Perspective | Published:

Sildenafil in postprostatectomy erectile dysfunction (perspective)

International Journal of Impotence Researchvolume 31pages6164 (2019) | Download Citation

Abstract

Erectile dysfunction (ED) is a common side effect to radical prostatectomies, even with nerve-sparing procedures. To ameliorate the problem so-called “penile rehabilitation” programs have been developed. The most widely used method of this is subscribing sildenafil or other PDE5-inhibitors to patients following surgery. This is based on a theory that these drugs may increase penile oxygenation and provide antiapoptotic factors (primarily NO and cGMP), thus protecting the penile tissue in a period with reduced nerve function following the surgery. Preclinical studies have confirmed the potential of sildenafil in this context and early human trials have suggested that a steady ingestion of sildenafil might protect the structural integrity of the penis. However, subsequent well-designed trials have not been able to confirm the initial findings. This fits well with sildenafil’s mechanism of action because it does not actually induce erections or the production of either nitric oxide or cGMP. Rather, the drug enhances effects of an erectile response induced by neurotransmitters from the cavernous nerves. Therefore, sildenafil should no longer be offered as a sole means of penile rehabilitation. Rather, more research is needed, and clinicians need to apply a broader concept of sexual rehabilitation in postprostatectomy ED.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-Year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415.

  2. 2.

    Walz J, Burnett AL, Costello AJ, Eastham JA, Graefen M, Guillonneau B, et al. A critical analysis of the current knowledge of surgical anatomy related to optimization of cancer control and preservation of continence and erection in candidates for radical prostatectomy. Eur Urol. 2010;57:179.

  3. 3.

    Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol. 1982;128:492.

  4. 4.

    Fode M, Frey A, Jakobsen H, Sonksen J. Erectile function after radical prostatectomy: do patients return to baseline? Scand J Urol. 2016;50:160.

  5. 5.

    Burnett AL. Rationale for cavernous nerve restorative therapy to preserve erectile function after radical prostatectomy. Urology. 2003;61:491.

  6. 6.

    Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz DT,I. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest. 1993;91:437.

  7. 7.

    Hatzimouratidis K, Burnett AL, Hatzichristou D, McCullough AR, Montorsi F, Mulhall JP. Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: a critical analysis of the basic science rationale and clinical application. Eur Urol. 2009;55:334.

  8. 8.

    Iacono F, Giannella R, Somma P, Manno G, Fusco F, Mirone V. Histological alterations in cavernous tissue after radical prostatectomy. J Urol. 2005;173:1673.

  9. 9.

    Vignozzi L, Morelli A, Filippi S, Vannelli GB, Mungai S, Marini M, et al. Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat. Int J Impot Res. 2008;20:60.

  10. 10.

    Mulhall JP, Muller A, Donohue JF, Mullerad M, Kobylarz K, Paduch DA, et al. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate. J Sex Med. 2008;5:1126.

  11. 11.

    Kovanecz I, Rambhatla A, Ferrini M, Vernet D, Sanchez S, Rajfer J, et al. Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res. 2008;20:202.

  12. 12.

    Ozden E, Ozturk B, Kosan M, Tezel GG, Aki FT, Gur S, et al. Effect of sildenafil citrate on penile weight and physiology of cavernous smooth muscle in a post-radical prostatectomy model of erectile dysfunction in rats. Urology. 2011;77:761.

  13. 13.

    Sirad F, Hlaing S, Kovanecz I, Artaza JN, Garcia LA, Rajfer J, et al. Sildenafil promotes smooth muscle preservation and ameliorates fibrosis through modulation of extracellular matrix and tissue growth factor gene expression after bilateral cavernosal nerve resection in the rat. J Sex Med. 2011;8:1048.

  14. 14.

    Schwartz EJ, Wong P, Graydon RJ. Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol. 2004;171:771.

  15. 15.

    Iacono F, Prezioso D, Somma P, Chierchia S, Galasso R, Micheli P. Histopathologically proven prevention of post-prostatectomy cavernosal fibrosis with sildenafil. Urol Int. 2008;80:249.

  16. 16.

    Padma-Nathan H, McCullough AR, Levine LA, Lipshultz LI, Siegel R, Montorsi F, et al. Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int J Impot Res. 2008;20:479.

  17. 17.

    McCullough AR, Levine LA, Padma-Nathan H. Return of nocturnal erections and erectile function after bilateral nerve-sparing radical prostatectomy in men treated nightly with sildenafil citrate: subanalysis of a longitudinal randomized double-blind placebo-controlled trial. J Sex Med. 2008;5:476.

  18. 18.

    Montorsi F, Brock G, Lee J, Shapiro J, Van PH, Graefen M, et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol. 2008;54:924.

  19. 19.

    Montorsi F, Brock G, Stolzenburg JU, Mulhall J, Moncada I, Patel HR, et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT). Eur Urol. 2014;65:587.

  20. 20.

    Pavlovich CP, Levinson AW, Su LM, Mettee LZ, Feng Z, Bivalacqua TJ, et al. Nightly vs on-demand sildenafil for penile rehabilitation after minimally invasive nerve-sparing radical prostatectomy: results of a randomized double-blind trial with placebo. BJU Int. 2013;112:844.

  21. 21.

    Kim DJ, Hawksworth DJ, Hurwitz LM, Cullen J, Rosner IL, Lue TF, et al. A prospective, randomized, placebo-controlled trial of on-demand vs. nightly sildenafil citrate as assessed by Rigiscan and the international index of erectile function. Andrology. 2016;4:27.

  22. 22.

    Jo JK, Jeong SJ, Oh JJ, Lee SW, Lee S, Hong SK, et al. Effect of starting penile rehabilitation with sildenafil immediately after robot-assisted laparoscopic radical prostatectomy on erectile function recovery: a prospective randomized trial. J Urol. 2018;199:1600.

  23. 23.

    Francis SH, Corbin JD. Sildenafil: efficacy, safety, tolerability and mechanism of action in treating erectile dysfunction. Expert Opin Drug Metab Toxicol. 2005;1:283.

  24. 24.

    Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL, et al. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci USA. 2002;99:4061.

  25. 25.

    Tal R, Teloken P, Mulhall JP. Erectile function rehabilitation after radical prostatectomy: practice patterns among AUA members. J Sex Med. 2011;8:2370.

Download references

Author information

Affiliations

  1. Department of Urology, Herlev and Gentofte Hospital, Herlev, Denmark

    • Mikkel Fode
    • , Christian Fuglesang S. Jensen
    •  & Peter Busch Østergren

Authors

  1. Search for Mikkel Fode in:

  2. Search for Christian Fuglesang S. Jensen in:

  3. Search for Peter Busch Østergren in:

Conflict of interest

MF is a speaker for Astellas Pharma and Ferring Pharmaceuticals and an advisory board member for Astellas Pharma. PBØ is a speaker for Astellas Pharma, Ferring Pharmaceuticals, and Ipsen, and an advisory board member for Astellas Pharma and Ipsen. CFSJ declare that he has no conflict of interest.

Corresponding author

Correspondence to Mikkel Fode.

About this article

Publication history

Received

Accepted

Published

Issue Date

DOI

https://doi.org/10.1038/s41443-018-0102-y