Skip to main content
SpringerLink
Log in
Book cover

Men's Sexual Health and Fertility pp 229–245Cite as

Effects of Phosphodiesterase-5 Inhibitors on Testicular and Sperm Function

  • Chapter
  • First Online:

  • 1524 Accesses

Abstract

Phosphodiesterase-5 inhibitors (PDE-5i) are the mainstay of treatment for erectile dysfunction. Over the years, however, they have also been investigated as a potential option for the management of male infertility beyond improving suboptimal erections stemming from the stressors of infertility. Several mechanisms for the effects of these medications have been proposed. The focus of many of these investigations has been the effect of PDE-5i on sperm function and spermatogenesis. Most of the published data to date suggests a favorable effect of PDE-5i on sperm function and spermatogenesis, or no effect at all. The process of sperm capacitation, in which spermatozoa undergo transformation within the female genital tract in order to bind to the zona pellucida, initiate of the acrosome reaction, and fertilize of an egg, may also be impacted by PDE-5i. The contractile elements associated with the transport of spermatozoa, including those surrounding the seminiferous tubules, efferent ducts, and epididymal ducts, may also be affected by PDE-5i. Furthermore, PDE-5i have the potential to influence the vas deferens, seminal vesicles, and prostate.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Lenzi A, Lombardo F, Salacone P, Gandini L, Jannini EA. Stress, sexual dysfunctions, and male infertility. J Endocrinol Invest. 2003;26:72–6.

    CAS  PubMed  Google Scholar 

  2. Tur-Kaspa I, Segal S, Moffa F, Massobrio M, Meltzer S. Viagra for temporary erectile dysfunction during treatments with assisted reproductive technologies. Hum Reprod. 1999;14:1783–4.

    Article  CAS  PubMed  Google Scholar 

  3. Kalsi JS, Bahadur G, Muneer A, Ozturk O, Christopher N, Ralph DJ, et al. Novel PDE5 inhibitors for the treatment of male erectile dysfunction. Reprod Biomed Online. 2003;7:456–61.

    Article  CAS  PubMed  Google Scholar 

  4. Aversa A, Mazzilli F, Rossi T, Delfino M, Isidori AM, Fabbri A. Effect of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males. Hum Reprod. 2000;15:131–4.

    Article  CAS  PubMed  Google Scholar 

  5. Kaplan B, Ben-Rafael Z, Peled Y, Bar-Hava I, Bar J, Orvieto R. Oral sildenafil may reverse secondary ejaculatory dysfunction during infertility treatment. Fertil Steril. 1999;72:1144–5.

    Article  CAS  PubMed  Google Scholar 

  6. Lu S, Zhao Y, Hu J, Li X, Zhang H, You L, Chen ZJ. Combined use of phosphodiesterase-5 inhibitors and selective serotonin reuptake inhibitors for temporary ejaculation failure in couple undergoing assisted reproductive technologies. Fertil Steril. 2009;91(5):1806–8.

    Article  CAS  PubMed  Google Scholar 

  7. Byun JS, Lyu SW, Seok HH, Kim WJ, Shim SH, Bak CW. Sexual dysfunctions induced by stress of timed intercourse and medical treatment. BJU Int. 2013;111(4 Pt B):227–34.

    Article  Google Scholar 

  8. Jannini EA, Lombardo F, Salacone P, Gandini L, Lenzi A. Treatment of sexual dysfunctions secondary to male infertility with sildenafil citrate. Fertil Steril. 2004;81(3):705–7.

    Article  PubMed  Google Scholar 

  9. Dimitriadis F, Giannakis D, Pardalidis N, Zikopoulos K, Paraskevaidis E, Giotitsas N, et al. Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity. Asian J Androl. 2008;10:115–33.

    Article  CAS  PubMed  Google Scholar 

  10. First international consultation on erectile dysfunction: sponsored by World Health Organization (WHO), International Consultation on Urological Disease (ICUD), and Société Internationale d'Urologie (SIU). Paris, 1–3 July 1999.

    Google Scholar 

  11. Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, et al. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Natl Acad Sci U S A. 2000;97:3702–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Baxendale RW Burslem F Phillips SC. Phosphodiesterase type 11 (PDE11) cellular localization: progress towards defining a physiological role in testis and/or reproduction. J Urol Suppl. 2001;165:[abstract]1395.

    Google Scholar 

  13. Mostafa T. Oral phosphodiesterase-5 inhibitors and sperm functions. Int J Impot Res. 2008;20(6):530–6.

    Article  CAS  PubMed  Google Scholar 

  14. Pomara G, Morelli G, Canale D, Turchi P, Caglieresi C, Moschini C, Liguori G, Selli C, Macchia E, Martino E, Francesca F. Alterations in sperm motility after acute oral administration of sildenafil or tadalafil in young, infertile men. Fertil Steril. 2007;8(4):860–5.

    Article  Google Scholar 

  15. De Lefièvre L, Lamirande E, Gagnon C. The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction. J Androl. 2000;21:929–37.

    PubMed  Google Scholar 

  16. Rago R, Salacone P, Caponecchia L, Marcucci I, Flori C, Sebastianelli A. Effect of vardenafil on semen parameters in infertile men: a pilot study evaluating short-term treatment. J Endocrinol Invest. 2012;35(10):897–900.

    CAS  PubMed  Google Scholar 

  17. Glenn DR, McVicar CM, McClure N, Lewis SE. Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. Fertil Steril. 2007;87(5):1064–70.

    Article  CAS  PubMed  Google Scholar 

  18. Ali ST, Rakkah NI. Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy. Pak J Pharm Sci. 2007;20(1):35–42.

    Google Scholar 

  19. du Plessis SS, de Jongh PS, Franken DR. Effect of acute in vivo sildenafil and in vitro 8-bromo-cGMP treatments on semen parameters and sperm function. Fertil Steril. 2004;81:1026–33.

    Article  PubMed  Google Scholar 

  20. Andrade JR, Traboulsi A, Hussain A, Dubin NH. In vitro effects of SC and phentolamine, drugs used for erectile dysfunction, on human sperm motility. Am J Obstet Gynecol. 2000;182:1093–5.

    Article  CAS  PubMed  Google Scholar 

  21. Burger M, Sikka SC, Bivalacqua TJ, Lamb DJ, Hellstrom WJ. The effect of sildenafil on human sperm motion and function from normal and infertile men. Int J Impot Res. 2000;12(4):229–34.

    Article  CAS  PubMed  Google Scholar 

  22. Jarvi K, Dula E, Drehobl M, Pryor J, Shapiro J, Seger M. Daily vardenafil for 6 months has no detrimental effects on semen characteristics or reproductive hormones in men with normal baseline levels. J Urol. 2008;179:1060–5.

    Article  PubMed  Google Scholar 

  23. Purvis K, Muirhead GJ, Harness JA. The effects of sildenafil on human sperm function in healthy volunteers. Br J Clin Pharmacol. 2002;53:53S.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Hellstrom WJ, Overstreet JW, Yu A, Saikali K, Shen W, Beasley Jr CM, Watkins VS. Tadalafil has no detrimental effect on human spermatogenesis or reproductive hormones. J Urol. 2003;170(3):887–91.

    Article  CAS  PubMed  Google Scholar 

  25. Hellstrom WJ, Gittelman M, Jarow J, Steidle C, McMurray J, Talley D, Watts S, Mitchell CL, McGill JM. An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20 mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study. Eur Urol. 2008;53(5):1058–65.

    Article  CAS  PubMed  Google Scholar 

  26. Khalaf MA, Abbas MF, El-Fakahany HM. Effects of chronic tadalafil use on the testes and sperm parameters of old albino rats. Andrologia. 2012;44 Suppl 1:370–5.

    Article  PubMed  Google Scholar 

  27. Dimitriadis F, Tsambalas S, Tsounapi P, Kawamura H, Vlachopoulou E, Haliasos N, Gratsias S, Watanabe T, Saito M, Miyagawa I, Sofikitis N. Effects of phosphodiesterase-5 inhibitors on Leydig cell secretory function in oligoasthenospermic infertile men: a randomized trial. BJU Int. 2010;106(8):1181–5.

    Article  CAS  PubMed  Google Scholar 

  28. Baxendale RW, Fraser LR. Mammalian sperm phosphodiesterases and their involvement in receptor-mediated cell signaling important for capacitation. Mol Reprod Dev. 2005;71:495–508.

    Article  CAS  PubMed  Google Scholar 

  29. Fournier V, Leclerc P, Cormier N, Bailey JL. Implication of calmodulin-dependent phosphodiesterase type 1 during bovine sperm capacitation. J Androl. 2003;24:104–12.

    CAS  PubMed  Google Scholar 

  30. De Lefievre L, Lamirande E, Gagnon C. The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction. J Androl. 2000;21:929–37.

    CAS  PubMed  Google Scholar 

  31. Biel M, Sautter A, Ludwig A, Hofmann F, Zong X. Cyclic nucleotide-gated channels—mediators of NO: cGMP-regulated processes. Naunyn Schmiedebergs Arch Pharmcol. 1998;358:140–4.

    Article  CAS  Google Scholar 

  32. Scipioni A, Stefanini S, Santone R, Giorgi M. Immunohistochemical localization of PDE% in Leydig and myoid cells of prepuberal an adult rat testis. Histochem Cell Biol. 2005;124:401–7.

    Article  CAS  PubMed  Google Scholar 

  33. Cuadra DL, Chan PJ, Patton WC, Stewart SC, King A. Type 5 phosphodiesterase regulation of human sperm motility. Am J Obstet Gynecol. 2000;182:1013–5.

    Article  CAS  PubMed  Google Scholar 

  34. Setchell BP, Maddocks S, Brooks DE, Knobil E, Neill JD, editors. The physiology of reproduction. New York: Raven Press; 1994. p. 1063–175.

    Google Scholar 

  35. Francis SH. Phosphodiesterase 11: is it a player in human testicular function? Int J Impot Res. 2005;17:216–23.

    Article  Google Scholar 

  36. Wayman C, Phillips S, Lunny C, Webb T, Fawcett L, Baxendale R, et al. Phosphodiesterase 11 regulation of spermatozoa physiology. Int J Impot Res. 2005;17:216–23.

    Article  CAS  PubMed  Google Scholar 

  37. Middendorff R, Muller D, Mewe M, Mukhopadhyay AK, Holstein AF, Davidoff MS. The tunica albuginea of the human testis is characterized by complex contraction and relaxation activities regulated by cyclic GMP. J Clin Endocrinol Metab. 2002;87:3486–99.

    Article  CAS  PubMed  Google Scholar 

  38. Middendorff R, Muller D, Wichers S, Holstein AF, Davidoff MS, Holstein AF, Muller D. Generation of cyclic guanosine monophosphate by heme oxygenases in the human testis—a regulatory role for carbon monoxide in sertoli cells? Biol Reprod. 2000;63:651–7.

    Article  CAS  PubMed  Google Scholar 

  39. Sundkvist E, Jaeger R, Sager G. Pharmacological characterization of the ATP-dependent low K(m) guanosine 3′,5′-cyclic mono- phosphate (cGMP) transporter in human erythrocytes. Biochem Pharmacol. 2002;63:945–9.

    Article  CAS  PubMed  Google Scholar 

  40. Mewe M, Bauer CK, Muller D, Middendorff R. Regulation of spontaneous contractile activity in the bovine epididymal duct by cyclic guanosine 5’-monophosphate-dependent pathways. Endocrinology. 2006;147:2051–62.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  PubMed  Google Scholar 

  42. Bilge SS, Kesim Y, Kurt M, Aksoz E, Celik S. Possible role of sildenafil in inhibiting rat vas deferens contractions by influencing the purinergic system. Int J Urol. 2005;12:829–34.

    Article  CAS  PubMed  Google Scholar 

  43. 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;131:871–4.

    Article  CAS  PubMed  Google Scholar 

  44. Wang L, Chopp M, Szalad A, Liu Z, Bolz M, Alvarez FM, et al. Phosphodiesterase-5 is a therapeutic target for peripheral neuropathy in diabetic mice. Neuroscience. 2011;193:399–410.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Patil CS, Singh VP, Singh S, Kulkarni SK. Modulatory effect of the PDE-5 inhibitor sildenafil in diabetic neuropathy. Pharmacology. 2004;72:190–5.

    Article  CAS  PubMed  Google Scholar 

  46. Ali ST, Rakkah NI. Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy. Pak J Pharm Sci. 2007;20:36–42.

    CAS  PubMed  Google Scholar 

  47. Kamenov ZA. Comparison of the first intake of vardenafil and tadalafil in patients with diabetic neuropathy and diabetic erectile dysfunction. J Sex Med. 2011;8:851–64.

    Article  PubMed  Google Scholar 

  48. La Vignera S. Seminal vesicles of infertile patients with male accessory gland infection: ultrasound evaluation after prolonged treatment with tadalafil, a selective phosphodiesterase-5 inhibitor. Andrologia. 2012.

    Google Scholar 

  49. Dimitriadis F, Tsounapi P, Saito M, Watanabe T, Sylakos A, Tsabalas S. Is there a role for PDE5 inhibitors in the management of male infertility due to defects in testicular or epididymal function? Curr Pharm Des. 2009;15:3506–20.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Urology, Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA

    Nathaly François

  2. Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA

    Raunak D. Patel

  3. Division of Urology, Department of Surgery, Southern Illinois University School of Medicine, 301 N. Eighth Street, 4B, Springfield, IL, 62702, USA

    Tobias S. Köhler

Authors
  1. Nathaly François
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raunak D. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tobias S. Köhler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tobias S. Köhler .

Editor information

Editors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    John P. Mulhall

  2. Department of Urology, Kaiser Permanente, Oakland Medical Center, Oakland, California, USA

    Wayland Hsiao

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

François, N., Patel, R.D., Köhler, T.S. (2014). Effects of Phosphodiesterase-5 Inhibitors on Testicular and Sperm Function. In: Mulhall, J., Hsiao, W. (eds) Men's Sexual Health and Fertility. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0425-9_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0425-9_13

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-0424-2

  • Online ISBN: 978-1-4939-0425-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation