Current therapeutic strategies for premature ejaculation and future perspectives

Asian Journal of Andrology

Volumn 13, Issue 4, 2011, Pages 550-557

  Xin, Zhong Cheng ^a   Zhu, Yi Chen ^b   Yuan, Yi Ming ^a   Cui, Wan Shou ^a   Jin, Zhe ^a   Li, Wei Ren ^a   Liu, Tao ^a  

^a PEKING UNIVERSITY FIRST HOSPITAL   (China)

^b CAPITAL MEDICAL UNIVERSITY   (China)

Author keywords

5 HT; dapoxetine; premature ejaculation; selective serotonin reuptake inhibitor; sexual disorder; treatment

Indexed keywords

ALPHA 1 ADRENERGIC RECEPTOR BLOCKING AGENT; ANTIDEPRESSANT AGENT; CITALOPRAM; CLOMIPRAMINE; DAPOXETINE; FLUOXETINE; LIDOCAINE; LOCAL ANESTHETIC AGENT; PAROXETINE; PHOSPHODIESTERASE V INHIBITOR; PRILOCAINE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; SILDENAFIL; TRAMADOL; VARDENAFIL;

BEHAVIOR THERAPY; BLEEDING; BONE DENSITY; DIARRHEA; DIZZINESS; DRUG MECHANISM; ERECTILE DYSFUNCTION; FATIGUE; HEADACHE; HUMAN; INSOMNIA; LOOSE FECES; MALE; NAUSEA; OFF LABEL DRUG USE; PARESTHESIA; PREMATURE EJACULATION; PRIAPISM; REVIEW; SEXUAL BEHAVIOR; SEXUAL DYSFUNCTION; SIDE EFFECT; SKIN IRRITATION; SWEATING; VOMITING; YAWNING;

ADRENERGIC ALPHA-1 RECEPTOR ANTAGONISTS; ANIMALS; ANTIDEPRESSIVE AGENTS; DRUG COMBINATIONS; EJACULATION; ERECTILE DYSFUNCTION; HUMANS; LIDOCAINE; MALE; MODELS, ANIMAL; PHOSPHODIESTERASE 5 INHIBITORS; PRILOCAINE; SEROTONIN UPTAKE INHIBITORS; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SEXUAL DYSFUNCTIONS, PSYCHOLOGICAL; TRAMADOL;

EID: 79960053700     PISSN: 1008682X     EISSN: 17457262     Source Type: Journal    
DOI: 10.1038/aja.2010.130     Document Type: Review

References (96)

1. Eliasson R. Human Semen and Fertility Regulation in Men. St Louis, , MO: Mosby; 1976. p44.
2. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281: 537-44. (Pubitemid 29081307)
3. Carson C, Gunn K. Premature ejaculation: definition and prevalence. Int J Impot Res 2006; 18 (Suppl 1): S5-13. (Pubitemid 44330307)
4. McMahon CG, Althof SE, Waldinger MD, Porst H, Dean J et al. An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine (ISSM) ad hoc committee for the definition of premature ejaculation. J Sex Med 2008; 5: 1590-606. (Pubitemid 352044417)
5. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. J Eur Urol 2010; 57: 804-14.
6. Semans JH. Premature ejaculation: a new approach. South Med J 1956; 49: 353-8.
7. Masters WM, Johnson VE. Human Sexual Inadequacy. Boston, , MA: Little, Brown and Company; 1970.
8. Metz M, McCarthy B. Coping with Premature Ejaculation:How to Overcome PE, Please Your Partner and Have Great Sex. Oakland, , CA: New Harbinger; 2003. p79.
9. Lawrence JS, Madakasira S. Evaluation and treatment of premature ejaculation: a critical review. Int J Psychiatry Med 1992; 22: 77-97.
10. Hawton K, Catalan J, Martin P, Fagg J. Long-term outcome of sex therapy. Behav Res Ther 1986; 24: 665-75. (Pubitemid 17213221)
11. Gurkan L, Oommen M, Hellstrom W. Premature ejaculation: current and future treatments. Asian J Androl 2008; 10: 102-9.
12. Althof S. The psychology of premature ejaculation: therapies and consequences. J Sex Med 2006; 3 (Suppl 4): 324-31. (Pubitemid 44269835)
13. Perelman MA. A new combination treatment for premature ejaculation: a sex therapists perspective. J Sex Med 2006; 3: 1004-12. (Pubitemid 44644712)
14. Schapiro B. Premature ejaculation: a review of 1130 cases. J Urol 1943; 50: 374-9.
15. 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. (Pubitemid 39273766)
16. Waldinger MD. Towards evidenced based drug treatment research on early ejaculation: a critical evaluation of methodology. Int J Impot Res 2003; 15: 309-13. (Pubitemid 37376933)
17. Giuliano F. 5-Hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention. Trends Neurosci 2007; 30: 79-84. (Pubitemid 46164860)
18. Olivier B, van Oorschot R, Waldinger MD. Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Int Clin Psychopharmacol 1998; (Suppl 6): S9-14. (Pubitemid 28372346)
19. Waldinger M, Olivier B. Utility of selective serotonin reuptake inhibitors in premature ejaculation. Curr Opin Invest Drugs 2004; 5: 743-7.
20. Gur E, Lerer B, Newman ME. Chronic clomipramine and triiodothyronine increase serotonin levels in rat frontal cortex in vivo: relationship to serotonin autoreceptor activity. J Pharmacol Exp Ther 1999; 288: 81-7. (Pubitemid 29113476)
21. Eaton H. Clomipramine in the treatment of premature ejaculation. J Int Med Res 1973; 1: 432-4.
22. Strassberg DS, de Gouveia Brazao CA, Rowland DL, Tan P, Slob AK. Clomipramine in the treatment of rapid (premature) ejaculation. J Sex Marital Ther 1999; 25: 89-101. (Pubitemid 29183826)
23. Waldinger MD, Zwinderman AH, Olivier B. On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixeddose study with stopwatch assessment. Eur Urol 2004; 46: 510-6. (Pubitemid 39206295)
24. Haensel SM, Rowland DL, Kallan KT. Clomipramine and sexual function in men with premature ejaculation and controls. J Urol 1996; 156: 1310-5. (Pubitemid 26307601)
25. Althof SE, Levine SB, Corty EW, Risen CB, Stern EB et al. A double-blind crossover trial of clomipramine for rapid ejaculation in 15 couples. J Clin Psychiatry 1995; 56: 402-7.
26. Kim SC, Seo KK. Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with premature ejaculation: a double-blind, placebo controlled study. J Urol 1998; 159: 425-7. (Pubitemid 28049248)
27. PattersonWM. Fluoxetine induced sexual dysfunction (letter). J Clin Psychiatry 1993; 54: 71. (Pubitemid 23078214)
28. Waldinger MD, van de Plas A, Pattij T, van Oorschot R, Coolen LM et al. The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment. Psychopharmacology (Berl)2002; 160: 283-9. (Pubitemid 34230680)
29. Kilic S, Ergin H, Baydinc YC. Venlafaxine extended release for the treatment of patients with premature ejaculation: a pilot, single-blind, placebo-controlled, fixeddose crossover study on short-term administration of an antidepressant drug. Int J Androl 2005; 28: 47-52. (Pubitemid 40203732)
30. Montague DK, Jarow J, Broderick G, Dmochowski RR, Heaton JP et al. AUA guideline on the pharmacologic management of premature ejaculation. J Urol 2004; 172: 290-4.
31. Lue TF, Giuliano F, Montorsi F, Rosen RC, Andersson KE et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2004; 1: 6-23. (Pubitemid 40424662)
32. McMahon CG, Abdo C, Incrocci L, Perelman M, Rowland D et al. Disorders of orgasm and ejaculation in men. J Sex Med 2004; 1: 58-65. (Pubitemid 40424667)
33. Seftel AD. Male and Female Sexual Dysfunction. London: Mosby; 2004. pp204-37.
34. Waldinger MD. Premature ejaculation: definition and drug treatment. Drugs 2007; 67: 547-68. (Pubitemid 46440312)
35. Dent LA, Brown WC, Murney JD. Citalopram-induced priapism. Pharmacotherapy 2002; 22: 538-41. (Pubitemid 34270040)
36. Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 2007; 167: 1246-51. (Pubitemid 46998495)
37. Halperin D, Reber G. Influence of antidepressants on hemostasis. Dialogues Clin Neurosci 2007; 9: 47-59. (Pubitemid 46607130)
38. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry 2001; 62 (Suppl 3): 10-21. (Pubitemid 32164676)
39. Giuliano F, Clement P. Serotonin and premature ejaculation: from physiology to patient management. Eur Urol 2006; 50: 454-66. (Pubitemid 44189074)
40. Walsh PC. Campbell-Walsh Urology. 9th edn, Vol. 1. Philadelphia, , PA: Saunders- Elsevier; 2007. pp750-87.
41. Fuller RW. Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci 1994; 55: 163-7. (Pubitemid 24187116)
42. de Montigny C, Blier P, Caille G, Kouassi E. Pre- and postsynaptic effects of zimelidine and norzimelidine on the serotoninergic system: single cell studies in the rat. Acta Psychiatr Scand Suppl 1981; 290: 79-90. (Pubitemid 11156103)
43. Waldinger MD, Schweitzer DH, Olivier B. On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions. J Sex Med 2005; 2: 121-31. (Pubitemid 40468200)
44. Blier P, Montigny DC. Electrophysiological investigations on the effect of repeated zimelidine administration on serotonergic neurotransmission in the rat. J Neurosci 1983; 3: 1270-8. (Pubitemid 13060722)
45. Chaput Y, Blier P, de Montigny C. In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotoninergic terminals. J Neurosci 1986; 6: 2796-801. (Pubitemid 16026058)
46. Blier P, Chaput Y, de Montigny C. Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptors: an electrophysiological study in the rat brain. Naunyn Schmiedebergs Arch Pharmacol 1988; 337: 246-54.
47. Lintz W, Becker R, Gerloff J, Terlinden R. Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 4th communication: drops (without ethanol). Arzneimittelforschung 2000; 50: 99-108. (Pubitemid 30114837)
48. Frink MC, Hennies HH, Engelberger W, Haurand M, Wilffert B. Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung 1996; 46: 1029-36. (Pubitemid 26391736)
49. Salem EA, Wilson SK, Bissada NK, Delk JR, Hellstrom WJ et al. Treatment of premature ejaculation with tramadol HCL. J Sex Med 2008; 5: 188-93.
50. Safarinejad MR, Hosseini SY. Safety and efficacy of tramadol in the treatment of premature ejaculation. J Clin Psychopharmacol 2006; 26: 27-31.
51. Laumann EO, Nicolosi A, Glasser DB, Paik A, Gingell C et al. Sexual problems among women and men aged 40-80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. Int J Impot Res 2005; 17: 39-57. (Pubitemid 40299993)
52. Jannini EA, Lombardo F, Lenzi A. Correlation between ejaculatory and erectile dysfunction. Int J Androl 2005; 28 (2 Suppl): 40-5. (Pubitemid 41719772)
53. Mancina R, Filippi S, Marini M, Morelli A, Vignozzi L et al. Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens. Mol Human Reprod 2005; 11: 107-15. (Pubitemid 40331291)
54. Kriegsfeld LJ, Demas GE, Huang PL, Burnett AL, Nelson RJ. Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS2/2). Physiol Behav 1999; 67: 561-6. (Pubitemid 29488535)
55. McMahon C, Stuckey B, Andersen M, Purvis K, Koppiker N et al. Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation. J Sex Med 2005; 2: 368-75. (Pubitemid 40744377)
56. Ekmekcioglu O, Inci M, Demirci D, Tatlisen A. Effects of sildenafil citrate on ejaculation latency, detumescence time, and refractory period: placebo-controlled, double-blind, crossover laboratory setting study. Urology 2005; 65: 347-52. (Pubitemid 40248026)
57. Salonia A, Maga T, Colombo R, Scattoni V, Briganti A et al. A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol 2002; 168: 2486-9. (Pubitemid 35402646)
58. Aversa A, Pili M, Francomano D, Bruzziches R, Spera E et al. Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation. Int J Impot Res 2009; 21: 221-7.
59. Mathers MJ, Klotz T, Roth S, Lummen G, Sommer F. Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised prospective and crossover study. Andrologia 2009; 41: 169-75.
60. Abdel-Hamid IA, El Naggar EA, El Gilany AH. Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation. Int J Impot Res 2001; 13: 41-5. (Pubitemid 32274649)
61. Mondaini N, Ponchietti R, Muir GH, Montorsi F, di Loro F et al. Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time. Int J Impot Res 2003; 15: 225-8. (Pubitemid 36928916)
62. 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.
63. Kim SW, Lee SH, Paick JS. In vivo rat model to measure hypogastric nerve stimulationinduced seminal vesicle and vasal pressure responses simultaneously. Int J Impot Res 2004; 16: 427-32. (Pubitemid 39319043)
64. Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy. Eur Urol 1995; 28: 126-30.
65. Basar MM, Yilmaz E, Ferhat M, Basar H, Batislam E. Terazosin in the treatment of premature ejaculation: a short-term follow-up. Int Urol Nephrol 2005; 37: 773-7. (Pubitemid 43124245)
66. Xin ZC, Chung WS, Choi YD, Seong DH, Choi YJ et al. Penile sensitivity in patients with primary premature ejaculation. J Urol 1996; 156: 979-81. (Pubitemid 26269813)
67. Xin ZC, Choi YD, Rha KH, Choi HK. Somatosensory evoked potentials in patients with primary premature ejaculation. J Urol 1997; 158: 451-5. (Pubitemid 27327684)
68. Xin ZC, Choi YD, Seong DH, Choi HK. Sensory evoked potential and the effect of SScream in premature ejaculation. Yonsei Med J 1995; 36: 397-401.
69. Xin ZC, Choi YD, Lee WH, Chun DC, Choi HK et al. Changes in ejaculatory latency and penile vibratory threshold with SS-cream in patients with primary premature ejaculation. Sex Dysfunct 1998; 1: 89-93.
70. Xin ZC, Choi YD, Lee SH, Choi HK. Efficacy of a topical agent SS-cream in the treatment of premature ejaculation: preliminary clinical studies. Yonsei Med J 1997; 38: 91-5. (Pubitemid 27211736)
71. Choi HK, Jung GW, Moon KH, Moon KH, Xin ZC et al. Clinical study of SS-cream in patients with lifelong premature ejaculation. Urology 2000; 55: 257-61. (Pubitemid 30069927)
72. Tian L, Xin ZC, Xin H, Fu J, Yuan YM et al. Effect of renewed SS-cream on spinal somatosensory evoked potentials in rabbits. Asian J Androl 2004; 6: 15-8. (Pubitemid 38418332)
73. Busato W, Galindo CC. Topical anaesthetic use for treating premature ejaculation: a double-blind, randomized, placebo-controlled study. BJU Int 2004; 93: 1018-21. (Pubitemid 38758626)
74. Atikeler MK, Gecit I, Senol FA. Optimum usage of prilocaine-lidocaine cream in premature ejaculation. Andrologia 2002; 34: 356-9. (Pubitemid 35463780)
75. Morales A, Barada J, Wyllie MG. A review of the current status of topical treatments for premature ejaculation. BJU Int 2007; 100: 493-501. (Pubitemid 47205483)
76. Giuliano F. Interview with Dr Francois Giuliano (by Christine McKillop). New avenues in the pharmacological treatment of premature ejaculation. Eur Urol 2007; 52: 1254-7.
77. Waldinger MD. Relevance of an evidence-based ejaculation time cutoff point for neurobiological research of premature ejaculation. J Comp Neurol 2005; 493: 46-50. (Pubitemid 41636185)
78. Gengo PJ, Giuliano F, McKenna KE, Chester A, Lovenberg T et al. Monoaminergic transporter binding and inhibition profile of dapoxetine, a medication for the treatment of premature ejaculation. J Urol 2005; 173 (Suppl 4): 239-44.
79. Andersson KE, Mulhall JP, Wyllie MG. Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for on-demand treatment of premature ejaculation. BJU Int 2006; 97: 311-5.
80. Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJ 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. (Pubitemid 44331385)
81. Buvat J, Tesfaye F, Rothman M, Rivas DA, Giuliano F. 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: 957-68.
82. Shabsigh R, Broderick G, Miloslavsky M, Bull S, Nilsson-Neijber A. Long-term safety and tolerability of dapoxetine for the treatment of men with premature ejaculation. Proceedings of the 21st Annual Congress of the European Association of Urology; 5-8 April 2006; Paris, France. European Association of Urology: Arnhem, The Netherlands, 2006.
83. Taber MT, Wright RN, Molski TF, Clarke WJ, Brassil PJ et al. Neurochemical, pharmacokinetic, and behavioral effects of the novel selective serotonin reuptake inhibitor BMS-505130. Pharmacol Biochem Behav 2005; 80: 521-8. (Pubitemid 40299354)
84. Azam U. Late-stage clinical development in lower urogenital targets: sexual dysfunction. Br J Pharmacol 2006; 147 (2 Suppl): S153-9. (Pubitemid 43237581)
85. Henry R, Morales A. Topical lidocaineprilocaine spray for the treatment of premature ejaculation: a proof of concept study. Int J Impot Res 2003; 15: 277-81. (Pubitemid 37101662)
86. Dinsmore WW, Hackett G, Goldmeier D, Waldinger M, Dean J et al. Topical eutectic mixture for premature ejaculation (TEMPE): a novel aerosol-delivery form of lidocaineprilocaine for treating premature ejaculation. BJU Int 2007; 99: 369-75. (Pubitemid 46103119)
87. Padma-Nathan H, Yeager JL. An integrated analysis of alprostadil topical cream for the treatment of erectile dysfunction in 1732 patients. Urology 2006; 68: 386-91. (Pubitemid 44175491)
88. Cremers T, de Boer P, Liao Y, Bosker FJ, den Boer JA et al. Augmentation with a 5- HT1A, but not a 5-HT1B receptor antagonist critically depends on the dose of citalopram. Eur J Pharmacol 2000; 397: 63-74. (Pubitemid 30323812)
89. Williamson IJ, Turner L, Woods K, Wayman CP, van der Graaf PH. The 5-HT1A receptor antagonist robalzotan enhances SSRI-induced ejaculation delay in the rat. Br J Pharmacol 2003; 138 (Suppl 1): PO32.
90. de Jong TR, Pattij T, Veening JG, Dederen PJ, Waldinger MD et al. Citalopram combined with WAY 100635 inhibits ejaculation and ejaculationrelated Fos immunoreactivity. Eur J Pharmacol 2005; 509: 49-59. (Pubitemid 40248785)
91. Filippi S, Morelli A, Vignozzi L, Vannelli GB, Marini M et al. Oxytocin mediates the estrogen-dependent contractile activity of endothelin-1 in human and rabbit epididymis. Endocrinology 2005; 146: 3506-17. (Pubitemid 41058122)
92. Shi WG, Wang XJ, Liang XQ, Liu ZQ, Huang MJ et al. Selective resection of the branches of the two dorsal penile nerves for primary premature ejaculation. Zhonghua Nan Ke Xue 2008; 14: 436-8.
93. Waldinger MD, Olivier B. Animal models of premature and retarded ejaculation. World J Urol 2005; 23: 115-8. (Pubitemid 41051501)
94. Olivier B, Chan JS, Pattij T, de Jong TR, Oosting RS et al. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions? Int J lmpot Res 2006; 18 (Suppl 1): S14-23. (Pubitemid 44330308)
95. Pattij T, de Jong T, Uitterdijk A, WaldingerMD, Veening JG et al. Individual differences in male rat ejaculatory behavior: searching for models to study ejaculation disorders. Eur J Neurosci 2005; 22: 724-34. (Pubitemid 41192282)
96. Pattij T, Olivier B, Waldinger MD. Animal models of ejaculatory behavior. Curr Pharm Des 2005; 11: 4069-77. (Pubitemid 41672478)