This web only provides the extract of this article. If you want to read the figures and tables, please reference the PDF full text on Blackwell Synergy. Thank you.
- Original Article -
Efficacy and tolerability of vardenafil in Asian men with
erectile dysfunction
Hui Meng Tan1,3, Chong Min
Chin2, Chong Beng Chua3, Edsal
Gatchalian4, Apichat
Kongkanand5, Clarence Lei Chang
Moh6, Foo Cheong Ng7, Krisada
Ratana-Olarn8, Dennis
Serrano4, Akmal Taher9, Ismail
Tambi10, Anupan Tantiwong11,
Michael Wong Yuet Chen12, Wai-Chun
Yip13
1Subang Jaya Medical Centre, Selengor 47500, Malaysia;
2National University Hospital, Singapore 119074;
3University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia;
4Manila Doctors Hospital, Ermita, Metro Manila, the Philippines;
5Chulalongkorn University Hospital, Bangkok 10330, Thailand;
6Normah Hospital, 93050 Kuching, Malaysia;
7Changi General Hospital, Singapore 529889;
8Ramathibodi Hospital, Bangkok 10400, Thailand;
9University of Indonesia, Jakarta 10430, Indonesia;
10Damai Service Hospital, Kuala Lumpur 51200, Malaysia;
11Siriraj Hospital, Mahidol University,
10700 Bangkok, Thailand; 12Mount Elizabeth Medical Centre, Singapore228510;
13Kwong Wah Hospital, Kowloon, Hong Kong, China
Abstract
Aim: To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 (PDE-5) inhibitor, in men of
Asian ethnicity with erectile dysfunction (ED).
Methods: In this prospective, double-blind, multinational study, Asian
men were randomized to receive vardenafil (10 mg) or placebo (4:1 ratio) for 12 weeks. The primary efficacy
variables were the International Index of Erectile Function erectile function domain (IIEF-EF), and Sexual Encounter
Profile (SEP) questions related to penetration and intercourse completion. Significant mean improvements were
required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included
the Global Assessment Question (GAQ) on erection
improvement. Results: Least-squares mean baseline IIEF-EF
domain scores (vardenafil 14.6, placebo 13.4) were consistent with moderate ED.
After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo
(22.4 vs. 14.3; P < 0.001). Vardenafil was associated with significant improvements from baseline in least squares (LS)
mean success rates for SEP-2 (vardenafil 82.2
vs. placebo 43.6; P < 0.001) and SEP-3 (vardenafil 66.1
vs. placebo 24.0; P < 0.001). Positive GAQ responses were reported by 81.8% of vardenafil recipients
vs. 24.3% of placebo recipients. Adverse events were reported by
25.4% of the vardenafil group, the majority mild and
transient. Conclusion: Vardenafil (10 mg) is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add
to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range
of patient populations. (Asian J Androl 2008 May; 10: 495_502)
Keywords: Asian males; erectile dysfunction; impotence; phosphodiesterase inhibitors; sexual dysfunction; vardenafil
Correspondence to: Dr Hui Meng Tan, Faculty of Medicine, University of Malaya, 1, SS12/1A, Subang Jaya, 47500 Petaling Jaya, Selangor
Malaysia.
Tel: +60-3563-06777 Fax: +60-3563-06571
E-mail: perandro@streamyx.com
Received 2007-10-26 Accepted 2008-01-12
DOI: 10.1111/j.1745-7262.2008.00388.x
1 Introduction
Erectile dysfunction (ED) is a globally prevalent
condition, having detrimental effects on overall quality
of life, and providing a considerable source of emotional
stress for men and their partners [1_3]. The prevalence
of ED is expected to rise as populations age, with the
largest projected increases anticipated in Asia, Africa and
South America [4, 5]. According to age-adjusted
predictions made using conservative projections for
population growth, the number of men worldwide with ED
could increase to 322 million by 2019 [5].
Phosphodiesterase type-5 (PDE-5) inhibitors are the
first-line therapeutic option in the treatment of ED. The
phosphodiesterase (PDE) group of enzymes terminate
cyclic nucleotide signals, and PDE-5 is by far the most
active PDE involved in the termination of cyclic
guanosine monophosphate (cGMP) signalling in the corpus
cavernosum [6]. Inhibition of PDE-5 potentiates the
biological activity of cGMP in the corpus cavernosum,
increasing smooth muscle relaxation and, therefore,
improving erections, in the presence of a sexual stimulus [7].
The PDE-5 inhibitor vardenafil has been introduced
for the treatment of ED in various countries worldwide
since 2001 [8]. It has been effective and well-tolerated
in a broad range of patient populations, including those
with diabetes mellitus [9, 10], hypertension [11] and ED
following prostatectomy [12] or spinal cord injury [13].
The majority of previously reported clinical studies
of vardenafil have involved mostly Caucasian populations
[14_17]. Therefore, it is necessary to investigate the
safety and efficacy of vardenafil in other ethnic groups.
For example, Asian men might differ from Caucasian
men with regard to the polymorphic expression of key
enzymes responsible for drug metabolism [18, 19], and
in particular those that contribute to the metabolism of
vardenafil, such as CYP3A and CYP2C9 [18_20]. Moreover, there are differences between ethnic populations
with regard to perceptions of, and attitudes towards, ED
and cultural trends in medical practice [21, 22]. The study
evaluated the efficacy and tolerability of vardenafil in men
of Asian ethnicity with ED of broad-spectrum etiology.
2 Materials and methods
2.1 Study design
This prospective, randomized, double-blind,
placebo-controlled, fixed-dose, parallel-group study, conducted
between March 2003 and April 2004, assessed the safety
and efficacy of vardenafil (10 mg) for the treatment of
ED in Asian men. Fourteen centres in six countries
participated in the study: Malaysia (4), Singapore (3),
Thailand (3), the Philippines (2), Hong Kong, China (1) and
Indonesia (1).
The study protocol was approved by the appropriate
independent ethics committee at each site, and the study
was performed in accordance with the Good Clinical
Practice guidelines of the International Conference on
Harmonisation of Technical Requirements for the
Registration of Pharmaceuticals for Human Use, and the
principles of the Declaration of Helsinki. All patients
provided written informed consent.
2.2 Patients
Men aged ¡Ý 20 years with ED of > 6 months'
duration were enrolled. Patients were required to have been in
a stable heterosexual relationship for > 6 months.
At least 50% of attempts to obtain, penetrate with, or maintain an
erection must have failed during at least four separate
attempts at intercourse during the 4-week baseline period.
The main exclusion criteria were: physiological or
psychological disorders that would significantly impair
erectile function; history of radical prostatectomy;
retinitis pigmentosa; and uncontrolled diabetes mellitus. The
following medications were contraindicated: any drugs for
the treatment of ED including PDE-5 inhibitors,
anticoagulants (except antiplatelet agents), androgens or
anti-androgens, nitrates or nitric oxide donor medications;
cytochrome P450 3A4 inhibitors; and alpha blocking agents.
2.3 Study medication
After a 4-week baseline period, patients were
randomized (in a 4:1 ratio) to receive 12 weeks' treatment
with vardenafil (10 mg) or placebo. The 10 mg vardenafil
dose was selected as this is the recommended starting
dose for the majority of patients. Patients were advised
to dispense one tablet per instance of intended sexual
intercourse, and to take the study medication at least
30 min before sexual intercourse, with a maximum of
one dose daily. The treatment phase was followed by a
7-day observation period. Randomization codes were
computer-generated at Bayer Schering Pharma AG (Leverkusen, Germany).
2.4 Efficacy variables
The primary efficacy variables used to assess
erectile function were: (i) the International Index of Erectile
Function erectile function domain (IIEF-EF) score [23];
(ii) success rates for vaginal penetration, as assessed using
the Sexual Encounter Profile question 2 (SEP-2); and
(iii) success rates for maintaining penile rigidity for
completion of intercourse, as assessed using the Sexual
Encounter Profile question 3 (SEP-3). For the efficacy
of vardenafil to be satisfactorily demonstrated,
significant improvements following vardenafil treatment
vs. placebo for all three of the primary variables, from
baseline to week 12 or last observation carried forward
(LOCF) were necessary.
Secondary efficacy variables included IIEF-EF
domain scores, penetration success rates (SEP-2) and
intercourse completion rates (SEP-3) at 4, 8 and 12 weeks
or LOCF. Responses to SEP questions on the
achievement of erection (SEP-1), hardness of erection (SEP-4),
overall satisfaction with sexual experience (SEP-5),
ejaculation (SEP-6) and the Global Assessment Question
(GAQ) "Has the treatment you have been taking during
the last 4 weeks improved your erections?" were also
assessed at 4, 8 and 12 weeks or LOCF.
2.5 Safety assessments
Safety assessments included the reporting of adverse
events, laboratory tests (haematology, clinical chemistry,
urinalysis), monitoring of vital signs (heart rate and blood
pressure) and 12-lead electrocardiography.
2.6 Statistical methods
Sample size estimates were based on the assumptions of Student's independent
t-test. Assuming a standard deviation of 8.0 for the IIEF-EF domain score, a
total of 338 patients were necessary to show a clinically
meaningful difference of 5 points between vardenafil and
placebo, with an overall power of 90 %.
The safety population included all patients who had
received at least one dose of study medication and for
whom post-baseline safety data were provided. All
patients who received at least one dose of study
medication and provided at least one measurement for all three
primary efficacy variables were included in the intent to
treat (ITT) population. Analysis of IIEF-EF domain
scores, assessed at 4, 8 and 12 weeks, was performed
using an LOCF approach. For diary questions, mean
success rates over the baseline and treatment periods
were averaged for all patients, and were reported as the
overall mean per patient success rate. These efficacy
variables were assessed using analysis of covariance, with
baseline response as covariate (ANCOVA), to determine
the effects of vardenafil treatment. Statistical analysis
of the secondary variable GAQ was performed using
logistic regression
3 Results
3.1 Patients
A total of 413 men of Asian ethnicity were screened
for eligibility and 358 of these were randomized to
treatment (Figure 1). Of these patients, 348 were eligible for
inclusion in the safety population (276 vardenafil, 72
placebo). The ITT population comprised 334 patients
(264 vardenafil, 70 placebo), who received study
medication and provided data for all three major efficacy
variables. Forty three patients (12.0%) prematurely
discontinued study participation during the 12-week
treatment period.
Patients in the study population had a mean age of
54.6 years (range 23_78 years) and a mean weight of
72 kg. There were no relevant differences in
demographic characteristics or baseline clinical variables
between the two treatment groups (Table 1). The mean
baseline erectile function domain scores were 14.6 and
13.4 in the vardenafil and placebo groups, respectively,
consistent with a diagnosis of moderate ED (Table 2). A
total of 224 patients had previously used sildenafil. The
mean (SE) number of study medication doses taken per
week was 2.80 (1.38) in the vardenafil group and 2.40
(1.18) in the placebo group.
3.2 Efficacy
Following 12 weeks' treatment, the LS mean
(standard error [SE]) IIEF-EF domain score in men
receiving vardenafil (10 mg) was 22.40 (0.42); significantly
greater than the score of 14.30 (0.78) observed in men
receiving placebo (P < 0.001). Vardenafil treatment was
also associated with significant improvements in the
other two primary efficacy variables after 12 weeks'
treatment (P < 0.001). The LS mean (SE) SEP-2 per
patient success rates were 82.2 (2.0) and 43.6 (3.8) for
vardenafil and the placebo, respectively. The LS mean
(SE) SEP-3 per patient success rates were 66.1 (2.5) in
the vardenafil group and 24.0 (4.7) in the placebo group
(Table 2). For all three primary efficacy variables,
clinically significant therapeutic effects had occurred by the
time of the first assessment (4 weeks after the start of
treatment) with small additional improvements noted
after this time-point (Figures 2_4).
Success rates for SEP-1, SEP-4, SEP-5 and SEP-6
questions at 12 weeks were all significantly improved
following vardenafil treatment compared with placebo
(P < 0.001; Table 3). After 12 weeks, a significantly
greater percentage of patients responded positively to
the GAQ: 81.8% for vardenafil recipients
vs. 24.3% for placebo recipients
(P < 0.001) (Table 2).
3.3 Safety
In total, 70 (25.4%) patients in the vardenafil group
and 12 (16.7%) patients in the placebo group
experienced treatment-emergent adverse events. As a result
of adverse events, six patients (2.2%) discontinued the
study, all of them in the study medication group. The
most frequent treatment-emergent adverse events were
headache, flushing, nasal congestion and dizziness
(Table 4). Adverse events were slightly more frequent
in the vardenafil group than in the placebo group;
however, the majority were of mild intensity and were
transient, resolving spontaneously by the end of the
observation period.
Three patients in the vardenafil group reported
serious adverse events, one of which was found to be
drug-related. In this reported case the patient suffered
moderate chest discomfort, which resolved following
discontinuation of treatment.
4 Discussion
ED has substantial negative effects on a patient's
quality of life [1, 3] and a considerable emotional impact
on the lives of men and their partners, potentially
depriving them of intimacy and diminishing their
self-esteem [2, 24]. It has been predicted that the prevalence
of ED in Asian countries will show greater increases in
the future than non-Asian countries [4, 5]. The Asian
Men's Attitudes to Life Events and Sexuality (Asian
MALES) study confirms that ED is equally prevalent in
Asian countries. The prevalence of ED varied by region,
and across all regions it was found to increase with age.
The study also found that self-reported comorbid
illnesses were associated with the presence of ED, and
that men with ED exhibited significantly greater
dissatisfaction with all assessed aspects of quality of life. Less
than half of men with self-reported ED in the Asian
MALES Phase I study had sought treatment for their
problem [25]. The findings of this study highlight the
need to investigate the efficacy and safety of PDE-5
inhibitors in Asian populations.
In the present study, a broad population of men of
Asian ethnicity were recruited from Hong Kong (China),
Indonesia, the Philippines, Malaysia, Singapore and
Thailand. ED was of moderate severity and mostly of
organic etiology. Treatment with vardenafil (10 mg)
improved ED, as demonstrated by clinically relevant and
statistically significant improvements in the IIEF-EF
domain score, and vaginal penetration success rates and
intercourse completion rates (assessed using the SEP-2
and SEP-3 diary questions). Early treatment effects were
evident, with most of the beneficial effects of vardenafil
therapy observed after 4 weeks of treatment. After
12 weeks' treatment with vardenafil, the mean IIEF-EF
domain score increased from 14.7 to 22.8. This change
represents an improvement of the classification of the
mean score from "moderate ED" to "mild ED". By
comparison, the mean IIEF-EF domain score in placebo
recipients showed only a small increase (from 13.5 to
14.3), and remained within the category of moderate ED.
Major clinical improvement was also demonstrated by
the number of positive answers to the GAQ, provided by
81.8% of men receiving vardenafil, and 24.3% of
placebo recipients (P < 0.001).
In previous double-blind, randomized studies
performed in Caucasian populations, mean IIEF-EF domain
scores were 22.1 following 12 weeks' treatment with
vardenafil 10 mg, and the number of positive answers to
the GAQ was 76%. Per-patient success rates for
SEP-2 and SEP-3 were 77.8% and 70.3%, respectively [14,
16]. Recently, vardenafil has been demonstrated to be
effective and well tolerated in men of Eastern Asian
ethnicity [24]. In that particular double-blind,
randomized study in an Eastern Asian population, a mean
IIEF-EF domain score of 24.2 was achieved following
treatment with vardenafil, with the number of positive
responses to the GAQ being 85.1%. Mean per-patient
response success rates for SEP-2 and SEP-3 were 88.2
and 69.4, respectively [24]. Therefore, a comparison of
the present results with other published data confirms
that the efficacy of vardenafil is similar among Asian and
Caucasian men with ED. Moreover, the magnitude of
effect on the EF domain is similar to that observed in
double-blind studies of sildenafil [26].
The present study also confirms the favorable
tolerability profile of vardenafil previously established in
Caucasian and other populations [8, 15, 17, 24, 27_29].
Vardenafil was well-tolerated, with the most
frequently-occurring adverse events (headache, flushing, nasal
congestion and dizziness), consistent with the vasodilatory
activity of PDE-5 inhibitors [7, 8].
Vardenafil was effective and well-tolerated in the
treatment of ED of moderate severity in a male population of
Asian ethnicity. Vardenafil significantly improved
erectile function, as measured by IIEF-EF domain scores,
responses to SEP diary questions and the GAQ,
following 12 weeks' treatment. Significant improvements were
observed after 4 weeks' treatment compared with the
placebo. These results add to the increasing amount of
data indicating that vardenafil is suitable for the
treatment of ED in a broad range of patient populations.
Acknowledgement
This study was sponsored by Bayer Schering Pharma
AG. The authors wish to acknowledge the contribution
of each of the study centres described in this paper (listed
alphabetically within each country).
Hong Kong, China: In Chak Law, Lok Sang Leung, Wai Chun Yip (Kwong Wah Hospital, Kowloon, Hong
Kong, China).
Indonesia: Ponco Birowo, Muhammad Fitrah, Hendra
Herman, Mohammad Johan, Heru Prasetya, Nur Rasyid,
Akmal Taher, Taufan Tenggara (University of Indonesia,
CiptoMangun Kusumo General Hospital).
Malaysia: Khairullah Haji Abdullah (Megah Medical
Specialist Centre); Chong Beng Chua (University Malaya
Medical Centre); Mohamad Afzal bin Farikhullah Khan
(University Malaya Medical Centre); Ming Lee (University
Malaya Medical Centre); Clarence Chang Moh Lei (Normah Medical Specialist Centre); Peter Eng Pin Ng
(Megah Medical Specialist Centre); Mohamad Ismail bin
Mohamad Tambi (Damai Service Hospital); Margaret Chin
Heng Tan (University Malaya Medical Centre).
Philippines: Eduardo Ranillo Gatchalian (Manila
Doctors Hospital); Dennis P Serrano (Manila Doctors
Hospital).
Singapore: Lim Kok Bin (Singapore General Hospital);
Michael Wong Yuet Chen (Mount Elizabeth Medical Centre); Ng Foo Cheong (Changi General Hospital); Chan
Yee Fong (Singapore General Hospital); Sim Hong Gee
(Singapore General Hospital); Ho Siew Hong (Changi
General Hospital); May Chng Siok Hong (Singapore
General Hospital); Chua Wei Jin (National University Hospital);
Winnie Foo Wen Jing (Changi General Hospital); Ng Kok
Kit (Changi General Hospital); Fong Yan Kit (Changi
General Hospital); Chin Chong Min (National University
Hospital); Ketul K Shah (Changi General Hospital).
Thailand: Apichat Kongkanand (Chulalongkorn Hospital); Krisada Ratana-Olarn (Ramathobodi Hospital);
Anupan Tantiwong (Siriraj Hospital).
References
1 Sanchez-Cruz J J, Cabrera-Leon A, Martin-Morales A, Fernandez
A, Burgos R, Rejas J. Male erectile dysfunction and
health-related quality of life. Eur Urol 2003; 44:
245_53.
2 Martin-Morales A, Meijide F, Garcia N, Artes
M, Munoz A. Efficacy of vardenafil and influence on self-esteem and
self-confidence in patients with severe erectile dysfunction. J Sex
Med 2007; 4: 440_7.
3 Mallis D, Moisidis K, Kirana PS, Papaharitou S, Simos
G, Hatzichristou D. Moderate and severe erectile dysfunction
equally affects life satisfaction. J Sex Med 2006; 3:
442_9.
4 McKinlay JB. The worldwide prevalence and epidemiology of
erectile dysfunction. Int J Impot Res 2000; 12 (Suppl
4): S6_S11.
5 Aytac IA, McKinlay JB, Krane RJ. The likely worldwide
increase in erectile dysfunction between 1995 and 2025 and some
possible policy consequences. BJU Int 1999; 84:
50_6.
6 Lin CS, Lin G, Lue TF. Cyclic nucleotide signaling in cavernous
smooth muscle. J Sex Med 2005; 2: 478_91.
7 Eardley I. Vardenafil: a new oral treatment for erectile
dysfunction. Int J Clin Pract 2004; 58: 801_6.
8 Montorsi F, Salonia A, Briganti A, Barbieri L, Zanni G, Suardi
N, et al. Vardenafil for the treatment of erectile dysfunction: a
critical review of the literature based on personal clinical
experience. Eur Urol 2005; 47: 612_21.
9 Ziegler D, Merfort F, van Ahlen H, Yassin A, Reblin T,
Neureither M. Efficacy and safety of flexible-dose vardenafil
in men with type 1 diabetes and erectile dysfunction. J Sex
Med 2006; 3: 883_91.
10 Valiquette L, Montorsi F, Auerbach S; Vardenafil Study Group.
First-dose success with vardenafil in men with erectile
dysfunction and associated comorbidities: RELY-I. Int J Clin Pract
2006; 60: 1378_85.
11 Rubio-Aurioles E, Porst H, Eardley I, Goldstein I;
Vardenafil-Sildenafil Comparator Study Group. Comparing vardenafil
and sildenafil in the treatment of men with erectile
dysfunction and risk factors for cardiovascular disease: a randomized,
double-blind, pooled crossover study. J Sex Med 2006; 3:
1037_49.
12 Nehra A, Grantmyre J, Nadel A, Thibonnier M, Brock G.
Vardenafil improved patient satisfaction with erectile hardness,
orgasmic function and sexual experience in men with erectile
dysfunction following nerve sparing radical prostatectomy. J
Urol 2005; 173: 2067_71.
13 Giuliano F, Rubio-Aurioles E, Kennelly M, Montorsi F, Kim
ED, Finkbeiner AE, et al; Vardenafil Study Group. Efficacy
and safety of vardenafil in men with erectile dysfunction caused
by spinal cord injury. Neurology 2006; 66: 210_6.
14 Porst H, Rosen R, Padma-Nathan H, Goldstein I, Giuliano F,
Ulbrich E, et al. The efficacy and tolerability of vardenafil, a
new, oral, selective phosphodiesterase type 5 inhibitor, in
patients with erectile dysfunction: the first at-home clinical
trial. Int J Impot Res 2001; 13: 192_9.
15 Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier
M, Taylor T, et al. Vardenafil for treatment of men with
erectile dysfunction: efficacy and safety in a randomized,
double-blind, placebo-controlled trial. J Androl 2002; 23: 763_71.
16 Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier
M, Taylor T, et al; Vardenafil Study Group. Sustained efficacy
and tolerability of vardenafil, a highly potent selective
phosphodiesterase type 5 inhibitor, in men with erectile dysfunction:
results of a randomized, double-blind, 26-week
placebo-controlled pivotal trial. Urology 2003; 61 (Suppl): 8_14.
17 Cheng E. Real-life safety and efficacy of vardenafil in the
treatment of erectile dysfunction-results from 30,010 US
Patients. J Sex Med 2007; 4: 432_9.
18 Kim K, Johnson JA, Derendorf H. Differences in drug
pharmacokinetics between East Asians and Caucasians and the role of
genetic polymorphisms. J Clin Pharmacol 2004; 44: 1083_105.
19 Chowbay B, Zhou S, Lee EJ. An interethnic comparison of
polymorphisms of the genes encoding drug-metabolizing
enzymes and drug transporters: experience in Singapore. Drug
Metab Rev 2005; 37: 327_78.
20 Lamba JK, Lin YS, Schuetz EG, Thummel KE. Genetic
contribution to variable human CYP3A-mediated metabolism. Adv
Drug Deliv Rev 2002; 54: 1271_94.
21 Crimmel AS, Conner CS, Monga M. Withered Yang: a review
of traditional Chinese medical treatment of male infertility and
erectile dysfunction. J Androl 2001; 22: 173_82.
22 Nicolosi A, Moreira ED Jr, Shirai M, Bin Mohd Tambi MI,
Glasser DB Epidemiology of erectile dysfunction in four
countries: cross-national study of the prevalence and
correlates of erectile dysfunction. Urology 2003; 61: 201_6.
23 Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J,
Mishra A. The international index of erectile function (IIEF): a
multidimensional scale for assessment of erectile dysfunction.
Urology 1997; 49: 822_30.
24 Chen KK, Paick JS, Ishii N. The efficacy and safety of vardenafil
in East Asian men with erectile dysfunction. J Sex Med 2007;
4: 753_61.
25 Tan HM, Low WY, Ng CJ, Chen KK, Sugita M, Ishii N,
et al. Prevalence and correlates of erectile dysfunction (ED) and
treatment seeking for ED in Asian men: the Asian Men's
Attitudes to Life Events and Sexuality (Asian MALES) study. J
Sex Med 2007; 4: 1582_92.
26 Rosen RC, Cappelleri JC, Gendrano N 3rd. The International
Index of Erectile Function (IIEF): a state-of-the-science review.
Int J Impot Res 2002; 14: 226_44.
27 Rosen R, Shabsigh R, Berber M, Assalian P, Menza M,
Rodriguez-Vela L, et al; Vardenafil Study Site Investigators.
Efficacy and tolerability of vardenafil in men with mild
depression and erectile dysfunction: the depression-related
improvement with vardenafil for erectile response study. Am J
Psychiatry 2006; 163: 79_87.
28 Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T,
Taylor T; Vardenafil Diabetes Study Group. Vardenafil, a new
phosphodiesterase type 5 inhibitor, in the treatment of
erectile dysfunction in men with diabetes: a multicenter
double-blind placebo-controlled fixed-dose study. Diabetes Care 2003
26: 777_83.
29 Brock G, Nehra A, Lipshultz LI, Karlin GS, Gleave M, Seger
M, et al. Safety and efficacy of vardenafil for the treatment of
men with erectile dysfunction after radical retropubic
prostatectomy. J Urol 2003 170: 1278_83.
|