Advances in Treatment for Premature Ejaculation

European Urological Review, 2008;3(1):102-5

Not every complaint of ejaculation is the result of an ejaculatory ‘disorder’. For example, a man may believe himself to be ejaculating prematurely, even though he is doing so within a normal ejaculation time. On the other hand, some men regularly complain of early ejaculation occurring very soon after penetration. Both examples are part of a debate on the definition of premature ejaculation (PE) that has existed since the 1970s, and which has given rise to sometimes fierce debate.

History of Premature Ejaculation
Since the beginning of the last century, PE has been regarded as an expression of an unconscious psychological conflict. It has also been attributed to urological disturbances, and many different treatments have been recommended over the years.1 A clearer understanding of the differences in aetiology and treatment has resulted from the classification, introduced in 1943 by the German endocrinologist Bernhard Schapiro, of two types of PE: A and B.2 Later, the types became known as primary (lifelong) PE and secondary (acquired) PE, respectively,3 and were included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision) (DSM-IVTR), which is the American Psychiatric Association (APA) classification system of mental disorders.4

The Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(Text Revision) Definition
Until 1980, the year in which the DSM-III was published by the APA, there was no official definition of PE. In the first part of the 20th century, psychoanalysts considered a man to be suffering from PE when ejaculation occurred so quickly after vaginal penetration that a woman had little chance of getting sexually aroused. In the absence of any official definition, it was a loosely accepted idea that a man suffered from PE when he consistently ejaculated within one minute after penetration. In 1970, William Masters and Virginia Johnson rejected this idea by stating that a man has PE when he is unable to control his ejaculation to satisfy his female partner in more than 50% of intercourses.5 Masters and Johnson strongly refuted a short ejaculation time as a criterion for the definition of PE. Their view influenced the first official definition of PE, made in the DSM-III in 1980. According to the DSM-III, a man is defined as having PE when “ejaculation occurs before the individual wishes it, because of recurrent and persistent absence of reasonable voluntary control of ejaculation and orgasm during sexual activity.”6 It is clear that the DSM-III defined PE solely in terms of an absence of voluntary ‘control’, without paying attention to the time that passes before a man actually ejaculates (the ejaculation time). After its publication, the DSM-III definition of PE has given rise to debate among psychiatrists about the meaning of the word ‘control’. The result of this debate was that in the next version, the DSM-III-R, published in 1987, the word control was no longer mentioned in the definition. Instead, PE was defined as “persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it.”7The new defining criterion ‘short ejaculation time’ remained in the two other DSM editions: the DSM-IV (1994) and the DSM-IV-TR (2000).4 However, as little evidence-based research into ejaculation time had been conducted in the 1980s, a quantification of the ‘short’ ejaculation time was not mentioned in the DSM-IV definition. In contrast, the definition of PE in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), which is the classification system of the World Health Organization (WHO), does mention a cut-off point for the ejaculation time.8 According to the ICD-10, a man has PE when he ejaculates within 15 seconds after penetration. However, the ICD-10 makes no reference to any study where this figure had been reported as outcome data.9

Research into Ejaculation Time
In the mid-1990s, Waldinger et al. postulated that in the general male population there is variability in the intravaginal ejaculation latency time (IELT), which is defined as the time between vaginal penetration and intravaginal ejaculation.10 However, it was only in 2005 that such variability was demonstrated in men.11 In a stopwatch study, financed by Pfizer International, the IELT was measured in a random cohort of men in the general population of five countries – The Netherlands, UK, Spain, Turkey and the US – during a one-month period.11 The study demonstrated for the first time that in the general male population the IELT has a skewed distribution, with a median IELT of 5.4 minutes (confidence interval [CI] 0.55–44.1 minutes). However, such a continuum of the ejaculation time had previously also been observed using various cohorts of laboratory male Wistar rats.12,13 Based on this continuum, a new animal model for PE was presented. In addition, it was postulated that there are three endophenotypes of male rats: rats that always ejaculate after a short time of copulatory behaviour, i.e. rapid ejaculating rats; rats that ejaculate after a normal ejaculation latency time, i.e. normal ejaculating rats; and rats that ejaculate after a long ejaculation latency time, i.e. sluggish ejaculating rats. It was also postulated that lifelong PE in men represents a specific phenotype and is characterised by specific symptomatology.14

1. Waldinger MD, Lifelong premature ejaculation: from authority-based to evidence-based medicine, BJU Int, 2004;93:201–7.
2. Schapiro B, Premature: a review of 1130 cases, J Urol, 1943; 50: 374–9.
3. Godpodinoff ML, Premature ejaculation: clinical subgroups and etiology, J Sex Marital Therapy, 1989;15:130–4.
4. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (4th edition, Text Revision) (DSMIV- TR), Washington: American Psychiatric Association, 2000.
5. Masters WH, Johnson VE, Premature ejaculation. In: Masters WH, Johnson VE (eds), Human Sexual Inadequacy, Boston: Little, Brown and Co, 1970:92–115
6. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (3rd edition) (DSM-III), Washington, DC: American Psychiatric Association, 1980.
7. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised) (DSM-III-R), Washington, DC: American Psychiatric Association, 1987.
8. World Health Organization, The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research, 1993.
9. Waldinger MD, Schweitzer DH, Changing paradigms from an historical DSM-III and DSM-IV view towards an evidence based definition of premature ejaculation. Part I: Validity of DSM-IV-TR, J Sex Med, 2006;3:682–92.
10. Waldinger MD, Berendsen HHG, Blok BFM, et al., Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system, Behav Brain Res, 1 998; 92:111–18.
11. Waldinger MD, Quinn P, Dilleen M, et al., A multi-national population survey of intravaginal ejaculation latency time, J Sex Medicine, 2005;2:492–7.
12. Pattij T, de Jong T, Uitterdijk A, et al., Individual differences in male rat ejaculatory behavior: searching for models to study ejaculation disorders, Eur J Neurosci, 2005;22: 724–34.
13. Pattij T, Olivier B, Waldinger MD, Animal models of ejaculatory behaviour, Curr Pharm Des, 2005;11:4069–77.
14. Waldinger MD, The neurobiological approach to premature ejaculation (review), J Urol, 2002;168:2359–67.
15. Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH, Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data, J Sex Medicine,2005; 2: 498–507.
16. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B, An empirical operationalization study of DSM-IV diagnostic criteria for premature ejaculation, Intern J Psych Clin Pract,1998; 2: 287–93.
17. Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH, The majority of men with lifelong premature ejaculation prefer daily drug treatment: an observational study in a consecutive group of Dutch men, J Sex Med, 2007;4: 1028–37.
18. McMahon CG, Althof S, Waldinger MD, Porst H, et al., 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; Epub ahead of print.
19. Althof S, The psychology of premature ejaculation: therapies and consequences, J Sex Med, 2006:4:324–31.
20. Carani C, Isidori AM, Granata A, et al., Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients,< i>J Clin Endocrinol Metab, 2005;90: 6472–9.
21. Shamloul R, El-Nashaar A, Chronic prostatitis in premature ejaculation: a cohort study in 153 men, J Sex Med, 2006;3: 150–54.
22. Trinchieri A, Magri V, Cariani L, et al., Prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome, Arch Ital Urol Androl, 2007;79:67–70.
23. Patrick DL, Althof SE, Pryor JL, et al., Premature ejaculation: an observational study of men and their partners, J Sex Med, 2005; 2:358–67.
24. Waldinger MD, Schweitzer DH, Changing paradigms from an historical DSM-III and DSM-IV view towards an evidence based definition of premature ejaculation. Part II: Proposals for DSM-V and ICD-11, J Sex Med, 2006;3:693–705.
25. Waldinger MD, The need for a revival of psychoanalytic investigations into premature ejaculation, J Mental Health Gender, 2006;3:390–96.
26. Waldinger MD, Premature ejaculation: State of the art, Urol Clin North Am, 2007;34:591–9.
27. Waldinger MD, Schweitzer DH, The use of old and recent DSM definitions of premature ejaculation in observational studies: a contribution to the present debate for a new classification of PE in the DSM-V, J Sex Medicine, 2008;5:1079–87.
28. Waldinger MD, Premature ejaculation: different pathophysiologies and etiologies determine its treatment,J Sex Marital Ther, 2008;34:1–13.
29. 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.
30. Waldinger MD, Premature ejaculation: definition and drug treatment, Drugs, 2007;67:547–68.
31. Safarinejad MR, Hosseini SY, Safety and efficacy of tramadol in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study,J Clin Psychopharmacol, 2006;26:27–31.
32. Salem EA, Wilson SK, Bissada NK, et al., Tramadol HCL has promise in on-demand use to treat premature ejaculation, J Sex Med, 2008;5:188–93.
33. 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.
34. Dapoxetine: LY210448, Drugs in R&D, 2005;6307–11.
35. Pryor JL, Althof SE, Steidle C, et al., Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation: integrated analysis of two randomized, double-blind, placebo-controlled trials, Lancet, 2006;368: 929–37.
36. Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH, Geometric mean IELT and premature ejaculation: Appropriate statistics to avoid overestimation of treatment efficacy, J Sex Medicine,2008;5:492–9.
37. Dinsmore WW, Hackett G, Goldmeier D, et al., Topical eutectic mixture for premature ejaculation (TEMPE): a novel aerosol-delivery form of lidocaine-prilocaine for treating premature ejaculation,BJU Int, 2007;99:369–75.
38. Waldinger MD, Schweitzer DH, Premature ejaculation and pharmaceutical company-based medicine: The dapoxetine case, J Sex Med, 2008;5:966–97.
39. Waldinger MD, Editorial. New challenges: the need for independency, Sexologies, 2008;17:3–4.