World Journal of Urology

, Volume 23, Issue 2, pp 102–108 | Cite as

Lifelong premature ejaculation: definition, serotonergic neurotransmission and drug treatment

  • Marcel D. WaldingerEmail author
Topic Paper


The ejaculation distribution theory (EDT) postulates a biological continuum of the intravaginal ejaculation latency time (IELT) in men. Such an continuum has recently been found in two epidemiological stopwatch studies. In addition, a continuum of ejaculation latency time has also been demonstrated in laboratory rats. It is suggested that the invariable parts of ejaculation, i.e. premature and retarded ejaculation are highly influenced by genetic and neurobiological factors. In contrast, superimposed on biological roots, ejaculation of men, in the middle part of the continuum, is probably more easily influenced by environmental and psychological factors. A meta-analysis of 35 daily SSRI and clomipramine treatment studies demonstrated a similar efficacy for paroxetine, clomipramine, sertraline and fluoxetine, with paroxetine exerting the strongest effect on ejaculation. Based on fundamental insights into serotonergic neurotransmission, it is suggested that on-demand conventional SSRI treatment will not lead to similarly impressive ejaculation delay as that found after daily conventional SSRI treatment. Future studies with SSRIs with short half-lives, short Tmax and high Cmax should elucidate whether these pharmacokinetic properties are able to affect the pharmacodynamics of 5-HT neurons in such a way that immediate clinically relevant ejaculation delay occurs.


Premature ejaculation Epidemiology Serotonin Dapoxetine Paroxetine 


  1. 1.
    Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B (2004) Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. J Impot Res 16:369–381CrossRefPubMedGoogle Scholar
  2. 2.
    Schapiro B (1943) Premature ejaculation, a review of 1130 cases. J Urol 50:374–379Google Scholar
  3. 3.
    Eaton H (1973) Clomipramine in the treatment of premature ejaculation. J Int Med Res 1:432–434Google Scholar
  4. 4.
    Assalian P (1988) Clomipramine in the treatment of premature ejaculation. J Sex Res 24:213–215Google Scholar
  5. 5.
    Shilon M, Paz GF, Hommonai ZT (1984) The use of phenoxybenzamine treatment in premature ejaculation. Fertil Steril 42:659–661PubMedGoogle Scholar
  6. 6.
    Waldinger MD, Hengeveld MW, Zwinderman AH (1994) Paroxetine treatment of premature ejaculation: a double-blind, randomised, placebo-controlled study. Am J Psychiatry 151:1377–1379PubMedGoogle Scholar
  7. 7.
    Althof SE (2005) Psychological treatment strategies for rapid ejaculation: rationale, practical aspects, and outcome. World J Urol (this issue)Google Scholar
  8. 8.
    Assalian P (2005) Guidelines for pharmacotherapy of premature ejaculation. World J Urol (this issue)Google Scholar
  9. 9.
    Hartmann U, Schedlowski M, Kruger THC (2005) Cognitive and partner-related factors in rapid ejaculation: differences between dysfunctional and functional men. World J Urol (this issue)Google Scholar
  10. 10.
    Waldinger MD (2003) Towards evidence-based drug treatment research on premature ejaculation: a critical evaluation of methodology. J Impot Res 15:309–313CrossRefPubMedGoogle Scholar
  11. 11.
    Waldinger MD (2004) Lifelong premature ejaculation: from authority-based to evidence-based medicine. BJU Int 93:201–207CrossRefPubMedGoogle Scholar
  12. 12.
    Tanner BA (1973) Two case reports on the modification of the ejaculatory response with the squeeze technique. Psychother Res Pract 10:297Google Scholar
  13. 13.
    Cooper AJ, Magnus RV (1984) A clinical trial of the beta blocker propranolol in premature ejaculation. J Psychosom Res 28:331–336CrossRefPubMedGoogle Scholar
  14. 14.
    Althof SE, Levine SB, Corty EW, Risen CB, Stern EB (1995) A double-blind crossover trial of clomipramine for rapid ejaculation in 15 couples. J. Clin Psychiatry 56:402–407Google Scholar
  15. 15.
    Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B (1998) An empirical operationalization study of DSM-IV diagnostic criteria for premature ejaculation. Int J Psychiatry Clin Pract 2:287–293Google Scholar
  16. 16.
    Masters WH, Johnson VE (1970) Premature ejaculation. In: Masters WH, Johnson VE (eds) Human sexual inadequacy. Little, Brown, Boston, pp 92–115Google Scholar
  17. 17.
    Waldinger MD, Berendsen HHG, Blok BFM, Olivier B, Holstege G (1998) Premature ejaculation and SSRI-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res 92:111–118CrossRefPubMedGoogle Scholar
  18. 18.
    Waldinger MD, Olivier B (2000) Selective serotonin reuptake inhibitors (SSRIs) and sexual side effects: differences in delaying ejaculation. In: Sacchetti E, Spano P (eds) Advances in preclinical and clinical psychiatry, vol 1, Fluvoxamine: established and emerging roles in psychiatric disorders. Excerpta Medica, Milan, pp 117–130Google Scholar
  19. 19.
    Waldinger MD (2002) The neurobiological approach to premature ejaculation.J Urol 168:2359–2367CrossRefPubMedGoogle Scholar
  20. 20.
    Waldinger MD, Quinn P, Dilleen M, Mundayat R, Schweitzer DH, Boolell M (2005) A multinational population survey of intravaginal ejaculation latency time. J Sex Med (in press)Google Scholar
  21. 21.
    Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH (2005) Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data. J Sex Med (in press)Google Scholar
  22. 22.
    Waldinger MD, Schweitzer DH, Olivier B (2005) On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions. J Sex Med 2:121–131CrossRefGoogle Scholar
  23. 23.
    Patrick DL, Althof SE, Pryor JL, Rosen R, Rowland DL, Ho KF, McNulty P, Rothman M, Jamieson C (2005) Premature ejaculation: an observational study of men and their partners. J Sex Med 2:358–367CrossRefGoogle Scholar
  24. 24.
    Rowland DL (2005) Psychophysiology of ejaculatory function and dysfunction. World J Urol (this issue)Google Scholar
  25. 25.
    Waldinger MD, Schweitzer DH (2005) Retarded ejaculation in men: an overview of psychological and neurobiological insights. World J Urol (this issue)Google Scholar
  26. 26.
    Pattij T, De Jong T, Uitterdijk A, Waldinger MD, Veening JG, Van der Graaf PH, Olivier B (2003) Searching for models to study ejaculation disorders. Behav Pharmacol 14 [Suppl 1]:S80–81Google Scholar
  27. 27.
    Olivier B, Chan J, Pattij T, de Jong T, Oosting R, Veening J, Waldinger MD (2005) Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions? Int J Impot Res (in press)Google Scholar
  28. 28.
    Waldinger MD, Olivier B (2005) Animal models of premature and delayed ejaculation. World J Urol (this issue)Google Scholar
  29. 29.
    Olivier B, Van Oorschot R, Waldinger MD (1998) Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Int Clin Psychopharmacol 13 [Ssuppl 6]:S9–S14Google Scholar
  30. 30.
    Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Linberg P et al. (1981) Effects of a new type of 5-HT receptor agonist on male rat sexual behaviour. Pharmacol Biochem Behav 15:785–792CrossRefPubMedGoogle Scholar
  31. 31.
    Foreman MM, Hall JL, Love RL (1998) The role of the 5-HT2 receptor in the regulation of sexual performance of male rats. Life Sci 45:1263–1270CrossRefGoogle Scholar
  32. 32.
    Kara H, Aydin S, Agargun Y, Odabas O, Yilmiz Y (1996) The efficacy of fluoxetine in the treatment of premature ejaculation: a double-blind, placebo controlled study. J Urol 156:1631–1632CrossRefPubMedGoogle Scholar
  33. 33.
    Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B (1998) Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline. J Clin Psychopharmacol 18:274–281CrossRefPubMedGoogle Scholar
  34. 34.
    Waldinger MD, Zwinderman AH, Olivier B (2001) Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone. J Clin Psychopharmacol 21:293–297Google Scholar
  35. 35.
    Waldinger MD, Zwinderman AH, Olivier B (2001) SSRIs and ejaculation: a double-blind, randomised, fixed-dose study with paroxetine and citalopram. J Clin Psychopharmacol 21:556–560Google Scholar
  36. 36.
    Waldinger MD, Zwinderman AH, Olivier B (2003) Antidepressants and ejaculation: a double-blind, randomized, fixed-dose study with mirtazapine and paroxetine. J Clin Psychopharmacol 23:467–470Google Scholar
  37. 37.
    Novaretti JPT, Pompeo ACL, Arap S (2002) Selective serotonin uptake inhibitor in the treatment of premature ejaculation. Brazil J Urol 28:116–122Google Scholar
  38. 38.
    Atmaca M, Kuloglu M, Tezcan E, Semercioz A (2002) The efficacy of citalopram in the treatment of premature ejaculation: a placebo-controlled study. Int J Impot Res 14:502–505CrossRefPubMedGoogle Scholar
  39. 39.
    Mos J, Mollet I, Tolboom JTBM, Waldinger MD, Olivier B (1999) A comparison of the effects of different serotonin reuptake blockers on sexual behaviour of the male rat. Eur Neuropsychopharmacol 9:123–135CrossRefPubMedGoogle Scholar
  40. 40.
    Waldinger MD, Zwinderman AH, Olivier B (2004) On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment. Eur Urol 46:510–516Google Scholar
  41. 41.
    Segraves RT, Saran A, Segraves K, Maguire E (1993) Clomipramine vs placebo in the treatment of premature ejaculation: a pilot study. J Sex Marital Ther 19:198–200PubMedGoogle Scholar
  42. 42.
    Haensel SM, Rowland DL, Kallan KTHK, Slob AK (1996) Clomipramine and sexual function in men with premature ejaculation and controls. J Urol 156:1310–1315CrossRefPubMedGoogle Scholar
  43. 43.
    Abdel-Hamid IA, El Naggar EA, El Gilany AH (2001) Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation. Int J Impot Res 13:41–45CrossRefPubMedGoogle Scholar
  44. 44.
    McMahon CG, Touma K (1999) Treatment of premature ejaculation with paroxetine hydrochloride. Int J Impot Res 11:241–245CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Psychiatry and NeurosexologyLeyenburg Haga Hospital
  2. 2.Department of PsychopharmacologyUtrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for NeurosciencesThe Netherlands

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