eau-ebu update series 5 (2007) 197–205
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
Medical Management of BPH: Role of Plant Extracts
Stephan Madersbacher *, Anton Ponholzer, Ingrid Berger, Martin Marszalek
Department of Urology and Andrology, Donauspital, Vienna, Austria
Article info
Abstract
Keywords:
Lower urinary tract
symptoms
LUTS
Medical therapy
Plant extracts
Meta-analysis
Guidelines
Objectives: Since decades plant extracts belong to the most popular
drugs for lower urinary tract symptoms (LUTS) due to benign prostatic
hyperplasia (BPH)/benign prostatic enlargement (BPE). Herein we review
biological mechanisms, the placebo effect, results of clinical trials, the
role of meta-analyses and guideline recommendations.
Methods: Review of the literature with particular reference to long-term
(study period 6 months) controlled trials and of BPH-guideline recommendations.
Results: Only few of the large number of available studies meet the
criteria defined by the WHO-BPH consensus conference. The few, placebo-controlled, long-term (study period 6 months) studies suggest a
positive effect of some extracts (saw palmetto, ß-sitosterol, urtica, saw
palmetto/urtica combination) on LUTS, an effect on uroflow, post-void
residual volume, prostate volume and PSA was not consistently demonstrable. Randomised trials against active comparators (a1-blocker,
5a-reductase inhibitors) are difficult to interpret. Due to the lack of
prospective studies, several meta-analyses have been published that
can not replace prospective studies according to WHO-BPH recommendations. None of the BPH-guidelines currently recommends plant
extracts, yet universally conclude that this is an interesting approach.
Conclusions: Further prospective studies according to WHO-standards
are required to reliably determine the role of plant extracts in contemporary LUTS-management.
# 2007 European Association of Urology and European Board of Urology.
Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Urology and Andrology, Donauspital,
Langobardenstrasse 122, A-1220 Vienna, Austria. Tel. +43 1 28802 3700; Fax: +43 1 28802 3780.
E-mail address: [email protected] (S. Madersbacher).
1.
Introduction
Since decades plant extracts belong to the most
popular drugs in the medical management of lower
urinary tract symptoms (LUTS) due to benign
prostatic hyperplasia/benign prostatic enlargement
(BPE). Market shares of plant extracts reach up to
30–50% in countries with a long tradition of
phytotherapy such as Austria, Germany and France
[1–3]. Worldwide more than 100 different preparations generated from 30 different plants are in
clinical use. The development of a1-blockers and
1871-2592/$ – see front matter # 2007 European Association of Urology and European Board of Urology. doi:10.1016/j.eeus.2007.04.004
Published by Elsevier B.V. All rights reserved.
198
eau-ebu update series 5 (2007) 197–205
5a-reductase-inhibitors (5ARIs) forced producers of
plant extracts to present studies meeting the
standards to the WHO-consensus conference [4].
To date only five studies with plant extracts meeting
these criteria have been published, only three were
placebo-controlled.
Herein we review biological mechanisms, placebo
effect, results of clinical trials, the role of metaanalyses and guidelines recommendations.
2.
Methods
In depth review of the literature with particular reference to
long-term (study period 6 months) controlled trials, metaanalyses and of guideline recommendations.
3.
Standards for medical BPH-trials
The WHO-BPH conference has set standards regarding clinical trials to assess the role of medical
therapy [4]: prospective, randomised against placebo or standard therapy (a1-blockers, 5a-reductase
inhibitors) and with a study period of 12 months. All
major BPH-guidelines respect these recommendations. In the clinical part of this manuscript we
therefore concentrate on studies meeting these
criteria with the exception that we also considered
studies with a follow-up period of 6 months. All
other designs (shorter study duration, small sample
size, lack of randomisation etc.) allow no reliable
conclusions and were not reviewed herein.
Key message: The WHO-BPH conference has
defined standards for medical BPH-trials, studies
not meeting these criteria allow no valuable
conclusions.
4.
Placebo effect
One has to be aware that there is a significant
and long-lasting placebo effect of any therapy for
LUTS [5]. This placebo effect is demonstrable for
subjective and objective parameters and underlines the need for placebo-controlled trials to
clearly prove clinical efficacy [5]. In a recent
review in European Urology we have analysed the
placebo effect of all long-term controlled placebo
controlled medical trials for LUTS in elderly men
[6]. The mean improvement of symptom score after
12 months under placebo was 21.4% (range: 4.8–
34%), after 24 months 10.9% (range: 1.5%–24.5%)
and after 4.5 years 15.9% (7.9–23.8%) [6]. Qmax
improved for a mean of 12.4% after 12 months
(0–27%), 5.3% after 24 months (2.6%–14.8%) and
7.5% (1.8%–13.2%) after 4.5 years [6]. The mean
decrease of the symptom score in the placebocontrolled trials with plant extracts reviewed
herein was 4.7 points (Table 1). The placebo
response showed remarkable differences in the
various trials most likely caused by different
inclusion/exclusion criteria, study designs, dosing
etc (Table 1) [6]. The mechanisms leading to
this prolonged placebo response remain poorly
understood, yet condition-specific factors and selfmanagement, patient-specific factors and trialspecific factors are likely to be involved [6,7]. This
prominent placebo effect underlines the need
of – ideally placebo – controlled trials to assess
clinical efficacy. Although WHO-BPH guidelines
suggest randomisation against placebo or standard
therapy, others have proposed that at least one
placebo controlled trial should be available for each
extract.
Key message: The considerable placebo effect
underlines the need of placebo controlled trials to
document clinical efficacy.
5.
Origin, components and suggested
mechanisms of plant exrtacts
A large number of different plants have been used
for the preparation of plant extracts (Table 2). Some
of these stem from roots, seeds, bark or fruits of a
single plant only (monopreparations); others are
combination preparations of two or more plants
[8,9]. The origin of plant extracts currently used is
listed in Table 2. The number of components
identified in plant extracts is constantly increasing;
the most important ones are phytosterols,
ß-sitosterols, fatty acids and lectins (Table 2). In
parallel, numerous biological mechanisms of plant
extracts such as 5a-reductase inhibition, aromatase
activity, androgen blockade, a1-blockade, inhibition
of prostaglandin synthesis, anti-inflammatory
activity etc. have been proposed based on in vitro
data (Table 2). The majority of experimental studies
used supraphysiologic doses thus hindering an
extrapolation to the in vivo situation; moreover data
on pharmacodynamics and bioavailability are scant
[8]. Although these mechanisms have been documented in vitro, there is no convincing evidence that
any of these mechanisms acts also in vivo. For
instance, a reduction of prostate volume or serum
PSA has not been shown in any clinical trial; these
observations suggest that a 5a-reduction or antiandrogenic activity is not demonstrable in vivo.
The marginal effect on bladder outlet obstruction
Table 1 – Changes of IPSS and Qmax of all prospective, randomized trials with plant extracts and a study period of I6 months
Ref.
Study-arm
Dosing
Study length
Patients
IPSS mean (SD)
Baseline
10
13
16
17
19
20
21
24
25
320 mg/die
5 mg/die
320 mg/die
0.4 mg/die
160 mg/bid
20 mg/tid
130 mg/die
459 mg/die
500 mg/bid
160/120/die
5 mg/die
160/120/die
0.4 mg/die
6 mo
6 mo
12 mo
12 mo
12 mo
12 mo
6 mo
6 mo
6.mo
6 mo
12 mo
12 mo
12 mo
12 mo
6 mo
6 mo
12 mo
12 mo
12 mo
12 mo
553
545
350
354
112
113
100
100
88
89
114
112
233
243
30
30
245
244
71
69
15.7 (5.9)
9.9 (5.4)
15.7 (5.7)
9.5 (5.5)
15.3 (4.3)
10.8 (5.5)
15.4 (5.2)
11.0 (6.0)
15.7 (5.7)
15.0
15.0 (5.3)
14.3
14.9 (4.7)
7.5 (4.4)
15.1 (4.2)
12.8 (4.5)
16.0 (4.6)
7.8 (4.9)
14.9 (5.2)
12.1 (5.6)
13.0 (0.5#)
18.7 (0.3#)
#
18.5 (0.3 )
13.8 (0.5#)
17.6 (3.7)
10.9 (4.5)
17.7 (3.8)
12.2 (5.1)
no validated questionnaire
no validated questionnaire
11.3 (6.5)
6.5 (5.8)
11.8 (6.6)
6.2 (5.2)
20.4 (4)
11
21.0 (4)
10
Change
6.2
6.6
4.4
4.4
0.7
0.7
7.4*
2.3
8.2*
2.8
5.7*
4.7
6.7*
5.5
69%*
29%
4.8
5.6
9.4
11
Baseline
10.6 (2.8)
10.8 (3.1)
10.9 (3.9)
11.2 (4.0)
11.4 (3.5)
11.6 (4.3)
9.9 (2.5)
10.2 (2.8)
10.6 (3.3)
11.3 (2.7)
11.0 (0.2)
10.7 (0.3)
10.9 (3.1)
11.1 (2.9)
10.3 (5.2)
11.8 (6.4)
12.4 (4.5)
12.8 (4.0)
not available
not available
Study end
13.3
14.0
12.7
13.0
11.8
11.6
15.2
11.4
19.4
15.7
13.8
12.3
Change
(5.7)
(4.7)
(8.6)
(6.1)
(0.5)
(0.5)
+2.1*
+2.8
+1.8
+1.9
+0.4
+0.0
+5.3*
+1.2
+8.8*
+4.4
+2.8
+1.6
(5.1)
(5.1)
(6.4)
(6.8)
+0.2
+0.3
+2.2
+2.6
(6.7)
(7.4)
(5.2)
(4.9)
#
##
10.5
12.1
14.6
15.4
eau-ebu update series 5 (2007) 197–205
11
Saw palmetto
Finasteride
Saw palmetto
Tamsulosin
Saw palmetto
Placebo
ß-Sitosterol
Placebo
ß-Sitosterol
Placebo
Stinging root
Placebo
Pumpking seed
Placebo
Rye Pollen
Placebo
Saw palmetto/Urtica
Finasteride
Saw palmetto/Urtica
Tamsulosin
Study end
Qmax [ml/sec] mean (SD)
SD: standard deviation.
Statistical significant difference.
#
Standard error of the mean (SEM) instead of standard deviation.
##
No detailed information, yet no difference between plant extract and placebo.
*
199
200
eau-ebu update series 5 (2007) 197–205
Table 2 – Origin, components and postulated mechanism of plant extracts
Origin of plant extracts
Hypoxis rooperi
Serenoa repens/Sabal serrulata
Pygeum africanum
Secale cereale
Cucurbita pep
South African star grass
Saw palmetto berry
African plum
Rye pollen
Pumpkin seeds
Components of plant etxracts
Phytosterols
ß-sitosterol
D-5-sterols
D-7-sterols
Campesterol
Stigmasterol
Lupenone
Lupeol
Terpenoids
Fatty acids
Lectins
Plant oils
Postulated mechanism of plant extracts
Anti-inflammatory effects
Decrease of SHBG
Inhibition of aromatase
Improvement of detrusor function
Action on a-adrenergic receptors
Alteration of cholesterol metabolism
Inhibition of 5a-reductase
Anti-androgenis/oestrogenic effects
Interference with growth factors
Free radical scavengers
Fig. 1 – Improvement of IPSS in all prospective, randomized
trials with a study period I6 months. See also Table 1.
Polysaccharides
Flavanoids
Phyto-oestrogens
Coumestrol
Genistein
Germany, for instance, more than 30 different
preparations are on the market. The by far most
intensively studied product of this group is a
n-hexan-liposterol-extract (Permixon1) which is very
popular in France [10,11]. This product is a complex
mixture of free fatty acids and their esters, phytosterols, aliphatic alcohols and various polyprenic
compounds that has been tested in two large scale
prospective randomised trials against standard
therapy (Table 1, Figs. 1 and 2) [10,11]. Carraro
et al randomised 1.098 patients into a Permixon1and a finasteride-arm [10]. The study period was
6 months. At study end, improvements of the IPSS
(Permixon1: 6.2 points; finasteride: 6.6 points) and
quality of life were identical in both arms [10]. The
rise in Qmax was slightly higher under finasteride
(finasteride: +2.8 ml/sec; Permixon1: +2.1 ml/sec;
(see below) casts doubts on the proposed a-blockade. Finally it is unknown which component of plant
extracts is responsible for the proposed mechanisms.
Key message: The in vivo mechanism of any plant
extract remains to be identified.
6.
Clinical results
6.1.
Saw palmetto
Saw palmetto is derived from olive-sited berries of
the saw palmetto tree and is the most popular
phytotherapeutic agent in BPH-management. In
Fig. 2 – Improvement of Qmax in all prospective,
randomized trials with a study period I6 months. See also
Table 1.
eau-ebu update series 5 (2007) 197–205
p = 0.035) [10]. Reduction of PSA and prostate volume
were demonstrable for finasteride only. This study
has been criticised for the short study period of
6 months particularly regarding the fact that
finasteride exerts its full clinical efficacy after
3–6 months and the lack of a placebo arm [10]. It
is therefore unknown whether results of this trial
exceed the putative placebo effect. In another largescale trial Permixon1 has been tested in a 12 months
study randomised against tamsulosin. A total of
704 patients entered this trial. Results regarding
Qmax and IPSS were identical in both arms [11]. Both
products were well tolerated, yet ejaculatory disorders were more frequent under tamsulosin [11].
The authors concluded that both products are equal
effective regarding the medical management of
LUTS. Also this study has been criticised for the
lack of a placebo arm [11]. There exists one large
scale placebo controlled 12-months trial with
Permixon1 that has randomised 198 patients into
each arm. This trial was only briefly described in a
recent meta-analysis [12]. Unfortunately, this key
trial has never been published [12]. At least regarding Qmax and nocturia there was no difference to
placebo after 12 months [12]. The only 12 months,
placebo controlled trial with a saw palmetto product
published in the peer-reviewed literature has been
recently reported by Bent et al in the New England
Journal of Medicine [13]. In this highly published,
industry-independent and probable best designed
phytotherapy trial 225 patients were followed for
12 months [13]. In this trial, changes of the AUAsymptom score (saw palmetto: 0.7; placebo: 0.7),
the Qmax (saw palmetto: +0.4 ml/sec; placebo:
+0.0 ml/sec), prostate volume (saw palmetto:
+3.8 ml; placebo: +5.0 ml), PVR (saw palmetto:
+14 ml; placebo: +19 ml) were identical between
saw palmetto and placebo. The authors provided
several explanations for the discrepancy of this
negative study to the summary of prior evidence
[13]. The authors, for instance, argued that blinding
was effective. Since saw palmetto has a strong,
pungent odour, the authors speculated that many
previous studies might not have achieved adequate
blinding [13]. Inadequate blinding has the potential
to reduce response in men who are given placebo
(who may be aware they are taking placebo),
artificially increasing the comparative efficacy of
saw palmetto [13].
Several meta-analyses for saw palmetto have
been published [12,14,15]. In 2004 Boyle et al presented the most recent meta-analysis. In total 14
randomized and open trials with 4.280 patients were
analysed, only three randomized trials had a
study period of 6 months or longer [12]. In this
201
meta-analysis the IPSS decreased by 4.8 points and
the Qmax by 2.2 ml/sec under Permixon1; the
respective changes under placebo were 4.5 IPSSpoints and for the Qmax 1.2 ml/sec [12]. Wilt et al
investigated saw palmetto extracts in another metaanalysis based on 18 randomized trials with a total
of 2.939 men [14]. The mean symptom-improvement
was 1.4 points, the Qmax by 1.9 ml/sec and nocturiaepisodes decreased by 0.8 [14]. The conclusion of this
meta-analysis is hampered by the fact that 11
different extracts in different concentrations and
different extraction techniques were included [14].
Only two trials fulfilled the WHO-BPH criteria. The
authors concluded that there is evidence that saw
palmetto extracts improve symptoms and Qmax yet
also stated that further controlled trials according to
BPH-criteria are required before definitive conclusions can be drawn.
Key message: Despite the fact that saw palmetto
is the most intensively studied and used plant
extract, no definitive conclusion can be made at
this time point. Further placebo-controlled trials
according to WHO-criteria are necessary.
6.2.
Hypoxis rooperi (South African star grass)
This extract contains mainly ß-sitosterol, which is
thought to be the major active component, with
other sterols being detected in the lesser extent. The
most widely used extract of star grass is Harzol1.
This product has been investigated on one placebocontrolled trial with 200 patients (Table 1, Figs. 1
and 2) [16]. After 6 months the IPSS decreased by 2.3
points under placebo and by 7.4 points under
Harzol1, the difference of Qmax against placebo
was quite high, 4 ml/sec [16]. Klippel et al investigated another ß-Sitosterol extract (Azuprostat1;
65 mg bid) in a placebo-controlled trial for 6 months.
(Table 1, Figs. 1 and 2) [17]. Also in this study the
plant extract was clearly superior to placebo: the
IPSS improved by 8.2 points under the plant extract
in comparison to only 2.8 points under placebo
( p < 0.01) [17]. The absolute increase of the Qmax in
this trial was 8.8 ml/sec (!) with the plant extract.
This ‘‘dramatic’’ improvement is far higher than
that of a1-blockers and 5a-reductase inhibitors,
indicating that these data have to be interpreted
with caution. The increase of the Qmax in the
placebo arm (+4.4 ml/sec) was also unusually high.
One meta-analysis is available that has analysed
pooled data of 5 prospective studies with a total of
516 patients; the study period was 4–26 weeks [18].
The mean difference of the IPSS between placebo
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eau-ebu update series 5 (2007) 197–205
and ß-sitosterol was 4.9 points, the Qmax increased
by 34% and the post void residual volume by 24%.
The authors of this meta-analysis were unable to
provide a valid conclusion because in these four
trials three different extracts were used [18].
Key message: The two 6-months placebo-controlled trials provide encouraging data that need
to be confirmed by studies according to WHO-BPH
criteria.
void residual volume were identical under placebo
and the plant extract (Table 1, Figs. 1 and 2)
[20].
Key message: One study meeting the WHOBPH criteria showed a slight effect on LUTS yet
no impact on objective parameters. Further
studies according to WHO-BPH criteria are
required.
6.5.
6.3.
Stinging nettle (Urtica dioica)
The roots of the stinging nettle contain a mixture of
water- and alcohol-soluble compounds including
lectins, phenols, sterols and lignins. There are at
least 16 different preparations of this extract
available that is particularly popular in Germany.
Recently a 12-months placebo controlled trial with
one stinging root extract (Bazoton-uno1; 459 mg/die)
has been reported. (Table 1, Figs. 1 and 2) [19]. A total
of 226 patients were randomized 1:1 into a placebo
and plant extract arm. After 12 months, the IPSS
decreased by 5.7 points with the plant extract and by
4.7 points under placebo, this one point difference
reached statistical significance ( p = 0.02) [19].
Changes of Qmax, post void residual volume and
quality of life were identical under placebo and the
plant extract [19]. The plant extract was well
tolerated. In summary the only difference in this
well-designed trial was a one-point difference of the
IPSS after 12 months, yet no effect on Qmax, post
void residual volume and quality of life. The clinical
relevance of this finding is questionable. All other
trials with stinging nettle extracts do not fullfill
current quality criteria; meta-analyses are not
available.
Key message: One placebo-controlled study
meeting the WHO-criteria demonstrates a slight
effect on LUTS, yet no impact on objective
parameters; further studies are required before
definitive conclusions can bedrawn.
6.4.
Rye pollen (Secale cereale)
The commercial preparation ‘‘Cernilton1’’ is a pollen
extract prepared from several plants found growing
in countries such as Sweden. This drug is available
across Europe and is manufactured by microbial
digestion of the pollen. There is only one placebo
controlled trial with a study duration of 6 months
available that has included only 60 patients [21]. The
improvement of LUTS (no validated questionnaire,
just one question) was 69% for Cernilton1 and 29% for
placebo, changes of Qmax were identical under
Cernilton1 and plabebo [21]. One meta-analysis that
has included only 4 studies is available; three of
these studies had a very short duration (12–16
weeks) only one study had a duration of 24 weeks
[22]. The authors concluded that due to the limited
number of studies, small sample sizes and short
study period no viable conclusions can be made
[22].
Key message: No study meeting the WHO-BPH
criteria is available; therefore no conclusion can
be drawn. Further placebo-controlled trials are
mandatory.
6.6.
African plum (Pygeum africanum)
In traditional African medicine a tea made from the
powdered bark of this tall evergreen tree is drunk to
control urinary disorders in men. Today, this
supplement is commonly used in France, Germany
and Austria (Tadenan1). None of the studies fulfilled
WHO-criteria, there is even no 6-months controlled
trial available [23].
Pumpking seed extracts
One study meeting the WHO-criteria is available.
In this placebo-controlled trial 476 patients were
included and followed for 12 months [20]. At study
end, the IPSS declined by 6.7 point under the
plant extract (Prosta Fink forte1, 500 mg/die) and by
5.5 points under placebo [20]. This one point
difference was statistical significant. Changes of
Qmax, quality of life, prostate volume and post
Key message: No study meeting the WHO-BPH
criteria is available; therefore no conclusion can
be drawn.
6.7.
Combination products
Many manufacturers of plant extract produce not
only mono- but also combination extracts although
there is no scientific evidence for an additive or even
eau-ebu update series 5 (2007) 197–205
potentising effect. One combination product of (saw
palmetto/stinging nettle; Prostagutt1 forte) has been
tested against finasteride in a large scale (489
patients) prospective, randomized 12-months trial
(Table 1, Figs. 1 and 2) [24]. The IPSS decreased by 4.8
points under placebo and by 5.6 points under
finasteride; there was no difference between the
two study arms [24]. Also regarding Qmax, both
study arms yielded comparable improvements
(plant extract: 2.2 ml/sec; finasteride: 2.6 ml/sec)
[24]. The combination product had no effect on
prostate volume; finasteride reduced prostate
volume by 15% [24]. Both products were well
tolerated, erectile dysfunction (2.8%) and reduced
ejaculate volume (2%), however, were more frequent
under finasteride [24]. The same combination
(Prostagutt1 forte) has been compared to tamsulosin
in a 12-month prospective, randomized trial [25].
The IPSS improved in both study arms by 9 points.
Detailed data on Qmax, post void residual volume
and prostate volume were not presented [25].
Key messages: Two studies meeting the WHOBPH criteria suggest a similar efficacy as standard
therapy. Further studies with a placebo arm are
required to clearly document the clinical efficacy.
7.
The role of meta-analyses
As shown above, a number of meta-analyses
have been published for various plant extracts
[12,15,18,22,23]. The major problem of all metaanalyses is the fact that their quality strongly
depends on the quality of studies entering the
meta-analysis. It is therefore not surprising that the
authors of almost all meta-analyses concluded that
further prospective trials are needed before definitive conclusions can be drawn. Meta-analyses can
not supplement prospective trials according to
WHO-BPH-criteria.
8.
Recommendations of BPH-guidelines
All major BPH-guidelines, such as those of the EAU,
the AUA or of the German Urologists make statements regarding the role of plant extracts in
contemporary management of elderly men with
LUTS [26–28]. In general, these guidelines are quite
sceptical regarding the role of plant extracts. The
guidelines of the German Urologists state ‘‘For some
plant extracts there is evidence of clinical efficacy
based on the results of randomised controlled trials
that all require confirmation’’ [26]. The most recent
203
published update of the EAU-guidelines states: ‘‘The
mode of action of phytotherapeutic agents is
unknown. The biological effects are unclear
although a few RCTs show encouraging data. These
drugs are not recommended for the treatment of
elderly men with LUTS suggestive of benign prostatic obstruction’’ [27]. Finally, the AUA-guidelines
conclude that ‘‘Phytotherapeutic agents cannot be
recommended for treatment of BPH at this time. . . .
mechanisms of action, effectiveness, and safety of
these agents have not been well documented in
multicenter, clinical trials with independent data
monitoring’’ [28].
Despite these critical conclusions all BPH-guidelines underline that phytotherapy is an interesting
approach that deserves further evaluation, in
particular more studies meeting the WHO-criteria
(placebo arm). The EAU and German BPH-guidelines
are currently updated, yet is it unlikely that different
recommendations regarding the role of plant
extracts will be made.
9.
Conclusions
As repeatedly emphasised a definitive conclusion
regarding the role of plant extracts in the current
management of LUTS in elderly men can not be
made to date. Although a handful studies meeting
the WHO-BPH criteria are available, convincing
evidence for their clinical efficacy is still lacking.
None of the three 12 months placebo-controlled
trials available to date has demonstrated an effect
on prostate volume, PSA, Qmax or post void residual
volume. Interestingly, the two trials against an
active comparator revealed identical efficacy as
tamsulosin and finasteride. One attractive aspect
of plant extracts is their good tolerability that
renders this approach particularly attractive for
sexually active men who want to avoid sexual side
effects of a1-blockers and 5ARIs.
In parallel to a1-blockers or 5a-reducatse inhibitors, there should be at least one 12-months placebo
controlled trial available. It is worth to note that
clinical efficacy of a1-blockers and 5ARIs has been
convincingly demonstrated in a number of placebocontrolled trials [6]. However, these studies are very
expensive and it is very unlikely that the producers
of plant extracts will make these investments,
particularly facing the fact that reimbursement,
e.g. in Germany, is no more granted. Furthermore
plant extracts can not be patented. Finally, the
data of e.g. one saw palmetto extract can not
be extrapolated to another one due to different
origins, extraction techniques and compositions.
204
eau-ebu update series 5 (2007) 197–205
Hence, each extracts needs to be analysed separately.
The data of the prospective trials and metaanalyses presented above suggest a slight positive
effect on LUTS; an effect on urodynamic parameters
such as Qmax or post void residual volume is less
convincing. An impact of PSA or prostate volume
has not been demonstrated, data on the impact of
the natural history (risk of acute urinary retention,
surgery) are lacking. Due to these data plant extracts
should only be offered to patients with bothersome
LUTS without significant benign prostatic obstruction and a low risk of progression. Patients, however,
should be instructed that the definitive proof of their
efficacy is still lacking and that they are currently
not recommended by BPH-guidelines.
Conflict of interest
The authors have nothing to disclose.
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CME questions
Please visit www.eu-acme.org/europeanurology
to answer these CME questions on-line. The CME
credits will then be attributed automatically.
1. Which statement regarding plant extracts is
correct?
A. Plant extracts induce a reduction of prostate
volume by about 20%.
B. Plant extracts lower serum prostate-specific
antigen by 15%.
C. Plant extracts are recommended by the AUA
and EAU guidelines.
D. None of the above.
2. Which statement regarding the mechanism of
plant extracts is correct?
A. Plant extracts have a 5a-reductase activity in
vivo.
B. The exact mechanism of plant extracts in vivo
in unknown.
C. Plant extracts inhibit the aromatase in vivo.
D. Plant extracts have no in vitro efficacy.
3. The role of meta-analyses in the assessment of
plant extracts:
A. Meta-analyses provide no relevant conclusions.
B. Meta-analyses can supplement prospective
trials according to WHO-BPH criteria.
C. Meta-analyses cannot supplement prospective trials according to WHO-BPH criteria.
D. Meta-analyses have convincingly documented the clinical efficacy of plant extracts.
4. The clinical efficacy of plant extracts:
A. Plant extracts increase the maximum flow
rate by >7 ml/s in the majority of studies.
B. Plant extracts reduce the postvoid residual
volume by 50%.
C. Plant extracts reduce the risk of prostate
surgery by 50%.
D. The majority of plant extracts have a slight
positive effect of lower urinary tract symptoms (LUTS).
5. Which group of patients will most likely benefit
from plant extracts?
A. Patients with severe LUTS and a high risk of
progression.
B. Patients with mild/moderate LUTS and no
relevant benign prostatic obstruction.
C. Patients with high postvoid residual volume
and large prostates.
D. Patients with bladder stones and upper urinary tract dilatation.
6. Which statement of the EAU-BPH guidelines
regarding plant extracts is correct?
A. Strong recommendation of the use of plant
extracts as a primary treatment.
B. Plant extracts are indicated in men at a high
risk of disease progression.
C. Plant extracts are clearly indicated in men
with minimal symptoms and no impairment
of quality of life.
D. No clear recommendation for plant extracts.