Is there a role for phosphodiesterase type-5 inhibitors in the treatment of premature ejaculation

International Journal of Impotence Research

Volumn 23, Issue 1, 2011, Pages 17-23

  Aversa, A ^a   Francomano, D ^a   Bruzziches, R ^a   Natali, M ^a   Spera, G ^a   Lenzi, A ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Intravaginal ejaculatory latency time; nitric oxide; sexual distress; therapy

Indexed keywords

ALPHA ADRENERGIC RECEPTOR STIMULATING AGENT; ARGININE; CLOMIPRAMINE; CYCLIC GMP; DAPOXETINE; ENDOTHELIN; ENDOTHELIN RECEPTOR; FLUOXETINE; LIDOCAINE; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OXYTOCIN; OXYTOCIN RECEPTOR; PAROXETINE; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; SILDENAFIL; TADALAFIL; TRAMADOL; VARDENAFIL;

ANALGESIC ACTIVITY; ANTINOCICEPTION; BLOOD BRAIN BARRIER; COMBINATION CHEMOTHERAPY; DROWSINESS; DRUG ABSORPTION; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDICATION; DRUG MECHANISM; DRUG PENETRATION; EJACULATION; EPIDIDYMIS; ERECTILE DYSFUNCTION; HUMAN; LIBIDO DISORDER; MONOTHERAPY; NAUSEA; NONHUMAN; OFF LABEL DRUG USE; PATHOPHYSIOLOGY; PENIS ERECTION; PREMATURE EJACULATION; PRIORITY JOURNAL; QUALITY OF LIFE; RECEPTOR UPREGULATION; RETROGRADE EJACULATION; REVIEW; SEXUAL SATISFACTION; SIGNAL TRANSDUCTION; SMOOTH MUSCLE RELAXATION; WITHDRAWAL SYNDROME; XEROSTOMIA;

CLINICAL TRIALS AS TOPIC; EJACULATION; HUMANS; MALE; PHOSPHODIESTERASE INHIBITORS; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SEXUAL DYSFUNCTIONS, PSYCHOLOGICAL;

EID: 79951954522     PISSN: 09559930     EISSN: 14765489     Source Type: Journal    
DOI: 10.1038/ijir.2010.34     Document Type: Review

References (55)

1. Porst H, Montorsi F, Rosen RC, Gaynor L, Grupe S, Alexander J. The Premature Ejaculation Prevalence and Attitudes (PEPA) survey: prevalence, comorbidities, and professional help-seeking. Eur Urol 2007; 51: 816-824. (Pubitemid 46097263)
2. Jannini EA, Lombardo F, Lenzi A. Correlation between ejaculatory and erectile dysfunction. Int J Androl 2005; 28(Suppl 2): 40-45. (Pubitemid 41719772)
3. Laumann EO, Nicolosi A, Glasser DB, Paik A, Gingell C, Moreira E 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)
4. Waldinger MD, Quinn P, Dilleen M, Mundayat R, Schweitzer DH, Boolell M. A multinational population survey of intravaginal ejaculation latency time. J Sex Med 2005; 2: 492-497. (Pubitemid 40975833)
5. McMahon CG, Abdo C, Incrocci L, Perelman M, Rowland D, Waldinger M et al. Disorders of orgasm and ejaculation in men. J Sex Med 2004; 1: 58-65. (Pubitemid 40424667)
6. 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: 358-367. (Pubitemid 40744376)
7. McMahon CG, Althof S, Waldinger MD, Porst H, Dean J, Sharlip I et al. International Society for Sexual Medicine Ad Hoc Committee for Definition of Premature Ejaculation. 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: 338-350. (Pubitemid 352019206)
8. Althof S, Rowland D. Identifying constructs and criteria for the diagnosis of premature ejaculation: implication for making errors of classification. BJU Int 2008; 102: 708-712.
9. Abdel-Hamid IA. Phosphodiesterase 5 inhibitors in rapid ejaculation: potential use and possible mechanisms of action. Drugs 2004; 64: 13-26. (Pubitemid 38125626)
10. Loughney K, Hill TR, Florio VA, Uher L, Rosman GJ, Wolda SL et al. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 30,50-cyclic nucleotide phosphodiesterase. Gene 1998; 216: 139-147. (Pubitemid 28389111)
11. Schultheiss D, Mü ller SV, Nager W, Stief CG, Schlote N, Jonas U et al. Central effects of sildenafil (Viagra) on auditory selective attention and verbal recognition memory in humans: a study with event-related brain potentials. World J Urol 2001; 19: 46-50. (Pubitemid 33777032)
12. Sato Y, Horita H, Kurohata T, Adachi H, Tsukamoto T. Effect of the nitric oxide level in the medial preoptic area on male copulatory behavior in rats. Am J Physiol 1998; 274: R243-R247.
13. Castellano M, Rizzoni D, Beschi M, Muiesan ML, Porteri E, Bettoni G et al. Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans. J Hypertens 1995; 13: 1153-1161.
14. Krukoff TL. Central regulation of autonomic function: no brakes? Clin Exp Pharmacol Physiol 1998; 25: 474-478. (Pubitemid 28298574)
15. Pfaus JG. Neurobiology of sexual behavior. Curr Opin Neurobiol 1999; 9: 751-758.
16. Hull EM, Lumley LA, Matuszewich L, Dominguez J, Moses J, Lorrain DS. The roles of nitric oxide in sexual function of male rats. Neuropharmacology 1994; 33: 1499-1504. (Pubitemid 24353746)
17. Kim TS, Ko IG, Sung YH, Kim SE, Kim BK, Park SK et al. Vardenafil increases cell proliferation in the dentate gyrus through enhancement of serotonin expression in the rat dorsal raphe. J Korean Med Sci 2009; 24: 1099-1104.
18. Heuer O, Uckert S, Machtens SA, Stief CG, Tsikas D, Frölich JC et al. Effects of various nitric oxide donating agents on the contractility and cyclic nucleotide turnover of human seminal vesicles in vitro. Urology 2002; 59: 958-962. (Pubitemid 34522200)
19. Dixon JS, Jen PY. Development of nerves containing nitric oxide synthase in the human male urogenital organs. Br J Urol 1995; 76: 719-725.
20. 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: 185-189. (Pubitemid 47081077)
21. Jen PY, Dixon JS, Gosling JA. Co-localization of nitric oxide synthase, neuropeptides and tyrosine hydroxylase in nerves supplying the human post-natal vas deferens and seminal vesicle. Br J Urol 1997; 80: 291-299.
22. Grozdanovic Z, Goessl C. Comparative localization of heme oxygenase-2 and nitric oxide synthase in the autonomic innervation to the human ductus deferens and seminal vesicle. J Urol 1999; 162: 2156-2161.
23. Uckert S, Bazrafshan S, Sonnenberg JE, Kuczyk MA. Effects of phosphodiesterase inhibitors on the contractile responses of isolated human seminal vesicle tissue to adrenergic stimulation. J Sex Med 2009; 6: 408-414.
24. Machtens S, Ckert S, Stief CG, Tsikas D, Frlich JC, Jonas U. Effects of various nitric oxide-donating drugs on adrenergic tension of human seminal vesicles in vitro. Urology 2003; 61: 479-483. (Pubitemid 36206569)
25. Bultmann R, Klebroff W, Starke K. Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms. Eur J Pharmacol 2002; 436: 135-143. (Pubitemid 34142408)
26. Bialy M, Beck J, Abramczyk P, Trzebski A, Przybylski J. Sexual behavior in male rats after nitric oxide synthesis inhibition. Physiol Behav 1996; 60: 139-143. (Pubitemid 126335864)
27. Moriyama N, Nasu K, Takeuchi T, Akiyama K, Murata S, Nishimatsu H et al. Quantification and distribution of alpha 1- adrenoceptor subtype mRNAs in human vas deferens: comparison with those of epididymal and pelvic portions. Br J Pharmacol 1997; 122: 1009-1014. (Pubitemid 27494211)
28. Hisasue S, Furuya R, Itoh N, Kobayashi K, Furuya S, Tsukamoto T. Ejaculatory disorder caused by a-1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission. Int J Urol 2006; 13: 1311-1316. (Pubitemid 44453698)
29. Vignozzi L, Filippi S, Morelli A, Luconi M, Jannini E, Forti G et al. Regulation of epididymal contractility during semen emission, the first part of the ejaculatory process: a role for estrogen. J Sex Med 2008; 5: 2010-2016.
30. Aversa A, Caprio M, Antelmi A, Brama M, Greco E, Fabbri A et al. Acute tadalafil exposure stimulates aromatase expression in human adipocytes in vitro. J Sex Med 2009; 6(Suppl 5): 403.
31. Medina P, Segarra G, Torondel B, Chuan P, Domenech C, Vila JM et al. Inhibition of neuroeffector transmission in human vas deferens by sildenafil. Br J Pharmacol 2000; 131: 871-874.
32. Kriegsfeld LJ, Demas GE, Huang PL, Burnett AL, Nelson RJ. Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-). Physiol Behav 1999; 67: 561-566. (Pubitemid 29488535)
33. Jain NK, Patil CS, Singh A, Kulkarni SK. Sildenafil-induced peripheral analgesia and activation of the nitric oxidecyclic GMP pathway. Brain Res 2001; 909: 170-178. (Pubitemid 32710130)
34. Wang WF, Minhas S, Ralph DJ. Phosphodiesterase 5 inhibitors in the treatment of premature ejaculation. Int J Androl 2006; 29: 503-509. (Pubitemid 44350960)
35. Rosenberg MT, Adams PL, McBride TA, Roberts JN, McCallum SW. Improvement in duration of erection following phosphodiesterase type 5 inhibitor therapy with vardenafil in men with erectile dysfunction: the ENDURANCE study. Int J Clin Pract 2009; 63: 27-34.
36. Chen J, Keren-Paz G, Bar-Yosef Y, Matzkin H. The role of phosphodiesterase type 5 inhibitors in the management of premature ejaculation: a critical analysis of basic science and clinical data. Eur Urol 2007; 52: 1331-1339. (Pubitemid 47446018)
37. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1-12. (Pubitemid 26120810)
38. McMahon CG, Stuckey BG, Andersen M, Purvis K, Koppiker N, Haughie S et al. Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation. J Sex Med 2005; 2: 368-375. (Pubitemid 40744377)
39. Aversa A, Pili M, Francomano D, Bruzziches R, Spera E, La Pera G et al. Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation. Int J Impot Res 2009; 21: 221-227.
40. Aversa A, Mazzilli F, Rossi T, Delfino M, Isidori AM, Fabbri A. Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males. Hum Reprod 2000; 15: 131-134. (Pubitemid 30035112)
41. Mondaini N, Ponchietti R, Muir GH, Montorsi F, Di Loro F, Lombardi G 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: 225-228. (Pubitemid 36928916)
42. Gökçe A, Demirtas A, Halis F, Ekmekcioglu O. In vitro measurement of ejaculation latency time (ELT) and the effects of vardenafil on ELT on lifelong premature ejaculators: placebo-controlled, double-blind, cross-over laboratory setting. Int Urol Nephrol 2010; 42: 881-887.
43. 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: 169-175.
44. Wang WF, Wang Y, Minhas S, Ralph DJ. Can sildenafil treat primary premature ejaculation? A prospective clinical study. Int J Urol 2007; 14: 331-335. (Pubitemid 46669039)
45. Abdel-Ahmid IA, El-Naggar EA, El-Gilany AH. Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation. Int J Impotence Res 2001; 13: 41-45.
46. Mattos RM, Marmo Lucon A, Srougi M. Tadalafil and fluoxetine in premature ejaculation: prospective, randomized, double-blind, placebo-controlled study. Urol Int 2008; 80: 162-165. (Pubitemid 351440510)
47. Chen J, Mabjeesh NJ, Matzkin H, Greenstein A. Efficacy of sildenafil as adjuvant therapy to selective serotonin reuptake inhibitor in alleviating premature ejaculation. Urology 2003; 61: 197-200. (Pubitemid 36151740)
48. 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: 2486-2489. (Pubitemid 35402646)
49. Hosseini MM, Yarmohammadi H. Effect of fluoxetine alone and in combination with sildenafil in patients with premature ejaculation. Urol Int 2007; 79: 28-32. (Pubitemid 47051814)
50. Porst H, McMahon CG, Althof SE, Sharlip I, Bull S, Aquilina JW et al. Baseline characteristics and treatment outcomes for men with acquired or lifelong premature ejaculation with mild or no erectile dysfunction: integrated analyses of two phase 3 dapoxetine trials. J Sex Med 2010; 7: 2231-2242.
51. Linton KD, Wylie KR. Recent advances in the treatment of premature ejaculation. Drug Des Devel Ther 2010; 4: 1-6.
52. 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. (Pubitemid 43167087)
53. Salem EA, Wilson SK, Bissada NK, Delk JR, Hellstrom WJ, Cleves MA. Tramadol HCL has promise in on-demand use to treat premature ejaculation. J Sex Med 2008; 5: 188-193.
54. Eradiri O, Sista S, Lai JC-K, Danyluk A, Brett V. Bioavailability of extended release and immediate-release formulations of tramadol HCl. J Clin Pharmacol 2006; 46: 1091-1096.
55. Aversa A, Caprio M, Antelmi A, Armani A, Greco EA, Brama M et al. Exposure to phosphodiesterase type 5 inhibitors stimulates aromatase expression in human adipocytes in vitro. J Sex Med 2011 (e-pub ahead of print); doi:10.1111/j.1743-6109.2010.02152.x.