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Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy

International Journal of Impotence Research volume 20, pages 479–486 (2008)Cite this article

Abstract

Four weeks after bilateral nerve-sparing radical retropubic prostatectomy, men with normal erectile function before surgery were randomized to double-blind sildenafil (50 or 100 mg) or placebo nightly for 36 weeks, followed by an 8-week drug-free period before assessment of erectile function. Enrollment was prematurely ceased and only 76 men completed because, assuming a placebo response rate similar to the published literature (for example, 34% in meta-analysis), the 25% response at blinded interim review suggested a lack of treatment effect. On the contrary, spontaneous erectile function (a combined score of ⩾8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to ‘Were erections good enough for satisfactory sexual activity?’) occurred in only 4% of the placebo group (n=1 of 25) versus 27% (n=14 of 51, P=0.0156, Fisher's exact test) of the sildenafil group. Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections.

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References

  1. McCullough AR . Prevention and management of erectile dysfunction following radical prostatectomy. Urol Clin North Am 2001; 28: 613–627.

    Article  CAS  PubMed  Google Scholar 

  2. Walsh PC, Partin AW, Epstein JI . Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol 1994; 152: 1831–1836.

    Article  CAS  PubMed  Google Scholar 

  3. Klein LT, Miller MI, Buttyan R, Raffo AJ, Burchard M, Devris G et al. Apoptosis in the rat penis after penile denervation. J Urol 1997; 158: 626–630.

    Article  CAS  PubMed  Google Scholar 

  4. User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT . Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol 2003; 169: 1175–1179.

    Article  PubMed  Google Scholar 

  5. Zippe CD, Raina R, Thukral M, Lakin MM, Klein EA, Agarwal A . Management of erectile dysfunction following radical prostatectomy. Curr Urol Rep 2001; 2: 495–503.

    Article  CAS  PubMed  Google Scholar 

  6. Meuleman EJ, Mulders PF . Erectile function after radical prostatectomy: a review. Eur Urol 2003; 43: 95–102.

    Article  CAS  PubMed  Google Scholar 

  7. Montorsi F, Guazzoni G, Strambi LF, Da Pozzo LF, Nava L, Barbieri L et al. Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. J Urol 1997; 158: 1408–1410.

    Article  CAS  PubMed  Google Scholar 

  8. Schwartz EJ, Wong P, Graydon RJ . Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol 2004; 171: 771–774.

    Article  PubMed  Google Scholar 

  9. Montorsi F, Maga T, Strambi LF, Salonia A, Barbieri L, Scattoni V et al. Sildenafil taken at bedtime significantly increases nocturnal erections: results of a placebo-controlled study. Urology 2000; 56: 906–911.

    Article  CAS  PubMed  Google Scholar 

  10. Rabbani F, Patel M, Scardino PT . Time course of recovery of potency after bilateral nerve sparing radical prostatectomy. J Urol 2004; 171 (Suppl 4): 310.

    Article  Google Scholar 

  11. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822–830.

    Article  CAS  PubMed  Google Scholar 

  12. Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH . Diagnostic evaluation of the erectile function domain of the International Index of Erectile function. Urology 1999; 54: 346–351.

    Article  CAS  PubMed  Google Scholar 

  13. Hong EK, Lepor H, McCullough AR . Time dependent patient satisfaction with sildenafil for erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (RRP). Int J Impot Res 1999; 11: S15–S22.

    Article  PubMed  Google Scholar 

  14. Catalona WJ, Ramos CG, Carvalhal GF . Contemporary results of anatomic radical prostatectomy. CA Cancer J Clin 1999; 49: 282–296.

    Article  CAS  PubMed  Google Scholar 

  15. Catalona WJ, Carvalhal GF, Mager DE, Smith DS . Potency, continence and complication rates in 1870 consecutive radical retropubic prostatectomies. J Urol 1999; 162: 433–438.

    Article  CAS  PubMed  Google Scholar 

  16. Fowler Jr FJ, Barry MJ, Lu-Yao G, Wasson J, Roman A, Wennberg J . Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey. Urology 1995; 45: 1007–1013.

    Article  PubMed  Google Scholar 

  17. Robinson JW, Moritz S, Fung T . Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma. Int J Radiat Oncol Biol Phys 2002; 54: 1063–1068.

    Article  PubMed  Google Scholar 

  18. Dubbelman YD, Dohle GR, Schroder FH . Sexual function before and after radical retropubic prostatectomy: a systematic review of prognostic indicators for a successful outcome. Eur Urol 2006; 50: 711–718.

    Article  PubMed  Google Scholar 

  19. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J . Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990; 170: 843–850.

    Article  CAS  PubMed  Google Scholar 

  20. Bush PA, Aronson WJ, Buga GM, Rajfer J, Ignarro LJ . Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum. J Urol 1992; 147: 1650–1655.

    Article  CAS  PubMed  Google Scholar 

  21. Azadzoi KM, Kim N, Brown ML, Goldstein I, Cohen RA, Saenz de Tejada I . Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. J Urol 1992; 147: 220–225.

    Article  CAS  PubMed  Google Scholar 

  22. Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I . Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest 1993; 91: 437–442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Moreland RB . Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence. Int J Impot Res 1998; 10: 113–120.

    Article  CAS  PubMed  Google Scholar 

  24. Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996; 8: 47–52.

    CAS  PubMed  Google Scholar 

  25. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM . Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998; 159: 2164–2171.

    Article  CAS  PubMed  Google Scholar 

  26. Katz SD . Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. Congest Heart Fail 2003; 9: 9–15.

    Article  CAS  PubMed  Google Scholar 

  27. Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S . Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000; 36: 845–851.

    Article  CAS  PubMed  Google Scholar 

  28. Desouza C, Parulkar A, Lumpkin D, Akers D, Fonseca VA . Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes. Diabetes Care 2002; 25: 1336–1339.

    Article  CAS  PubMed  Google Scholar 

  29. Nakamizo T, Kawamata J, Yoshida K, Kawai Y, Kanki R, Sawada H et al. Phosphodiesterase inhibitors are neuroprotective to cultured spinal motor neurons. J Neurosci Res 2003; 71: 485–495.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M et al. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 2002; 33: 2675–2680.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was funded by Pfizer Inc. Editorial assistance was provided by Deborah M Campoli-Richards of Complete Healthcare Communications, Inc., and was funded by Pfizer Inc.

Author information

Author notes

  1. H Padma-Nathan, A R McCullough, L A Levine, L I Lipshultz, R Siegel, F Montorsi, F Giuliano and G Brock: R Siegel: R Siegel was an employee of Pfizer at the time of this research.

  2. The other members of the Study Group are Professor Robert Andrianne, Belgium; David Bell, Canada; Gregory Broderick, USA; Serge Carrier, Canada; Professor Beatrice Cuzin, France; Harry Jeoffrey Deeths, USA; Wayne Hellstrom, USA; Sender Herschorn, Canada; Ronald W Lewis, USA; Raymond C Rosen, USA; Ridwan Shabsigh, USA; Phillip Stricker, Australia.

Authors and Affiliations

  1. Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    H Padma-Nathan

  2. Department of Urology, New York University School of Medicine, New York University Medical Center, New York, NY, USA

    A R McCullough

  3. Department of Urology, Rush Medical College, Rush University, Chicago, IL, USA

    L A Levine

  4. Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

    L I Lipshultz

  5. Sexual Health Team, Pfizer Inc, New York, NY, USA

    R Siegel

  6. Department of Urology, University Vita Salute San Raffaele, Milan, Italy

    F Montorsi

  7. Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France

    F Giuliano

  8. Department of Urology, University of Western Ontario, London, ON, Canada

    G Brock

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on behalf of the Study Group

Corresponding author

Correspondence to A R McCullough.

Additional information

Author Disclosures

Gerald Brock: Consultant, investigator for clinical research, and speakers bureau member for Pfizer Inc, Lilly-ICOS, Bayer, GSK, Johnson & Johnson, Coloplast and AMS.

Francois Giuliano: Investigator for clinical and preclinical research, meeting lecturer, and member of advisory board for Pfizer Inc, Bayer-GSK, Lilly-ICOS, Johnson & Johnson; preclinical research for Solvay Pharmaceuticals, Roche; investigator for preclinical research and meeting lecturer for Sanofi-Aventis.

Larry Levine: Consultant for Pfizer Inc, Lilly-ICOS, Auxillium, Johnson & Johnson; investigator for clinical research for Pfizer Inc, Bayer-GSK, Auxillium; lecturer for Pfizer Inc, Lilly-ICOS, Schering-Plough.

Larry Lipshultz: Consultant for Pfizer Inc, Lilly-ICOS, Auxillium, and Solvay Pharmaceuticals; investigator for clinical research for Pfizer Inc and Lilly-ICOS.

Andrew McCullough: Consultant for Pfizer Inc, Lilly-ICOS, Auxillium, Johnson & Johnson; investigator for clinical research for Pfizer Inc, Lilly-ICOS, Bayer-GSK, Guilford Pharmaceuticals, Ion Channel, Johnson & Johnson and Schering Plough; advisory board and lecturer for Pfizer Inc, Lilly-ICOS and Auxillium.

Francesco Montorsi: Consultant for American Medical System, Bayer-GSK, Johnson & Johnson, Lilly ICOS, Pfizer Inc and Takeda.

Harin Padma-Nathan: Consultant, received grant support (for this and other clinical trials) from, and participated in CME educational program for Pfizer Inc, Lilly-ICOS, Bayer-GSK, NexMed and Palatin Technologies.

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Padma-Nathan, H., McCullough, A., Levine, L. 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 20, 479–486 (2008). https://doi.org/10.1038/ijir.2008.33

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