Combined on-demand sildenafil citrate and tramadol hydrochloride is an effective and safe treatment for premature ejaculation: A randomized placebo-controlled double-blind clinical trial

References

• Wang J, Wang D. The diagnosis and treatment of ejaculatory dysfunction. Transl Androl Urol. 2018;7(Suppl S5):AB028–AB028. doi: 10.21037/tau.2018.AB028
   Google Scholar
• McMahon CG, Althof SE, Waldinger MD, 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(7):1590–1606. doi: 10.1111/j.1743-6109.2008.00901.x
   PubMed Web of Science ®Google Scholar
• Bar-Or D, Salottolo KM, Orlando A, et al. A randomized double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of two doses of the tramadol orally disintegrating tablet for the treatment of premature ejaculation within less than 2 minutes. Eur Urol. 2012;61(4):736–743. doi: 10.1016/j.eururo.2011.08.039
   PubMed Web of Science ®Google Scholar
• Giuliano F, Patrick DL, Porst H, et al. Premature Ejaculation: Results from a Five-Country European Observational Study. Eur Urol. 2008;53(5):1048–1057. doi: 10.1016/j.eururo.2007.10.015
   PubMed Web of Science ®Google Scholar
• Patrick DL, Althof SE, Pryor JL, et al. Original research—ejaculatory disorders: premature ejaculation: An observational study of men and their partners. J Sex Med. 2005;2(3):358–367. doi: 10.1111/j.1743-6109.2005.20353.x
   PubMed Web of Science ®Google Scholar
• Wylie KR, Ralph D. Premature ejaculation: The current literature. Curr Opin Urol. 2005;15(6):393–398. doi: 10.1097/01.mou.0000186844.40506.98
   PubMed Web of Science ®Google Scholar
• McMahon C. Premature Ejaculation: Past, Present, and Future Perspectives. J Sex Med. 2005;2:94–95. doi: 10.1111/j.1743-6109.2005.20368.x
   PubMed Web of Science ®Google Scholar
• Xin Z-C, Zhu Y-C, Yuan Y-M, et al. Current therapeutic strategies for premature ejaculation and future perspectives. Asian J Androl. 2011;13(4):550–557. doi: 10.1038/aja.2010.130
   PubMed Web of Science ®Google Scholar
• Kurkar A, Abulsorour S, Gamal R, et al. Treatment of premature ejaculation: a new combined approach. Egypt Rheumatol Rehabil. 2015;42(1):39–44. doi: 10.4103/1110-161X.155649
   Google Scholar
• Linton KD, Wylie KR. Recent advances in the treatment of premature ejaculation. Drug Design Develop Therapy. 2010(4).
   Google Scholar
• James M M-S, Cooper K, Kaltenthaler E, et al. Tramadol for premature ejaculation: a systematic review and meta-analysis. BMC Urol. 2015;15(1):6. doi: 10.1186/1471-2490-15-6
   PubMedGoogle Scholar
• McMahon CG, Touma K. Treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 single-blind placebo controlled crossover studies. J Urol. 1999;161(6):1826–1830. doi: 10.1016/S0022-5347(05)68816-7
   PubMed Web of Science ®Google Scholar
• Morales A. Evolving therapeutic strategies for premature ejaculation: the search for on-demand treatment – topical versus systemic. CUAJ. 2012;6(5):380–385. doi: 10.5489/cuaj.12002
   Google Scholar
• Pastore AL, Palleschi G, Leto A, et al. A prospective randomized study to compare pelvic floor rehabilitation and dapoxetine for the treatment of lifelong premature ejaculation. Int JAndrology. 2012;35(4):528–533. doi: 10.1111/j.1365-2605.2011.01243.x
   PubMedGoogle Scholar
• La Pera G, Nicastro A. A new treatment for premature ejaculation: the rehabilitation of the pelvic floor. J Sex & Marital Therapy. 1996;22(1):22–26. doi: 10.1080/00926239608405302
   PubMed Web of Science ®Google Scholar
• Salem EA, Wilson SK, Bissada NK, et al. ORIGINAL RESEARCH–EJACULATORY DISORDERS: Tramadol HCL has promise in on-demand use to treat premature ejaculation. J Sex Med. 2008;5(1):188–193. doi: 10.1111/j.1743-6109.2006.00424.x
   PubMed Web of Science ®Google Scholar
• Serefoglu EC, Saitz TR, Trost L, et al. Premature ejaculation: do we have effective therapy? Transl Androl Urol. 2013;2(1):45–53. doi: 10.3978/j.issn.2223-4683.2013.01.02
   PubMedGoogle Scholar
• Serefoglu EC, Saitz TR. New insights on premature ejaculation: a review of definition, classification, prevalence and treatment. Asian J Androl. 2012;14(6):822–829. doi: 10.1038/aja.2012.108
   PubMed Web of Science ®Google Scholar
• Waldinger MD. Emerging drugs for premature ejaculation. Expert Opin Emerg Drugs. 2006;11(1):99–109. doi: 10.1517/14728214.11.1.99
   PubMedGoogle Scholar
• Gameel TA, Tawfik AM, Abou-Farha MO, et al. On-demand use of tramadol, sildenafil, paroxetine and local anaesthetics for the management of premature ejaculation: a randomised placebo-controlled clinical trial. Arab J Urol. 2013;11(4):392–397. doi: 10.1016/j.aju.2013.05.003
   PubMedGoogle Scholar
• Sotomayor M. The burden of premature ejaculation: the patient’s perspective. J Sex Med. 2005;2(SUPPL. 2):110–114. doi: 10.1111/j.1743-6109.2005.20371.x
   PubMedGoogle Scholar
• Althof SE, McMahon CG, Waldinger MD, et al. An update of the international society of sexual medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med. 2014;2(2):60–90. doi: 10.1002/sm2.28
   PubMed Web of Science ®Google Scholar
• Frink MC, Hennies HH, Englberger W, et al. Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung. 1996;46(11):1029–1036.
   PubMed Web of Science ®Google Scholar
• Ogata J, Minami K, Uezono Y, et al. The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in xenopus oocytes. Anesthesia & Analgesia. 2004;98(5):1401–1406. doi: 10.1213/01.ANE.0000108963.77623.A4
   PubMed Web of Science ®Google Scholar
• Hara K, Minami K, Sata T. The effects of tramadol and its metabolite on glycine, ??-Aminobutyric AcidA, and N-Methyl-d-aspartate receptors expressed in xenopus oocytes. Anesthesia & Analgesia. 2005;100(5):1400–1405. table of contents. doi: 10.1213/01.ANE.0000150961.24747.98
   PubMed Web of Science ®Google Scholar
• 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(1):27–31. doi: 10.1097/01.jcp.0000195110.79027.3f
   PubMed Web of Science ®Google Scholar
• Szkutnik-Fiedler D, Kus K, Balcerkiewicz M, et al. Concomitant use of tramadol and venlafaxine - evaluation of antidepressant-like activity and other behavioral effects in rats. Pharmacol Rep. 2012;64(6):1350–1358. doi: 10.1016/S1734-1140(12)70932-5
   PubMed Web of Science ®Google Scholar
• Shiga Y, Minami K, Shiraishi M, et al. The inhibitory effects of tramadol on muscarinic receptor-induced responses in xenopus oocytes expressing cloned M(3) receptors. Anesth Analg. 2002;95(5):1269–1273. doi: 10.1097/00000539-200211000-00031
   PubMed Web of Science ®Google Scholar
• Shiraishi M, Minami K, Uezono Y, et al. Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and xenopus laevis oocytes expressing cloned M1 receptors. J Pharmacol Exp Ther. 2001;299(1):255–260.
   PubMed Web of Science ®Google Scholar
• Shiraishi M, Minami K, Uezono Y, et al. Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in xenopus oocytes expressing alpha 7 receptors. Br J Pharmacol. 2002;136(2):207–216. doi: 10.1038/sj.bjp.0704703
   PubMed Web of Science ®Google Scholar
• Abdel-Hamid IA. Phosphodiesterase 5 inhibitors in rapid ejaculation: potential use and possible mechanisms of action. Drugs. 2004;64(1):13–26. doi: 10.2165/00003495-200464010-00002
   PubMed Web of Science ®Google Scholar
• Medina P, Segarra G, Torondel B, et al. Inhibition of neuroeffector transmission in human vas deferens by sildenafil. Br J Pharmacol. 2000;131(5):871–874. doi: 10.1038/sj.bjp.0703657
   PubMed Web of Science ®Google Scholar
• Pfaus JG. Neurobiology of sexual behavior. Curr Opin Neurobiol. 1999;9(6):751–758. doi: 10.1016/S0959-4388(99)00034-3
   PubMed Web of Science ®Google Scholar
• Aversa A, Francomano D, Bruzziches R, et al. Is there a role for phosphodiesterase type-5 inhibitors in the treatment of premature ejaculation? Int J Impot Res. 2011;23(1):17–23. doi: 10.1038/ijir.2010.34
   PubMed Web of Science ®Google Scholar
• Eassa BI, El-Shazly MA. Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation. Asian J Androl. 2013;15(1):138–142. doi: 10.1038/aja.2012.96
   PubMed Web of Science ®Google Scholar
• Kaynar M, Kilic O, Yurdakul T. On-demand tramadol hydrochloride use in premature ejaculation treatment. Urology. 2012;79(1):145–149. doi: 10.1016/j.urology.2011.09.031
   PubMed Web of Science ®Google Scholar
• Kirby EW, Carson CC, Coward RM. Tramadol for the management of premature ejaculation: a timely systematic review. Int J Impot Res. 2015;27(4):121–127. doi: 10.1038/ijir.2015.7
   PubMed Web of Science ®Google Scholar
• Kurkar A, Elderwy AA, Abulsorour S, et al. A randomized, double-blind, placebo-controlled, crossover trial of? on-demand? tramadol for the treatment of premature ejaculation. Urol Ann. 2015;7(2):205. doi: 10.4103/0974-7796.150481
   PubMedGoogle Scholar
• Wong BLK, Malde S. The use of tramadol “on-demand” for premature ejaculation: a systematic review. Urology. 2013;81(1):98–103. doi: 10.1016/j.urology.2012.08.037
   PubMed Web of Science ®Google Scholar
• Wu T, Yue X, Duan X, et al. Efficacy and safety of tramadol for premature ejaculation: a systematic review and meta-analysis. Urology. 2012;80(3):618–624. doi: 10.1016/j.urology.2012.05.035
   PubMed Web of Science ®Google Scholar
• Yang L, Qian S, Liu H, et al. Role of tramadol in premature ejaculation: a systematic review and meta-analysis. Urol Int. 2013;91(2):197–205. doi: 10.1159/000348826
   PubMed Web of Science ®Google Scholar
• El-Hamd M A. Efficacy and safety of daily use of tadalafil in treatment of patients with premature ejaculation: a randomised placebo-controlled clinical trial. Andrologia. 2018;50(5). doi: 10.1111/and.13005
   Web of Science ®Google Scholar
• Aversa A, Pili M, Francomano D, et al. Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation. Int J Impot Res. 2009;21(4):221–227. doi: 10.1038/ijir.2009.21
   PubMed Web of Science ®Google Scholar
• Hosseini MM, Yarmohammadi H. Effect of fluoxetine alone and in combination with sildenafil in patients with premature ejaculation. Urol Int. 2007;79(1):28–32. doi: 10.1159/000102909
   PubMed Web of Science ®Google Scholar
• Karabakan M, Keskin E, Akdemir S, et al. Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction. Int Braz J Urol. 2017;43(2):317–324. doi: 10.1590/s1677-5538.ibju.2016.0376
   PubMed Web of Science ®Google Scholar
• Men C, Yu L, Yuan H, et al. Efficacy and safety of phosphodiesterase type 5 inhibitors on primary premature ejaculation in men receiving selective serotonin reuptake inhibitors therapy: a systematic review and meta-analysis. Andrologia. 2016;48(9):1066–1073. doi: 10.1111/and.12540
   Web of Science ®Google Scholar
• Wang WF, Wang Y, Minhas S, et al. Can sildenafil treat primary premature ejaculation? A prospective clinical study. Int J Urol. 2007;14(4):331–335. doi: 10.1111/j.1442-2042.2007.01606.x
   PubMed Web of Science ®Google Scholar
• Chen J, Keren-Paz G, Bar-Yosef Y, et al. 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(5):1331–1339. doi: 10.1016/j.eururo.2007.08.005
   PubMed Web of Science ®Google Scholar
• Salonia A, Maga T, Colombo R, et al. A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol. 2002;168(6):2486–2489. doi: 10.1016/S0022-5347(05)64174-2
   PubMed Web of Science ®Google Scholar
• Sun Y, Luo D, Yang L, et al. Efficacy of phosphodiesterase-5 inhibitor in men with premature ejaculation: a New systematic review and meta-analysis. Urology. 2015;86(5):947–955. doi: 10.1016/j.urology.2015.06.051
   PubMed Web of Science ®Google Scholar
• Krishnappa P, Fernandez-Pascual E, Carballido J, et al. Sildenafil/Viagra in the treatment of premature ejaculation. Int J Impot Res. 2019;31(2):65–70. doi: 10.1038/s41443-018-0099-2
   PubMed Web of Science ®Google Scholar