Biology Reference
In-Depth Information
(
8.6
2.4) experienced greater improvement in IPSS than those with moderate
LUTS (
1.7). A significant reduction of bladder storage symptoms and an
increase in the BPH II and QoL were also noted in the treatment arm while no
significant changes in Q
max
were registered. From the later findings, the authors
concluded that extraprostatic pathophysiological mechanisms related to an
impairment of the activity of the NO-system might be involved in the etiology of
LUTS (McVary et al.
2007a
). The efficacy and safety of tadalafil (CIALIS
3.6
) were
also investigated in a randomized, double-blind, placebo-controlled study in men
with moderate-to-severe LUTS secondary to BPH. Following a 4-week placebo
run-in phase, 281 men were randomized to 5 mg tadalafil for 6 weeks, followed by
dose escalation to 20 mg for another 6 weeks or placebo for 12 weeks. Primary end
point was the change in IPSS after 6 and 12 weeks of treatment. Secondary efficacy
endpoints included patient IPSS, QoL, BPH II, and the LUTS
global assessment
questionnaire
(GAQ), as well as parameters from uroflowmetric measurements
(Q
max
). After 6 weeks and 12 weeks, tadalafil showed significant improvement in
those with LUTS, the respective mean change from baseline in IPSS was
™
2.8 in
tadalafil group vs.
1.7
(placebo). Mean subscores related to irritative and obstructive symptoms also
significantly improved in patients who had received tadalafil. Except for BPH II
after 6 weeks, all assessments of the disease-related QoL had significantly
improved after treatment with tadalafil. In contrast, no significant changes in
uroflowmetric values were observed. (McVary et al.
2007b
). In an 8-week rando-
mized, double-blind, placebo-controlled, multicenter study, Stief et al. (
2008
)
examined the efficacy of vardenafil (LEVITRA
1.2 in the placebo group (6 weeks) and
3.8 (verum) vs.
) in a cohort of 222 men
™
(aged 45-64 years) presenting with LUTS/BPH (IPSS
12). Patients were rando-
mized either to vardenafil (10 mg twice daily) or placebo. Efficacy outcome
included changes in peak urinary flow rate, as well as scores from the IPSS and a
nine-item BPH-specific QoL questionnaire (UROLIFE QoL 9). After treatment, a
decrease of 5.9 points in the IPSS was observed in the vardenafil group vs. 3.6
points in the placebo group. Significant changes in the IPSS subscores for storage
and voiding symptoms and an improvement in the UROLIFE QoL were also noted
in the vardenafil group. Since baseline values were already close to normal, Q
max
and postvoiding residual urine volume did not change significantly with treatment
(Stief et al.
2008
). It was shown more recently that sildenafil treatment also
improves Q
max
and Q
ave
(mean average flow rate) rates in men with LUTS sugges-
tive of BPE. A single dose of the PDE5-inhibitor (100 mg) resulted in an improve-
ment in Q
max
in 29 of 38 patients. Q
ave
and the mean voided volumes of the patients
also increased while no significant differences were registered in the Q
max
,Q
ave
,
and voided volumes of the control group before and after placebo (G
ulcer et al.
2008
). These results support the use of PDE5 inhibitors for treating LUTS and
urinary obstruction secondary to BPE. The combination of the PDE5 inhibitors silden-
afil (25 mg once daily) or tadalafil (10 mg once daily) and the alpha-adrenoceptor
antagonist alfuzosin (10 mg once daily) to treat LUTS has also been evaluated. Men
with previously untreated LUTS (and ED) were randomized to either alfuzosin,
sildenafil, or tadalafil or the combination of the alpha-blocker and a PDE5 inhibitor
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