Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment – topical versus systemic
AbstractPremature ejaculation (PE) is a common sexual dysfunction affecting20% to 30% of men worldwide. Definitions of PE vary, but itis typically characterized by short intravaginal ejaculatory latencytime (IELT) with concomitant sexual dissatisfaction and distress.PE may be lifelong or acquired, but its etiology remains unclear.Treatment of PE typically involves pharmacotherapy, particularlywhen lifelong. Although there are numerous reports on the offlabeluse of selective serotonin reuptake inhibitors (SSRIs) andother compounds, only 2 treatments have been evaluated in randomizedcontrolled phase 3 clinical trials: PSD502 and dapoxetine(SSRI). Both significantly improved IELT and patient-reportedoutcome domains of ejaculatory control, sexual satisfaction, anddistress as measured by the index of premature ejaculation (IPE),compared with placebo. They constitute the focus of this review.Evidence demonstrated that PSD502, dapoxetine and other SSRIsall significantly improve the symptoms of PE. Systemic use of SSRIspresents risks associated with the known pharmacology of thisclass. PSD502 allows for topical on-demand treatment appliedapplied immediately before intercourse, and is not associated withsystemic adverse events.
Rowland DL, McMahon C, Abdo C, et al. Disorders of orgasm and ejaculation in men. J Sex Med
Montague DK, Jarow J, Broderick G. Erectile dysfunction guideline update panel. AUA guideline on
the pharmacologic management of premature ejaculation. J Urol 2004;172:290-4. http://dx.doi.
McMahon CG, Althof S, Waldinger MD. An evidence-based definition of lifelong premature ejaculation:
report of the International Society for Sexual Medicine Ad Hoc Committee for the definition of premature
ejaculation. BJU Int 2008;102:338-50. http://dx.doi.org/10.1111/j.1464-410X.2008.07755.x
Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and
premature ejaculation. Eur Urol 2010;57:804-14. http://dx.doi.org/10.1016/j.eururo.2010.02.020
Jannini EA, Porst H. A practical approach to premature ejaculation. J Sex Med 2011:8 (suppl 4):301-3.
Henry R, Morales A, Wyllie M. Topical eutectic-like mixture for premature ejaculation. Expert Opin
Priligy (dapoxetine) receives first regulatory approvals for the treatment of premature ejaculation (PE)
in Finland and Sweden. Medical News Today. February 17, 2009. http://medicalnewstoday.com/
articles/139293.php (Accessed September 13, 2012).
Waldinger MD, Rietschel M, Nothern NM. Familial occurrence of primary premature ejaculation. Psychiatr
Genet 1998;8:37-40. http://dx.doi.org/10.1097/00041444-199800810-00007
Buvat J. Pathophysiology of premature ejaculation. J Sex Med 2011;8(suppl 4):316-27. http://dx.doi.
Jern P, Santtila P, Johansson A, et al. Evidence for a genetic etiology to ejaculatory dysfunction. Int J
Impot Res 2009;21:62-7. http://dx.doi.org/10.1038/ijir.2008.61
Santtila P, Jern P, Westberg L. The dopamine transporter gene (DAT1) polymorphism is associated
with premature ejaculation. J Sex Med 2010;7:1538-46. http://dx.doi.org/10.1111/j.1743-
Janssen PK, Baker SC, Rethelyi J, et al. Serotonin transporter promoter region (5-HTTLPR) polymorphism
is associated with intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.
J Sex Med 2009;6:276-84. http://dx.doi.org/10.1111/j.1743-6109.2008.01033.x
Schapiro B. Premature ejaculation: a review of 1130 cases. J Urol 1943;50:374-7.
Porst H. An overview of pharmacotherapy in premature ejaculation. J Sex Med 2011;8(suppl 4):335-41.
Dinsmore W, Wyllie M. PSD502 improves ejaculatory latency, control and sexual satisfaction when applied
topically 5 min before intercourse in men with premature ejaculation: results of a phase III, multicentre,
double-blind, placebo-controlled study. BJU Int 2009;103:940-9. http://dx.doi.org/10.1111/j.1464-410X.2009.08456.x
Kendirci M, Salem E, Hellstrom WJG. Dapoxetine, a novel selective serotonin transport inhibitor for the
treatment of premature ejaculation. Ther Clin Risk Manag 2007;3:277-89. http://dx.doi.org/10.2147/
Patel K, Hellstrom WJ. Central regulation of ejaculation and the therapeutic role of serotonergic agents
in premature ejaculation. Curr Opin Investig Drugs 2009;10:681-90.
Henry R, Morales A. Topical lidocaine-prilocaine spray for the treatment of premature ejaculation: a
proof of concept study. Int J Impot Res 2003;15:277-81. http://dx.doi.org/10.1038/sj.ijir.3901011
Carson C, Wyllie M. Improved ejaculatory latency, control, and sexual satisfaction when PSD502 is applied
topically in men with premature ejaculation: Results of a Phase III, double-blind, placebo-controlled study.
J Sex Med 2010;7:3179-89. http://dx.doi.org/10.1111/j.1743-
Morales A, Barada J, Wyllie MG. A review of the current status of topical treatments for premature
ejaculation. BJU Int 2007;100:493-501. http://dx.doi.org/10.1111/j.1464-410X.2007.07051.x
Atikeler MK, Gecit I, Senol FA. Optimun usage of prilocaine-lidocaine cream in premature ejaculation.
Andrologia 2002;34:356-9. http://dx.doi.org/10.1046/j.1439-0272.2002.00511.x
Busato W, Galindo CC. Topical anesthetic use for treating premature ejaculation: a double-blind, randomized,
placebo-controlled study. BJU Int 2004;93:1018-21. http://dx.doi.org/10.1111/j.1464-
Choi HK, Jung GW, Moon KH, et al. Clinical study of SS-cream in patients with lifelong premature ejaculation.
Urology 2000;55:257-61. http://dx.doi.org/10.1016/S0090-4295(99)00415-X
Waldinger MD, Zwinderman AH, Schweitzer DH. 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. http://dx.doi.org/10.1038/sj.ijir.3901172
Waldinger MD, Hengeveld W, Zwinderman AH. Effect of SSRI antidepressants on ejaculation: a doubleblind,
randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J
Clin Psychopharmacol 1998;18:274-81. http://dx.doi.org/10.1097/00004714-199808000-00004
Pryor JL, Althof SE, Steidle C. Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation:
an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006;368:929-37.
Shabsigh R, Patrick DL, Rowland DL. Perceived control over ejaculation is central to treatment benefit in
men with premature ejaculation: results from phase III trials with dapoxetine. BJU Int 2008;102:824-8.
Buvat J, Tesdaye F, Rothman M, et al. Dapoxetine for the treatment of premature ejaculation: results from
a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries. Eur Urol 2009;55:957-67.
McMahon C, Kim SW, Park NC, et al. Treatment of premature ejaculation in the Asia-Pacific region: results
from a phase III double-blind, parallel-group study of dapoxetine. J Sex Med 2010;7:256-68. http://
Gunnel D, Middleton N, Whitley E, et al. Why are suicide rates rising in young men but falling in the
elderly? A time-series analysis of trends in England and Wales. Soc Sci Med 2003;57:595-611.
Hall WD. How have had the SSRI antidepressants affected suicide risk? Lancet 2006;367:1959-62. http://dx.doi.org/10.1016/S0140-6736(06)68860-0
McMahon, CG, Althof SE, Kaufman JM, et al. Efficacy and safety of dapoxetine for the treatment of premature ejaculation: Integrated analysis of results from five phase 3 trials. J Sex Med 2011;8:524-39.
How to Cite
You, the Author(s), assign your copyright in and to the Article to the Canadian Urological Association. This means that you may not, without the prior written permission of the CUA:
- Post the Article on any Web site
- Translate or authorize a translation of the Article
- Copy or otherwise reproduce the Article, in any format, beyond what is permitted under Canadian copyright law, or authorize others to do so
- Copy or otherwise reproduce portions of the Article, including tables and figures, beyond what is permitted under Canadian copyright law, or authorize others to do so.
The CUA encourages use for non-commercial educational purposes and will not unreasonably deny any such permission request.
You retain your moral rights in and to the Article. This means that the CUA may not assert its copyright in such a way that would negatively reflect on your reputation or your right to be associated with the Article.
The CUA also requires you to warrant the following:
- That you are the Author(s) and sole owner(s), that the Article is original and unpublished and that you have not previously assigned copyright or granted a licence to any other third party;
- That all individuals who have made a substantive contribution to the article are acknowledged;
- That the Article does not infringe any proprietary right of any third party and that you have received the permissions necessary to include the work of others in the Article; and
- That the Article does not libel or violate the privacy rights of any third party.