IJIR: Your Sexual Medicine Journal

https://doi.org/10.1038/s41443-019-0122-2

ARTICLE

Efficacy and safety of dapoxetine/sildenafil combination tablets in

the treatment of men with premature ejaculation and concomitant
erectile dysfunction—DAP-SPEED Study
Murat Tuken1 Mehmet Gokhan Culha
●
2 ●
Ege Can Serefoglu 3

Received: 22 November 2018 / Revised: 29 December 2018 / Accepted: 10 January 2019

© Springer Nature Limited 2019

Abstract
Premature ejaculation (PE) and erectile dysfunction (ED) are the most prevalent sexual disorders in men. ED is commonly
reported among patients with PE. Although recent guidelines recommend to treat ED first in men with both PE and ED, this
recommendation is not based on evidence and there are limited data about the efficacy and safety of dapoxetine/sildenafil
combination therapy for these patients. The aim of this study is to evaluate the clinical efficacy and safety of the dapoxetine/
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sildenafil combination (Dapoxil® 30/50 mg film-coated tablet) in the treatment of patients with PE and concomitant ED. In a
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single-center, single-arm, open-label clinical study conducted between October 2016 and September 2017, 74 patients with
lifelong or acquired PE and ED were included. All patients were instructed to record their intravaginal ejaculatory latency
time (IELT) with a stopwatch for 4 weeks. After the screening, they were requested to complete Premature Ejaculation
Diagnostic Tool (PEDT), Premature Ejaculation Profile (PEP), and International Index of Erectile Function-Erectile
Function (IIEF-EF) questionnaires before the treatment. The patients received on demand Dapoxil® 1–3 h before sexual
intercourse for the next 4 weeks (2 days a week and no more than once a day). The patients were also assessed with global
impression of change (GIC) question for the treatment satisfaction and the side effects were recorded. The study was
completed with 53 patients (53/74, 71.62%). Mean age of the patients was 45.32 ± 10.05 years. At the end of the 4-week
treatment period, the geometric mean IELT of the patients significantly increased (from 22.72 ± 15.16 to 68.25 ± 82.33 s; p <
0.001). Similarly, significant improvements were observed in the mean PEP index score (0.86 ± 0.72 vs. 2.36 ± 1.13; p <
0.001) and mean IIEF-EF domain score (13.17 ± 3.33 vs. 24.60 ± 3.96; p < 0.001). According to the GIC results, 81.13% of
the patients were satisfied with the treatment. Non-serious adverse events occurred in 10 patients (18.87%) and 4 (7.55%) of
these patients dropped out of the treatment. The most common adverse events were headache, palpitation, and flushing. The
dapoxetine/sildenafil combination therapy significantly improves the IELT values and patient reported outcome measures of
PE patients who also suffer from ED. Although several side effects were reported, these were mild and transient.

Introduction and negative personal consequences [1]. PE exerts a

Premature ejaculation (PE) is a male sexual dysfunction
characterized by a short intravaginal ejaculatory latency
time (IELT), inability to delay or control ejaculation,
* Ege Can Serefoglu
egecanserefoglu@hotmail.com
1
University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training
& Research Hospital, Department of Urology, Istanbul, Turkey
2
University of Health Sciences, Okmeydani Training & Research
Hospital, Department of Urology, Istanbul, Turkey
3
Bahceci Health Group, Department of Urology, Istanbul, Turkey
psychological burden on both men and their partners,
resulting in a significant detrimental effect on the rela-
tionship [2, 3]. Over the last two decades the treatment
of PE has shifted from psychotherapy to pharmacother-
apy, where the mainly prescribed drugs are selective
serotonin reuptake inhibitors (SSRIs) and phosphodies-
terase type-5 (PDE5) inhibitors [4]. Dapoxetine is the first
medication specifically developed for the on-demand
treatment of PE [5] and its efficacy has been demon-
strated in the several well-designed meta-analyses [6, 7].
However, several studies demonstrated that discontinua-
tion to the effective on-demand dapoxetine treatment is
relatively high [8, 9], indicating the need for alternative
treatments.

Erectile dysfunction (ED) is defined as the inability to
achieve or maintain an erection sufficient for satisfactory
sexual performance [10]. Studies have estimated that
23–30% of men with ED also suffer from PE [11, 12]. In
men with both PE and ED, the American Urological
Association recommends to first treat the patient’s ED
[13]. On the contrary, European Urology Guidelines [14]
supports the use of PDE5 inhibitors, alone or in combi-
nation with other therapies, in PE patients with or
without ED problem, considering the recently published
data related to this issue [15–17]. However, the evidence
as to whether PDE5 inhibitors are effective in the treat-
ment of PE is controversial, due to the poor study
design and lack of appropriate endpoints of the published
literature [18, 19].
Phase 1 studies of dapoxetine have confirmed that it does
not have any pharmacokinetic interactions with PDE5
inhibitors (i.e. tadalafil 20 mg and sildenafil 100 mg) [20].
To our knowledge, there are not any clinical trials, which
specifically assessed the outcomes of any PDE5 inhibitor
plus dapoxetine-containing tablets among patients who
complain with PE and ED.
Therefore, the aim of this study is to evaluate the clinical
efficacy and safety of the dapoxetine/sildenafil combination
tablets (Dapoxil® 30/50 mg film-coated tablets, Neutec Ilac
San. Tic. AS, Turkey) in the treatment of patients with PE
and concomitant ED.
Patients and methods
A total of 74 treatment naïve lifelong/acquired PE and ED
patients were prospectively included to this single-center,
single-arm, open-label, 8-week clinical trial conducted
between October 2016 and September 2017. All the patients
were married heterosexual men in a stable relationship for at
least 6 months. Moreover patients with prostatitis, major
psychiatric disorder, drug abuse, hormonal problems, and a
history of receiving other treatments for PE were excluded
from the study.
After obtaining their written informed consents, the
patients were requested to complete the Turkish validation
of Premature Ejaculation Diagnostic Tool (PEDT) [21] to
confirm the diagnosis of PE. Patients whose PEDT score
were greater than 10 were included to the study. In addition,
Turkish validation of Premature Ejaculation Profile (PEP)
[22] were completed by the patients. PEP is a 4-item (each
assessed on five-point response scales) self-administered
questionnaire designed for evaluating the key elements of
PE (i.e. control, distress, interpersonal difficulty, and sexual
satisfaction) [23]. Finally, International Index of Erectile
Function-Erectile Function (IIEF-EF) domain were admi-
nistered [24] to assess the ED status.
M. Tuken et al.
A detailed medical history (which included sexual his-
tory) was obtained and a complete physical examination
was performed to all patients. Moreover vital signs (fever,
pulse, blood pressure) of the patients were recorded for the
safety analyses. Laboratory tests (complete blood count,
biochemistry analysis, urine analysis) and electro-
cardiogram (12 leads) were also performed.
Patients who are eligible to take part in the study
underwent a 4-week screening period where they were
asked to record their IELT by stopwatch method [25] along
with the number of sexual intercourses during this period.
After the 4-week screening period, eligible patients were
given on-demand dapoxetine/sildenafil, 30/50 mg film-
coated tablets (Dapoxil® 30/50 mg film-coated tablets,
Neutec Ilac San. Tic. AS, Turkey) to be used 1–3 h before
sexual intercourse for 4 weeks of treatment period. Patients
were also requested to have at least two coitus attempts each
week during this period. Moreover, they were prohibited to
use condoms or topical anesthetic creams and advised not to
have pauses during intercourse or to have interrupted
intromission.
After 4 weeks of treatment, the IELT records of the
patients were collected and the questionnaires (i.e. PEP,
IIEF-EF) were administered again. Moreover, the global
impression of change (GIC) question was asked and the
answers of the patients were recorded. Finally all the
laboratory tests (complete blood count, biochemistry ana-
lysis, urine analysis) and electrocardiogram were repeated
after the treatment and all the adverse events were
evaluated.
Statistical analyses were performed by the SAS program
(NC, USA). In addition to the descriptive statistics, Wil-
coxon test and Student's t-test were used for the comparison
of the variables. The level of significance was accepted
as statistical evaluation (α = 0.05). Power analysis
was conducted for a pilot study. For the proportion of
eligible patients who completed the evaluation form (95%
CI, margin of error 0.05), at least 75 patients were
required [26].
This study was approved by the clinical research ethics
committee of University of Health Sciences, Bakirkoy Dr.
Sadi Konuk Training & Research Hospital, and the per-
mission of Turkish Medicine and Medical Device Agency
was obtained. The study was conducted in accordance with
the Declaration of Helsinki and Good Clinical Practice. The
study has been registered to clinicaltrials.gov with the
registration number NCT02939495.
Results
The study was completed with 53 patients (71.62%). Four
patients could not complete the study due to side effects and
Efficacy and safety of dapoxetine/sildenafil combination tablets in the treatment of men with premature. . .

Table. 1 Demographic characteristics of the patients (n = 53) Table. 3 Efficacy of the dapoxetine/sildenafil film-coated tablet
Mean ± SD Range (min–max) Pre-treatment Post-treatment p

Age (years) 45.32 ± 10.05 24–63 IELT (s) 22.72 ± 15.16 68.25 ± 82.33 <0.001*
BMI (kg/m2) 27.35 ± 3.78 21.6–36.8 IELT (fold increase- N/A 3.08 (2.33–4.09) <0.001*
IELT (s) 22.72 ± 15.16 5–60 range)
PEDT total score 16.85 ± 2.42 12–20 PEP index score 0.86 ± 0.72 2.36 ± 1.13 <0.001*
PEP index score 0.86 ± 0.72 0–2.75 IIEF-EF 13.17 ± 3.33 24.60 ± 3.96 <0.001*
IIEF-EF 13.17 ± 3.33 4–21 * Wilcoxon test
BMI body mass index, IIEF-EF International Index of Erectile IIEF-EF International Index of Erectile Function-Erectile Function
Function-Erectile Function Domain, IELT intravaginal ejaculation Domain, IELT intravaginal ejaculation latency time, PEP premature
latency time, PEDT Premature Ejaculation Diagnostic Tool, SD ejaculation profile
standard deviation

Table. 4 Adverse events of the dapoxetine/sildenafil film-coated tablet

Table. 2 Distribution of co-morbidities of the patients treatment
Co-morbidities N % Adverse event Subject Percentage

Diabetes mellitus 3 5.67 Headache 5 6.76

Hypertension 4 7.56 Flushing 3 4.06
Chronic obstructive pulmonary disease 1 1.89 Palpitation 2 2.70
No medical history 45 84.91 Dyspepsia 2 2.70
Fatigue 2 2.70
Nausea 1 1.35

17 patients did not attend follow-up visits. Mean age of the

patients was 45.32 ± 10.05 years (24–63 years). Before the
treatment, geometric mean IELT of the patients was 22.72
± 15.16 s (5–60 s), mean PEDT score was 16.85 ± 2.42
mean PEP index score (the mean of all four measures) was
0.86 ± 0.72 (0–2.75) and IIEF-EF score was 13.17 ± 3.33
(Table 1). The distribution of co-morbidities of the patients
is detailed in Table 2. On-demand dapoxetine/sildenafil
treatment modestly increased the mean IELT at the end of
one month (68.25 ± 82.33; p < 0.001). Moreover, scores
obtained from each PEP question and from the PEP index
score significantly improved (p < 0.001 for each). Similarly
significant improvements were observed in the mean IIEF-
EF domain score (p < 0.001) (Table 3).
According to the GIC, 81.13% of the patients were
satisfied with the treatment. There were no abnormal find-
ings in the vital signs, laboratory tests, and ECG findings
before and after the treatment. Adverse effects were
observed in 10 patients (18.87%) and 4 (7.55%) of these
patients dropped out the treatment. The most common
adverse events were headache, palpitation, and flushing
(Table 4).
Discussion
The findings of this clinical trial revealed that dapoxetine/
sildenafil treatment can effectively ameliorate the PE and
ED symptoms, without causing any clinically significant
adverse effects. Although several meta-analyses confirmed
the efficacy and safety of PDE5 inhibitors (alone or in
combination with other therapies) in PE patients (with or
without ED problem) [15–19], the majority of these clinical
trials are criticized because of their poor study design. To
our knowledge, the efficacy and safety of a film-coated
tablet containing dapoxetine/sildenafil combination have
not been assessed before.
Introduction of the SSRIs for the treatment of PE has
revolutionized the treatment of this prevalent sexual dis-
order [27]. On demand or daily SSRI therapies are asso-
ciated with significant increases in the geometric mean
IELT (between 2.6- and 13.2-folds) [28]. However, sexual
side effects of these drugs limit their use as an important
proportion of PE patients report decreased libido, anejacu-
lation, and ED when they are taking SSRIs [9, 29, 30].
Therefore, the combination of an SSRI with a PDE5 inhi-
bitor may prolong time until ejaculation to a greater extent
than an SSRI alone and may minimize the risk of ED.
Moreover, PE patients have a tendency to initiate multiple
sexual intercourses in order to satisfy their partners and
PDE5 inhibitors may be beneficial for them by reducing
their post-ejaculatory refractory time and improving their
erections in their later attempts. PDE5 inhibitors may also
increase the confidence and decrease performance anxiety
of the PE patients and thus improve their overall sexual
satisfaction.

The findings of a recent meta-analysis confirmed that
PDE5 inhibitors (sildenafil, tadalafil, or mirodenafil) plus
SSRIs (paroxetine, fluoxetine, or dapoxetine) are superior to
SSRIs alone in delaying the IELT and increasing the coitus
episodes [17]. Other studies also demonstrated that patients
using SSRI plus PDE5 inhibitor combination reported sig-
nificantly greater intercourse satisfaction than those
receiving SSRIs alone [31–33].
Regardless of the SSRI treatment, epidemiological stu-
dies revealed that a significant proportion of men with PE
also report ED [34]. Some PE patients may confuse their
early ejaculation problem with ED and some others
experience erection problems due to their performance
anxiety. On the contrary, ED patients may rush to reach
orgasm before losing their erection and this may result in
PE. Many biological theories have also tried to elucidate the
associations between ED and PE such as reduction of nitric
oxide bioavailability in ejaculatory glands [35] and
increased adrenergic tension in seminal vesicles [36]. The
PDE5 inhibitors may inhibit the contractions of the vas
deferens, seminal vesicle, prostate, and urethra, may induce
a state of peripheral analgesia, may augment the total
duration of erection and thus may lessen the central sym-
pathetic output [37].
To our knowledge, there is only one randomized-
controlled trial which demonstrated that in men with PE
and comorbid ED, PDE5 inhibitors plus dapoxetine pro-
vides meaningful treatment benefit and is generally well
tolerated [37]. Pharmacokinetic studies revealed that
dapoxetine and PDE5 inhibitors (tadalafil or sildenafil) have
no clinically important interactions with each other [20].
The findings of our clinical trial are in accordance with
these previous studies. We have observed more than three-
fold increase in the geometric mean IELT and patients
reported improved PEP outcomes, similar to the initial
clinical experience with dapoxetine therapy [5]. Moreover,
patients recorded almost two-fold higher mean IIEF-EF
scores, indicating better erections during their sexual
intercourses. Of the patients, 81.13% indicated that they
were satisfied whereas 18.87% reported several mild side
effects. Safety data from the meta-analysis suggest that the
incidence of the most frequent adverse events (headache
and flushing) observed in our study was comparable to
previously published data for PDE5 inhibitors and, like-
wise, these adverse events were generally mild [38]. No
clinically significant changes were observed in vital signs,
laboratory tests, and ECG findings in our study confirming
the safety of the dapoxetine/sildenafil combination therapy.
Our study has some limitations. First of all, having a
placebo group would definitely increase the overall quality
of our study and the sample size could be larger for
increasing the reliability of the results. Moreover, almost
30% of the patients were excluded for not coming to the
M. Tuken et al.
control visits. Although this percentage can seem relatively
high, we have previously observed that our patients and
their partners are hesitating to record their IELT with a
stopwatch, which results in discontinuation to the study
[21]. In spite of these limitations, this is the first study
demonstrating the efficacy and safety of a dapoxetine/sil-
denafil containing oral tablets for the treatment of PE,
concomitant with ED. These tablets can facilitate the
treatment of these prevalent sexual problems by improving
both the ejaculation time and erection quality.
The dapoxetine/sildenafil combination therapy sig-
nificantly improves the IELT values and patient reported
outcome measures of PE patients who also suffer from ED.
Future randomized-controlled trials are warranted to con-
firm the efficacy and safety of this combination therapy.
Acknowledgements The authors would like to thank Neutec Ar-Ge
San & Tic AS Clinical Research Department for their cooperation.
Funding This study has been sponsored by Neutec Ar-Ge San & Tic
AS (Turkey).
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Publisher’s note: Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
References
1. Serefoglu EC, McMahon CG, Waldinger MD, Althof SE, Shindel
A, Adaikan G, et al. An evidence-based unified definition of
lifelong and acquired premature ejaculation: report of the Second
International Society for Sexual Medicine Ad Hoc Committee for
the Definition of Premature Ejaculation. Sex Med. 2014;2:41–59.
2. Patrick DL, Althof SE, Pryor JL, Rosen R, Rowland DL, Ho KF,
et al. Premature ejaculation: an observational study of men and
their partners. J Sex Med. 2005;2:358–67.
3. Rowland DL, Patrick DL, Rothman M, Gagnon DD. The psy-
chological burden of premature ejaculation. J Urol.
2007;177:1065–70.
4. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel
AW, Adaikan PG, et al. An update of the International Society of
Sexual Medicine’s Guidelines for the Diagnosis and Treatment of
Premature Ejaculation (PE). Sex Med. 2014;2:60–90.
5. Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJ, Shab-
sigh R, et al. Efficacy and tolerability of dapoxetine in treatment of
premature ejaculation: an integrated analysis of two double-blind,
randomised controlled trials. Lancet. 2006;368:929–37.
6. Yue FG, Dong L, Hu TT, Qu XY. Efficacy of dapoxetine for the
treatment of premature ejaculation: a meta-analysis of randomized
clinical trials on intravaginal ejaculatory latency time, patient-
reported outcomes, and adverse events. Urology. 2015;85:856–61.
7. Castiglione F, Albersen M, Hedlund P, Gratzke C, Salonia A,
Giuliano F. Current pharmacological management of premature
ejaculation: a systematic review and meta-analysis. Eur Urol.
2016;69:904–16.
Efficacy and safety of dapoxetine/sildenafil combination tablets in the treatment of men with premature. . .
8. Park HJ, Park NC, Kim TN, Baek SR, Lee KM, Choe S. Dis-
continuation of dapoxetine treatment in patients with premature
ejaculation: a 2-year prospective observational study. Sex Med.
2017;5:e99–e105.
9. Mondaini N, Fusco F, Cai T, Benemei S, Mirone V, Bartoletti R.
Dapoxetine treatment in patients with lifelong premature ejacu-
lation: the reasons of a “Waterloo”. Urology. 2013;82:620–4.
10. NIH Consensus Conference. Impotence. NIH Consensus Devel-
opment Panel on Impotence. JAMA. 1993;270:83–90.
11. Fugl-Meyer K, Fugl-Meyer AR. Sexual disabilities are not sin-
gularities. Int J Impot Res. 2002;14:487–93.
12. McMahon CG, Lee G, Park JK, Adaikan PG. Premature ejacu-
lation and erectile dysfunction prevalence and attitudes in the
Asia-Pacific region. J Sex Med. 2012;9:454–65.
13. Montague DK, Jarow J, Broderick GA, Dmochowski RR, Heaton
JP, Lue TF, et al. AUA guideline on the pharmacologic man-
agement of premature ejaculation. J Urol. 2004;172:290–4.
14. Hatzimouratidis K, Giuliano F, Moncada I, Muneer A, Salonia A,
Verze P, Guideline Associates: Parnham A, Serefoglu EC. EAU
guidelines on erectile dysfunction, premature ejaculation, penile
curvature and priapism. Arnhem, The Netherlands: EAU Guide-
lines Office; 2018.
15. Bai Y, Pu C, Han P, Li J, Yuan H, Tang Y, et al. Selective
serotonin reuptake inhibitors plus phosphodiesterase-5 inhibitors
for premature ejaculation: a systematic review and meta-analysis.
Urology. 2015;86:758–64.
16. Sun Y, Luo D, Yang L, Tang C, Yang T, Hu X, et al. Efficacy of
phosphodiesterase-5 inhibitor in men with premature ejaculation:
a new systematic review and meta-analysis. Urology.
2015;86:947–54.
17. Men C, Yu L, Yuan H, Cui Y. Efficacy and safety of phospho-
diesterase type 5 inhibitors on primary premature ejaculation in
men receiving selective serotonin reuptake inhibitors therapy: a
systematic review and meta-analysis. Andrologia.
2016;48:978–85.
18. Asimakopoulos AD, Miano R, Finazzi Agro E, Vespasiani G,
Spera E. Does current scientific and clinical evidence support the
use of phosphodiesterase type 5 inhibitors for the treatment of
premature ejaculation? A systematic review and meta-analysis. J
Sex Med. 2012;9:2404–16.
19. McMahon CG, McMahon CN, Leow LJ, Winestock CG. Efficacy
of type-5 phosphodiesterase inhibitors in the drug treatment of
premature ejaculation: a systematic review. BJU Int.
2006;98:259–72.
20. Dresser MJ, Desai D, Gidwani S, Seftel AD, Modi NB. Dapox-
etine, a novel treatment for premature ejaculation, does not have
pharmacokinetic interactions with phosphodiesterase-5 inhibitors.
Int J Impot Res. 2006;18:104–10.
21. Serefoglu EC, Cimen HI, Ozdemir AT, Symonds T, Berktas M,
Balbay MD. Turkish validation of the premature ejaculation
diagnostic tool and its association with intravaginal ejaculatory
latency time. Int J Impot Res. 2009;21:139–44.
22. Serefoglu EC, Yaman O, Cayan S, Asci R, Orhan I, Usta MF,
et al. The comparison of premature ejaculation assessment ques-
tionnaires and their sensitivity for the four premature ejaculation
syndromes: results from the Turkish society of andrology sexual
health survey. J Sex Med. 2011;8:1177–85.
23. Patrick DL, Giuliano F, Ho KF, Gagnon DD, McNulty P, Roth-
man M. The Premature Ejaculation Profile: validation of self-
reported outcome measures for research and practice. BJU Int.
2009;103:358–64.
24. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra
A. The international index of erectile function (IIEF): a multi-
dimensional scale for assessment of erectile dysfunction. Urology.
1997;49:822–30.
25. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B. An
empirical operationalization study of DSM-IV diagnostic criteria
for premature ejaculation. Int J Psychiatry Clin Pract.
1998;2:287–93.
26. Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, et al. A
tutorial on pilot studies: the what, why and how. BMC Med Res
Methodol. 2010;10:1.
27. Saitz TR, Serefoglu EC. Advances in understanding and treating
premature ejaculation. Nat Rev Urol. 2015;12:629–40.
28. Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B.
Relevance of methodological design for the interpretation of
efficacy of drug treatment of premature ejaculation: a systematic
review and meta-analysis. Int J Impot Res. 2004;16:369–81.
29. Salonia A, Rocchini L, Sacca A, Pellucchi F, Ferrari M, Carro
UD, et al. Acceptance of and discontinuation rate from paroxetine
treatment in patients with lifelong premature ejaculation. J Sex
Med. 2009;6:2868–77.
30. McMahon CG, Porst H. Oral agents for the treatment of premature
ejaculation: review of efficacy and safety in the context of the
recent International Society for Sexual Medicine criteria for life-
long premature ejaculation. J Sex Med. 2011;8:2707–25.
31. Salonia A, Maga T, Colombo R, Scattoni V, Briganti A, Cestari
A, et al. A prospective study comparing paroxetine alone versus
paroxetine plus sildenafil in patients with premature ejaculation. J
Urol. 2002;168:2486–9.
32. Mattos RM, Marmo Lucon A, Srougi M. Tadalafil and fluoxetine
in premature ejaculation: prospective, randomized, double-blind,
placebo-controlled study. Urol Int. 2008;80:162–5.
33. Lee WK, Lee SH, Cho ST, Lee YS, Oh CY, Yoo C, et al.
Comparison between on-demand dosing of dapoxetine alone and
dapoxetine plus mirodenafil in patients with lifelong premature
ejaculation: prospective, randomized, double-blind, placebo-con-
trolled, multicenter study. J Sex Med. 2013;10:2832–41.
34. Corona G, Rastrelli G, Limoncin E, Sforza A, Jannini EA, Maggi
M. Interplay between premature ejaculation and erectile dys-
function: a systematic review and meta-analysis. J Sex Med.
2015;12:2291–300.
35. Uckert S, Oelke M, Stief CG, Andersson KE, Jonas U, Hedlund P.
Immunohistochemical distribution of cAMP- and cGMP-
phosphodiesterase (PDE) isoenzymes in the human prostate. Eur
Urol. 2006;49:740–5.
36. Uckert S, Bazrafshan S, Scheller F, Mayer ME, Jonas U, Stief CG.
Functional responses of isolated human seminal vesicle tissue to
selective phosphodiesterase inhibitors. Urology. 2007;70:185–9.
37. McMahon CG, Giuliano F, Dean J, Hellstrom WJ, Bull S, Tesfaye
F, et al. Efficacy and safety of dapoxetine in men with premature
ejaculation and concomitant erectile dysfunction treated with a
phosphodiesterase type 5 inhibitor: randomized, placebo-con-
trolled, phase III study. J Sex Med. 2013;10:2312–25.
38. Yuan J, Zhang R, Yang Z, Lee J, Liu Y, Tian J, et al. Comparative
effectiveness and safety of oral phosphodiesterase type 5 inhibi-
tors for erectile dysfunction: a systematic review and network
meta-analysis. Eur Urol. 2013;63:902–12.