 1996; Chapple 1996; Roehrborn 1996; McConnell
1998
).
Two previous reviews of phytotherapy in the treatment of BPH
were not structured systematic reviews or quantitative meta-anal-
ysis (
Buck 1996; Lowe 1996). They included information from
nonrandomized or uncontrolled studies and therefore may have
overestimated treatment effectiveness. The number of randomized
trials included in these previous reports were less than we identi-
fied. The inclusion of an EMBASE and Phytodok search identi-
fied five studies not listed in MEDLINE. If our search had been
restricted to English language journals we would have missed 13
(62%) trials.
Despite abstracting and analyzing 21 randomized trials that in-
cluded over 3,000 participants, many studies did not report out-
comes data in a consistent fashion. Several did not report means
and standard deviations making completion of a quantitative sys-
tematic review difficult. Multiple attempts to contact the trialists
enabled us to obtain additional information from 10 studies (Lowe
1998
). Only six studies reported results from standardized and
validated urologic symptom scales (
Carraro 1996; Metzker 1996;
Sökeland 1997; Bauer 1999; Marks 2000; Gerber 2001). One trial
reported results from a scale that had not been standardized or
validated (
Braeckman 1997). All of these studies were rated as hav-
ing adequate treatment all ocation concealment. Two of these trials
were reported subsequently to our original review. Most studies
were conducted prior to the development of validated urologic
symptom scale scores. Results from these scales have been demon-
strated to be the most valid and clinically relevant endpoints for
assessing treatment effectiveness in men with mild to moderate
symptoms of BPH (
McConnell 1994). Secondary outcomes were
combinable in only the minority of trials; mean urine flow (5 tri-
als), peak urine flow (12 trials), residual volume (6 trials), nocturia
(11 trials), and prostate size (3 trials). The treatment duration
was short with only two studies having follow up of at least six
months duration. Studies utilized different doses and preparations
of Serenoa repens or were per formed in combination with other
phytotherapeutic compounds. The most frequently reported dose
was 160 mg of Serenoa repens twice per day.
Several statistical issues in combining the data in our analysis need
to be mentioned. For the “self-rating of symptom improvement”
outcome, there was significant heterogeneity in the treatment ef-
fects. Ideally, when significant heterogeneity of treatment effect is
present, meta-regression should be explored to understand reasons
for the differences. However, this was not possible here because of
the lack of studies and lack of standardized reporting of meaningful
clinical covariates. Nonetheless, if an overall quantitative estimate
is deemed to be useful, then a random effects model that incorpo-
rates between studies heterogeneity would be more appropriate as
we have done. Five of the six (
Mandressi 1983; Champault 1984;
Carbin 1990; Metzker 1996; Braeckman 1997) studies had signif-
icant treatment ef fects and th e second largest study also trended in
the same direction, thus reducing the likelihood that the pooling
produced a false positive result. Due to the high baseline response
rate in the control groups in several studies and the wide range
6Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
of the baseline rates, the choice of treatment effect metric used to
combine outcomes may also affect the results. Compared with the
pooled random effects risk ratio (RR 1.75; 95% CI 1.21 to 2.54),
the pooled odds ratio is much higher (OR 5.33; 95% CI 2.00
to 14.24). The odds ratio is frequently used to approximate the
risk ratio in the clinical trial setting. In this case, the high pooled
odds ratio creates a false impression that Serenoa repens is far more
efficacious. We choose the more conservative metric provided by
the risk ratio in our analysis.
We were not able to determine if Serenoa repens prevented long
term complications of BPH such as acute urinary retention or
the need for surgical interventions. Previous studies have demon-
strated that finasteride is eff ective in relieving BPH symptoms, re-
ducing the development of acute urinary retention and the need
for surgical intervention in men with large prostates (i.e. > 40
cc) and moderate to severe symptoms (
Boyle 1996; McConnell
1998
). However, fewer than one third of men with BPH have
prostate glands greater than 40 cc in size (
Wasson 1998). In men
with “large prostates the absolute rate of acute urinary retention
or symptomatic progression requiring surgical intervention is less
than 3% per year. In our review, the mean prostate volume in stud-
ies reporting prostate size was 44 cc. The available data did not
allow us to determine if prostate volume was an important pre-
dictor of outcomes. Additionally, there were no reported studies
comparing Serenoa repens with alpha adrenergic blockers that met
inclusion criteria. One study compared Serenoa repens to alfuzosin
but the duration of follow up was only three weeks (
Grasso 1995).
The Committee on Other Medical Therapies of the Fourth In-
ternational Consultation on BPH concluded th at: most plant ex-
tract preparations have different components; it is not known what
mechanisms of action demonstrated in vitro might be responsible
for clinical effects; short-term randomized studies suggest clini-
cal efficacy for some preparations; and studies were usually inade-
quate due to the me thodology utilized, small numbers and short
duration of study. Of greatest importance is the completion of
additional high quality studies of long duration to fully evaluate
the efficacy and safety of ph ytotherapeutic products for treatment
of BPH.
Until completion of these studies and/or regulation of these prod-
ucts the lack of universal definitions, practices, and standards
within the supplement industry place the onus on the physician
to judge product quality and efficacy. Manufacturers/companies
of plant extracts often use different e xtraction processes. There is
no evidence that the extract from one manufacturer is equivalent
of another’s. Additionally, since the active ingredient(s) are not
known, it is possible th at one product might have clinical efficacy
while another does not. Each companys product must be tested to
evaluate clinical efficacy and bioactivity. A recent review in Con-
sumer Reports highlights the importance of this issue. Their inde-
pendent analyses demonstrated wide variation in the amount of
Serenoa repens contained in each tablet regardless of the product’s
labeling (
Consumer Reports 2000).
The following recommendations have been made for assessing
quality measures (these do not directly address clinical efficacy
or safety) in selecting high-quality and reliable preparations of
phytotherapeutic products manufactured in the United States (
McKinney 1999).
1. The manufacturer tests raw ingredients for purity and
potency prior to inclusion into a product.
2. The product is manufactured in a pharmaceutically li-
censed facility registered with the Food and Drug Ad-
ministration.
3. The product’s ingredients meet the applicable United
States Pharmacopoeia (USP) standards.
4. All finished products are analyzed for purity and po-
tency following production by an independent labora-
tory using established methods to e nsure that the prod-
uct meets label claims and is of good quality.
In some cases, this information can be found on product labeling.
All reputable manufacturers will keep certificates of laboratory
results for each finished batch of product on file. These should be
available to physicians and pharmacists on request.
A U T H O R S C O N C L U S I O N S
Implications for practice
Extracts from th e saw palmetto pl ant, Serenoa repens, provide mild
to moderate improvement in urinary symptoms and flow mea-
sures in men with benign prostatic hyperplasia. Compared to fi-
nasteride, Serenoa repens produces similar improvements in uri-
nary symptoms and flow measure, is associated with fewer adverse
treatment effects and costs less. The long-term effectiveness and
safety of Serenoa repens as well as its ability to prevent compli-
cations from BPH, including the need for surgical intervention,
are not known. While Serenoa repens may be a useful treatment
option patients and providers need to be aware that there are no
guarantees regarding product purity and potency.
Implications for research
Additional placebo controlled trials are needed as well as stud-
ies that compare Serenoa repens to alpha antagonists. Future trials
should be of sufficient size and duration to detect important differ-
ences in clinically relevant e ndpoints. At a minimum these studies
should assess and repor t the mean and standard deviations at base-
line and conclusion for the following variables: age, number en-
rolled and completing the study, standardized urologic symptom
scale scores, mean and peak urine flow, voided volume, prostate
size, residual urine volume, complications from BPH, need for
subsequent therapy and long term adverse effects of Serenoa repens.
7Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Note: The United States National Institute of Diabetes and Dis-
eases of the Kidney is sponsoring a large, multicenter RCT to eval-
uate the efficacy and adverse events of Serenoa repens compared
to placebo or Pygeum africanum. This trial will involve approx-
imately 3000 men and follow them up for at least 4 years. The
primary endpoint will be change in BPH progression measured by
the IPSS, bother, need for surgical intervention, and acute urinary
retention when completed
A C K N O W L E D G E M E N T S
This work was partially funded by Grant Number R24 AT001293
from the National Center for Complementary and Alternative
Medicine (NCCAM). The contents of this systematic review are
solely the responsibility of the authors and do not necessarily rep-
resent the official views of the NCCAM or the National Institutes
of Health. We also wish to thank Maurizio Tiso, Margaret Haugh,
and Rich Crawford for their work in translating and abstracting
data from the non-English language studies.
R E F E R E N C E S
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cia. Medical treatment of benign prostatic hyperplasia: efficacy of
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Wasson 1998
Wasson JH. Finasteride to prevent morbidity from benign pro-
static hyperplasia. N Engl J Med 1998;612-6 13. [MEDLINE:
1998129156]
References to other published versions of this review
Wilt 1998
Wilt TJ, Ishani A, Stark G, Mac Donald R, Lau J, Mulrow C. Saw
palmetto extracts for treatment of benign prostatic hyperplasia: a
systematic review. JAMA 1998;280(18):1604–9.
Wilt 2002
Wilt T, Ishani A, Mac Donald R. Serenoa repens for benign p rostatic
hyperplasia. Cochrane Database of Systematic Reviews 2002, Issue 3.
Art. No.: CD001423. DOI: 10.1002/14651858.CD001423 2002,
(3). [: ISSN 1464–780X]
Indicates the major publication for the study
10Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of included stu dies [ordered by study ID]
Bauer 1999
Methods Number of sites unknown
Randomization: unclear
Patients blinded; providers blinded
Participants Geographic region: Germany/Italy
Study setting: community
n = 101
Age range: not reported
mean: 66.1
Race: Wh ite
Diagnostic criteria: confirmed diagnosis of BPH with enlargement of the prostate, symptoms of obstruc-
tion and a maximum flow of less than 15 ml/s
Interventions Control: matching placebo
Treatment: Sabal extract (LG166/S) 160 mg bid
Study duration: 6 months
Lost to follow up: 3?
Outcomes Symptom improvement-
IPSS symptom score
Peak urine flow
Prostate volume
Sexual function
Dropouts due to side effects: 0%
Notes Exclusions: patients treated for BPH within 1 month of the trial start; prostate cancer; acute urinary tract
infection; chronic prostatitis; neurogenic bladder
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
11Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Boccafoschi 1983
Methods Single-site study
Randomization: Sealed envelopes
Patients blinded; providers blinded
Participants Geographic region: Italy
Study setting: community
n = 22
Age range: 54-78 mean: 68.0
Race: Wh ite
Diagnostic criteria: Men with symptomatic BPH not in need of surgery
Interventions Control: matching placebo
Treatment: Permixon 160mg twice daily
Study duration: 8.5 weeks
Lost to follow up: None
Outcomes Dysuria (4-point scale)
Peak urine flow
Mean urine flow
Voiding time
Total voided volume
Pollachiuria
Dropouts due to side effects: not reported
Notes Exclusions: Cancer; currently on other medication; urinary tract infection
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Braeckman 1997
Methods Number of sites unknown
Randomization: sequentially numbered sealed opaque envelopes
Patients blinded; providers blinded
Participants Geographic region: Belgium
Study setting: community
n = 238
Age range: 57-73 mean: 65
Race: Wh ite
Diagnostic criteria: Peak urine flow 5-15mls/sec; residual urine volume less/equal 60mls; Personal score
list 0-4; No global physician assessment
12Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Braeckman 1997 (Continued)
Interventions Control: matching placebo
Treatment: Serendar 160mg twice daily
Study duration: 12 weeks
Lost to follow up: 5%
Outcomes Symptom improvement
Peak urine flow
Mean urine flow
Total voided volume
Bladder residual volume
Prostate size
Dropouts due to side effects: < 1%
Notes Exclusions: Age > 80 years; prostate/other cancers ; urine flow < 5mls/sec or > 15mls/sec; residual volume
> 60mls; currently on medications; urinary tract infection
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Carbin 1990
Methods Multisite study
Randomization: random allocation according to a centrally controlled code list
Patients blinded; providers blinded
Participants Geographic region: Sweden and Denmark
Study setting: community
n = 55
Age range: 51-72 mean 61.6
Race: Wh ite
Diagnostic criteria: The presence of BPH on the basis of history, clinical examination of the prostate and
acid phosphatase determination
Interventions Control: matching placebo
Treatment: Combination phytotherapy: Curbicin (Sabal serrulata 80mg and Cucurbita pepo L. 80mg)
Study duration: 12 weeks
Lost to follow up: 4%
13Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Carbin 1990 (Continued)
Outcomes Dysuria
Mean urine flow
Voiding time
Bladder residual volume
Nocturia
Patient self-evaluation
Dropouts due to side effects: none
Notes Exclusions: Need of imminent surgery due to symptom se verity; bladder residual urine > 300 ml; previous
treatment with Curbicin
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Carraro 1996
Methods Multisite study
Randomization: computer-generated randomization code
Patients blinded; providers blinded
Participants Geographic region: Nine European countries
Study setting: community
n = 1098
Age range: 49-88 mean 64.5
Race: Wh ite
Diagnostic criteria: BPH diagnosed by digital rectal exam (DRE);
International Prostate Symptom Score (IPSS) > 6; Maximun urinary flow between 4-15mL/s (with a
urine volume at least 150ml, and a postvoiding residue of <200ml); prostate size >25ml; serum prostate-
specific antigen (PSA) < 10ng/ml (prostates less than or equal to 60ml) or 15ng/ml (prostates > 60ml);
good mental and physical condition
Interventions Control: finasteride 5mg (Proscar) plus placebo (morning) and two placebos (evening)
Treatment: Permixon 160mg plus placebo twice daily
Study duration: 26 weeks
Lost to follow up: 13.4%
Outcomes Symptom improvement-IPSS symptom score (0-35 points)
Quality of life score (0-6 points)
Sexual function score (0-20 points)
Peak urine flow
Mean urine flow
Total voided volume
14Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Carraro 1996 (Continued)
Bladder residual volume
Prostate size (volume)
Serum PSA
Dropouts due to side effects: 4% (28 Permixon and 14 finasteride)
Notes Exclusions: Prostate cancer; bladder disease; abnormal liver function; diuretics or drugs with antiandro-
genic or alpha-receptor properties in the preceding 3 months; urogenital infections; disease potentially
affecting micturition
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Champault 1984
Methods Number of sites unknown
Randomization: unclear
Patients blinded; providers blinded
Participants Geographic region: France
Study setting: community
n = 110
Age range: not reported mean: not reported
Race: Wh ite
Diagnostic criteria: Peak urine flow; mean urine flow; residual urine volume; (No details given)
Interventions Control: matching placebo
Treatment: PA109 80mg twice daily
Average follow-up: 4 weeks
Lost to follow up: 15%
Outcomes Dysuria
Mean urine flow
Bladder residual volume
Nocturia
Patient self-rating
Physician self-rating
Dropouts due to side effects: not reported
Notes Exclusions: Prostate cancer
Risk of bias
15Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Champault 1984 (Continued)
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Cukier 1985
Methods Multisite study
Randomization: numbered or coded identical containers administered sequentially
Patients blinded; providers blinded
Participants Geographic region: France
Study setting: community
n = 168
Age range: not reported
Mean 69
Race: Wh ite
Diagnostic criteria: Patients with “prostatism or for whom surgery was not indicated (no mechanical or
infectious complications)
Interventions Control: matching placebo
Treatment: Permixon 160mg twice daily
Study duration: 10 weeks
Lost to follow up: 13%
Outcomes Symptom score (# of daily mictions)
Dysuria (4-point scale)
Bladder residual volume
Nocturia
Dropouts due to side effects: not reported
Notes Exclusions: Symptoms for at least 6 months
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
16Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Descotes 1995
Methods Multisite study
Randomization:noted but method not stated
Patients blinded; providers blinded
Participants Geographic region: France
Study setting: community
n = 215
Age range: not reported mean: 66.3
Race: Wh ite
Diagnostic criteria: Mild-moderate (stage I or II) BPH; Dysuria: daytime and nocturnal urinary f requency
(>2 nocturnal micturitions, excluding those at bedtime and on awakening) of at least 8 wee ks; maximun
urinary flow > or equal to 5mL/s
Interventions Control: matching placebo
Treatment: Permixon 160mg twice daily
Study duration: 4 weeks
Lost to follow up: 18%
Outcomes Dysuria
Peak urine flow
Mean change in daytime urinary frequency
Nocturia
Patient-based global efficacy
Physician-based global efficacy
Dropouts due to side effects: 1 (complaints of fatigue, depression and stomach upset)
Notes Exclusions: Excessively mild or severe symptoms of BPH including incontinence, bladder distension,
urine flow< 5mls/sec; cancer; prior treatment for BPH; urogenital infection; hematuria; diabetes; any
prior surgery which could induce dysuria
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Emili 1983
Methods Single-site study
Randomization: noted but method not stated
Patients blinded; providers blinded
17Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Emili 1983 (Continued)
Participants Geographic region: Italy
Study setting: community
n = 30
Age range: 44-78 mean: not reported
Race: Wh ite
Diagnostic criteria: Men with manageable BPH
Interventions Control: matching placebo
Treatment: Permixon 160mg twice daily
Study duration: 4 weeks
Lost to follow up: none
Outcomes Peak urine flow
Mean urine flow
Bladder residual volume
Prostate size (qualitative scale used)
Nocturia
Dropouts due to side effects: none
Notes Exclusions:BPH prior treament
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Gabric 1987
Methods Multisite study
Randomization: unclear
Patients blinded; providers blinded
Participants Geographic region: Croatia
Study setting: community
n = 30
Age range: 40-82 mean: 65.0
Race: Wh ite
Diagnostic criteria: BPH, stage I-II (Vahlensieck)
Interventions Control: placebo
Treatment: Combination phytotherapy: Prostagutt (Sabal serrulata and Urtica dioca)
Study duration: 6 weeks
Lost to follow up: none
18Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Gabric 1987 (Continued)
Outcomes Peak urine flow (uroflow)
Bladder residual volume
Dropouts due to side effects: none
Notes Exclusions: Stage IV prostate adenoma; bacterial prostatitis; cystitis; urethritis
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Gerber 2001
Methods Multisite or single-site: NA
Randomization: computer number table
Patients blinded; providers blinded
Participants Geographic region: USA
Study setting: community
n = 85
Age range: 45 or older
mean: 65
Race: not reported
Diagnostic criteria: IPSS score 8 or greater
Interventions Control: placebo
Treatment: Saw palmetto 160mg twice daily
Study duration: 6 months
Lost to follow up: 7%
Outcomes Symptom improvement-
IPSS symptom score
Quality of Life score
Peak urine flow
Dropouts due to side effects: 1% (1 saw palmetto)
Notes Exclusions: prostate surgery; history of prostate cancer or urethral stricture; treated with finasteride, saw
palmetto or other alternative th erapy (past 6 months); or treated with al pha-blocker (within 1 month)
Risk of bias
Item Authors judgement Description
19Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Gerber 2001 (Continued)
Allocation concealment? Yes A - Adequate
Lobelenz 1992
Methods Multisite study
Randomization: computer-generated randomization code
Patients blinded; providers blinded
Participants Geographic region: Germany
Study setting: community
n = 60
Age range: 40-82 mean: not reported
Race: Wh ite
Diagnostic criteria: BPH, stage I-II; peak urine flow < 20ml/s
Interventions Control: matching placebo
Treatment: Sabal extract 100mg once per day
Study duration: 6 weeks
Lost to follow up: none
Outcomes Peak urine flow
Mean urine flow
Dropouts due to side effects: none
Notes Exclusions: Not reported
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Mandressi 1983
Methods Number of sites unknown
Randomization: Identical packaging
Patients blinded; providers blinded
Participants Geographic region: Italy
Study setting: community
n = 60
Age range: 50-80 mean: not reported
Race: Wh ite
Diagnostic criteria: Men with symptomatic BPH confirmed on rectal examination.
20Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mandressi 1983 (Continued)
Interventions Control 1: matching placebo
Control 2: Pygeum africanum extract
Treatment: Permixon 320mg daily
Study duration: 4 weeks
Lost to follow up: unclear
Outcomes Patient self-rating
Dysuria (pain on voiding)
Urgency
Tenesmus
Difficult urination
Post-voiding residue
Pollachiuria
Nocturia
Dropouts due to side effects: none
Notes Exclusions: Details not given
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Marks 2000
Methods Single-site study
Randomization: table of random numbers
Patients blinded
Participants Geographic region: USA
Study setting: community
n = 44
Age range: 45-80
mean 64
Race: white 73%,
black 7%, Asian 11%
Diagnostic criteria: moderate to severe BPH with enlarged prostate (DRE), IPSS score of 9 or greater,
PSA < 15ng/ml, prostate volume 30cc or greater
Interventions Control: placebo
Treatment: Saw palmetto herbal blend (saw palmetto 106mg, nettle root extract 80mg, pumpkin seed oil
extract 160mg, vitamin A 190mg).
Study duration: 6 months
Lost to follow up: 7%
21Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Marks 2000 (Continued)
Outcomes Symptom improvement-
IPSS symptom score
Peak urine flow
Post-void residual volume
PSA
Prostate volume
Dropouts due to side effects: 0%
Notes Exclusions: concurrent use of alpha blockers; use of finasteride, phytotherapy within last 18 months or
alpha blockers within last month; chronic prostatitis; previous bladder or prostate surgery; neurogenic
bladder,
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Mattei 1990
Methods Single-site study
Randomization: noted but method not stated
Patients blinded; providers blinded
Participants Geographic region: Italy
Study setting: community
n = 40
Age range: 45-72 mean: not reported
Race: Wh ite
Diagnostic criteria: Men with managable BPH
Interventions Control: matching placebo
Treatment: Talso (Serenoa repens e xtract) 160mg twice daily
Study duration: 13 weeks
Lost to follow up: 5%
Outcomes Dysuria (symptom score 0-4)
Bladder residual volume (incomplete emptying - symptom score 0-4)
Discomfort (Pollachiuria - symptom score 0-4)
Daytime frequency
Nocturia
Prostate size
Dropouts due to side effects: 1 patient from each group due to “stomach pains”. Unclear relation to
therapy
22Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mattei 1990 (Continued)
Notes Exclusions: Urogenital disease; prostate cancer
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Metzker 1996
Methods Single-site study
Randomization: computer-generated randomization code
Patients blinded; providers blinded
Participants Geographic region: Germany
Study setting: community
n = 40
Age range: 52-84 mean: 65.5
Race: Wh ite
Diagnostic criteria: BPH, Alken stage I-II
Interventions Control: matching placebo
Treatment: Combination phytotherapy: Prostagutt forte (Sabal 160mg and Urtica 120mg) 1 capsule twice
per day
Study duration: 48 weeks
Lost to follow up: 7.5%
Outcomes Symptom improvement-IPSS symptom score
Peak urine flow
Bladder residual volume
Patient self-evaluation
Dropouts due to side effects: none
Notes Exclusions: Age < 50 years; cancer; taking other prostate medications/contrainidicated medications; in-
fections; recent or current urinary tract operations
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
23Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Pannunzio 1986
Methods Single-site study
Randomization: noted but method not stated
Patients not blinded; providers not blinded
Participants Geographic region: Italy
Study setting: community
n = 60
Age range: 44-78 mean: not reported
Race: Wh ite
Diagnostic criteria: Men with BPH without prior treatment; bladder residual volume of < 150ml
Interventions Control: Depostat (gestonorone caproato 200mg) intra-muscularly every week for 8 weeks
Treatment: Permixon 160mg twice daily
Study duration: 8 weeks
Lost to follow up: none
Outcomes Dysuria (% of subjects with symptoms)
Pollachiuria
Nocturia
Peak urine flow
Voiding time
Prostate size
Dropouts due to side effects: none
Notes Exclusions: Cancer; urogenital infections
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Reece Smith 1986
Methods Single-site study
Randomization: random allocation with numbered folders
Patients blinded; providers blinded
Participants Geographic region: United Kingdom
Study setting: community
n = 80
Age range: 55-80 mean: 66.6
Race: Wh ite
Diagnostic criteria: Men with symptomatic BPH with symptoms scored by an investigator and symptoms
scored with a self-assessment questionnaire
24Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Reece Smith 1986 (Continued)
Interventions Control: matching placebo
Treatment: Permixon 160mg twice daily
Study duration: 12 weeks
Lost to follow up: 12.5%
Outcomes Mean urine flow
Bladder residual volume
Investigator assessment (symptom score 0-2)
Patient self-assessment data
Libido
Dropouts due to side effects: 2 patients from the treatment group (nausea and vomiting)
Notes Exclusions: Malignant disease or “whose symptoms not fulfilling entry criteria
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Roveda 1994
Methods Single-site study
Randomization: random allocation using tables of random numbers
Patients not blinded; providers not blinded
Participants Geographic region: Italy
Study setting: community
n = 30
Age range: 55-76 mean: 62.9
Race: Wh ite
Interventions Control: Serenoa repens 640mg rectal capsule once a day
Treatment: Serenoa repens 160mg oral capsules four times a day
Study duration: 4 weeks
Lost to follow up: none
Outcomes Dysuria
Bladder residual volume
Prostate size
Pollachiuria
Overall effect of treatment summary
Dropouts due to side effects: none
25Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Roveda 1994 (Continued)
Notes Exclusions: Age < 50 and > 80; on current medication; prior treatment for BPH
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
Sökeland 1997
Methods Multisite study
Randomization: computer-generated randomization code
Patients blinded; providers blinded
Participants Geographic region: Germany
Study setting: community
n = 543 (516 ther apy trial)
Age range: 50-88 mean: not reported
Race: Wh ite
Diagnostic criteria: BPH, stage I-II (Alken)
Interventions Control: finasteride 5mg plus placebo (2 capsules per day in a double dummy design)
Treatment: Combination phytother apy: PRO 160/120 (Sabal extract 160mg and Urtica extract 120mg)
2 capsules daily
Study duration: 12 weeks
Lost to follow-up: 5% (Data from 489 subjects were used in therapy effect analysis and data from 516
subjects used for side effects analysis)
Outcomes Symptom improvement-IPSS symptom score
Quality of life - American Urological Association Score
Peak urine flow
Bladder residual volume
Prostate size (volume)
Dropouts due to side effects: (no details given)
Notes Exclusions: < 50 years of age; BPH III or > (Alken); PSA > 10ng/l; cancer; taking other prostate medications;
infections; severe concomitant disease that warrants therapy
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes A - Adequate
26Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Tasca 1985
Methods Single-site study
Randomization: noted but method not stated
Patients blinded; providers blinded
Participants Geographic region: Italy
Study setting: community
n = 30
Age range: 49-81 mean: 61.5
Race: Wh ite
Diagnostic criteria: Stage I and Stage II prostatic adenomas
Interventions Control: matching placebo
Treatment: PA109 160mg twice daily.
Study duration: 8 weeks
Lost to follow up: 10%
Outcomes Dysuria (% reporting)
Peak urine flow
Mean urine flow
Total voided volume
Pollachiuria-daytime (% reporting)
Pollachiuria-nocturnal (% reporting)
Urgency (% reporting)
Dropouts due to side effects: 1 patient from the treatment group
Notes Exclusions: Details not given
Risk of bias
Item Authors judgement Description
Allocation concealment? Unclear B - Unclear
Convert lost to f/u “ns to %. Check Bauer for dropouts.
Characteristics of excluded studies [ordered by study ID]
Adriazola Semino 1992 Serenoa repens versus active control (Prazosin). No indication of randomization.
Comar 1986 Study duration unknown.
27Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
Di Silverio 1992 Tissue study investigating the antiestrogenic effect of Serenoa repens versus placebo.
Gerber 1998 Open-label study, no control group.
Grasso 1995 Average treatment duration < than 1 month.
Strauch 1994 Enzyme study (inhibition of 5 alpha-reductase) comparing Serenoa repens versus finasteride in a 1 week,
open, randomized, active-controlled study.
Sökeland 2000 Dual publication.
Weisser 1997 E nzyme study investigating the influence of Sabal serrulata (versus placebo) on epithelial and stromal
enzyme activities of BPH tissue.
28Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
D A T A A N D A N A L Y S E S
Comparison 1. Serenoa repens versus placebo
Outcome or subgroup title
No. of
studies
No. of
participants
Statistical method Effect size
1 Symptom Score (points) 1 205 Mean Difference (IV, Random, 95% CI) -1.41 [-2.52, -0.30]
2 IPSS total score, mean change
(0-no sx to 35-severe sx)
1 79 Mean Difference (IV, Random, 95% CI) -2.03 [-4.70, 0.30]
3 Patient self-rating for improved
symptoms (# men rating very
good to good)
6 659 Risk Ratio (M-H, Random, 95% CI) 1.76 [1.21, 2.56]
4 Physician-assessed improvement
of symptoms
3 524 Risk Ratio (M-H, Random, 95% CI) 1.72 [1.11, 2.66]
5 Nocturia (times/evening) 10 634 Mean Difference (IV, Random, 95% CI) -0.76 [-1.21, -0.31]
6 Qmax (mL/s) 9 723 Mean Difference (IV, Random, 95% CI) 1.86 [0.60, 3.12]
7 Mean urine flow (ml/s) 4 382 Mean Difference (IV, Random, 95% CI) 2.23 [1.18, 3.27]
8 Residual volume (mL) 6 450 Mean Difference (IV, Random, 95% CI) -22.95 [-42.33, -
3.56]
9 Prostate size (cc) 2 243 Mean Difference (IV, Random, 95% CI) -2.14 [-10.93, 6.65]
10 Study withdrawals 7 Risk Ratio (M-H, Random, 95% CI) Subtotals only
Comparison 2. Serenoa repens/Sabal urtica (PRO 160/120) versus finasteride
Outcome or subgroup title
No. of
studies
No. of
participants
Statistical method Effect size
1 IPSS total score, mean change 2 1440 Mean Difference (IV, Random, 95% CI) 0.37 [-0.45, 1.19]
2 Nocturia (times/evening) 1 1097 Mean Difference (IV, Random, 95% CI) -0.05 [-0.49, 0.39]
3 Qmax (mL/sec) 2 1440 Mean Difference (IV, Random, 95% CI) -0.74 [-1.66, 0.18]
4 Mean urine flow (mL/sec) 1 951 Mean Difference (IV, Random, 95% CI) -0.40 [-0.95, 0.15]
5 Residual volume (mL) 1 445 Mean Difference (IV, Random, 95% CI) 5.70 [-5.42, 16.82]
6 Prostate size (cc) 1 951 Mean Difference (IV, Random, 95% CI) 4.80 [1.42, 8.18]
Comparison 3. Serenoa repens versus Pygeum afric a num
Outcome or subgroup title
No. of
studies
No. of
participants
Statistical method Effect size
1 Nocturia (times/evening) 1 40 Mean Difference (IV, Random, 95% CI) -0.20 [-1.69, 1.29]
29Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Comparison 4. Serenoa repens/Sabal urtica (PRO 160/120) versus placebo
Outcome or subgroup title
No. of
studies
No. of
participants
Statistical method Effect size
1 IPSS total score, mean change 1 40 Mean Difference (IV, Random, 95% CI) -3.06 [-6.75, -0.25]
2 Qmax (mL/s) 1 40 Mean Difference (IV, Random, 95% CI) 1.60 [-1.67, 4.87]
Comparison 5. Serenoa repens versus gestonorone caproate
Outcome or subgroup title
No. of
studies
No. of
participants
Statistical method Effect size
1 Qmax (mL/s) 1 60 Mean Difference (IV, Random, 95% CI) 2.01 [1.36, 2.64]
Analysis 1.1. Comparison 1 Serenoa repens versus placebo, Outcome 1 Symptom Score (points).
Review: Serenoa repens for benign prostatic hyperplasia
Comparison: 1 Serenoa repens versus placebo
Outcome: 1 Symptom Score (points)
Study or su bgroup Serenoa repens Placebo Mean Difference Weight Mean Difference
N Mean(SD) N M e an(SD) IV,Random,95% CI IV,Random,95% CI
Braeckman 1997 106 3.69 (4.12) 99 5.1 (3.98) 100.0 % -1.41 [ -2.52, -0.30 ]
Total (95% CI) 106 99
100.0 % -1.41 [ -2.52, -0.30 ]
Heterogeneity: not applicable
Test for overall effect: Z = 2.49 (P = 0.013)
-10 -5 0 5 10
Favors S. re pens Favors placebo
30Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.2. Comparison 1 Serenoa repens versus placebo, Outcome 2 IPSS total score, mean change (0-
no sx to 35-severe sx).
Review: Serenoa repens for benign prostatic hyperplasia
Comparison: 1 Serenoa repens versus placebo
Outcome: 2 IPSS total score, mean ch ange (0-no sx to 35-severe sx)
Study or su bgroup Serenoa repens Placebo Mean Difference Weight Mean Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Gerber 2001 39 -4.4 (5.9) 40 -2.2 (5.4) 100.0 % -2.20 [ -4.70, 0.30 ]
Total (95% CI) 39 40
100.0 % -2.20 [ -4.70, 0.30 ]
Heterogeneity: not applicable
Test for overall effect: Z = 1.73 (P = 0.084)
-10 -5 0 5 10
Favors S. re pens Favors placebo
Analysis 1.3. Comparison 1 Serenoa repens versus placebo, Outcome 3 Patient self-rating for improved
symptoms (# men rating very good to good).
Review: Serenoa repens for benign prostatic hyperplasia
Comparison: 1 Serenoa repens versus placebo
Outcome: 3 Patient self-rating for improved symptoms (# men rating very good to good)
Study or su bgroup Serenoa repens Placebo Risk Ratio Weight Risk Ratio
n/N n/N M-H,Random,95% CI M-H,Random,95% CI
Braeckman 1997 84/125 62/113 23.6 % 1.22 [ 1.00, 1.51 ]
Carbin 1990 22/27 3/28
8.1 % 7.60 [ 2.57, 22.49 ]
Champault 1984 44/55 30/55
22.4 % 1.47 [ 1.11, 1.93 ]
Descotes 1995 58/82 63/94
23.7 % 1.06 [ 0.87, 1.29 ]
Mandressi 1983 18/20 8/20
16.3 % 2.25 [ 1.29, 3.92 ]
Metzker 1996 16/20 2/20
6.0 % 8.00 [ 2.11, 30.34 ]
Total (95% CI) 329 330
100.0 % 1.76 [ 1.21, 2.56 ]
Total events: 242 (Serenoa repens), 168 (Placebo)
Heterogeneity: Tau
2
= 0.14; Chi
2
= 30.12, df = 5 (P = 0.00001); I
2
=83%
Test for overall effect: Z = 2.98 (P = 0.0029)
0.1 0.2 0.5 1.0 2.0 5.0 10.0
Favors placebo Favors S. repens
31Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.4. Comparison 1 Serenoa repens versus placebo, Outcome 4 Physician-assessed improvement of
symptoms.
Review: Serenoa repens for benign prostatic hyperplasia
Comparison: 1 Serenoa repens versus placebo
Outcome: 4 Physician-assessed improvement of symptoms
Study or su bgroup Serenoa repens Placebo Risk Ratio Weight Risk Ratio
n/N n/N M-H,Random,95% CI M-H,Random,95% CI
Braeckman 1997 74/125 41/113 35.3 % 1.63 [ 1.23, 2.17 ]
Champault 1984 45/55 16/55
29.5 % 2.81 [ 1.83, 4.33 ]
Descotes 1995 46/82 44/94
35.2 % 1.20 [ 0.90, 1.60 ]
Total (95% CI) 262 262
100.0 % 1.72 [ 1.11, 2.66 ]
Total events: 165 (Serenoa repens), 101 (Placebo)
Heterogeneity: Tau
2
= 0.12; Chi
2
= 10.58, df = 2 (P = 0.01); I
2
=81%
Test for overall effect: Z = 2.44 (P = 0.015)
0.1 0.2 0.5 1.0 2.0 5.0 10.0
Favors placebo Favors S. repens
Analysis 1.5. Comparison 1 Serenoa repens versus placebo, Outcome 5 Nocturia (times/evening).
Review: Serenoa repens for benign prostatic hyperplasia
Comparison: 1 Serenoa repens versus placebo
Outcome: 5 Nocturia (times/evening)
Study or subgroup Serenoa repens Placebo Mean Difference Weight Mean Difference
N Mean(SD) N M e an(SD) IV,Random,95% CI IV,Random,95% CI
Boccafoschi 1983 11 1.8 (2.01) 11 2.1 (1.79) 5.4 % -0.30 [ -1.89, 1.29 ]
Carbin 1990 26 1.4 (1.02) 27 2 (1.04)
13.8 % -0.60 [ -1.15, -0.05 ]
Champault 1984 47 1.7 (1.16) 41 2.7 (1.09)
14.6 % -1.00 [ -1.47, -0.53 ]
Cukier 1985 43 2.2 (1.97) 47 2.9 (1.99)
11.0 % -0.70 [ -1.52, 0.12 ]
Descotes 1995 82 1.4 (1.81) 94 1.5 (1.94)
13.8 % -0.10 [ -0.65, 0.45 ]
Emili 1983 15 1.7 (1.9) 15 2.3 (1.9)
6.7 % -0.60 [ -1.96, 0.76 ]
Mandressi 1983 20 1.7 (2.41) 20 3.1 (2.46)
5.8 % -1.40 [ -2.91, 0.11 ]
Mattei 1990 19 1.5 (1.48) 19 4 (1.48)
9.8 % -2.50 [ -3.44, -1.56 ]
-4 -2 0 2 4
Favors S. re pens Favors placebo
(Continued . . . )
32Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(. . . Continued)
Study or subgroup Serenoa repens Placebo Mean Difference Weight Mean Difference
N Mean(SD) N M e an(SD) IV,Random,95% CI IV,Random,95% CI
Reece Smit h 1986 33 1.9 (1.2) 37 1.9 (1.4) 13.2 % 0.0 [ -0.61, 0.61 ]
Tasca 1985 14 0.9 (2.02) 13 1.9 (1.99)
5.8 % -1.00 [ -2.51, 0.51 ]
Total (95% CI) 310 324
100.0 % -0.76 [ -1.21, -0.31 ]
Heterogeneity: Tau
2
= 0.30; Chi
2
= 26.49, df = 9 (P = 0.002); I
2
=66%
Test for overall effect: Z = 3.34 (P = 0.00084)
-4 -2 0 2 4
Favors S. re pens Favors placebo
Analysis 1.6. Comparison 1 Serenoa repens versus placebo, Outcome 6 Qmax (mL/s).
Review: Serenoa repens for benign prostatic hyperplasia
Comparison: 1 Serenoa repens versus placebo
Outcome: 6 Qmax (mL/s)
Study or subgroup Serenoa repens Placebo Mean Difference Weight Mean Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Boccafoschi 1983 11 13.7 (7.03) 11 12.2 (7.03) 4.4 % 1.50 [ -4.38, 7.38 ]
Braeckman 1997 106 13.2 (5.76) 99 12.2 (5.6)
40.0 % 1.00 [ -0.56, 2.56 ]
Champault 1984 46 16.1 (19.19) 39 10.6 (17.67)
2.5 % 5.50 [ -2.34, 13.34 ]
Descotes 1995 82 15.3 (13.04) 94 13.5 (13.96)
9.1 % 1.80 [ -2.19, 5.79 ]
Emili 1983 15 13.7 (4.37) 15 9.4 (4.37)
14.0 % 4.30 [ 1.17, 7.43 ]
Gabric 1987 15 14.6 (5.57) 14 10.8 (5.39)
9.1 % 3.80 [ -0.19, 7.79 ]
Gerber 2001 39 11.7 (16.05) 40 14.3 (16.25)
3.0 % -2.60 [ -9.72, 4.52 ]
Reece Smit h 1986 33 8.5 (7.12) 37 8.6 (7.12)
12.5 % -0.10 [ -3.44, 3.24 ]
Tasca 1985 14 16.2 (7.03) 13 11.8 (7.03)
5.3 % 4.40 [ -0.91, 9.71 ]
Total (95% CI) 361 362
100.0 % 1.86 [ 0.60, 3.12 ]
Heterogeneity: Tau
2
= 0.40; Chi
2
= 8.91, df = 8 (P = 0.35); I
2
=10%
Test for overall effect: Z = 2.89 (P = 0.0038)
-10 -5 0 5 10
Favors placebo Favors S. repens
33Serenoa repens for benign prostatic hyperplasia (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons,