Improving bph symptoms and sexual dysfunctions with a saw palmetto preparation? results from a pilot trial
PHYTOTHERAPY RESEARCHPhytother. Res. (2012)Published online in Wiley Online Library(wileyonlinelibrary.com) DOI: 10.1002/ptr.4696
Improving BPH symptoms and sexualdysfunctions with a saw palmetto preparation?Results from a pilot trial
Andreas Suter,1,4* Reinhard Saller,2 Eugen Riedi3 and Michael Heinrich41Medical Department, A. Vogel Bioforce AG, Roggwil, Switzerland2Institute of Natural Medicine, Zurich University Hospital, Zurich, Switzerland3Urological practice, Chur, Switzerland4School of Pharmacy, University of London, University College London, London, United Kingdom
In elderly men, benign prostatic hyperplasia (BPH) is a major risk factor for sexual dysfunctions (SDys).
Additionally, the standard treatments for BPH symptoms, alpha blockers and 5-alpha-reductase inhibitors, causeSDys themselves. Preparations from saw palmetto berries are an efﬁcacious and well-tolerated symptomatictreatment for mild to moderate BPH and have traditionally been used to treat SDys. We conducted an openmulticentric clinical pilot trial to investigate whether the saw palmetto berry preparation ProstasanW inﬂuencedBPH symptoms and SDys. Eighty-two patients participated in the 8-week trial, taking one capsule of 320 mg sawpalmetto extract daily. At the end of the treatment, the International Prostate Symptom Score was reduced from14.4 Æ 4.7 to 6.9 Æ 5.2 (p < 0.0001); SDys measured with the brief Sexual Function Inventory improved from22.4 Æ 7.2 to 31.4 Æ 9.2 (p < 0.0001), and the Urolife BPH QoL-9 total improved from 162.7 Æ 47.9 to105.0 Æ 56.3 (p < 0.0001). Investigators’ and patients’ assessments conﬁrmed the good efﬁcacy, and treatmentwas very well tolerated and accepted by the patients. Correlation analyses conﬁrmed the relationship betweenimproved BPH symptoms and reduced SDys. This was the ﬁrst trial with saw palmetto to show improvementin BPH symptoms and SDys as well. Copyright 2012 John Wiley & Sons, Ltd.
Keywords: benign prostatic hyperplasia; sexual dysfunctions; clinical trial; saw palmetto; Serenoa repens.
and clinically signiﬁcant association between LUTS and
various types of sexual dysfunctions in ageing menworldwide. From epidemiological data, Rosen et al.
The prostate is a ﬁbromuscular glandular organ that lies
(2005) concluded that, compared with patients without
between the urinary bladder and the pelvic ﬂoor and
BPH-symptoms, patients with BPH-symptoms were at
surrounds the prostatic urethra (Dixon, 2005). Starting
a 3.7-fold higher risk of developing erectile dysfunction
around the age of 40, the prostatic tissue enclosing the
during the 2-year period following the onset of BPH-
urethra starts growing; this nonmalignant growth is
symptoms. Additionally, the severity of the LUTS
known as benign prostate hyperplasia (BPH) (Isaacs
symptoms was correlated with more frequent and more
and Coffey, 1989). It leads to constriction of the
severe occurrence of erectile and ejaculatory dysfunctions
urethra and gives rise to associated lower urinary tract
symptoms (LUTS), such as urgency, frequency, noc-
The main medical treatments for BPH symptoms
turia, incomplete bladder emptying and weak urine
include alpha blockers such as tamsulosin, doxazosin
stream. LUTS occur in about one third of all men in
and alfuzosin (Novara et al., 2006) that provide fast
their 60s and half of men older than 80 (McVary,
relief of the LUTS symptoms (Kaplan, 2004) or the
2006), even though the histological presence of BPH is
5-alpha-reductase-inhibitors ﬁnasteride and dutasteride,
observed in more than 90% of men in this age group
which lead to symptom relief after 6–9 months and are
most favourable in patients with large prostates (Dull
In addition to obstructive and irritative symptoms,
et al., 2002). Both treatment options show beneﬁcial
BPH also negatively inﬂuences sexual functions (Gur
effects on the BPH symptoms; however, they also each
et al., 2008). Epidemiological studies show that, along
have a signiﬁcant negative impact on sexual functions.
with the general ageing process, BPH-related LUTS
The main sexual dysfunction reported under alpha
are a key factor in development of erectile dysfunctions
blocker therapy is retrograde or abnormal ejaculation,
and ejaculatory disorders (Braun et al., 2003; Boyle
which occurs in 4–18% of patients taking tamsulosin, with
et al., 2004), representing a stronger risk factor than
rise to 30% during long-term use (Carbone and Hodges,
diabetes, hypertension, heart disease or hyperlipidemia
2003). Studies on 5-alpha-reductase inhibitors report
(Rosen et al., 2003). Overall, there appears to be a clear
sexual dysfunctions with a frequency of 2.1–38%,with erectile dysfunctions being most prominent, followedby decreased libido and ejaculatory disorders (Erdemir
* Correspondence to: Andreas Suter, A. Vogel Bioforce AG, MedicalDepartment, Roggwil, Switzerland.
et al., 2008). Sexual dysfunctions are the most
often reported adverse events under 5-alpha-reductase-
Copyright 2012 John Wiley & Sons, Ltd.
inhibition, with similar frequencies reported for ﬁnasteride
willingness to honestly answer questions on sexuality
and dutasteride (Naslund and Miner, 2007).
and written informed consent given by the patient.
Preparations made from the berries of saw palmetto
Exclusion criteria included lack of libido because of a
Serenoa repens (W. Bartram) Small (synonym Sabal
psychiatric disease or a depressive mood, occurrence of
serrulata (Michx.) Schult.f.) have a long standing use in
lack of libido in the judgement of the investigator within
the treatment of mild to moderate BPH symptoms.
the last 2 months, patients with severe vascular disorders
The plant, which is indigenous to Florida, was ﬁrst used
(microangiopathies), severe diabetes mellitus, patients
by white settlers in the United States not only for treat-
with hypertension who were on a stable antihypertensive
ment of LUTS but, interestingly, also as a treatment for
medication for less than 2 months, known neuropathies,
erectile dysfunctions, to improve testicular atrophy and
known poor compliance of the patient, participation in
sperm production, and as a genitourinary and sexual
a clinical trial within the last 2 months prior to the study
stimulant (Bennett and Hicklin, 1998). More than 30
start, alcohol and drug abuse and planned surgeries
controlled clinical trials have been conducted to investi-
within the observation period. The participants were
gate BPH treatment with saw palmetto preparations,
prohibited from regular application (>1 unit/2 weeks) of
which generally consist of 320 mg lipophilic berry
extract per day (Ulbricht et al., 2006). Compared with
inhibitors and intake of PDE-5-inhibitors less than 4 days
placebo, the studies demonstrate good efﬁcacy of long-
prior to the ﬁrst study visit. If not taken continuously for
term saw palmetto use to treat BPH symptoms; the
3 months as stable medication, the following concomitant
results are similar to ﬁnasteride (Carraro et al., 1996)
medications were also not allowed: 5-alpha-reductase in-
and tamsulosin (Debruyne et al., 2004), but saw
hibitors, alpha-antagonists, nonsteroidal anti-inﬂammatory
palmetto has a much better safety proﬁle than these
drugs (NSAIDs) (synthetics and phytochemicals), para-
substances particularly in regards to sexual dysfunctions
cetamol and synthetic antidepressive agents.
(Wilt et al., 2002). As modes of action, in vitro andin vivo inhibition of both isoforms of the 5-alpha-reductase (Habib et al., 2005; Abe et al., 2009) and
anti-inﬂammatory activities (Breu et al., 1992; Iglesias-Gato et al., 2011) have been reported, as well as
This was an open clinical trial with total study duration
inhibition of autonomous receptors in the lower urinary
of 9 weeks per patient, which consisted of a 1-week
untreated run-in phase and a subsequent treatment
It is very desirable to ﬁnd a treatment that not only
period of 8 weeks. At each visit, efﬁcacy parameters
improves the symptoms of BPH but also has no negative
were recorded as detailed in the succeeding text. The
or possibly even a beneﬁcial impact on sexual dysfunctions
run-in phase was carried out to observe if BPH
(Skolarus and Wei, 2009). With this as a goal, we carried
symptoms and sexual dysfunctions remained stable.
out a clinical pilot trial investigating whether a standar-
The test medication was a lipophilic saw palmetto berry
dized saw palmetto product inﬂuenced sexual dysfunctions
extract with a daily dosage of one capsule, containing
in patients with mild to moderate BPH.
320 mg extract (ProstasanW, batch nr. 025070, drugextractant ratio 9–12 : 1, extractant ethanol 96% V/V;manufactured by A. Vogel Bioforce AG, Roggwil,Switzerland. The berries are from A. Vogel Bioforce’sown organic certiﬁed cultivation in Florida, USA.) The
extract complied with the provisions of the EuropeanPharmacopoeia for saw palmetto fruit. One capsule of
this batch contained 275 mg fatty acids, which comprisedof 29.5% lauric acid, 39.2% oleic and linoleic acid,
The study was carried out between June 2009 and
13.5% myristic acid and 10% palmitic acid.
October 2010 in two urological and four general
At the second visit, each patient received one bottle
practices in Switzerland, in patients with at least moder-
with 90 capsules and compliance was checked by count-
ate BPH symptoms and sexual dysfunctions, such as
ing the remaining tablets at the ﬁnal study visit.
erectile dysfunctions or lack of drive. The trial was
Changes in BPH symptoms were evaluated using the
approved by the relevant cantonal ethical committees
IPSS, sexual dysfunctions with the bSFI and the Urolife
and was carried out in accordance with the provisions
BPH Quality of Life-9 (Urolife QoL-9) questionnaire.
of good clinical practice and the ethical obligations of
The bSFI is a validated instrument with two questions
the Declaration of Helsinki. The Swiss regulatory
about sexual drive, three on erections, two on ejacula-
authority Swissmedic notiﬁed the study that is registered
tion, four on problem assessment and one question on
in the international clinical trial registry ClinicalTrials.
the overall satisfaction. Each question is rated on a
gov, identiﬁer number NCT01021267.
corresponding scale from 0 (most severe problem) to 4
Inclusion criteria were as follows: male patients
(no problem) (O’Leary et al., 1995). The Urolife QoL-9
between 18–80 years of age with International Prostate
questionnaire is also a validated score with one question
Symptom Score (IPSS) >7, presence of BPH symptoms
each on desire, erection and satisfaction; each is rated on
for at least 2 months, patients suffering from sexual
a 100 mm visual analogue scale, ranging from 0 (most
dysfunction (erectile dysfunction and/or decrease of
severe problem) to 100 (no problem at all) (Lukacs
libido) for at least 2 months, sexual drive component
et al., 1997). Two questionnaires were used instead of
of the brief Sexual Function Inventory (bSFI) <5,
only one to achieve a better validity of changes in sexual
desire and possibility of sexual activity (masturbation,
dysfunctions. No validated German version was avail-
sexual partnership), no organic impairment preventing
able for either questionnaire, and thus they were ﬁrst
sexual practice (physical or vascular impairment, etc.),
translated to German by two independent translators.
Copyright 2012 John Wiley & Sons, Ltd.
SAW PALMETTO IN BPH AND SEXUAL DYSFUNCTIONS
From these two translated versions, one German version
Table 1. Demographic baseline characteristics of the per protocol
was compiled, which was then re-translated to English by
two other translators, to be compared with the originalversion. The German version was then corrected and
used by a German speaking doctor in his daily practice.
Based on his experiences, further corrections were
made, and ﬁnal versions of the German scores were
completed. At end of the treatment, global assessment
of efﬁcacy by the patient and the investigator was given
on a 4-point scale (very good, good, moderate or bad).
Safety parameters included the occurrence of adverse
events and the global assessment of safety by the patient
and the investigator at the end of the treatment as very
good, good, moderate or poor. Additionally, questions
were asked about the patients’ daily routines. The
patients were asked if they would take the medication
again, how important it was for them to use herbaltreatment, and whether they would prefer a herbal remedy
during the treatment period was assessed as good when
over a synthetic compound. Investigators were asked
80–120% of the test medication was taken; 78.6% of the
if they would use the test medication again and were
patients fulﬁlled this criterion, only 7.1% of the patients
asked to provide reasons if they answered afﬁrmatively.
took less than 80% of the medication.
As this was an open clinical pilot trial, descriptive statistics
There were no signiﬁcant differences between the
were used using Excel (Microsoft Corporation, Redmond,
intention to treat population and the per protocol popu-
Washington, USA) and SAS Version 9.2 (SAS Institute,
lation in all parameters; therefore, the results of per
Enhanced Logging Facilities, Cary, NC, USA). For the
protocol population will be shown. There were also no
outcome measures, IPSS, bSFI and Urolife QoL, within
statistical changes in the efﬁcacy parameters during the
group comparisons of changes from visit 1 to visit 2, from
time period without treatment (between visit 1 and visit
visit 1 to visit 3, and from visit 2 to visit 3, were performed
2), showing that the symptoms were stable and did not
using the Wilcoxon test for paired differences. Correla-
alter within a short time frame; thus, only results from
tions between changes in IPSS and bSFI, IPSS and Urolife
visit 2 (the start of treatment) and visit 3 (the end of
QoL-9, and bSFI and Urolife QoL-9 were analysed by
calculating Pearson’s coefﬁcient of correlation.
The IPSS was reduced by 51%, from 14.4 Æ 4.7 to6.9 Æ 5.2, after 8 weeks of treatment (p < 0.0001) (Fig. 1).
A score from 0 to 7 is deﬁned as mild, from 8 to 19 as
moderate and from 20 to 35 as severe BPH symptoms.
A total of 82 patients were recruited, forming the
At the beginning of the treatment, 18.8% of all patients
intention-to-treat population. Thirteen patients had at
had severe and 78.3% had moderate symptoms; by the
least one major protocol deviation and were excluded
ﬁnal visit, this shifted to 63.8% patients with mild, 31.9%
from the per protocol population, which was used for
with moderate, and only 4.3% with severe symptoms.
ﬁnal analysis. Deviations included one patient with IPSS
Looking at the single items contributing to the score,
<7 at inclusion, one with sexual drive component of
they were all signiﬁcantly improved to the same extent,
bSFI >5 at inclusion, four patients with disallowedconcomitant medication and seven patients who didnot return to the participating practice after the ﬁrstvisit. Reasons for discontinuation of treatment includedone instance of the death of a patient’s wife, two adverseevents (nausea that was seen as related to the studymedication and an unrelated transient ischemic attack)and in four cases the patients did not show up at all tothe follow-up visits. The patients were 57.3 Æ 11.1 yearsold and baseline characteristics as well as the agedistribution in the population were without pathological
ﬁndings. Details are shown in Table 1.
One centre recruited the majority of the patients
(n = 54), and the other ﬁve centres the remaining 15patients. The baseline characteristics of the patients
Figure 1. Change of International Prostate Symptom Score (IPSS)
from this one centre did not differ signiﬁcantly
between the start and the end of treatment (per protocol population,
from those that form the other centres. Compliance
Copyright 2012 John Wiley & Sons, Ltd.
and none was superior to another. The average nycturia
the single centre experienced at least some improve-
score changed from 1.7 Æ 1.1 to 1.0 Æ 0.8, the obstructive
subscore from 8.1 Æ to 3.9 to 3.7 Æ 3.7, and the irritativesubscore from 6.3 Æ 2.6 to 3.2 Æ 2.3.
The Urolife QoL-9 total score saw an improvement
from 162.7 Æ 47.9 to 105.0 Æ 56.3 (p < 0.0001) (Fig. 3).
Contrary to the bSFI, the improvements in QoL-9 were
The total bSFI score improved from 22.4 Æ 7.2 to
signiﬁcant at all centres. All three single questions were
31.4 Æ 9.2 (p < 0.0001) (Fig. 2). The single item scores
also statistically signiﬁcantly improved, as detailed in
for sexual drive, erectile function, ejaculatory function,
problem assessment and sexual satisfaction were eachalso signiﬁcantly improved (p < 0.0001) (Table 2). Thebiggest relative improvements in single questions wereseen in the problem assessment domain, where ‘getting
Assessments by investigators and patients
and keeping an erection’ improved by 64%, and ‘havingproblems with lack of drive’ and ‘ejaculation’ each
The majority of the patients rated the efﬁcacy as
improved by 54%. ‘Feeling sexual drive within the last
very good (22%) or good (54%) and only 15% saw a
30 days’ improved by 47%, and ‘having an erection ﬁrm
small effect. The investigators assessed efﬁcacy more
enough to have sexual intercourse’ was scored as 42%
favourably, reporting 38% of the cases as being very
better, which, in absolute values, is a change from below
good, 44% good and only 7% patients with unchanged
‘fairly often’ to ‘usually’.
condition. When asked on what parameters the study
There was a centre effect, as mean values of the
medication had the best effect, 8% of the patients indi-
centre with the most patients exhibited a signiﬁcant
cated erectile function, 26% libido and 66% erectile
improvement, whereas the other 15 patients pooled
together from the other centres only exhibited a trend
Of the total 82 patients, 62 patients would take the
(p = 0.12). Of these 15 patients, eight saw an improve-
capsules again (data are missing from six patients); and
ment, four no change and three a worsening of their
in 91% of all cases, the investigators would use the
state, whereas the vast majority of the patients from
Figure 2. Improvement of brief Sexual Function Inventory (bSFI) at
Figure 3. Improvement of the Urolife benign prostate hyperplasia
the start and the end of therapy (per protocol population, n = 69;
(BPH) quality of life-9 (QoL-9) total score between the start and
the end of therapy (per protocol population, n = 69; p < 0.0001).
Table 2. Single item scores of the bSFI and Urolife BPH QoL
BPH, benign prostate hyperplasia; bSFI, brief sexual function inventory.
Copyright 2012 John Wiley & Sons, Ltd.
SAW PALMETTO IN BPH AND SEXUAL DYSFUNCTIONS
Similarly, investigators regarded tolerability in 90.8%of the cases as very good and 5.3% as good.
In this pilot trial, we wanted to assess if a saw palmettoberry preparation had an inﬂuence on both, prostatesymptoms and sexual dysfunctions. We ﬁrst examinedthe improvement in BPH symptoms as measured withthe IPSS, which is the standard instrument to measureseverity of BPH symptoms (Simpson, 1997). Weobserved a greater than 50% reduction, indicating agood treatment response that was in the efﬁcacy rangeobserved for saw palmetto treatments in other trials on
Figure 4. Single item scores of the brief Sexual Function Inventory
BPH and larger than the effect of placebo. A survey of
(bSFI) at the start and the end of treatment, normalized to a scale
seven clinical trials for a lipophilic saw palmetto prepar-
of 0–10 (0 = worst state, 10 = best) (n = 69).
ation describes the observation of a total of 2555patients that were observed with average treatment
For 61% of the patients, it was very important that
duration of 300 days and a mean initial IPSS value of
the medication was of herbal origin and 97% of them
14.72. At the end of the treatment, IPSS was reduced
would, given the same efﬁcacy and safety, prefer herbal
to a synthetic drug. Investigators stated that the most
clinical trials, 320 mg lipophilic saw palmetto berry
important reason to apply this saw palmetto preparation
extract was used daily and, after 6 months, the IPSS
was the good safety observed in 95% of all cases,
followed by the efﬁcacy observed in 93% of patients.
(Bauer et al., 1999) with respective reductions underplacebo of 13.9% and 13.6%.
Secondly and more importantly, we assessed whether
the treatment had a positive inﬂuence on concomitantsexual dysfunctions. Four previous clinical trials of saw
We carried out correlation analyses to assess if changes
palmetto treatment for BPH also evaluated changes in
in IPSS, bSFI and Urolife QoL-9 were associated. There
sexual dysfunctions as a secondary parameter, with
was a negative correlation between changes in the IPSS
mixed results. However, the patients in these trials had
score and the bSFI (Pearson’s rho = À0.366; p = 0.002)
mainly BPH symptoms, not necessarily sexual dysfunc-
and a positive correlation between changes in the IPSS
tions (SDys) as well. Using the International Index of
Erectile Function (IIEF), Willetts et al. (2003) observed
p = 0.002), indicating that less urinary problems were
a trend of improvement, with an increase from 51.5 to
associated with better assessment of sexual function.
55.1 after 12 weeks of saw palmetto treatment compared
Furthermore, there was a high negative correlation
with a small decrease from 49.4 to 48.7 with placebo
between the bSFI and Urolife QoL-9, showing that both
(Willetts et al., 2003), and Sinescu et al. (2011) reported
questionnaires were valid for evaluating sexual dysfunc-
a signiﬁcant improvement of the IIEF from 44.4 to 50.8
tions and consequently assessed changes to the same
after 24 months of treatment (Sinescu et al., 2011). In the
degree (Pearson’s rho = À0.607; p < 0.0001).
trial conducted by Gerber et al. (2001), the patients had
Subgroup analyses conﬁrmed these ﬁndings, showing
to ﬁll out a non-speciﬁed ‘sexual function question-
that patients with a higher IPSS at inclusion (IPSS 20–35)
naire’; results indicated no change with either placebo
exhibited better improvements in their bSFI (p = 0.029)
or saw palmetto treatment (Gerber et al., 2001). In an
and in their Urolife QoL-9 (p = 0.032) values than did
open trial, Bauer et al. (1999) asked if the treatment
patients with lower IPSS (8–19). Comparing younger
had an inﬂuence on patients ‘sexual activity’; responses
patients (21–50 years) to older patients (51–80 years) did
indicated that it mostly remained unchanged with two
not show a signiﬁcant difference regarding changes of
patients reporting an increase (Bauer et al., 1999).
IPSS, bSFI and Urolife QoL-9, or did concomitant
Taken together, data from these trials are insufﬁcient
medication have an inﬂuence on these parameters.
to convincingly show that saw palmetto had a positiveinﬂuence on BPH-related SDys.
To determine this, it was important to conﬁrm at
inclusion that the patients in our trial deﬁnitely sufferedfrom SDys; all the patients in our trial had obvious
Five patients reported six adverse events, including
SDys, based on comparisons of the initial values from
nausea, eructation and acid regurgitation, all of which
the bSFI and the Urolife QoL-9 in our trial with
were mild in nature and seen as related to the study
epidemiological. O’Leary et al. (2003) observed an
medication, and two incidents of a transient ischemic
average total bSFI score of 27.7 in a population of
attack in the same patient and a mild pruritus, which
1883, >50-year-old men in the United States (O’Leary
were not related to the study medication. From the total
et al., 2003), whereas in our study the same age group
82 patients, data from six patients were missing on the
had a lower initial value of 20.1. In another study, the
safety assessment; from the remaining patients, 89.5%
patients with ages of 36.9 Æ 12.0 years displayed an
rated tolerability as very good and 6.6% as good.
average total bSFI of 33.5 Æ 2.2 (Collins et al., 2002)
Copyright 2012 John Wiley & Sons, Ltd.
compared with the total initial bSFI of 26.3 Æ 6.6
from 24.9 to 27.14, and subdomains for erection and
observed in our 21–50-year-old patients. A large study
satisfaction did not change signiﬁcantly (Kim et al.,
of 2829 LUTS patients with an average age of 65.9 years
2010). In a large open trial with 839 enrolled patients
evaluated Urolife QoL-9 scores and found an initial total
suffering from LUTS caused by BPH, 10 mg alfuzosin
value of 8.8 Æ 0.1 (scale 0–30) (Lukacs et al., 2000),
was taken daily for 2 years. The initial IPSS of 15.5 was
whereas in our study an initial score of 170.3 Æ 47.0 (scale
reduced by 7 points, whereas the total initial bSFI value
0–300) was recorded for the 51–80 year patient group.
of 21.5 improved only slightly during the treatment
period, leading to the assessment by the authors that
success regarding improvement of SDys in this
the treatment at least ‘did not have any deleterious
study population. Both scores for SDys changed sig-
effect on sexual dysfunctions’ (Elhilali et al., 2006). A
niﬁcantly, the bSFI by 40.2% and the Urolife QoL-9
further open clinical trial with 10 mg alfuzosin showed,
by 35.5%. Looking at the subscores, ‘sexual drive’
besides a signiﬁcant improvement of the IPSS after
and ‘erectile function’, almost the same degree of
1 year of treatment, a signiﬁcant improvement of the
improvement was seen for both scores, with 35.3%
bother score of the Danish Prostatic Symptom Score
and 37% in the bSFI and 33.9% and 36.7% in the
questionnaire for sexual dysfunction (van Moorselaar
Urolife QoL-9, respectively. The major difference
et al., 2005) whereas a study comparing tamsulosin/
between these two scores is caused by the more
solifenacin either alone or in combination in patients
weighted problem assessment domain of the bSFI. It
with LUTS also saw improved IPSS, but observed no
has been shown that both questionnaires are equally
signiﬁcant changes in the IIEF (Seo et al., 2011). The
sensitive in assessing sexual dysfunctions, which was
IPSS reductions of about 6 to 7 points found in these
also substantiated by the correlation analysis. Inter-
studies with alpha-blockers were similar to those
estingly, we observed that it was almost impossible
observed in placebo-controlled trials (van Kerrebroeck
for patients to ﬁll out the bSFI without doctor’s help,
et al., 2000; Nordling, 2005), but were not superior to
whereas the Urolife QoL-9 was quite easy for
the improvements in IPSS seen in our study. This is in
patients to ﬁll out alone. In summary, we have shown
line with the trials of Debruyne et al. (2004) and Zlotta
for the ﬁrst time that a saw palmetto intervention in
et al. (2005), which showed similar IPSS reductions
patients with BPH and SDys had a beneﬁcial inﬂu-
following treatment with a saw palmetto preparation
ence on both BPH symptoms and on SDys.
and tamsulosin (Debruyne et al., 2004; Zlotta et al.,
Our efﬁcacy results are of further importance when
2005). The main difference between our results
considering the other available options for simultaneous
and those of the cited studies on alpha blockers is
treatment of LUTS and SDys. It is currently debated
that patients under saw palmetto treatment may
whether alpha blockers or PDE inhibitors may be
experience an improvement in their SDys, whereas
beneﬁcial for treating symptoms of both disorders.
this effect cannot be expected from alpha-blocking
Experimental models have shown that a1-adrenergic
agents may improve erectile dysfunctions by inﬂuencing
It also remains doubtful whether PDE-5 inhibitors
the balance between contraction and relaxation of the
are a good treatment for both LUTS and SDys
corpus cavernosum smooth muscle, of which, relaxation
together. Clinical data for PDE-5 inhibitors has shown
leads to an erection (Hellstrom and Kendirci, 2006). On
a good improvement on erectile dysfunctions, but a
the other hand, experimental data also indicates that
small effect on BPH symptoms. McVary et al. (2007)
NO synthase and NO could play important roles in
saw a signiﬁcant improvement in the IPSS following
tissue from the urethra, corpus cavernosum, prostate,
12 weeks of treatment with 100 mg sildenaﬁl, with an
vas deferens and bladder neck (Ehren et al., 1994).
IPSS change of À6.3 versus À1.9 with placebo, as well
Reduced concentrations of NOS/NO in the prostate
as a signiﬁcant improvement of the IIEF erectile func-
and bladder increase smooth muscle tone and may
tion domain (McVary et al., 2007). In the trial of
improve prostatic cell proliferation (Mirone et al., 2011),
Roehrborn et al. (2008), the application of different
indicating that PDE-5-inhibitors, which increase the NO
dosages of tadalaﬁl demonstrated that an increased
concentration, may have positive effects on LUTS.
dosage correlated with increased IPSS improvement,
Initial clinical trials have been carried out with alpha
from +3.9 at 2.5 mg to +5.2 at 20 mg, with a dose of
blockers or PDE-5-inhibitors (Kaminetsky, 2006).
5 mg showing the best beneﬁt/risk ratio. After the
Clinical data with alpha blockers, however, has shown
treatment period of 12 weeks, improvement was also seen
a good treatment effect on BPH symptoms but only a
in the IIEF erectile function subdomain (Roehrborn et al.,
small positive inﬂuence on SDys. In a clinical trial where
2008). Vardenaﬁl (20 mg) taken twice daily for 8 weeks
patients with moderate to severe BPH symptoms took
improved the IPSS by 5.9 points, compared with
10 mg alfuzosin for 6 months, the IPSS decreased from
placebo with 3.6 points; signiﬁcant changes were also
18.93 to 9.59 points, and the Male Sexual Health
seen in the IIEF erectile dysfunction (ED), and the
Questionnaire (MSHQ) ejaculation subscore improved
Urolife QoL-9 improved by 27% compared with 7%
from 23.09 to 21.54; this was statistically signiﬁcant, but
under placebo (Stief et al., 2008). Although IPSS was
the clinical relevance remains doubtful with an improve-
improved in these trials, interestingly, changes in ﬂow
ment only of about 7%. The overall number of patients
rates were never reported. In total, clinical data for
with moderate to severe erectile dysfunctions decreased
PDE-5-inhibitors show a smaller improvement in LUTS
from 35% to 22% (Leungwattanakij et al., 2010). These
than that observed in our trial following saw palmetto
results were not conﬁrmed in another trial where
treatment, and our trial demonstrates better effects on
patients with BPH symptoms took 10 mg alfuzosin daily
ED. Interestingly, when assessing a broader spectrum
for 12 weeks. Results of this trial showed that IPSS
of SDys, as with the Urolife QoL-9 and not ED alone,
decreased signiﬁcantly from 17.92 to 12.07, but the
the results of our trials are at least comparable with
MSHQ ejaculatory subdomain worsened signiﬁcantly
Copyright 2012 John Wiley & Sons, Ltd.
SAW PALMETTO IN BPH AND SEXUAL DYSFUNCTIONS
One solution that has been discussed in the litera-
Association guideline for treatment of BPH symp-
ture for concomitant reduction of BPH symptoms
toms also advocates using a combination of alpha-
and ED is the combination of an alpha blocker with
blockers and 5-alpha-reductase inhibitors (McVary
a PDE-5-inhibitor. Data from three such clinical
et al., 2011), a protocol designed to achieve better
studies are presently available. One small trial inves-
efﬁcacy, but without fully considering the additive
tigated alfuzosin, sildenaﬁl or the combination on
side effect rates of these two drugs as shown in
LUTS and EDs. After 12 weeks of treatment, initial
combination trials (Mirone et al., 2011).
values of IPSS, which were between 16.9 and 17.8,
Our present trial has some limitations; it was
were reduced signiﬁcantly in all treatment groups
designed as an uncontrolled pilot trial to elucidate if
with the largest reduction (24.1%) in the combination
any effect of a saw palmetto treatment would be
group. The IIEF erectile function score was signiﬁ-
observed. Consequently, the size of the placebo effect
cantly improved by the combination and sildenaﬁl,
can only be estimated. Furthermore, there was a
but not in the alfuzosin group (Kaplan et al., 2007).
strong centre effect, as one centre recruited substan-
Another combination trial with sildenaﬁl or tamsulosin
tially more patients than the others, and these other
showed comparable results, with the largest IPSS
centres did have fewer responders than the main
improvement observed with the combination (À40.1%),
centre. Subgroup analysis did not unveil any signiﬁcant
differences in patient characteristics between these
(À28.2%); the IIEF improved signiﬁcantly with
centres; however, these analyses were limited by the
sildenaﬁl and the combination but not with tamsulosin
low number of patients in the other ﬁve centres to-
(Tuncel et al., 2010). In further trial, 100 mg udenaﬁl
gether. A further placebo-controlled clinical trial with
was added to a stable alpha-blocking therapy in
a more balanced patient distribution in the centres
patients with BPH and ED for 8 weeks. The IPSS was
would be the next step to conﬁrm our ﬁndings.
reduced by 2.8 points, and the IIEF-5 improved bymore than 5 points, indicating that a combination oradd-on therapy of udenaﬁl may be beneﬁcial (Chunget al., 2009). Comparing these data with the results
of our trial, with an IPSS-reduction of 51% andimproved SDys by 40.1% as measured with the bSFI,
This is the ﬁrst trial ever to indicate that saw palmetto
the saw palmetto treatment yielded efﬁcacy results similar
treatment had not only a good efﬁcacy in reducing
to the combination of an alpha blocker and a PDE-5-
BPH symptoms but also a concomitant effect on SDys.
We demonstrated that a saw palmetto treatment was
Phosphodiesterase-5-inhibitors are expensive treat-
as effective in reducing BPH symptoms as an alpha
ments; therefore, a cost-beneﬁt assessment is warranted
blocker or a 5-alpha-reductase inhibitor, but that, in
for further extensive PDE-prescription. In the USA, a
contrast to those treatments, saw palmetto was asso-
single dose of 25 mg sildenaﬁl costs about eight times
ciated with an improvement of SDys as measured with
as much as an alpha-blocking agent like 1 mg doxazosin
the bSFI and the Urolife QoL-9 score. Compared with
(Stafford and Radley, 2002) or 30 times more than
PDE-5-inhibitors, the saw palmetto treatment did not
0.4 mg tamsulosin in Germany (Schneider and Richling,
have the same efﬁcacy in improving ED, but did have
2008), whereas the cost for a daily dosage of Prostasan
the same treatment effect for overall change of SDys,
is in the lower range of an alpha blocker. These differ-
with a better reduction in IPSS. The cost of daily treat-
ences in price, in addition to the only moderate efﬁ-
ment with saw palmetto is much cheaper than with many
cacy, make it doubtful if PDE-5-inhibitors should be
other medications, for example, in Switzerland, the cost
advocated as standard treatments for BPH symptoms.
would be 0.75 Swiss francs for saw palmetto versus
When looking at safety and tolerability, our data
22.30 Swiss francs for 100 mg sildenaﬁl (Stebler, 2009).
were in accordance with the previous ﬁndings and
In our trial, we observed the same efﬁcacy results as have
indicated that saw palmetto was very well tolerated,
been seen for combination therapy with alpha blocker
in contrast to the standard treatments for LUTS. A
and PDE-5-inhibitor, but with much better tolerability
major problem for patients taking an alpha blocker
of the saw palmetto treatment. Based on these promising
and/or a 5-alpha-reductase inhibitor is the occurrence
results, which are also reﬂected by the good acceptance
of sexual adverse effects that cause many men to
of patients and investigators, we consider saw palmetto
discontinue treatment (Roehrborn, 2004). Study data
to be the ﬁrst line treatment for patients with mild and
show that 2–16% of all patients under alpha reduc-
moderate BPH symptoms, as it may also improve con-
tase inhibitor therapy experience EDs, decreased
comitant SDys, while having a very good tolerability
libido and decreased volume of ejaculate (twice the
frequency seen with placebo), whereas alpha-blockingagents, particularly tamsulosin, have been frequentlylinked with ejaculatory disorders in around 10% of all
patients (Gacci et al., 2011). In daily practice, theincidence rates may even be higher than in clinical
We would like to thank the following investigators for participating in
trials. In a large epidemiological study carried out with
this trial: Daniel Borer, Moerigen; Eva Ditrych, Bern; Simon Feldhaus,Brunnen; Manfred Hoesle, Zurich; and Felix Trinkler, Zollikon.
urologists and internal medicine physicians in theUnited States, doctors estimated that 18–27% of thepatients taking an alpha-blocking medication suffer
from ejaculatory disorders and 16–22% of men takinga 5-alpha-reductase-inhibitor suffer from EDs (Seftel
The study was ﬁnanced by A.Vogel Bioforce AG, where A. Suter is
et al., 2007). Nevertheless, the latest American Urology
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