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T
reatment
of
benign
prostatic
hyperplasia
R
ev
A
ssoc
M
ed
B
ras
2017; 63(2):95-99
97
caution inmen with suspected infravesical obstruction and
high post-voidal residual urine volume.
7-11
(
A
)
12
(
B
). Amul-
ticenter, randomized, non-blinded study, that included
treatment-naive patients with moderately symptomatic
BPH, concluded that a fixed dose of dutasteride/tamsulo-
sin may reduce the risk of clinical progression and improve
symptoms compared to expectant treatment, with op-
tional tamsulosin prescription (initiation of protocol-de-
fined therapy if symptoms did not improve).
20
(
A
)
Phosphodiesterase-5 inhibitors (iPDE5s)
Several studies demonstrate the effect of iPDE5s on the
treatment of BPH.
21-24
(
A
) The likely mechanisms of action
stem from effects on smooth muscle relaxation, endothe-
lial cell proliferation, improved blood flow, and activity on
the prostatic efferent nerves.
25
(
D
) Currently, tadalafil (5
mg once daily) is approved in Brazil for the treatment of
urinary symptoms associated with BPH. This indication
is based on double-blind randomized placebo-controlled
trials (RCT), that showed a significant reduction of I-PSS
after twelve weeks.
22,23,26,27
(
A
) A prospective placebo-con-
trolled study of tadalafil with tamsulosin used as an active
comparator showed that tadalafil led to a decrease in tam-
sulosin-like I-PSS as early as week 1.
23
(
A
) Since iPDE5 is
indicated for the treatment of erectile dysfunction, this
class of medication may be an option in the treatment of
patients presenting both disorders.
22,23,26
(
A
)
Combination therapy (iPDE5s and alpha-blockers)
The simultaneous use of iPDE5s and alpha-blockers may
cause symptomatic hypotension. Such a risk can be reduced
with tadalafil, uroselective alpha-blockers (tamsulosin, al-
fuzosin), low doses of alpha-blockers, separating doses for
several hours instead of using them simultaneously, or
waiting until the patient is taking a stable dose of a drug to
initiate the second one.
28
(
D
) A systematic review withmeta-
-analysis included seven RCTs [N=515 patients] and evalu-
ated the efficacy of iPDE5s alone or combined with alpha-
-blockers in the treatment of erectile dysfunction and LUTS,
with a follow-up ranging from60 days to three months. For
the treatment of erectile dysfunction, combination therapy
produced a statistically significant increase in the Interna-
tional Index of Erectile Function-Erectile Function (IIEF-EF)
compared with the group that used iPDE5s alone (MD 2.25,
95CI 0.07-4.43; six trials;
Ι
²=78%). In the treatment of LUTS,
the combination of iPDE5s and alpha-blockers produced
statistically significant reductions in I-PSS score (MD -4,21,
95CI -7.09–-1.32; five trials;
Ι
²=93%) and increase inmaximum
urinary flow (Q
max
) [MD 1.43, 95CI 0.38-2.47; four trials;
Ι
²=0%]. These results should be examined with caution on
account of the high heterogeneity between studies for some
outcomes, but we can infer that adding iPDE5s to alpha-
-blockers can improve BPH-LUTS.
29
(
A
)
Combination therapy (iPDE5s and i5ARs)
In an RCT with confidence intervals including clinically
unimportant differences, 696 men aged ≥ 45 years old and
with BPH were randomized to tadalafil 5 mg once daily
plus finasteride 5 mg/day or placebo plus finasteride 5 mg/
day for 26 weeks. Prostate symptoms were assessed by I-PSS.
At baseline, all patients had I-PSS ≥ 13 points, prostate
volume ≥ 30 cc and had never been treated with 5-phos-
phodiesterase inhibitors. 592 patients (85%) completed the
study. Combination therapy (tadalafil + finasteride) com-
pared to finasteride alone reduced the mean I-PSS after 26
weeks by 5.5 points vs. 4.5 points, respectively (minimum
mean square error of 1 point, 95CI 0.2-1.9 points). For this
comparison, the treatment-related adverse event rate (mild/
moderate) was 31% vs. 27% (p-value was not reported).
Combination therapy, compared to finasteride alone,
showed patient improvement, but not an overall impres-
sion of clinical improvement.
30
(
A
) Therefore, the addition
of tadalafil to finasteride may moderately improve urinary
symptoms in men with BPH.
30
(
A
)
The addition of tadalafil to finasteride cannot increase
the response to treatment clinically significantly at week
26, based on a post hoc secondary analysis of the RCT
described above.
30
(A)
Clinically significant response to
treatment was defined as a reduction ≥ 3 points or ≥ 25%
in the total I-PSS. Comparing the combination therapy
(tadalafil + finasteride) with finasteride alone at week 26,
the ≥ 3-point reduction in I-PSS was 71.4% vs. 70.2%, re-
spectively (not significant) and the ≥ 25% reduction in
I-PSS was 62% vs. 58.3% (not significant). Combination
therapy was significantly associated with greater satisfac-
tion with the treatment, in a pre-specified analysis.
31
(
B
)
In a subgroup analysis, also part of this study, includ-
ing 404 sexually active men, tadalafil plus finasteride
was associated with a higher score for erectile function
compared to finasteride alone (p<0.001 for all moments
analyzed).
30
(
A
)
R
ecommendation
•
•
Men with mild or moderate symptoms, with minimal
impact on quality of life, can be followed up with ac-
tive monitoring. (
A
)
•
•
Alpha-blockers are recommended in the treatment of
BPH-LUTS, with rapid symptom improvement, but its
mechanism of action does not interfere with disease
progression. (
A
)