ArticlePDF Available

Efficacy and Safety of Tadalafil 5 mg Administered Once Daily in Korean Men with Erectile Dysfunction: A Prospective, Multicenter Study

Authors:

Abstract and Figures

The aim of this study was to evaluate the efficacy of a daily dose of tadalafil 5 mg as well as its safety for the cardiovascular system in men with erectile dysfunction. This study included a total of 162 men who were administered a daily dose of tadalafil 5 mg between April and December of 2009. A total of 127 men completed the 8-week clinical trial. The International Index of Erectile Function (IIEF)-5, blood pressure, and heart rate were measured before treatment with tadalafil (V1) and 4 (V2) and 8 weeks (V3) after treatment with tadalafil. Adverse effects were assessed at V1, V2, and V3. In cases in which the International Prostate Symptom Score (IPSS) was ≥8 at V1, maximal flow rate (Qmax) and postvoid residual volume (PVR) were measured. The IIEF-5 values were 11.25±3.18, 14.56±3.79, and 16.91±3.56 at V1, V2, and V3, respectively, with significant improvement (V1 vs. V2, p<0.001; V1 vs. V3, p<0.001). The IPSS values were 10.59±5.56, 9.07±6.06, and 8.15±6.10 at V1, V2, and V3, respectively, and the differences were statistically significant (V1 vs. V2, p<0.001; V1 vs. V3, p<0.001). There were no significant differences in blood pressure or heart rate. Adverse effects were observed in 7 men (5.51%) at V2 and in 5 men (3.94%) at V3. Tadalafil 5 mg administered once-a-day may be effective in improving erectile function. Adverse effects on the cardiovascular system may be minimal. In addition, it is believed that this may also be effective in improving voiding symptoms.
Content may be subject to copyright.
Korean Journal of Urology
The Korean Urological Association, 2010 647 Korean J Urol 2010;51:647-652
www.kjurology. org
DOI:10.4111/kju.2010.51.9.647
Sexual Dysfunction
Efficacy and Safety of Tadalafil 5 mg Administered Once Daily in
Korean Men with Erectile Dysfunction: A Prospective, Multicenter
Study
Dong Hyuk Kang, Joo Yong Lee, Sung Yul Park, Hong Sang Moon, Tae Yoong Jeong1, Tag Keun Yoo2,
Hong Yong Choi, Hae Young Park, Tchun Yong Lee, Seung Wook Lee2
Department of Urology, Hanyang University College of Medicine, Seoul, 1Myongji Hospital, Kwandong University College of Medicine,
Goyang, 2Eulji Hospital, Eulji University College of Medicine, Seoul, Korea
Purpose: The ai m of th is stu dy was to evalua te the effic acy of a daily dose of t adala fil
5 mg as well as its safety for the cardiovascular system in men with erectile dysfunction.
Materials and Methods: This study included a total of 162 men who were administered
a daily dose of tadalafil 5 mg between April and December of 2009. A total of 127 men
completed the 8-week clinical trial. The International Index of Erectile Function
(IIEF)-5, blood pressure, and heart rate were measured before treatment with tadalafil
(V1) and 4 (V2) and 8 weeks (V3) after treatment with tadalafil. Adverse effects were
assessed at V1, V2, and V3. In cases in which the International Prostate Symptom Score
(IPSS) was 8 at V1, maximal flow rate (Qmax) and postvoid residual volume (PVR)
were measured.
Results: The IIEF-5 values were 11.25±3.18, 14.56±3.79, and 16.91±3.56 at V1, V2, and
V3, respectively, with significant improvement (V1 vs. V2, p0.001; V1 vs. V3, p
0.001). The IPSS values were 10.59±5.56, 9.07±6.06, and 8.15±6.10 at V1, V2, and
V3, respectively, and the differences were statistically significant (V1 vs. V2, p0.001;
V1 vs. V3, p0.001). There were no significant differences in blood pressure or heart
rate. Adverse effects were observed in 7 men (5.51%) at V2 and in 5 men (3.94%) at V3.
Conclusions: Tadalafil 5 mg administered once-a-day may be effective in improving
erectile function. Adverse effects on the cardiovascular system may be minimal. In addi-
tion, it is believed that this may also be effective in improving voiding symptoms.
Key Words: Erectile dysfunction; Safety; Tadalafil; Treatment outcome
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial
License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Article History:
received
12 July, 2010
accepted
17 August, 2010
Corresponding Author:
Seung Wook Lee
Department of Urology, Eulji Hospital,
Eulji University College of Medicine, 14,
Hangeulbiseok-gil, Nowon-gu, Seoul
139-711, Korea
TEL: +82-2-970-8306
FAX: +82-2-970-8349
E-mail: swleepark@gm ail.com
INTRODUCTION
Erectile dysfunction (ED) is defined as insufficient erection
or inability to maintain erection for satisfactory sexual
intercourse. ED is caused by a combination of factors such
as physiologic, neurologic, hormonal, arterial, and cav-
ernosal impairments [1]. ED affects about 150 million men
worldwide, and the number of subjects who suffer from ED
is expected to double by 2025 as the result of improved life
expectancy and the age-related nature of ED [2]. The phos-
phodiesterase type-5 inhibitors (PDE5i) used worldwide
are sildenafil, vardenafil HCl, and tadalafil, which have
been used to treat about 40 million patients with ED [3].
Tadalafil is an oral selective PDE5 inhibitor that improves
erectile function by provoking sexual stimulation through
the nitric oxide (NO)-cyclic guanosine monophosphate
(cGMP) pathway [4]. It has a longer half-life than other
drugs, and its duration of action is 36 hours. Many studies
have demonstrated that once-a-day treatment with low-
dose tadalafil is efficacious and safe. Daily treatment with
low-dose PDE5i has clinical implications because it en-
ables healthy men to have sexual intercourse at any time
Korean J Urol 2010;51:647-652
648 Kang et al
without taking the drug immediately before each inter-
course attempt. After administration of tadalafil in a dose
of 5 mg daily, tadalafil reaches a stable serum concentration
within 5 days, and because this drug has the longest half-
life among the PDE5i drugs, it is the most suitable for once-
a-day treatment [5]. Recently, there was evidence that
PDE5i improve lower urinary tract symptoms (LUTS).
However, there have been few studies of once-a-day treat-
ment with low-dose tadalafil in Korea. Therefore, this
study was conducted to evaluate the efficacy, safety, and
improvement in ED and LUTS after once-a-day treatment
with tadalafil 5 mg.
MATERIALS AND METHODS
1. Subjects and st udy design
A total of 162 men with ED were enrolled between April and
December of 2009. Of the 162 patients, 127 completed the
8-week clinical trial. This study was an open, prospective,
noncomparative study conducted in three centers of urol-
ogy in Korea and approved by the Institutional Review
Board. All subjects were assessed by using the 5-item ver-
sion of the International Index of Erectile Function
(IIEF)-5, and those who had an IIEF-5 score of 18 were
selected for the study. Subjects with ED were classified into
4 groups according to the cutoff value reported by Ahn et
al [6 ]: tho se with no ED (II EF-5 s core18), mild ED (14
IIEF-5 score18), moderate ED (10IIEF-5 score14),
and severe ED (IIEF-5 score10). The following subjects
were included in the study: those who (1) were between 40
and 70 years old, (2) had an IIEF-5 score 18 on screening,
and (3) had a willingness and the ability to participate in
this clinical study. The following subjects were excluded
from the study: those who (1) had shown hypersensitivity
reactions to PDE5i, (2) were on medication with drugs af-
fecting erectile function such as 5-alpha-reductase in-
hibitor within 1 month, (3) had been diagnosed with ED and
had undergone surgery, and (4) were on medication with
nitrate preparations and NO providers. Before the start of
the study (V1), information on the duration of illness,
smoking and drinking status, and past medical history was
collected. In addition, a physical examination including the
measurement of blood pressure (BP) and heart rate (HR),
12-lead electrocardiography, routine laboratory tests, and
urinalysis was performed. All subjects were given tadalafil
(Cialis) orally in a dose of 5 mg once-a-day immediately
after breakfast. They were asked to not take the drug more
than once daily. Its efficacy and safety were assessed at 4
(V2) and 8 weeks (V3) after the initial administration of the
drug. In 91 men (71.65%) with an International Prostate
Symptom Score (IPSS) of 8 at V1, the IPSS, maximal flow
rate (Qmax), and postvoid residual volume (PVR) as well
as the IIEF-5 were measured at V1, V2, and V3.
2. A sses s ment of efficacy and safet y
The efficacy of tadalafil 5 mg once-a-day was assessed by
using the IIEF-5 and Global Assessment Question (GAQ).
The IIEF-5 is a self-administered questionnaire that con-
sists of 5 domains assessing erectile function and inter-
course satisfaction. Higher scores in each domain reflect
better sexual function. The assessment of the efficacy of ta-
dalafil was supplemented by the dichotomous question
(GAQ), “Has the treatment you have taken over the past
8 weeks improved your erections?” For evaluation of the ef-
fects of tadalafil for LUTS, we measured the IPSS in all sub-
jects and LUTS were assessed only in subjects who had an
IPSS of 8 (n=91). In these subjects, Qmax and PVR to-
gether with the IIEF-5 score were assessed at V1, V2, and
V3. The subjects were further divided into 2 subgroups
[those with Qmax12 ml/sec (n=61, 67.03%) and those
with Qmax12 ml/sec (n=30, 32.97%)], and the efficacy
and safety of tadalafil were assessed for each. Safety evalu-
ation included history taking, physical examination, and
recording of adverse effects. The association of adverse ef-
fects with tadalafil was determined by the principal
investigator.
3. Statistical analysis
The intercourse satisfaction of the subjects was divided in-
to 4 categories: very satisfied, somewhat satisfied, some-
what dissatisfied, and very dissatisfied. “Being very sat-
isfied” and “being somewhat satisfied” were regarded as in-
tercourse satisfaction. Statistical comparisons of IPSS,
Qmax, and PVR before and after the use of tadalafil were
made with the paired t-test. Statistical analyses were per-
formed by using Open Office.org Calc (Open Office.org
version 3.2.0, Oracle Corp, Redwood Shores, CA, USA) and
MedCalc (MedCalc version 11.2.1.0, MedCalc Software,
Mariakerke, Belgium). A p-value of 0.05 was considered
statistically significant.
RESULTS
The mean age of the subjects was 55.88±6.35 years, and the
duration of ED was 7.84±3.75 months. The subjects’ mean
body mass index (BMI) was 25.32±3.38 kg/m2, and their
mean abdominal circumference was 87.50±5.31 cm. The
causes of ED were as follows: psychogenic etiologies in 13
men (10.24%), organic etiologies in 50 (39.37%), mixed eti-
ologies in 37 (29.13%), and unknown etiologies in 27 (21.26%).
The subjects with organic etiologies were classified into
small groups according to guidelines [7]. The organic etiol-
ogies were as follows: vascular ED in 22 (17.32%), neuro-
genic in 9 (7.09%), anatomical or structural in 5 (3.94%),
hormonal in 4 (3.15%), and drug-induced in 10 (7.87%). The
concurrent diseases were as follows: hypertension in 36
men (28.35%), diabetes mellitus (DM) in 41 (32.28%), be-
nign prostatic hyperplasia (BPH) in 33 (25.98%), chronic
obstructive pulmonary disease (COPD) in 10 (7.87%), ten-
sion headache in 2 (1.57%), ischemic stroke in 2 (1.57%),
and major depression disorder in 2 (1.57%) (Table 1). In se-
verity, 35 men (27.56%) had mild disease, 52 (40.94%) had
moderate, and 40 (31.5%) had severe. At V2, 21 men (12.96%)
and at V3, 14 men (9.93%) dropped out of the study. Table 2
Korean J Urol 2010;51:647-652
Efficacy and Safety of Tadalafil 5 mg Once-A-Day 649
TABLE 1. Patient characteristics at baseline
Characteristics
No. of patients 127
A
ge (years) 55.88±6.35
BMI (kg/m2) 25.32±3.38
Duration of erectile dysfunction (months) 7.84±3.75
Etiology of erectile dysfunction
Psychogenic (%) 13 (10.24)
Organic (%) 50 (39.37)
Mixed (%) 37 (29.13)
Unknown (%) 27 (21.26)
Underlying disease
Hypertension (%) 36 (28.35)
DM (%) 41 (32.28)
BPH (%) 33 (25.98)
COPD (%) 10 (7.87)
Tension headache (%) 2 (1.57)
Ischemic stroke (%) 2 (1.57)
Major depression disorder (%) 2 (1.57)
BMI: body mass index, DM: diabetes mellitus, BPH: benign pro-
static hyperplasia, COPD: chronic obstructive pulmonary diseas
e
TABLE 2. Reasons for drug discontinuation
No. of patients (%)
Total (%)
V2 V3
Patients completed 141 (82.04) 127 (78.40) 127 (78.40)
Patients discontinued 21 (12.96) 14 (8.64) 35 (21.60)
Insufficient response 7 (4.32) 5 (3.09) 12 (7.41)
Not returning for 11 (6.79) 7 (4.32) 18 (11.11)
follow-up
Uncontrollable 3 (1.85) 2 (1.23) 5 (3.08)
response
V
2: 4 weeks, V3: 8 weeks
TABLE 3. Result of IIEF-5, IPSS, Qmax, and PVR
V1 V2 V3 p-value
IIEF-5 11.25±3.18 14.56±3.79 16.91±3.56 0.001a
0.001b
Qmax (ml/s) (IPSS8, n=91) 13.85±4.38 13.97±4.41 14.04±4.40 0.124a
0.091b
Qmax (ml/s) (12 ml/sec, n=30) 8.46±1.51 8.61±1.87 8.87±2.06 0.218a
0.034b
Qmax (ml/s) (12 ml/sec, n=61) 16.34±2.68 16.43±2.74 16.41±2.89 0.304a
0.559b
PVR (ml) (IPSS8, n=91) 49.33±23.81 49.25±23.89 49.12±23.90 0.206a
0.052b
PVR (ml) (Qmax12 ml/sec, n=30) 48.26±24.49 48.31±24.60 47.75±24.26 0.685a
0.024b
PVR (ml) (Qmax12 ml/sec, n=61) 49.83±23.62 49.68±23.68 49.76±23.84 0.55a
0.547b
IIEF-5: International Index of Erectile Function-5, IPSS: International Prostate Symptom Score, Qmax: maximal flow rate, PVR:
post-void residual volume, V2: 4 weeks, V3: 8 weeks, a: V1 vs. V2, b: V1 vs. V3
shows the reasons for dropout.
The mean IIEF-5 score showed significant improvements
(Table 3). Regarding questions, the scores for all questions
were significantly higher (Fig. 1). At V1 with IPSS8, Qmax
and PVR were not significantly different. Only the IPSS
showed a significant difference between the groups. But,
in subjects with Qmax12 ml/sec, Qmax was improved sig-
nificantly at V3. PVR was also improved significantly at
V3. Otherwise, in subjects with Qmax12 ml/sec, Qmax
and PVR were not improved significantly (Table 3). There
were significant differences in Qmax (Fig. 2) and PVR be-
tween the 2 subgroups.
On the GAQ, 84 men (66.14%) reported “yes” at V2, and
95 men (74.80%) reported “yes” at V3. In intercourse sat-
isfaction after the endpoint of tadalafil administration, 59
men (46.46%) were “very satisfied,” 33 (25.98%) were
“somewhat satisfied,” 26 (20.47%) were “somewhat dissat-
isfied,” and 9 (7.09%) were “very dissatisfied.” Intercourse
satisfaction was observed in 92 men (72.44%), whereas 35
men expressed dissatisfaction by reason of ineffectiveness
(n=24, 68.57%), financial problems (n=5, 14.29%), and over
effect (n=6, 17.14%). A total of 74 men (58.27%) thought
that they could maintain normal erection during sexual
intercourse.
Adverse effects were observed in 7 men (5.51%) at V2 and
in 5 men (93.94%) at V3. Facial flushing was the most com-
mon adverse effect (n=3, 2.36% at V2; n=2, 1.57% at V3),
followed by headache (n=2, 1.57% each at V2 and V3), and
dizziness (n=2, 1.57% at V2; n=1, 0.79% at V3) (Table 4).
No subjects dropped out of the study as the result of adverse
effects.
The mean standing systolic BP was 126.95±7.18 mmHg
at V1, 127.55±7.87 mmHg at V2, and 127.28±7.83 mmHg
at V3 (V1 vs. V2, p=0.118; V1 vs. V3, p=0.396). The mean
standing diastolic BP was 82.12±4.00 mmHg at V1,
82.28±4.89 mmHg at V2, and 81.65±4.54 mmHg at V3 (V1
vs. V2, p=0.535; V1 vs. V3, p=0.087). The mean sitting sys-
Korean J Urol 2010;51:647-652
650 Kang et al
TABLE 4. Adverse effects 4 and 8 weeks after tadalafil treatmen
t
Adverse effects
No. of patients (%)
V2 V3
Cardiovascular disorders 3 (2.36) 2 (1.57)
 Facial flushing 3 (2.36) 2 (1.57)
Nervous system disorders 4 (3.15) 3 (2.36)
 Dizziness 2 (1.57) 1 (0.79)
 Headache 2 (1.57) 2 (1.57)
Patients with at least 1 7 (5.51) 5 (3.94)
adverse effect
V
2: 4 weeks, V3: 8 weeks
FIG. 1. There was a significant domain score increase in all ques-
tions (Q1 to Q5) of the International Index of Erectile Function
(IIEF)-5.
FIG. 2. In the group with maximal flow rate (Qmax) less than 12
ml/sec (n=30, 32.97%), there was a significant increase in Qmax
compared with that in the group with Qmax of 12 or more than
12 ml/sec (n=61, 67.03%).
tolic BP was 121.33±8.49 mmHg at V1, 121.82±7.76 mmHg
at V2, and 120.17±6.38 mmHg at V3 (V1 vs. V2, p=0.111;
V1 vs. V3, p=0.118). The mean sitting diastolic BP was
77.22±5.52 mmHg at V1, 77.28±4.86 mmHg at V2, and
77.13±5.19 mmHg at V3 (V1 vs. V2, p =0.890; V1 vs. V3,
p=0.855). The mean standing HR was 76.28±5.38 at V1,
76.48±7.12 at V2, and 75.94±5.22 at V3 (V1 vs. V2, p=0.676;
V1 vs. V3, p=0.073). The mean sitting HR was 76.25±5.51
at V1, 76.21±5.44 at V2, and 76.19±5.43 at V3 (V1 vs. V2,
p=0.740; V1 vs. V3, p=0.697). None of the differences in car-
diovascular system variables were statistically significant.
DISCUSSION
ED was reported to affect 18 million men in the United
States and 189 million men globally in 2004, 193 million
men in 2005, and 198 million men in 2006 [8,9]. ED is re-
lated to chronic conditions such as atherosclerosis, dia-
betes mellitus, and obesity that reduce arterial blood flow.
Endothelial dysfunction caused by such conditions is con-
sidered to be an important factor for ED [10,11].
PDE5i suppress the degradation of cGMP in the smooth
muscle cells of the corpus spongiosum, which maintains
the relaxation of the smooth muscle cells induced by NO
or nitrate [12]. After the introduction of sildenafil citrate
(Viagra, Pfizer Inc, New York, NY, USA) in 1998, more
than 30 million men with ED have taken these drugs [13].
Thereafter, vardenafil HCI (Levitra, Ganyer-GSK, Ratitan,
NJ, USA), tadalafil (Cialis, Lilly-ICOS, Indianapolis, IN,
USA), udenafil (Zydena, Dang-A Pharmaceutial Company,
Seoul, Korea), and mirodenafil (Mvix, SK Chemical, Seoul,
Korea) have been developed, with a high efficacy, a low inci-
dence of adverse effects, rapid onset of action, a longer dura-
tion of action, and a high specificity for PDE5 [14-17]. PDE5i
are currently first-line drugs for ED because of their high
efficacy, safety, and ease of use. Wespes et al have recom-
mended that men with ED should select the most effective
drug for themselves after the use of all available PDE5i
[18].
Previous studies have demonstrated that tadalafil im-
proves sexual functioning, intercourse satisfaction, and
quality of life for men and their female partners [19-21].
Tadalafil administered once-a-day eliminates the con-
ception that the use of this drug is limited to the sexual act
itself and instead improves sexual quality of life, unlike
on-demand products. Eardley et al reported that most men
have sexual intercourse within 30 minutes of their at-
tempt, regardless of the presence or absence of ED [22].
Fisher et al reported in a FEMALES study that 30% of men
and 34% of women do not perform a sexual act at a fixed
time [23]. These results suggest that sexual acts are not
performed at an expected time or during a fixed time period
and that there is a limitation in the use of PDE5i. The theo-
retical evidence for tadalafil administered once-a-day is
that desire for sexual intercourse is unexpected and sexual
intercourse is usually performed within a short period after
the decision.
Althof et al indicated that once-a-day treatment with ta-
dalafil 5 mg improves erection, vaginal penetration, and
overall sexual satisfaction compared with that in a placebo
Korean J Urol 2010;51:647-652
Efficacy and Safety of Tadalafil 5 mg Once-A-Day 651
group and that in both men with ED and their female part-
ners, erection achievement (99.0% and 96.6%, respectively),
vaginal penetration (98.6% and 97.4%, respectively), and
overall intercourse satisfaction (84.3% and 82.8%, respec-
tively) were excellent compared with the placebo group [24].
McVary et al stated that the IIEF-EF domain score and
IPSS were significantly higher 6 and 12 weeks after once-a-
day treatment with tadalafil 5 mg in the treatment group
than in the placebo group [25]. In our study, IIEF-5 scores
for all items were significantly increased after once-a-day
treatment with tadalafil 5 mg. As for intercourse satisfac-
tion, most men reported had intercourse satisfaction after
the use of tadalafil. Roehrborn et al reported that LUTS se-
condary to BPH were improved 4, 8, and 12 weeks after the
once-a-day administration of tadalafil 5 mg in the treat-
ment group as compared with the placebo group and that
there were no significant differences in Qmax between the
treatment and placebo groups [26]. Similarly, the IPSS was
significantly improved in this study, but Qmax and PVR
were not. However, in men with Qmax12 ml/sec, Qmax
and PVR were improved. Kaplan and Hatzichristou said,
“It is reasonable to assume that the reason why Qmax did
not improve is because flow rate was normal at baseline
[27]. There were no upper limits or exclusion criteria based
on flow rate and consequently, how can one expect to im-
prove a ‘normal’ flowrate?” So we think this was a very
meaningful study because there are no reports based on low
Qmax patients.
Because PDE5 exists in the vessels, bronchus, esoph-
agus, anal sphincter, urethra, and prostate, tadalafil caus-
es adverse effects in these organs. Seftel et al reported that
the most common treatment-emergent adverse events
were headache (15.7% vs. 6.3% with placebo), back pain
(8.8% vs. 0%), and dyspepsia (7.5% vs. 0%) after on-demand
20 mg tadalafil administration during 12 weeks [28].
Roehrborn et al documented that most men with ED toler-
ate a wide range of doses, so they can take the drug con-
tinually, and that there were no significant differences in
tadalafil-associated adverse effects between the treatment
and placebo groups [26].
Our study is subject to some limitations. First, there
were no placebo and control groups comparable to each
other. Second, this study had a limitation stemming from
a relatively short follow-up period (8 weeks). Third, we did
not restrict the use of alpha-blocker medication; therefore,
the results concerning LUTS cannot be regarded as a pure
effect of tadalafil. However, to the best of our knowledge,
this is the first such study in Korea. Further studies with
a larger sample size and a longer follow-up period are need-
ed to confirm our results.
CONCLUSIONS
There were a few mild adverse effects in men with ED taken
tadalafil 5 mg once-a-day. This treatment improved sexual
functioning, overall intercourse satisfaction, and LUTS.
The results of this study suggest that tadalafil 5 mg ad-
ministered once-a-day may be effective in the treatment of
ED with acceptable tolerability.
Conflicts of Interest
The authors have nothing to disclose.
REFEREN CES
1. Lue TF. Erectile dysfunction. N Engl J Med 2000;342:1802-13.
2. McKinlay JB. The worldwide prevalence and epidemiology of
erectile dysfunction. Int J Impot Res 2000;12(Suppl 4):S6-11.
3. Kim JJ, Moon DG. Past, present and future of PDE5 inhibitor.
Korean J Androl 2008;26:49-60.
4. Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins
V, et al. Efficacy and safety of tadalafil for the treatment of erectile
dysfunction: results of integrated analyses. J Urol 2002;168:1332-6.
5. Masson P, Lambert SM, Brown M, Shabsigh R. PDE-5 inhibitors:
current status and future trends. Urol Clin North Am 2005;32:
511-25.
6. Ahn TY, Lee DS, Kang W, Hong JH, Kim YS. Validation of an
abridged Korean version of the International Index of Erectile
Function (IIEF-5) as a diagnostic tool for erectile dysfunction.
Korean J Urol 2001;42:535-40.
7. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou
D, Montorsi F, et al. Guidelines on male sexual dysfunction: erec-
tile dysfunction and premature ejaculation. Eur Urol 2010;57:
804-14.
8. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for
erectile dysfunction in the US. Am J Med 2007;120:151-7.
9. Rubio-Aurioles E, Casabe A, Torres LO, Quinzanos L, Glina S,
Filimon I, et al. Efficacy and safety of tadalafil in the treatment
of Latin American men with erectile dysfunction: results of in-
tegrated analyses. J Sex Med 2008;5:1965-76.
10. Kim HW, Park WJ, Choi YS, Cho SY. The correlation between
erectile dysfunction and the severity of coronary artery involve-
ment in patients with coronary artery disease. Korean J Urol
2007;48:94-102.
11. Kam SC, Choi SM, Jeh SU, Lee SH, Hwa JS, Jung KH, et al.
Efficacy and safety of a herbal formula that mainly consists of cor-
nus officinalis for erectile dysfunction: a double-blind, place-
bo-controlled study. Korean J Urol 2007;48:741-7.
12. Lee U, Lee M, Kim SY, Ji YH, Hong JH, Ahn TY. Clinical efficacy
and safety of sildenafil in the men with erectile dysfunction in
Korea. Korean J Urol 2001;42:435-40.
13. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD,
Wicker PA. Oral sildenafil in the treatment of erectile dysfunction.
Sildenafil Study Group. N Engl J Med 1998;338:1397-404.
14. Yoo C, Park J, Kim W, Hong B, Hong J, Ahn TY. Comparison of
the efficacy, safety and patient preference of the phosphodiester-
ase type 5 inhibitors for the patients with erectile dysfunction
Korean J Urol 2007;48:219-25.
15. Ormrod D, Easthope SE, Figgitt DP. Vardenafil. Drugs Aging
2002;19:217-27.
16. Eardley I, Cartledge J. Tadalafil (Cialis) for men with erectile
dysfunction. Int J Clin Pract 2002;56:300-4.
17. Kuan J, Brock G. Selective phosphodiesterase type 5 inhibition
using tadalafil for the treatment of erectile dysfunction. Expert
Opin Investig Drugs 2002;11:1605-13.
18. Wespes E, Amar E, Hatzichristou D, Hatzimouratidis K, Montorsi
F, Pryor J, et al. EAU Guidelines on erectile dysfunction: an
update. Eur Urol 2006;49:806-15.
Korean J Urol 2010;51:647-652
652 Kang et al
19. Althof SE, Eid JF, Talley DR, Brock GB, Dunn ME, Tomlin ME,
et al. Through the eyes of women: the partners' perspective on
tadalafil. Urology 2006;68:631-5.
20. Rubio-Aurioles E, Kim ED, Rosen RC, Porst H, Burns P, Zeigler
H, et al. Impact on erectile function and sexual quality of life of
couples: a double-blind, randomized, placebo-controlled trial of
tadalafil taken once daily. J Sex Med 2009;6:1314-23.
21. Carson CC, Rajfer J, Eardley I, Carrier S, Denne JS, Walker DJ,
et al. The efficacy and safety of tadalafil: an update. BJU Int
2004;93:1276-81.
22. Eardley I, Dean J, Barn es T, Kirby M, Gla ss er D, Solanki J. The
sexual habits of British men and women over 40 years old. BJU
Int 2004;93:563-7.
23. Fisher WA, Rosen RC, Eardley I, Sand M, Goldstein I. Sexual ex-
perience of female partners of men with erectile dysfunction: the
female experience of men's attitudes to life events and sexuality
(FEMALES) study. J Sex Med 2005;2:675-84.
24. Althof SE, Rubio-Aurioles E, Kingsberg S, Zeigler H, Wong DG,
Burns P. Impact of tadalafil once daily in men with erectile dys-
function-including a report of the partners' evaluation. Urology
2010;75:1358-63.
25. McVary KT, Roehrborn CG, Kaminetsky JC, Auerbach SM,
Wachs B, Young JM, et al. Tadalafil relieves lower urinary tract
symptoms secondary to benign prostatic hyperplasia. J Urol
2007;177:1401-7.
26. Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L.
Tadalafil administered once daily for lower urinary tract symp-
toms secondary to benign prostatic hyperplasia: a dose finding
study. J Urol 2008;180:1228-34.
27. Kaplan SA, Hatzichristou D. Open to debate. The motion: PDE5
inhibitors will have a significant role in the treatment of BPH. Eur
Urol 2007;52:1523-7.
28. Seftel AD, Wilson SK, Knapp PM, Shin J, Wang WC, Ahuja S. The
efficacy and safety of tadalafil in United States and Puerto Rican
men with erectile dysfunction. J Urol 2004;172:652-7.
... RP was the first treatment for localized prostate cancer that benefits overall survival and cancer-specific survival (3). Furthermore, the introduction of pioneering nerve-sparing robot-assisted laparoscopic radical prostatectomy has significantly improved the potency rate after RP (4). Despite surgical technical advancements, many patients experience erectile dysfunction (ED) after prostatectomy because of cavernous nerve injury (CNI) (5). ...
Article
Background and objectives: Few studies were evaluated the effect of blindness on outcome in animal models, though a potential effect of blinding has been reported in clinical trials. We evaluated the effects of adipose tissue-derived stem cells (ADSCs) on cavernous nerve injury (CNI)-induced erectile dysfunction (ED) in the rat and examined how proper blinding of the outcome assessor affected treatment effect. Methods and results: We searched in Pubmed, EMBASE, Cochrane and Web of Science databases from inception to January 2019. We included CNI animal model, randomized controlled experiments, and ADSC intervention. Erectile function and structural changes were assessed by intracavernous pressure and mean arterial pressure (ICP/MAP) ratios, neuronal nitric oxide synthase (nNOS) levels, cavernous smooth muscle and collagen (CSM/collagen) ratios, and cyclic guanosine monophosphate (cGMP). Results: Nineteen studies were included in the final meta-analysis. The ICP/MAP ratio of the ADSC treatment group increased compared to the control group (SMD=1.33, 95%CI: 1.11∼1.56, I2=72%). The nNOS level (SMD=2.29, 95%CI: 1.74∼2.84, I2=75%), CSM/collagen (SMD=2.57, 95%CI: 1.62∼3.52; I2=85%), and cGMP (SMD=2.96, 95%CI: 1.82∼4.10, I2=62%) were also increased in the ADSC treatment group. Preplanned subgroup analysis was conducted to explore the source of heterogeneity. Five studies with blinded outcome assessment were significantly less effective than the unblinded studies (SMD=1.33, 95%CI: 0.86∼1.80; SMD=1.81, 95%CI: 1.17∼2.46, respectively). Conclusions: ADSCs might be effective in improving erectile function and structural change in CNI-induced ED. However, non-blinded outcome assessors might cause detection bias and overestimate treatment efficacy. Therefore, the ADSC efficacy must be further evaluated with a rigorous study design to avoid bias.
... [29] A randomized, double-blind, placebo-controlled trial evaluating the effects of a 12-week prescription of a 5 mg OaD dose of tadalafil among 354 Korean men with BPH reported beneficial effects of the treatment, with the drug being welltolerated. [30] With regards to safety, we identified only transient or mild adverse effects in our study group, which did not hinder participants' daily function. Moreover, the 5 mg tadalafil dose had no significant effect on vital signs, despite the vasodilation effects of tadalafil. ...
Article
Full-text available
Background: The primary aim of this study was to evaluate the effects of a once-a-day 5 mg dose of tadalafil, prescribed for 8 weeks, on the quality of life (QoL) of South Korean men with andropause symptoms, including erectile dysfunction (ED), using a single group, open-labeled, before-and-after preliminary trial. The secondary objective was to evaluate the effectiveness and safety of tadalafil for ED. Methods: Forty South Korean men (>35 years of age) with andropause symptoms including ED were enrolled into our trial. Andropause syndrome was defined using the androgen deficiency in aging males (ADAM) questionnaire and other screening tests, including testosterone levels. The following outcome measures were obtained at baseline and at 4 and 8 weeks of tadalafil treatment: physical examination, adverse effects, Short Form 12 Health Survey (SF-12) score, International Index of Erectile Function (IIEF-5) score, bioelectrical impedance analysis (BIA), and free radical testing. Results: Treatment increased the SF-12 Mental component score, used as a proxy measure of quality of life, from baseline to at 4 and 8 weeks (P < .05). In addition, the mean IIEF-5 score, which assesses sexual function, increased from baseline at 4 and 8 weeks (P < .05), with this increase being significant at both time points. No adverse effects were noted. Conclusion: Tadalafil (5 mg dose, once daily) is a safe and effective treatment to improve ED, and overall QoL, among Korean men with andropause symptoms, including ED.
... This prolonged half-life of tadalafil is due to the low volume of distribution, slow clearance by liver and nearly 80% bioavailability of the drug and the pharmacologic effect may persist for up to 36 h. 16 Because of this retention by the metabolism, many studies have been performed to optimize the therapeutic effect of tadalafil through modification in drug administration and dosage intervals, illustrating the differences between on-demand and daily treatment. ...
Article
Full-text available
The purposeof this study is to investigate and compare the effects of 5-mg once-daily tadalafil versus 5-mg alternate-day tadalafil in men with moderate-to-severe erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Between January 2012 and June 2013, 144 men presenting with an International Index of Erectile Function-5 (IIEF-5) score of <18 and an International Prostate Symptom Score (IPSS) of >8 were enrolled to the study. Patients were allocated the simple alternate randomization into Group I (5-mg once-daily tadalafil) and Group II (5-mg alternate-day tadalafil). Changes in IIEF scores, Sexual Encounter Profile Question 3 (SEP Q3) percentage, IPSS, uroflowmetry and post void residual at the first visit (V1), week 4 (V2) and week 12 (V3) were compared. No significant difference was found between the baseline patient characteristics of Group I and Group II. Treatment with 5-mg daily tadalafil demonstrated improvement in IIEF, SEP Q3 percentage and IPSS score between V1 and V2, and that between V1 and V3. Patients receiving 5-mg alternate-day tadalafil also showed a significant improvement in IIEF, SEP Q3 percentage, and IPSS score between V1 and V2, and that between V2 and V3. However, no significant improvements were found in any other parameters. There were no significant differences between Group I and Group II apart from IIEF scores in V2 (19.4 versus 17.9, respectively). The SEP Q3 percentage was also higher at the V2 visit for Group I and Group II (35.6 versus 30.9%). Even with no placebo control and short of LUTS medication control, the use of 5-mg once-daily or alternate-day treatment with tadalafil was well tolerated in patients and effectively improved the IIEF score, IPSS score and SEP Q3 percentage. Management of patients with 5-mg alternate-day tadalafil could be adequate for regular use in patients with ED and LUTS.International Journal of Impotence Research advance online publication, 3 July 2014; doi:10.1038/ijir.2014.19.
... Moreover, the mean half-life of tadalafil (17.5 hours) is longer than that of sildenafil and vardenafil (about 4 hours) [27]. The longer duration of the drug may allow patients with ED to enjoy sexual activity free from the burden of planning drug intake before intercourse, which can improve the patients' sexual quality of life [27][28][29]. ...
Article
Full-text available
Purpose To evaluate the efficacy and safety of tadalafil 5 mg once daily use in the treatment of erectile dysfunction (ED) after robot-assisted laparoscopic radical prostatectomy (RALP). Materials and Methods The study retrospectively evaluated 92 patients who underwent RALP at Dong-A University Hospital. The patients were surveyed by use of the abridged five-item version of the International Index of Erectile Function (IIEF-5) questionnaire, which was self-administered before surgery and at 6 months and 1 year after surgery. The 92 patients were classified into the tadalafil group (n=47) and the non-tadalafil group (n=45). Each group was then classified depending on the nerve-sparing (NS) procedure used: bilateral NS or unilateral NS. Results At 6 months, the total IIEF-5 scores of the tadalafil group and the non-tadalafil group were 10.0±3.4 and 7.0±4.0, respectively. At 1 year, the total IIEF-5 score in the tadalafil group was significantly greater than that in the non-tadalafil group (13.2±5.6 vs. 7.7±4.8, p<0.0001). Statistically significant improvements (p<0.05) were observed in the tadalafil group for all 5 domains of the IIEF-5 score, whereas in the non-tadalafil group there was no significant improvement in any of the domains at 1 year. The reported side effects were flushing (8.5%, n=4), headache (4.3%, n=2), and dizziness (2.1%, n=1). Conclusions In ED patients after NS RALP, a once-daily dose of tadalafil 5 mg was well tolerated and significantly improved EF compared with that in the non-tadalafil group.
... A duration of symptoms of at least 3 months is considered acceptable to establish a diagnosis of erectile dysfunction, except in some instances of trauma or surgery [5]. Erectile dysfunction affected about 150 million men worldwide in 2000, and this number is expected to double by 2025 as a result of improved life expectancy and the age-related nature of erectile dysfunction [6]. This disorder is also associated with lower overall life satisfaction scores, mental health quality of life (QoL) scores, and vitality QoL scores [7]. ...
Article
Full-text available
A rapid growth in the socioeconomic status of Koreans has triggered an unprecedented explosion of health information for the general population. Despite its obvious benefits, this increase in information could also result in potentially harmful effects for both consumers and professionals who do not use it appropriately. Thus, this study was conducted to evaluate the quality and accuracy of health information on erectile dysfunction from 10 nationwide daily newspapers. This study analyzed health information from 10 nationwide daily newspapers in Korea from January 2011 through December 2011. We reviewed the health information for quality by using evidence-based medicine tools and evaluated the accuracy of the information provided. Articles that simply summarized scientific congresses or journal articles and that did not include direct quotations were excluded, as were advertisements. A total of 47 articles were gathered. Among them, 27 (57.4%) contained inaccurate or misleading statements on the basis of an evidence-based medicine evaluation. These statements included using inappropriate surrogate outcomes as clinical endpoints (three cases, 6.4%), extrapolating nonhuman results to humans (two cases, 4.3%), exaggerating the significance of results (eight cases, 17.0%), and using incorrect words (14 cases, 29.8%). The rate of error was higher in the information from Korean sources than in that from international sources (22 cases vs. 5 cases). Approximately 57% of all articles on erectile dysfunction from 10 nationwide daily newspapers were found to contain inaccuracies.
Article
Introduction: Erectile dysfunction is a common condition among diabetic men. Many treatments are now available with variable responses. Aim: This study aimed to evaluate the effect of daily oral L-arginine plus tadalafil in diabetic patients with mild to moderate erectile dysfunction. Methods: A double-blinded, randomized, controlled clinical trial was conducted with 108 diabetic male patients. Each patient was assessed by medical and sexual histories, International Index of Erectile Function 5-item questionnaires, pharmaco-penile duplex ultrasonography, and serum testosterone level. Main Outcome Measure: Improvement in International Index of Erectile Function 5-item, serum testosterone level and pharmaco-penile duplex ultrasonography. Results: Erectile functions were significantly improved in all patients after treatment as compared with baseline and placebo (P < .001). Patients who received both drugs showed significant improvement compared to those treated with single drugs, as assessed by International Index of Erectile Function scores and total testosterone (P < .001). Pharmaco-penile ultrasound duplex results showed non-significant differences among patients treated with both drugs and those with each drug alone. Conclusion: Daily use of L-arginine with tadalafil significantly increased the International Index of Erectile Function scores and total testosterone levels as compared to each drug alone in diabetic patients with erectile dysfunction. No differences were found based on pharmaco-penile duplex findings
Article
Introduction: Erectile dysfunction is a common condition among diabetic men. Many treatments are now available with variable responses. Aim: This study aimed to evaluate the effect of daily oral L-arginine plus tadalafil in diabetic patients with mild to moderate erectile dysfunction. Methods: A double-blinded, randomized, controlled clinical trial was conducted with 108 diabetic male patients. Each patient was assessed by medical and sexual histories, International Index of Erectile Function 5-item questionnaires, pharmaco-penile duplex ultrasonography, and serum testosterone level. Main Outcome Measure: Improvement in International Index of Erectile Function 5-item, serum testosterone level and pharmaco-penile duplex ultrasonography. Results: Erectile functions were significantly improved in all patients after treatment as compared with baseline and placebo (P <.001). Patients who received both drugs showed significant improvement compared to those treated with single drugs, as assessed by International Index of Erectile Function scores and total testosterone (P <.001). Pharmaco-penile ultrasound duplex results showed non-significant differences among patients treated with both drugs and those with each drug alone. Conclusion: Daily use of L-arginine with tadalafil significantly increased the International Index of Erectile Function scores and total testosterone levels as compared to each drug alone in diabetic patients with erectile dysfunction. No differences were found based on pharmaco-penile duplex findings. El Taieb M, Hegazy E, Ibrahim A. Daily Oral L-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded, Randomized, Controlled Clinical Trial.
Article
Full-text available
Introduction: Erectile dysfunction is a common condition among diabetic men. Many treatments are now available with variable responses. Aim: This study aimed to evaluate the effect of daily oral l-arginine plus tadalafil in diabetic patients with mild to moderate erectile dysfunction. Methods: A double-blinded, randomized, controlled clinical trial was conducted with 108 diabetic male patients. Each patient was assessed by medical and sexual histories, International Index of Erectile Function 5-item questionnaires, pharmaco-penile duplex ultrasonography, and serum testosterone level. Main outcome measure: Improvement in International Index of Erectile Function 5-item, serum testosterone level and pharmaco-penile duplex ultrasonography. Results: Erectile functions were significantly improved in all patients after treatment as compared with baseline and placebo (P < .001). Patients who received both drugs showed significant improvement compared to those treated with single drugs, as assessed by International Index of Erectile Function scores and total testosterone (P < .001). Pharmaco-penile ultrasound duplex results showed non-significant differences among patients treated with both drugs and those with each drug alone. Conclusion: Daily use of l-arginine with tadalafil significantly increased the International Index of Erectile Function scores and total testosterone levels as compared to each drug alone in diabetic patients with erectile dysfunction. No differences were found based on pharmaco-penile duplex findings. El Taieb M, Hegazy E, Ibrahim A. Daily Orall-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded, Randomized, Controlled Clinical Trial. J Sex Med 2019; 19:1390-1397.
Article
Introduction Phosphodiesterase type 5 (PDE-5) hydrolyzes cyclic guanylate monophosphate (cGMP) specifically to 5′ GMP, promoting successful corporeal vascular relaxation and penile erection during sexual stimulation. Oral PDE-5 inhibitors such as sildenafil, vardenafil, tadalafil, and avanafil have provided noninvasive, effective, well-tolerated treatment for erectile dysfunction (ED) patients and, at the same time, stimulated both academic and clinical interests. Lately, some oral PDE-5 inhibitors were released as low-dose preparations with the concept of potential daily administration and long-term use. Aim To highlight the possible potential implications of low-dose long-term use of PDE-5 inhibitors. Method A systematic review was carried out until December 2015 based on a search of all concerned articles in MEDLINE, medical subjects heading (MeSH) databases, Scopus, The Cochrane Library, EMBASE, and CINAHL databases without language restriction. Key words used to assess the outcome and estimates for concerned associations were: PDE-5 inhibitors; erectile dysfunction; low-dose; long-term; sildenafil; tadalafil; vardenafil; avanafil. Main Outcome Measures Demonstrating different implications for low-dose long-term use of PDE-5 inhibitors. Results Low-dose and/or long-term use of PDE-5 inhibitors was shown to put forth beneficial sound effects in different medical implications with potentials that could be extended for different utilities. These implications included sexual, urogenital, cardiovascular, pulmonary, cutaneous, gastrointestinal, and reproductive, as well as neurological disorders. However, it is evident that most potential appliances were carried out experimentally on preclinical studies with off-label indications. Conclusion Making use of and exploring low-dose and/or long-term use of several PDE-5 inhibitors for their possible implications seem to be valuable in different medical disorders. Increased knowledge of the drug characteristics, comparative treatment regimens, optimal prescribing patterns, and well-designed clinical trials are needed before these agents can be recommended for use.
Article
Background Erectile dysfunction (ED) is a common male sexual disorder worldwide. Three oral phosphodiesterase type 5 inhibitors (PDE5Is) – sildenafil, tadalafil and vardenafil – are available for treatment of ED. This study quantitatively evaluated the therapeutic efficacy and safety of these medications to assist treatment decision making.Methods We used multiple criteria decision analysis (MCDA) to assess the totality of risk–benefit of PDE5Is. We created two models: (i) the overall model included ‘overall improvement in erections’ and ‘any adverse events’ and (ii) the detailed model included ‘erectile function domain’, ‘ability for sexual intercourse’, ‘duration of erection last’, ‘serious adverse events’, ‘headache’, ‘flushing’ and ‘dyspepsia’. We calculated a synthetic utility for each drug accounting for all of its benefits and risks.ResultsConsidering the overall risk–benefit, vardenafil had the highest synthetic utility among three medications; in the order of synthetic utilities: vardenafil (0.568), tadalafil (0.478) and sildenafil (0.437). However, when specific risk and benefit criteria were assessed, tadalafil had the highest synthetic utility (0.602) according to the conjoint evaluation (synthetic utility for vardenafil is 0.491 and sildenafil is 0.442, respectively). The sensitivity analysis based on the uncertainties of weight on risks of any adverse events (including serious adverse events and headache) suggested our results were robust.Conclusions This study provides a useful approach that comprehensively and systematically assesses and compares the risk–benefit of several treatment alternatives. Our study not only rank treatment alternatives by synthetic utilities based on the risk–benefit balance but also compare specific risk and benefit criteria between these medicines. Our results provide valuable evidence that can guide clinicians and patients in making treatment decisions.
Article
Full-text available
Purpose: The aim of this study was to evaluate the efficacy and safety of a herbal formula that mainly consists of Cornus officinalis for treating erectile dysfunction. Materials and methods: Eighty patients suffering with erectile dysfunction were enrolled in this randomized, double-blinded, placebo-controlled study. The average duration of erectile dysfunction of the herbal formula group (n=40) vs. the placebo group (n=40) were 19.33±18.13 months vs. 19.33±25.62 months, respectively. The safety variables we examined were the history, physical examination, vital signs, EKG, clinical laboratory tests and hormonal tests. Efficacy assessments included the International Index of Erectile Function (IIEF), the sexual encounter profile (SEP) diary and Global Assessment Questions (GAQ). Results: No significant changes in the laboratory values, hormone tests and blood pressure were observed in both groups. In comparison with the placebo group (6.57±11.72), the herbal formula group experienced a significant improvement of the IIEF (11.13±11.83) (p<0.05). When the herbal formula and placebo groups were divided by age and the IIEF score (age: 50 years and IIEF: 42) and then compared, the low IIEF group (IIEF≤ 42) and old age group (age ≥ 50) of the herbal formula group significantly improved their IIEF score (p<0.05). The herbal formula group significantly improved their GAQ score (p<0.05). The herbal formula was well tolerated. The common adverse events were headache (2.5%) and nausea (5%). Conclusions: In conclusion, the herbal formula that mainly consists Cornus officinalis was not only effective at improving erectile function, but it was also safe for the treatment of erectile dysfunction.
Article
Full-text available
Purpose: Erectile dysfunction (ED) may be considered as a clinical manifestation of generalized vascular disease. This study aimed to assess the correlation between ED and the severity of the involved coronary artery in patients with coronary artery disease (CAD). Materials and Methods: 255 men with CAD, who underwent coronary angiography (CAG), were evaluated for erectile function using a questionnaire that included a 5-item Version the International Index of Erectile Function (IIEF-5). Cardiovascular risk factors were also reviewed. The correlation between erectile function and the number of involved coronary vessels, age and number of accompanying cardiovascular risk factors were analyzed. Results: Of the patients, 59.6% had various degrees of ED, which were subdivided into mild (21.7%), moderate (14.5%) and complete (63.8%) according to the severity. The cardiovascular risk factors were hypertension, smoking, overweight, age, lipid abnormalities and diabetes in 67.8, 67.5, 47.1, 38.4, 28.6 and 19.6%, respectively. One, two and three coronary vessels were involved in 26.3, 27.4 and 21.2%, respectively, while 25.1% showed non specific finding on CAG, despite abnormal findings in the resting ECG and treadmill exercise test. Erectile function decreased significantly according to the increasing number of involved coronary vessels (p < 0.05), age (p < 0.001) and accompanying cardiovascular risk factors (p < 0.05). Of the cardiovascular risk factors, age, smoking and diabetes had negative effects on erectile function (p < 0.05) in patients with CAD. Conclusions: Statistically significant correlations were demonstrated between ED and the number of involved coronary vessels, age and the number of accompanying cardiovascular risk factors in patients with CAD. Furthermore, in patients with symptoms of chest discomfort, although CAG showed non specific findings, the possibility of hidden ED will need to be investigated.
Article
Full-text available
Purpose: To compare the clinical efficacy and safety of three phosphodiesterase type 5 (PDE5) inhibitors in the treatment of mele erectile dysfunction according to patient preference. Materials and Methods: Between January 2004 and August 2005, 113 male erectile dysfunctional patients were enrolled to this randomized, prospective, comparative, open-label, triple-crossover study of three PDE5 inhibitors. Patients were assigned to one of six medication schedules, and were prescribed a full dose of the drugs for 8 weeks, with a week of washout period prior to the next drug cycle. The International Index of Erectile Function (IIEF) scores and side effects related with each medication were obtained at the end of study. 48 patients finished all the medications, and completed the study with a global assessment questionnaire on their drug preference and reasons for that preference. Results: The mean age of the patients was 54.6 (33-73) years. The mean pre-treatment IIEF and EF domain scores (±S.D.) were 28.2±14.7 and 10.6 ±6.6, respectively. The scores were significantly improved, to 47.9+14.6 and 19.9±6.6 with sildenafil, to 49.7±12.3 and 21.3±5.8 with vardenafil, and to 47.9±14.9 and 19.8±7.2 with tadalafil (p<0.01). There were no significant differences in the scores or frequencies of side effects between the drugs. The preference percentages were 29.2, 29.2 and 35.4% for sildenafil, vardenafil and tadalafil, respectively. Patient preference was mainly due to improvement in erectile function (70.9%), such as rigid erection, prolonged erection and fast erection, and not to the infrequent rate of side effects (20.8%). Conclusions: There were no significant differences of the efficacy and safety among the three PDE5 inhibitors. The preference for a drug for the treatment of erectile dysfunction was mainly related to the efficacy on the improvement of erectile function rather than the less frequent side effects.
Article
Full-text available
Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male sexual dysfunctions. To present the updated version of 2009 European Association of Urology (EAU) guidelines on ED and PE. A systematic review of the recent literature on the epidemiology, diagnosis, and treatment of ED and PE was performed. Levels of evidence and grades of recommendation were assigned. ED is highly prevalent, and 5-20% of men have moderate to severe ED. ED shares common risk factors with cardiovascular disease. Diagnosis is based on medical and sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to the patient's complaints and risk factors. Treatment is based on phosphodiesterase type 5 inhibitors (PDE5-Is), including sildenafil, tadalafil, and vardenafil. PDE5-Is have high efficacy and safety rates, even in difficult-to-treat populations such as patients with diabetes mellitus. Treatment options for patients who do not respond to PDE5-Is or for whom PDE5-Is are contraindicated include intracavernous injections, intraurethral alprostadil, vacuum constriction devices, or implantation of a penile prosthesis. PE has prevalence rates of 20-30%. PE may be classified as lifelong (primary) or acquired (secondary). Diagnosis is based on medical and sexual history assessing intravaginal ejaculatory latency time, perceived control, distress, and interpersonal difficulty related to the ejaculatory dysfunction. Physical examination and laboratory testing may be needed in selected patients only. Pharmacotherapy is the basis of treatment in lifelong PE, including daily dosing of selective serotonin reuptake inhibitors and topical anaesthetics. Dapoxetine is the only drug approved for the on-demand treatment of PE in Europe. Behavioural techniques may be efficacious as a monotherapy or in combination with pharmacotherapy. Recurrence is likely to occur after treatment withdrawal. These EAU guidelines summarise the present information on ED and PE. The extended version of the guidelines is available at the EAU Web site (http://www.uroweb.org/nc/professional-resources/guidelines/online/).
Article
Introduction: Clinical research on erectile dysfunction (ED) has focused primarily on the male and the impact of treatment on their erectile function (EF) and sexual quality of life. However, ED affects the quality of life of both the male and the female partner. The literature examining the impact on the female partner resulting from treating the male's ED is somewhat limited. Aims: To determine the efficacy of tadalafil 5 mg taken once daily compared with placebo on men's EF and sexual quality of life, and to determine the impact of this treatment on the female partner's sexual quality of life. Main outcome measures: The co-primary outcome measures for this study were changes from baseline to end point in the EF domain of the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) question 2 (SEP-2) and question 3 (SEP-3), and the Sexual Quality of Life (SQoL) domain of the Sexual Life Quality Questionnaire (SLQQ) (subject and partner). Methods. Following a 4-week treatment-free run-in phase, 342 subjects and their partners were randomly assigned to either placebo (N = 78) or tadalafil 5 mg (N = 264) for 12 weeks. The subjects' and partners' responses to study measures were collected throughout the study. Results: Compared with placebo, tadalafil-treated subjects showed a significant improvement on efficacy measures (P < 0.001) including changes in the IIEF-EF, SEP-2 and SEP-3. In addition, the sexual quality of life of men and their female partners, as measured by the SQoL domain, was significantly improved with tadalafil 5 mg taken once daily (P < 0.001) compared with placebo. Conclusions: Tadalafil 5 mg once daily significantly improved EF and sexual quality of life for men with ED. In addition, the sexual quality of life of the female partners of the men treated with tadalafil was significantly improved.
Article
To evaluate the effect of tadalafil 5 mg taken once daily on efficacy (erection achievement and penetration) and overall sexual satisfaction in men with erectile dysfunction (ED) and their female partners. This retrospective analysis included data pooled from 2 multicenter, randomized, double-blind, placebo-controlled trials that included 505 couples (tadalafil, n=373; placebo, n=132) in which the men received tadalafil 5 mg once daily or placebo for 12 weeks. Individual Sexual Encounter Profile (SEP) diaries were completed independently by the male subject and his female partner after each sexual intercourse attempt. The mean per-subject/per-partner percentage of "yes" responses to SEP diary questions were assessed, as was agreement between subjects' and partners' responses. Subjects and partners in the tadalafil-treated group reported significantly greater improvements in the man's ability to achieve some erection, vaginal penetration, and overall sexual satisfaction compared with the placebo-treated group (P<.001). For all intercourse attempts, the mean per-couple percentage of agreement for those in the tadalafil and placebo groups, respectively, was high for erection achievement (99.0% and 96.6%), vaginal penetration (98.6% and 97.4%), and overall satisfaction (84.3% and 82.8%). Tadalafil 5 mg taken once daily as treatment for ED improved overall satisfaction for men and their female partners. This analysis demonstrates the high concordance among couples in their responses to the man's treatment for ED.
Article
Phosphodiesterase type 5 inhibitors are widely used to treat erectile dysfunction. Preliminary data have suggested phosphodiesterase type 5 inhibitor efficacy in men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia. After a 4-week placebo run-in period 1,058 men with benign prostatic hyperplasia lower urinary tract symptoms were randomly allocated to receive 12-week, once daily treatment with placebo or tadalafil (2.5, 5, 10 or 20 mg). The International Prostate Symptom Score least squares mean change from baseline to end point was significantly improved for 2.5 (-3.9, p = 0.015), 5 (-4.9, p <0.001), 10 (-5.2, p <0.001) and 20 mg (-5.2, p <0.001) tadalafil compared to placebo (-2.3). International Prostate Symptom Score improvements at 4, 8 and 12 weeks were significant for all tadalafil doses and they demonstrated a dose-response relationship. Tadalafil (2.5 mg) significantly improved the International Prostate Symptom Score obstructive subscore and the International Index of Erectile Function-Erectile Function domain, the latter in sexually active men with a history of erectile dysfunction. Statistically significant improvements were noted for 5, 10 and 20 mg tadalafil compared to placebo, as assessed by the International Prostate Symptom Score irritative and obstructive subscores, International Prostate Symptom Score Quality of Life, Benign Prostatic Hyperplasia Impact Index (nonsignificant for 10 mg), Global Assessment Question and International Index of Erectile Function-Erectile Function domain. No statistically significant effect of treatment compared to placebo was noted for peak flow at any tadalafil dose. Treatment emergent adverse events were infrequent in all tadalafil groups. Once daily tadalafil demonstrated clinically meaningful and statistically significant efficacy and it was well tolerated in men with benign prostatic hyperplasia lower urinary tract symptoms. Of the doses studied 5 mg tadalafil appeared to provide a positive risk-benefit profile.
Article
Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [corrected] in the corpus cavernosum and therefore increases the penile response to sexual stimulation. We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes. In a 24-week dose-response study, 532 men were treated with oral sildenafil (25, 50, or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the International Index of Erectile Function, a patient log, and a global-efficacy question. In the dose-response study, increasing doses of sildenafil were associated with improved erectile function (P values for increases in scores for questions about achieving and maintaining erections were <0.001). For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5). In the last four weeks of treatment in the dose-escalation study, 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil, as compared with 22 percent for those receiving placebo (P<0.001). The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo (P<0.001). Headache, flushing, and dyspepsia were the most common adverse effects in the dose-escalation study, occurring in 6 percent to 18 percent of the men. Ninety-two percent of the men completed the 32-week extension study. Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction.