ADULT UROLOGY
COMPARISON OF EFFICACY OF SILDENAFIL-ONLY,
SILDENAFIL PLUS TOPICAL EMLA CREAM, AND TOPICAL
ALI ATAN, M. MURAD BASAR, ALTUG TUNCEL, MEHMET FERHAT, KORAY AGRAS,
ABSTRACT Objectives. To compare the efficacy of sildenafil (Viagra) only, sildenafil plus topical anesthetic cream (EMLA), and topical EMLA-cream-only to that of placebo in treating premature ejaculation. Methods. A total of 84 patients were enrolled in this study. The duration of premature ejaculation in the patients ranged from 9 to 60 months (mean 32.5 Ϯ 14.6). Patients were randomized into four groups. Group 1 consisted of 20 patients who took placebo for 2 months. Groups 2 and 3 consisted of 20 and 22 patients, respectively, and they received 50 mg sildenafil 45 minutes before coitus for 2 months. In addition, patients in group 3 applied topical EMLA cream to the glans penis 15 minutes before coitus. The 22 patients in group 4 used topical EMLA-cream-only. After at least eight sexual attempts, the patients’ clinical responses were assessed using the patient self-description method. Effectiveness was described as improvement plus cure. Results. The effectiveness was 40% in group 1, 55% in group 2, 86.4% in group 3, and 77.3% in group 4. Of the groups, a significant difference was found in the effectiveness of the treatments (Pearson chi-square ϭ 0.00). No significant difference was found between groups 1 and 2 (P ϭ 0.26). Efficacy was more successful in groups 3 and 4 than in the others (P ϭ 0.00). The difference between groups 3 and 4 was not significant (Pearson chi-square ϭ 0.42). Conclusions. Sildenafil-only was not superior to placebo or combination treatment. Topical EMLA-cream- only had equal effectiveness to that of sildenafil plus topical EMLA treatment. The use of topical EMLA- cream-only seems to be an effective treatment of premature ejaculation.
UROLOGY 67: 388–391, 2006. Prematureejaculation(PE)hasbeenreportedas cal counseling are the initial approaches in the
treatment of PE. However, these techniques re-
Data from the National Health and Social Life Sur-
quire active involvement of the patients and their
vey have revealed a prevalence of 21% in men aged
partners. Some cultural and socioeconomic groups
may not be comfortable participating in these ther-
etiology of PE is not well understood, although it is
apies. Therefore, some pharmacologic agents have
well-recognized that ejaculation latency is primar-
been recommended for those in whom the behav-
ily affected by psychological, cognitive, and so-
Some selective serotonin re-uptake inhibitors
have been used to treat this sexual problem, with
From the Third Department of Urology, Ministry of Health, An-kara Numune Research and Training Hospital, Ankara, Turkey;
treatment regimens have been investigated as a
and Department of Urology, Kirikkale University, School of Med-icine, Kirikkale, Turkey
treatment option for PE. Currently, two new treat-
Reprint requests: Altug Tuncel, M.D., Third Department of
ments, topical anesthetic agents and oral sildenafil,
Urology, Ministry of Health, Ankara Numune Research andTraining Hospital, Sihhiye, Ankara 06120, Turkey. E-mail:
anesthetic agents are applied to the glans penis be-
Submitted: April 16, 2005, accepted (with revisions): Septem-
is a selective cyclic guanosine monophosphate-
Patient characteristics P
34.4 Ϯ 15.1 28.7 Ϯ 15.5 30.5 Ϯ 14.2 36.4 Ϯ 13.4 0.300*
KEY: PE ϭ premature ejaculation. Data presented as mean Ϯ standard deviation. * One-way analysis of variance.
specific phosphodiesterase type-5 (PDE-5) inhibitor,
TABLE II. Clinical responses
which has been used to treat erectile dysfunction. The administration of sildenafil has been found effec-
Improvement No Change
In this study, we compared the efficacy of silde-
nafil-only, sildenafil plus topical anesthetic cream
(EMLA), and topical EMLA-cream-only to placebo
MATERIAL AND METHODS
The study included 84 patients with PE, whose age ranged
ternatives was analyzed using Pearson’s correlation test. A
from 20 and 52 years at baseline (mean 38.1 Ϯ 9.0). PE was
P value of less than 0.05 was considered significant.
defined as persistent or recurrent ejaculation with minimalsexual stimulation before, at, or shortly after penetration and
before the person wished All the patients had an activesexual life.
The patients’ age and duration of PE in each
The duration of PE ranged from 9 to 60 months (mean
group are shown in No significant differ-
32.5 Ϯ 14.6). This was the time that the patients consider PE
ences were observed between patient age and PE
an important sexual problem. The patients underwent a med-ical and sexual history, including the first five questions of the
duration (one-way analysis of variance, P ϭ 0.085
International Index of Erectile Function, with a detailed phys-
for age and P ϭ 0.300 for PE duration).
The clinical responses are given for each group in
The exclusion criteria were the use of any treatment of PE
The effectiveness was 40% in group 1 (8 of
within the past 2 months, any disease and/or medication that
20), 55% in group 2 (11 of 20), 86.4% in group 3
required avoiding sildenafil use, the diagnosis of erectile dys-function according to the International Index of Erectile
(19 of 22), and 77.3% in group 4 (17 of 22). A
Function-5 score (less than 21), decreased libido, alcohol and
significant difference was found in treatment effec-
drug abuse, and the presence of organic or metabolic disorders
tiveness among the four groups (Pearson chi-
such as prostatitis, active urinary tract infection, diabetes mel-
square ϭ 0.00). No significant difference was
litus, acute or chronic renal failure, and thyroid disease.
found between groups 1 and 2 (P ϭ 0.26). Effi-
After the patients were informed about the efficacy and side
effects of the drugs, they were randomized into four groups.
ciency was more successful in groups 3 and 4 than
Group 1 consisted of 20 patients and took a placebo for 2
in the other groups (P ϭ 0.00). The difference be-
months. Groups 2 and 3 consisted of 20 and 22 patients, re-
tween groups 3 and 4 was not significant (Pearson
spectively, and they took 50 mg sildenafil (Viagra) 45 minutes
before coitus for 2 months. In addition, patients in group 3
Although the patients in groups 1 and 4 did not
applied topical EMLA cream (lidocaine 2.5%/prilocaine 2.5%)to the glans penis 15 minutes before coitus. The 22 patients in
report any side effects from treatment, headache
group 4 used topical EMLA-cream-only. The patients did not
was observed in 5 (25%) and 6 (27.3%) patients
and flushing in 4 (20%) and 7 (31.8%) patients in
After at least eight sexual attempts, the patients’ clinical
groups 2 and 3, respectively. However, none of
responses were classified as “no change,” “improvement,” and
these side effects was severe enough to stop the
“cure” according to patient self-report. Cure was defined asejaculation delayed until patient wished it, and improvement
was defined as an increase of ejaculation time compared withthe pretreatment time. Effectiveness was described as im-
provement plus cure. All side effects were recorded.
No consensus has been reached about the defini-
tion of Depending on the study, any ejacula-
STATISTICAL ANALYSIS
tion occurring within 1 to 7 minutes has been con-
Statistical analysis was performed with the Statistical Pack-
age for Social Sciences for Windows, version 8.0, software. The difference in age was calculated using one-way analysis of
number of penile thrusts, considering 8 to 15
variance. Subsequently, the effectiveness of the treatment al-
thrusts as a criterion for These cutoff points
UROLOGY 67 (2), 2006
superior to all other treatment methods in terms of
TABLE III. Side effects
ejaculatory latency time control and overall satis-
Side Effects (n ؍ 20) (n ؍ 20) (n ؍ 22) (n ؍ 22)
ported finding no significant differences between
the sildenafil and placebo groups in terms of intra-
vaginal ejaculatory latency time. Finally, no exact
evidence has shown sildenafil success in PE treat-
ment. In our study, no significant difference was
found between the sildenafil-only group and the
placebo group. In the placebo group, the success
rate was 40%. We could not explain the high suc-
cess rate in the placebo group. Our results indi-
cated that sildenafil-only was an ineffective treat-
Data presented as number of patients, with percentages in parentheses.
ment option for PE. Furthermore, sildenafil didnot augment the topical anesthetic cream’s effi-cacy. In the present study, the combination of sil-
for ejaculation time and thrust number were not
denafil and topical anesthetic cream had similar
derived from objective measurements but were
efficacy in PE treatment. A larger patient sample
subjectively chosen by the different investigators.
and placebo-controlled study in men with PE are
The absence of a clear, popular, and widely ac-
cepted definition of PE allows a “patient-depen-
An experimental study showed that application
dent” definition and a “patient-decided” diagno-
of topical anesthetics to the penis virtually abol-
In the light of published data, we used a
ished the display of penile reflexes in This
patient self-description method for assessing treat-
has also been confirmed in a clinical Berko-
vitch et reported that local anesthesia with
We used the definition of the American Psychi-
prilocaine-lidocaine cream applied to the penile
atric Association: PE that is persistent or recurrent
skin delayed ejaculation. Another study showed
ejaculation with minimal sexual stimulation be-
that topical lidocaine-prilocaine spray administra-
fore, at, or shortly after penetration and before the
tion to the glans penis led to eight times increased
person wished Many medical approaches are
intravaginal ejaculation latency time and improved
available, including antidepressants, such as clo-
sexual satisfaction in patients and their
mipramine, and selective serotonin re-uptake in-
Atikeler et documented that topical prilocaine-
hibitors, such as paroxetine, sertraline, fluoxetine,and selective and nonselective alpha-1 receptor
lidocaine cream application significantly provided
blockers (phenoxybenzamine, alfuzosin, terazo-
improved intravaginal ejaculation time compared
sin), topical anesthetic agents, and PDE-5 inhibi-
with placebo. In the present study, the topical
tors to treat PE, although none has been sufficient
EMLA cream plus sildenafil group and the topical
EMLA-cream-only group were superior to the pla-
Some recent studies have indicated that PDE-5
cebo and sildenafil-only groups. However, topical
inhibitors are effective in the treatment of PE. The
EMLA-cream-only was as effective as topical
efficacy of PDE-5 inhibitors has been suggested to
EMLA cream plus sildenafil. Hence, we concluded
be due to central and peripheral mechanisms. A
that topical EMLA-cream-only treatment is suffi-
possible peripheral mechanism includes decreased
contractile response on the vas deferens, seminal
The problems in using topical local anesthetics
vesicles, and urethra, peripheral analgesia, and ex-
in the treatment of PE are significant penile hy-
tended erection time. A possible central mecha-
poesthesia and vaginal numbness due to possible
nism is also composed of a decreased delivery of
transvaginal absorption. They may cause male and
female anorgasmia. However, these have not been
reported that sildenafil might be used to treat PE by
reducing postorgasmic refractory time. Salonia et
contraindicated for patients and/or their partners
compared the efficacy of paroxetine alone
with that of paroxetine plus sildenafil in a prospec-
In our study, no patient described anorgasmia due
tive study. They found that combination treatment
to penile hypoesthesia. However, we do not know
was superior to paroxetine alone in the treatment
whether female anorgasmia occurred in our study,
of PE. Another study showed that sildenafil in-
because the patients’ partners were not evaluated
gested as needed as a single treatment for PE in-
after treatment. This was a weak point of our study.
creased the ejaculatory latency time more than did
Also, partner satisfaction was not considered in
UROLOGY 67 (2), 2006 CONCLUSIONS
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MARIANNE B. MÜLLER, M.D. CURRICULUM VITAE Max Planck Institute of Psychiatry Kraepelinstraße 10 80804 Munich Germany Phone: +49-89-30622-288 Fax: Current Position: Head, Molecular Stress Physiology Group, MPI of Psychiatry EDUCATION 1987-1989 Student at the Rheinische Hochschule für Musik Köln (Cologne University of Music), instrumental music performance, piano 198
ADULT UROLOGY