REVIEW

CURRENT
OPINION Current medical treatment of lower urinary tract
symptoms/BPH: do we have a standard?
João Silva a,b,c, Carlos Martins Silva a,b,c, and Francisco Cruz a,b,c

Purpose of review
The pharmacological treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic
hyperplasia (BPH) is based on alpha-blockers and 5a-reductase inhibitors isolated or in combination.
Silodosin, an alpha-1A specific alpha-blocker is the only innovation in these groups of agents. This classical
paradigm is being challenged by antimuscarinics, 5-phosphodiesterase inhibitors (PDE5i) and b3-
adrenoreceptor agonists.
Recent findings
Silodosin is effective in reducing BPH/LUTS, including nocturia and shows little cardiovascular adverse
events. Antimuscarinic drugs isolated or in combination with alpha-blockers improve storage symptoms
without any harmful effect to the voiding function. PDE5i alone improve BPH/LUTS. Combination of PDE5i
with alpha-blockers provides better symptomatic control than alpha-blockers alone. A recent head-to-head
comparison of tadalafil 5 mg/day with tamsulosin 0.4 mg/day showed that these agents provided the
same improvement in BPH/LUTS and, surprisingly, the same improvement in the urinary flow. In fact,
previous studies with tadalafil had not shown any effect of tadalafil on flow. In addition, tadalafil but not
tamsulosin improved sexual function. Mirabegron, the first b3-adrenoreceptor agonist, while improving
BPH/LUTS in men with bladder outlet obstruction, do not decrease urinary flow or detrusor pressure.
Summary
The standard medical treatment for BPH/LUTS is still based on alpha-blockers, 5ARIs or its combination.
In the future, it is expected that BPH/LUTS treatment will become individualized, according to the type
of symptoms, presence of sexual dysfunction and risk of BPH progression. This will challenge our concept
of standard treatment for BPH/LUTS.
Keywords
benign prostatic hyperplasia, combined drug therapy, lower urinary tract symptoms, monotherapy

INTRODUCTION picture and the expectations of each patient should

Benign prostatic hyperplasia (BPH) is a major cause
of lower urinary tract symptoms (LUTS) in aging
men and frequently affects their quality of life
(QoL). Research aiming new more effective, well
tolerated and selective treatments for BPH/LUTS
has been hampered by the incomplete knowledge
of the mechanisms involved in cause and
progression of the disease. Moreover, the exact
mechanism by which the enlarged prostate causes
LUTS is not yet known.
Patients with BPH may have predominance of
one type of symptom over another and often symp-
toms cluster in different forms along the course of
the disease [1]. Therefore, BPH patients present with
variable spectrum of LUTS, the intensity and bother
of which is also highly variable. As a consequence
it is difficult to reckon that one treatment may fit
for all patients. As a corollary, an individualized
therapy that takes into account the specific clinical
probably be preferred. Moreover, erectile dysfunc-
tion is very prevalent in this age group. It is well
known that the presence and severity of LUTS are
independent risk factors for sexual dysfunction in
older men [2], making attractive the simultaneous
management of LUTS and erectile dysfunction.
In addition, caregivers cannot ignore that drugs
approved for BPH/LUTS treatment may also affect
sexual function.
a
Departement of Urology, Hospital S. João, bFaculty of Medicine and
c
IBMC, Institute for Molecular and Cell Biology, Porto, Portugal
Correspondence to Professor Dr Francisco Cruz, Urology Department,
Hospital de S. João, E.P.E., Alameda Professor Hernâni Monteiro, Porto
4200-319, Portugal. Tel: +351 225513654; fax: +351 225513655;
e-mail: cruzfjmr@med.up.pt
Curr Opin Urol 2014, 24:21–28
DOI:10.1097/MOU.0000000000000007

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 Benign prostatic hyperplasia
KEY POINTS

Silodosin is effective in reducing nocturia and shows
little cardiovascular adverse events.

Solifenacin and tamsulosin is more effective than
tamsulosin alone in reducing storage symptoms of
BPH/LUTS.

The effect of tadalafil on BPH/LUTS is similar to that
observed with alpha-blockers alone.
One should take in mind that the primary aim of
medical therapy for BPH is to improve LUTS and QoL.
It should also reduce the complications of the disease
progression, namely, urinary infections, urinary
retention, hydronephrosis and the need for surgery.
Thus, many men with enlarged prostates do not need
any pharmacological treatment. As a matter of fact,
approximately 65% of men initially managed by
watchful waiting were still satisfied at 5 years [3].
When pharmacological treatment is required,
the most commonly used drugs are a-blockers and
5-areductase inhibitors (5ARIs). The five extensively
available alpha-blockers are doxazosin, terazosin,
tamsulosin, alfuzosin and silodosin, the last one
being the only one that is a1A adrenoreceptor
specific. As for 5ARIs, two drugs are available,
finasteride and dutasteride. In addition, combi-
nation of these two classes of drugs has been shown
to be more effective in BPH/LUTS control than each
of the individual drugs alone [4,5].
However, other classes of drugs, such as anti-
muscarinics and 5-phosphodiesterase inhibitors
(PDE5i), have been recently investigated in the treat-
ment of BPH/LUTS, particularly when storage symp-
toms are persistent or predominant. Combination
of these drugs with alpha-blockers and 5ARIs has
already been investigated. In addition, the introduc-
tion of the b3-adrenoreceptor agonist, mirabegron,
may also represent an option for BPH/LUTS
treatment. Thus, the development of these drugs
open different pathways of BPH/LUTS management
that may contribute to individualize treatment
of BPH patients and challenge the actual standard
of care with alpha-blockers and 5ARIs, isolated or
in combination. Relevant evidence to support this
statement will be reviewed here.
CLASSICAL MEDICAL TREATMENTS FOR
LOWER URINARY TRACT SYMPTOMS/
BENIGN PROSTATIC HYPERPLASIA
Until a few years ago, the standard treatment of
BPH/LUTS consisted of alpha-blockers, 5ARIs and
the combination of these two kinds of drugs.
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Alpha blockers and 5a-reductase inhibitors
Alpha-blocker agents continue to be the most com-
monly used pharmacotherapy for BPH/LUTS [6,7].
According to the European Association of Urology
(EAU) guidelines alpha-blockers should be offered
to men with moderate-to-severe lower urinary
tract symptoms and are considered the first-line
drug treatment for these patients. The adrenergic
receptors are transmembrane glycoproteins and are
responsible for the prostatic tone that is regulated
by a1-adrenoceptors activated from endogenously
released noradrenaline [8,9]. Alpha-blockers rapidly
relieve LUTS presumably by relaxing smooth muscle
tone in the prostate and bladder neck. However, it is
also probable that the blockade of a1-adrenoceptors
outside the prostate, in the bladder and in the
spinal cord, plays a relevant role [8,9].
Silodosin is the last alpha-blocker to be investi-
gated in BPH/LUTS treatment and is the only one
selective to the a1A-adrenergic receptor subtype
that is predominant in the human prostate
&
[10,11 ]. Silodosin has a 162-fold greater affinity
for the a1A than for a1B adrenergic receptor and
about a 50-fold greater affinity for a1A than for a1D
adrenergic receptor [10]. Systematic analyses of
placebo-controlled studies show that doxazosin,
terazosin, alfuzosin, tamsulosin and silodosin are
similarly effective and statistically significantly bet-
ter than placebo in improving urinary flow and
&
reducing symptoms [12,13 ]. The common side-
effects reported are dizziness, headache, asthenia,
postural hypotension, rhinitis and sexual dys-
function, namely, retrograde/abnormal ejaculation
&
[13 ].
Direct comparisons between alpha-blockers are
limited. However, silodosin 8 mg was recently
compared against tamsulosin 0.4 mg and placebo
in a large randomized clinical trial (RCT) involving
1228 patients at least 50 years of age with Inter-
national Prostate Symptom Score (IPSS) at least 13
and Qmax between 4 and 15 ml/s (randomization
1 : 1 : 1). Both treatment groups showed statistical
improvements in IPSS over placebo. Silodosin was
not inferior to tamsulosin in improving both storage
and voiding LUTS [14]. In a further post-hoc
analysis, however, silodosin led to significant
improvements in nocturia over the tamsulosin
&
group [11 ]. Because of the high a1A selectivity,
silodosin has fewer cardiovascular side-effects
than the other alpha-blockers. Thus, in patients
with concomitant cardiovascular comorbidity/
comedication, this superselective agent may be
the drug of choice owing to its low drug-interaction
potential with antihypertensive agents. On the
contrary, silodosin shows the higher incidence
of ejaculatory dysfunction. The latter although
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 Current medical treatment of LUTS/BPH: do we have a standard? Silva et al.
frequently referred as retrograde ejaculation is in
fact a lack of emission. This adverse event should
be fully discussed with patients, in particular
with those younger or more sexually active, who
should be informed that it will disappear upon the
&
suspension of the medication [11 ,14].
Regarding 5ARIs, the two drugs available
differ in their activity against the 5-a-reductase iso-
enzymes. Finasteride inhibits preferentially type II
5-a-reductase and prevents by 70% the conversion
of testosterone to Dihydrotestosterone (DHT).
Dutasteride inhibits both type I and II isoenzymes
preventing 95% conversion of testosterone to DHT
[15,16]. In spite of these different profiles, there are
no relevant clinical differences between finasteride
and dutasteride. In a head-to-head trial of the two
drugs LUTS, Qmax and prostate volume variation
were similar for both drugs [17].
Contrary to alpha-blockers, these drugs have a
slow onset of action and a clinical benefit cannot
be noticed before at least 6 months of therapy in
most patients [4,5]. In addition, they are more
effective in larger prostate glands [18]. Reflecting
these characteristics EAU guidelines recommend
that 5ARIs should be offered to men who have
moderate-to-severe LUTS and enlarged prostates
(>40 ml) or elevated prostate specific antigen
concentrations (>1.4–1.6 mg/l) that are willing to
maintain treatment for a long period of time [7].
5ARIs reduce the risk of acute urinary retention
(AUR), BPH-related surgery and prevent BPH
progression. This is particularly relevant in patients
with large prostate glands and high total serum
Prostate-specific antigen (PSA) [4,19]. In addition,
in a post-hoc analysis of the Reduction by Dutas-
teride of Prostate Cancer Events study (REDUCE)
trial, it was observed that dutasteride in asympto-
matic or mildly symptomatic men decreased
the risk of BPH-related symptom appearance,
AUR and BPH-related surgery [20]. These findings,
however, do not grant the use of 5ARIs to BPH
prevention.
The adverse event profile of both drugs is very
similar. Overall, up to 10% of patients treated with
5ARIs report sexually related events, with erectile
dysfunction, decreased libido and decreased volume
of ejaculate occurring nearly twice than that in
placebo, particularly during the first year of treat-
ment [21]. There is no evidence that finasteride or
dutasteride cause different adverse events [17].
Combination of alpha blockers and
5a-reductase inhibitors
The distinct mechanisms of action of alpha-blockers
and 5ARIs, lead to the investigation of combination
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therapy. The Medical Therapy of Prostatic
Symptoms Study (MTOPS) compared the effects of
placebo, doxazosin, finasteride and combination
therapy in 3047 men [4], whereas the CombAT
compared the effects of tamsulosin, dutasteride or
a combination of both during 4 years in 4844 men
[19]. The latter had no placebo arm. These two
large long-term studies MTOPS and Combination
of Avodart1 and Tamsulosin study (ComBAT) have
demonstrated superiority of combination therapy
over monotherapy in preventing symptomatic
progression, risk of AUR and BPH-related surgery
[4,19]. The two studies differ however in the mean
prostate volume, the mean prostate volume in
CombAT study being greater than in MTOPS
(55.0 ml versus 36.3 ml), which might indicate that
a population at higher risk of progression was
studied in the ComBAT trial. The analysis of the
effect of combination therapy in prostates with
different volumes leads to the conclusion that com-
bination is more effective in large volume prostates
&
[22 ]. Today combination therapy with alpha-
blockers and 5ARIs is recommended by the AUA
and EAU for patients with moderate-severe symp-
toms and high risk of progression-enlarged pro-
states, above 40 ml, higher PSA and advanced
age [6,7]. In addition, combination therapy should
be accepted has a long-term treatment as the
advantage of combination is absent or very mild
in the first year of treatment [4,19].
The disadvantages of combination therapy are
the increased cost and the increased incidence
of side-effects, since there are concomitant effects
&
of both classes of drugs [22 ].
Combination therapy is most commonly
started when BPH-related symptoms are refractory
to monotherapy. However, neither MTOPS nor
ComBAT studies indicate when in clinical practice
should combination therapy be initiated, that is,
how long should patients remain in monotherapy
before the switch to the combination treatment.
In addition, the indication of combination therapy
as the initial choice is also vague. Most clinicians
tend to empirically use the combination therapy
from the start when patients are severely sympto-
matic and the risk of BPH progression is high.
ANTIMUSCARINICS
Detrusor overactivity has been identified in
approximately 45–50% of men with BPH and this
number increases with the severity of the obstruc-
tion. In patients with more severe forms of obstruc-
tion almost 90% may present detrusor overactivity
[23]. This urodynamic abnormality can result from
local factors within the bladder, such as denervation
www.co-urology.com 23
 Benign prostatic hyperplasia
hypersensitivity of cholinergic receptors, structural
changes resulting from urinary bladder ischaemia or
detrusor hyperthrophy [24]. The presence of bladder
outlet obstruction (BOO) and detrusor overactivity
does not necessarily imply a cause–effect relation-
ship, because detrusor overactivity can occur in
asymptomatic men [25]. In addition, urgency, fre-
quency and nocturia, the overactive bladder (OAB)
complex, increases in the aging male, in the same
proportion as in women [26]. Thus, management
of storage symptoms in BPH men can in theory
be achieved with antimuscarinic drugs, in the
same way as women. The administration of anti-
muscarinics in the presence of prostate enlargement
was traditionally contraindicated because of the fear
of precipitating acute urinary retention. However, it
is now well documented that antimuscarinics can
be safely administered at clinically recommended
doses to most men with BPH [27].
Treatment options with antimuscarinics include
monotherapy, add-on therapy after failure of an
initial treatment with alpha-blockers and fixed com-
binations of antimuscarinics with alpha-blockers
or 5ARIs.
Monotherapy with antimuscarinics
One study investigated safety of tolterodine versus
placebo in men with urodynamically demonstrated
BOO [28]. It was concluded that tolterodine was well
tolerated. Urinary flow rate was unaltered, and there
was no evidence of clinically meaningful changes
in voiding pressure and postvoid residual (PVR) or
urinary retention in the tolterodine arm versus
placebo [28].
Most of the RCT trials comparing antimuscar-
inics against placebo had a short duration (12 weeks)
and most used tolterodine 4 mg as the anti-
muscarinic drug. In general, entry criteria were
variable and included men with OAB symptoms,
urinary frequency (8 micturitions/24 h), urgency
episodes with or without urinary incontinence
and nocturia. However, exclusion criteria were
substantially more restrictive, by including PVR
more than 100 ml [29] or more than 200 ml [30].
In general, antimuscarinics significantly reduce
voiding frequency and urge incontinence compared
with placebo. Nocturia and IPSS were also numeri-
cally reduced although not reaching statistical
significance [29–32].
Muscarinic receptor antagonists were generally
well tolerated and the increase in PVR or the inci-
dence of AUR was in general similar in the anti-
muscarinics and placebo arms [28–32]. However,
in men that received fesoterodine 8 mg, 5.3% of
them had symptoms suggestive of urinary retention,
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a percentage that was higher than in the placebo
arm [29]. Despite these promising results anti-
muscarinics monotherapy was not further evaluated
in additional RCTs.
Add-on therapy
The addition of an antimuscarinics to BPH patients
with persistent storage symptoms after an initial
trial with alpha-blockers led to the appearance of
various studies with the intention of evaluating
the clinical efficacy of adding an antimuscarinic
drug to the established therapy.
Lee et al. [33], published the results of a prospec-
tive observational study assessing the efficacy of
adding tolterodine 4 mg to men with BOO and
detrusor overactivity previously treated with doxa-
zosin during 3 months. It was observed that 73%
of the nonresponder patients had a sympto-
matic improvement 3 months after the addition
of tolterodine.
Three other trials investigated the effect of add-
ing an antimuscarinics to patients with persistent
LUTS during alpha-blockers treatment [34–36].
In these nonplacebo-controlled studies, more than
100 men with BPH/LUTS refractory to antimus-
carinics were enroled. These studies demonstrated
that the addition of an antimuscarinics significantly
reduced LUTS and improved QoL. No acute urinary
retention was observed even in patients with
urodynamically proven mild or moderate BOO
and the addiction of the antimuscarinics did not
affect significantly the urine flow or residual urine
volume [34–36].
Combination therapy with alpha-blockers and
antimuscarinics
In 2006, Kaplan et al. [37] published the results of
Tolterodine and Tamsulosin In Men with LUTS
Including OAB: Evaluation of Efficacy and Safety
study (TIME) study, a well designed multicenter
randomized, double-blind, placebo-controlled trial
involving men 40 years or older who had a total IPSS
score 12, 8 micturitions per 24 h and 3 urgency
episodes per day. After the 12 weeks of the study,
patients in the combination arm [tolterodine
extended release (ER) and tamsulosin] reported
significant reductions in urgency episodes, number
of micturitions and nocturia as well as IPSS. The
medication was well tolerated with no differences
on voiding pattern, PVR or episodes of AUR. Inter-
estingly, in contrast with combination therapy, in
the TIMES study, the tolterodine monotherapy
was not effective. Besides this publication,
other works have been published involving other
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Number 1
January 2014
 Current medical treatment of LUTS/BPH: do we have a standard? Silva et al.
alpha-blockers like doxazosin and naftopidil
in association with other antimuscarinics like
propiverine, oxybutynine and solifenacine [38–40].
As a rule, the combination therapy was more effica-
cious in reducing voiding frequency, nocturia or IPSS
compared with alpha-blockers alone. The most
frequently reported side-effect in all trials was
xerostomia. There was also a mild increase in PVR,
although urinary retention occurred in 0.9–3.3%
[38–40].
Recently, the results of a phase II, dose
finding Solifenacin and Tamsulosin in Males with
Lower Urinary Tract Symptoms Associated with
Benign Prostatic Hyperplasia study (SATURN) study
designed to investigate a combination of tamsulosin
and solifenacin versus tamsulosin alone and placebo
in the treatment of men with LUTS were reported.
A total of 937 men aged at least 45 years with both
voiding and storage LUTS were randomized for
eight treatment groups: tamsulosin oral controlled
absorption system (OCAS) 0.4 mg; solifenacin 3, 6 or
9 mg; solifenacin 3, 6 or 9 mg and tamsulosin OCAS
0.4 mg; or placebo (2 : 4 : 4 : 4 : 4 : 1 : 1 : 1 rando-
mization ratio). Inclusion criteria included total IPSS
at least 13, a Qmax of 4.0–15.0 ml/s and the PVR had
to be inferior to 200 ml. Combination therapy did
not cause a significant improvement in total IPSS in
the total study population. However, combination
therapy was associated with significant improve-
ments in micturition frequency and voided volume
versus tamsulosin OCAS alone. In addition, a sig-
nificant improvement was found in the IPSS storage
subscore in all the combination groups against
tamsulosin alone. Mean PVR volume increased with
increasing solifenacin dose, whether given alone
or in combination. However, differences between
solifenacin doses were less pronounced for the com-
bination-therapy groups than for the solifenacin
monotherapy. The incidence of AUR was low in
all groups and showed no apparent relationship
with increasing solifenacin dose.
The conclusion is that combination therapy
with tamsulosin and solifenacin benefits the sub-
group of men with LUTS who had both voiding and
moderate-to-severe storage symptoms [41 ].
&
More recently, came to public attention the
results of the Solifenacin Succinate and Tamsulosin
Hydrochloride OCAS in males with moderate to
severe storage lower urinary tract symptoms study
(NEPTUNE) trial that aimed to assess the efficacy
and safety of a fixed-dose combination of solifenacin
and tamsulosin OCAS against tamsulosin OCAS
alone and placebo in men with moderate-to-severe
&&
storage and voiding symptoms [42 ]. In this double-
blind 12-week phase 3 study, 1334 men with a total
IPSS at least 13, Qmax between 4.0 and 12.0 ml/s, two
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or more urgency episodes per 24 had at least
8 micturitions per 24 h were recruited. They were
randomized to placebo, tamsolusin OCAS 0.4 mg,
solifenacin 6 mg and tamsulosin OCAS 0.4 mg
or solifenacin 9 mg and tamsulosin OCAS 0.4 mg.
The results of this study showed that the combi-
nation of solifenacin 6 mg and tamsulosin OCAS
significantly improved storage and voiding symp-
toms, as well as QoL parameters, over placebo.
However, more relevant, the combination therapy
was superior to the alpha-blockers alone in improv-
&&
ing storage symptoms and QoL [42 ].
Combination therapy with 5a-reductase
inhibitors and antimuscarinics
Chung et al. [43] conducted an open-label, fixed-
dose study to assess the efficacy and safety of
tolterodine ER in combination with dutasteride in
men with a large prostate (30 g) and persistent
storage LUTS unsuccessfully treated with 6 months
of dutasteride monotherapy. All patients were
given 4 mg tolterodine ER daily for 12 weeks and
maintained dutasteride. In the end of the study,
frequency, urgency and nocturia had decreased sig-
nificantly over baseline. Total IPSS had decreased
with dutasteride treatment from 19.3 to 14.3 and
further decreased with the addition of tolterodine to
7.1 (P < 0.001). Storage symptoms decreased from
9.8 to 4.5 after tolterodine (P < 0.001). Dry mouth
occurred in four (7.5%) individuals, constipation in
one (2%) and decreased sexual function in two
(3.9%). PVR increased by 4.2 ml, Qmax decreased
by 0.2 ml/s and no patients developed AUR.
The authors concluded that the addition of
tolterodine to men with large prostates and
persistent storage LUTS refractory to dutasteride
was effective, safe and well tolerated [43].
Furthermore, studies are required to verify
the efficacy of antimuscarinics in combination
with 5ARIs to treat BPH/LUTS in men with large
prostate glands.
THERAPY WITH b3-ADRENOCEPTOR
AGONISTS
The b3-adrenoceptor subtype is the principal
b-adrenoceptor in the bladder. It has been shown
that the stimulation of this receptor may increase
bladder capacity without interference in micturition
pressure, PVR or voiding contraction [44,45].
Moreover, several phase III studies that occurred
worldwide, which enroled more than 25% of
male patients, confirmed the efficacy, safety and
tolerability of the b3-agonist mirabegron in men
with LUTS [46]. In a recent published article, Nitti
www.co-urology.com 25
 Benign prostatic hyperplasia
&&
et al. [47 ], evaluated urodynamic parameters in
men with LUTS and BOO treated with mirabegron.
In this randomized, double-blind, parallel group,
placebo controlled, multicenter phase II study
with 12 weeks duration, 200 men with more than
45 years with LUTS and BOO were randomized
(1 : 1 : 1) in three groups (mirabegron 50 mg/mirabe-
gron 100 mg/placebo). After 12 weeks of treatment,
it was found that mirabegron 50 or 100 mg did not
impair Pdet Qmax or Qmax relative to placebo.
Also, both treatment arms showed a significant
decrease in micturition frequency versus placebo.
In addition, the 50 mg mirabegron group showed a
statistically significant decrease of urgency episodes.
The adverse event profile was similar in the three
&&
groups [47 ].
These findings that show the urodynamic
safety of mirabegron in male patients with LUTS
and BOO, are very promising and may open a new
pathway in the individualized treatment of patients
with BPH/LUTS.
COMBINATION THERAPY WITH
5-PHOSPHODIESTERASE INHIBITORS
WITH ALPHA-BLOCKERS
Epidemiologic and pathophysiologic links between
LUTS/BPH and erectile dysfunction have been
demonstrated [2,48]. Current medical therapy for
BPH/LUTS although efficacious, has the potential
for side-effects related to sexual function [49]. More-
over, PDE5i increase the concentration and prolong
the activity of intracellular cGMP, thus reducing
smooth muscle tone of the detrusor, prostate and
urethra [50]. It is believed that these mechanisms
may contribute to improve BPH/LUTS.
The appearance of the first study suggesting
the improvement of LUTS in patients treated
with PDE5i occurred in 2002 [51]. Since then, several
studies have been published using PDE5i alone or in
combination with alpha-blockers in the treatment
of BPH/LUTS.
&
Gacci et al. [52 ] recently published an excellent
meta-analysis that selected 12 articles, seven on
PDE5-Is versus placebo, with 3214 men, and five
on the combination of PDE5i with alpha-blockers
versus alpha-blockers alone, with 216 men. The
analysis of the different articles, concluded that
although the median follow-up of the trials was
only 12 weeks, the use of PDE5i alone was associated
with a significant improvement of the IPSS score
(2.8, P < 0.0001) and of the International Index
of Erectile Function (IIEF) score (þ5.5; P < 0.0001).
However, Qmax did not change after PDEi
administration, its value being similar to that of
the placebo arms. The association of PDE5i and
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alpha-blockers was superior to alpha-blockers
alone in improving IPSS score (1.8; P ¼ 0.05),
IIEF score (þ3.6; P < 0.0001), and, interestingly, also
&
Qmax (þ1.5; P < 0.0001) [52 ].
In the same issue of European Urology that
published the meta-analysis, a new randomized,
double-blind, multicenter, placebo-controlled,
parallel-group study was published that included
men at least 45 years of age with BPH/LUTS, IPSS
&&
at least 13 and Qmax between 4 and 15 ml/s [53 ].
After a 4-week placebo run-in, men were rando-
mized in three groups: placebo (n ¼ 172), tadalafil
5 mg (n ¼ 171) or tamsulosin 0.4 mg (n ¼ 168) once
daily for 12 weeks. Results revealed similar improve-
ments versus placebo in IPSS and BPH Impact
Index in both tamsulosin and tadalafil groups.
As one could expect, the IIEF score improved
versus placebo only with tadalafil arm. Surprisingly,
Qmax increased significantly versus placebo with
both tadalafil (2.4 ml/s; P ¼ 0.009) and tamsulosin
(2.2 ml/s; P ¼ 0.014) [53 ].
&&
In a further subanalysis of this study, the effect
of both treatments on ejaculatory and orgasmic
function was evaluated. Analysis of orgasm and
ejaculation was based on the IIEF-Orgasmic
Function domain (IIEF-Q9 [ejaculatory frequency]
and Q10 [orgasmic frequency]). Other measures
included IIEF-intercourse satisfaction, overall
satisfaction and erectile function domains. Tadalafil
significantly improved ejaculation, orgasm, inter-
course, erectile function and overall satisfaction
over placebo. Men receiving tamsulosin experi-
enced a decrease in both ejaculatory/orgasmic
frequency and overall satisfaction versus placebo,
with no significant effect on erectile function [54].
CONCLUSION
The treatment of BPH/LUTS is slowly but constantly
evolving. The men’s LUTS that were once regarded
as resulting exclusively from prostatic growth are
now considered as a result of a large number of other
organ dysfunctions, within and outside the urinary
tract. Men present with variable symptomato-
logy and the predominance of each symptom, in
particular the relative component of the storage and
voiding LUTS should individualize the therapeutic
approach. Prostate volume (and probably serum
PSA) to estimate the risk of progression and
the presence of sexual dysfunction may also be
considered in the initial therapeutic option. By
doing this one might expect to target more specifi-
cally BPH/LUTS leading to a larger improvement in
patient’s QoL. Thus, if we still have a standard
treatment for BPH/LUTS based on alpha-blockers,
5ARIs or its combination, it is most probable that in
Volume 24
Number 1
January 2014
 Current medical treatment of LUTS/BPH: do we have a standard? Silva et al.
the future this classical approach will be replaced
by an individualized treatment which will take into
account the type of predominant LUTS, prostate
gland characteristics and sexual function.
Acknowledgements
None.
Conflicts of interest
F.C. has received honoraria from Companies Astellas,
Recordati, Allergan, Janssen-Cilag, Pfizer. For the
remaining authors there were no conflicts of interest.
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