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Oral Therapy for Erectile Dysfunction

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Contemporary Treatment of Erectile Dysfunction

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

As defined by the NIH, erectile dysfunction (ED) is the repeated inability to get an erection firm enough for sexual intercourse (NIH consensus conference. Impotence. NIH consensus development panel on impotence. Journal of the American Medical Association, 270, 83–90, 1993). The International Consultation on Sexual Medicine defined ED as the consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual performance (Jardin, Recommendations of the 1st International Consultation on Erectile Dysfunction. Plymouth, UK: Health Publications Ltd, 2000). These definitions exclude other causes of sexual dysfunction including decreased libido and premature ejaculation. According to most recent studies, 15–30 million men report sexual dysfunction. Impotence has been studied for hundreds of years, but not until the past few decades have we been able to understand and treat so effectively. Even in the early 1900s it was known that vascular, neurologic, and hormonal milieu played a part in erections as physicians performed dorsal vein ligations and testicular transplants. Aphrodisiacs were the oral therapy of the day and included Chinese herbs and other common plant and food items that supposedly affected both desire and potency. However, the complex physiologic, neurologic, and psychological interaction is just starting to be appreciated.

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References

  1. NIH consensus conference (1993). Impotence. NIH consensus development panel on impotence. Journal of the American Medical Association, 270, 83–90.

    Google Scholar 

  2. Jardin, A. (2000). Recommendations of the 1st International Consultation on Erectile Dysfunction. Plymouth, UK: Health Publications Ltd.

    Google Scholar 

  3. Wessells, H., Joyce, G. F., Wise, M., & Wilt, T. J. (2007). Erectile dysfunction. The Journal of Urology, 177, 1675–1681.

    Article  PubMed  Google Scholar 

  4. Rosen, R. C., Hatzichristou, D., & Broderick, G. (2004). Clinical evaluation and symptom scales: Sexual dysfunction assessment in men. In T. Lue, R. Basson, & R. Rosen (Eds.), Sexual medicine: Sexual dysfunctions in men and women. Paris: Health Publications.

    Google Scholar 

  5. Lue, T. F. (2000). Erectile dysfunction. The New England Journal of Medicine, 342, 1802–1813.

    Article  CAS  PubMed  Google Scholar 

  6. Montague, D. K., Jarow, J. P., Broderick, G. A., et al. (2005). Chapter 1: The management of erectile dysfunction: An AUA update. Journal d’Urologie, 174, 230–239.

    Google Scholar 

  7. Wespes, E., Amar, E., Hatzichristou, D., et al. (2006). EAU Guidelines on erectile dysfunction: An update. European Urology, 49, 806–815.

    Article  PubMed  Google Scholar 

  8. Feldman, H. A., Goldstein, I., Hatzichristou, D. G., Krane, R. J., & McKinlay, J. B. (1994). Impotence and its medical and psychosocial correlates: Results of the Massachusetts Male Aging Study. The Journal of Urology, 151, 54–61.

    CAS  PubMed  Google Scholar 

  9. Burnett, A. L., Lowenstein, C. J., Bredt, D. S., Chang, T. S., & Snyder, S. H. (1992). Nitric oxide: A physiologic mediator of penile erection. Science, 257, 401–403.

    Article  CAS  PubMed  Google Scholar 

  10. Corbin, J. D., & Francis, S. H. (2002). Pharmacology of phosphodiesterase-5 inhibitors. International Journal of Clinical Practice, 56, 453–459.

    CAS  PubMed  Google Scholar 

  11. Rajfer, J., Aronson, W. J., Bush, P. A., Dorey, F. J., & Ignarro, L. J. (1992). Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. The New England Journal of Medicine, 326, 90–94.

    Article  CAS  PubMed  Google Scholar 

  12. Goldstein, I., Lue, T. F., Padma-Nathan, H., Rosen, R. C., Steers, W. D., & Wicker, P. A. (1998). Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. The New England Journal of Medicine, 338, 1397–1404.

    Article  CAS  PubMed  Google Scholar 

  13. Padma-Nathan, H., Stecher, V. J., Sweeney, M., Orazem, J., Tseng, L. J., & Deriesthal, H. (2003). Minimal time to successful intercourse after sildenafil citrate: Results of a randomized, double-blind, placebo-controlled trial. Urology, 62, 400–403.

    Article  CAS  PubMed  Google Scholar 

  14. Nichols, D. J., Muirhead, G. J., & Harness, J. A. (2002). Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: Absolute bioavailability, food effects and dose proportionality. British Journal of Clinical Pharmacology, 53(Suppl 1), 5S–12S.

    Article  CAS  PubMed  Google Scholar 

  15. Hellstrom, W. J., Gittelman, M., Karlin, G., et al. (2002). Vardenafil for treatment of men with erectile dysfunction: Efficacy and safety in a randomized, double-blind, placebo-controlled trial. Journal of Andrology, 23, 763–771.

    CAS  PubMed  Google Scholar 

  16. Hellstrom, W. J., Gittelman, M., Karlin, G., et al. (2003). Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: Results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology, 61, 8–14.

    Article  PubMed  Google Scholar 

  17. Montorsi, F., Padma-Nathan, H., Buvat, J., et al. (2004). Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: A randomized, double-blind, placebo-controlled trial. The Journal of Sexual Medicine, 1, 168–178.

    Article  CAS  PubMed  Google Scholar 

  18. Rajagopalan, P., Mazzu, A., Xia, C., Dawkins, R., & Sundaresan, P. (2003). Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction. Journal of Clinical Pharmacology, 43, 260–267.

    Article  CAS  PubMed  Google Scholar 

  19. Porst, H., Padma-Nathan, H., Giuliano, F., Anglin, G., Varanese, L., & Rosen, R. (2003). Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: A randomized controlled trial. Urology, 62, 121–125. Discussion 25–26.

    Article  PubMed  Google Scholar 

  20. Brock, G. B., McMahon, C. G., Chen, K. K., et al. (2002). Efficacy and safety of tadalafil for the treatment of erectile dysfunction: Results of integrated analyses. Journal d’Urologie, 168, 1332–1336.

    CAS  Google Scholar 

  21. Lewis, R. W., Sadovsky, R., Eardley, I., et al. (2005). The efficacy of tadalafil in clinical populations. The Journal of Sexual Medicine, 2, 517–531.

    Article  CAS  PubMed  Google Scholar 

  22. Stief, C., Porst, H., Saenz De Tejada, I., Ulbrich, E., & Beneke, M. (2004). Sustained efficacy and tolerability with vardenafil over 2 years of treatment in men with erectile dysfunction. International Journal of Clinical Practice, 58, 230–239.

    Article  CAS  PubMed  Google Scholar 

  23. Klotz, T., Mathers, M., Klotz, R., & Sommer, F. (2005). Why do patients with erectile dysfunction abandon effective therapy with sildenafil (Viagra)? International Journal of Impotence Research, 17, 2–4.

    Article  CAS  PubMed  Google Scholar 

  24. Pomeranz, H. D., & Bhavsar, A. R. (2005). Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): A report of seven new cases. Journal of Neuroophthalmology, 25, 9–13.

    Google Scholar 

  25. Carter, J. E. (2007). Anterior ischemic optic neuropathy and stroke with use of PDE-5 inhibitors for erectile dysfunction: Cause or coincidence? Journal of the Neurological Sciences, 262, 89–97.

    Article  CAS  PubMed  Google Scholar 

  26. Padma-Nathan, H., Eardley, I., Kloner, R. A., Laties, A. M., & Montorsi, F. (2002). A 4-year update on the safety of sildenafil citrate (Viagra). Urology, 60, 67–90.

    Article  PubMed  Google Scholar 

  27. Kloner, R. A., Jackson, G., Hutter, A. M., et al. (2006). Cardiovascular safety update of Tadalafil: Retrospective analysis of data from placebo-controlled and open-label clinical trials of Tadalafil with as needed, three times-per-week or once-a-day dosing. The American Journal of Cardiology, 97, 1778–1784.

    Article  CAS  PubMed  Google Scholar 

  28. Reffelmann, T., Kieback, A., & Kloner, R. A. (2008). The cardiovascular safety of tadalafil. Expert Opinion on Drug Safety, 7, 43–52.

    Article  CAS  PubMed  Google Scholar 

  29. Kostis, J. B., Jackson, G., Rosen, R., et al. (2005). Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference). The American Journal of Cardiology, 96, 85M–93M.

    Article  PubMed  Google Scholar 

  30. DeBusk, R., Drory, Y., Goldstein, I., et al. (2000). Management of sexual dysfunction in patients with cardiovascular disease: Recommendations of the Princeton Consensus Panel. The American Journal of Cardiology, 86, 62F–68F.

    Article  CAS  PubMed  Google Scholar 

  31. Carson, C. C., & Lue, T. F. (2005). Phosphodiesterase type 5 inhibitors for erectile dysfunction. BJU International, 96, 257–280.

    Article  CAS  PubMed  Google Scholar 

  32. Rendell, M. S., Rajfer, J., Wicker, P. A., & Smith, M. D. (1999). Sildenafil for treatment of erectile dysfunction in men with diabetes: A randomized controlled trial. Sildenafil Diabetes Study Group. Journal of the American Medical Association, 281, 421–426.

    Article  CAS  PubMed  Google Scholar 

  33. Brock, G., Nehra, A., Lipshultz, L. I., et al. (2003). Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. Journal d’Urologie, 170, 1278–1283.

    CAS  Google Scholar 

  34. Gontero, P., Fontana, F., Zitella, A., Montorsi, F., & Frea, B. (2005). A prospective evaluation of efficacy and compliance with a multistep treatment approach for erectile dysfunction in patients after non-nerve sparing radical prostatectomy. BJU International, 95, 359–365.

    Article  PubMed  Google Scholar 

  35. Hatzimouratidis, K. (2006). Sildenafil in the treatment of erectile dysfunction: An overview of the clinical evidence. Clinical Interventions in Aging, 1, 403–414.

    Article  CAS  PubMed  Google Scholar 

  36. Montorsi, F., Nathan, H. P., McCullough, A., et al. (2004). Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: A randomized, double-blind, placebo controlled trial. Journal d’Urologie, 172, 1036–1041.

    CAS  Google Scholar 

  37. McCullough, A. R., Barada, J. H., Fawzy, A., Guay, A. T., & Hatzichristou, D. (2002). Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction. Urology, 60, 28–38.

    Article  PubMed  Google Scholar 

  38. Brisson, T. E., Broderick, G. A., Thiel, D. D., Heckman, M. G., & Pinkstaff, D. M. (2006). Vardenafil rescue rates of sildenafil nonresponders: Objective assessment of 327 patients with erectile dysfunction. Urology, 68, 397–401.

    Article  PubMed  Google Scholar 

  39. Hatzichristou, D. G., Aliotta, P., Auerbach, S., et al. (2005). Erectile response to vardenafil in men with a history of nonresponse to sildenafil: A time-from-dosing descriptive analysis. Clinical Therapeutics, 27, 1452–1461.

    Article  CAS  PubMed  Google Scholar 

  40. Ellsworth, P., & Kirshenbaum, E. M. (2008). Current concepts in the evaluation and management of erectile dysfunction. Urologic Nursing, 28, 357–369.

    PubMed  Google Scholar 

  41. Giuliano, F., Bernabe, J., Brown, K., Droupy, S., Benoit, G., & Rampin, O. (1997). Erectile response to hypothalamic stimulation in rats: Role of peripheral nerves. The American Journal of Physiology, 273, R1990–R1997.

    CAS  PubMed  Google Scholar 

  42. Sato, Y., & Christ, G. J. (2000). Differential ICP responses elicited by electrical stimulation of medial preoptic area. American Journal of Physiology. Heart and Circulatory Physiology, 278, H964–H970.

    CAS  PubMed  Google Scholar 

  43. Chen, K. K., Chan, J. Y., & Chang, L. S. (1999). Dopaminergic neurotransmission at the paraventricular nucleus of hypothalamus in central regulation of penile erection in the rat. Journal d’Urologie, 162, 237–242.

    CAS  Google Scholar 

  44. Dula, E., Keating, W., Siami, P. F., Edmonds, A., O’Neil, J., & Buttler, S. (2000). Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. The Apomorphine Study Group. Urology, 56, 130–135.

    Article  CAS  PubMed  Google Scholar 

  45. Gontero, P., D’Antonio, R., Pretti, G., et al. (2005). Clinical efficacy of Apomorphine SL in erectile dysfunction of diabetic men. International Journal of Impotence Research, 17, 80–85.

    Article  CAS  PubMed  Google Scholar 

  46. Porst, H., Behre, H. M., Jungwirth, A., & Burkart, M. (2007). Comparative trial of treatment satisfaction, efficacy and tolerability of sildenafil versus apomorphine in erectile dysfunction – an open, randomized cross-over study with flexible dosing. European Journal of Medical Research, 12, 61–67.

    CAS  PubMed  Google Scholar 

  47. Filippi, S., Luconi, M., Granchi, S., et al. (2002). Endothelium-dependency of yohimbine-induced corpus cavernosum relaxation. International Journal of Impotence Research, 14, 295–307.

    Article  CAS  PubMed  Google Scholar 

  48. Morales, A., Condra, M., Owen, J. A., Surridge, D. H., Fenemore, J., & Harris, C. (1987). Is yohimbine effective in the treatment of organic impotence? Results of a controlled trial. Journal d’Urologie, 137, 1168–1172.

    CAS  Google Scholar 

  49. Reid, K., Surridge, D. H., Morales, A., et al. (1987). Double-blind trial of yohimbine in treatment of psychogenic impotence. Lancet, 2, 421–423.

    Article  CAS  PubMed  Google Scholar 

  50. Padma-Nathan, H., Goldstein, I., Klimberg, I., Coogan, C., Auerbach, S., & Lammers, P. (2002). Long-term safety and efficacy of oral phentolamine mesylate (Vasomax) in men with mild to moderate erectile dysfunction. International Journal of Impotence Research, 14, 266–270.

    Article  CAS  PubMed  Google Scholar 

  51. Gur, S., Kadowitz, P. J., Trost, L., & Hellstrom, W. J. (2007). Optimizing nitric oxide production by time dependent L-arginine administration in isolated human corpus cavernosum. Journal d’Urologie, 178, 1543–1548.

    CAS  Google Scholar 

  52. Kernohan, A. F., McIntyre, M., Hughes, D. M., Tam, S. W., Worcel, M., & Reid, J. L. (2005). An oral yohimbine/l-arginine combination (NMI 861) for the treatment of male erectile dysfunction: A pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects. British Journal of Clinical Pharmacology, 59, 85–93.

    Article  CAS  PubMed  Google Scholar 

  53. Becker, A. J., Uckert, S., Stief, C. G., et al. (2001). Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence. Urology, 57, 193–198.

    Article  CAS  PubMed  Google Scholar 

  54. da-Costa Goncalves, A. C., Leite, R., Fraga-Silva, R. A., et al. (2007). Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function. American Journal of Physiology. Heart and Circulatory Physiology, 293, H2588–H2596.

    Article  Google Scholar 

  55. Dorrance, A. M., Lewis, R. W., & Mills, T. M. (2002). Captopril treatment reverses erectile dysfunction in male stroke prone spontaneously hypertensive rats. International Journal of Impotence Research, 14, 494–497.

    Article  CAS  PubMed  Google Scholar 

  56. Hale, T. M., Okabe, H., Heaton, J. P., & Adams, M. A. (2001). Antihypertensive drugs induce structural remodeling of the penile vasculature. Journal d’Urologie, 166, 739–745.

    CAS  Google Scholar 

  57. Kifor, I., Williams, G. H., Vickers, M. A., Sullivan, M. P., Jodbert, P., & Dluhy, R. G. (1997). Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum. Journal d’Urologie, 157, 1920–1925.

    CAS  Google Scholar 

  58. Park, J. K., Kim, S. Z., Kim, S. H., Park, Y. K., & Cho, K. W. (1997). Renin angiotensin system in rabbit corpus cavernosum: Functional characterization of angiotensin II receptors. Journal d’Urologie, 158, 653–658.

    CAS  Google Scholar 

  59. Moyad, M. A. (2002). Dietary supplements and other alternative medicines for erectile dysfunction. What do I tell my patients? The Urologic Clinics of North America, 29, 11–22. vii.

    Article  PubMed  Google Scholar 

  60. Moyad, M. A., Barada, J. H., Lue, T. F., Mulhall, J. P., Goldstein, I., & Fawzy, A. (2004). Prevention and treatment of erectile dysfunction using lifestyle changes and dietary supplements: What works and what is worthless, part II. The Urologic Clinics of North America, 31, 259–273.

    Article  PubMed  Google Scholar 

  61. Kaufman, J., & Dietrich, J. (2006). Safety and efficacy of avanafil, a new PDE5 inhibitor for treating erectile dysfunction. The Journal of Urology, 175, 299.

    Google Scholar 

  62. Nehra, A. (2006). Hemodynamic effects of co-administration of avanafil and glyceryl trinitrate. The Journal of Sexual Medicine, 3, 209.

    Google Scholar 

  63. Kim, B. H., Lim, H. S., Chung, J. Y., et al. (2008). Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects. British Journal of Clinical Pharmacology, 65, 848–854.

    Article  CAS  PubMed  Google Scholar 

  64. Paick, J. S., Kim, S. W., Yang, D. Y., et al. (2008). The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction. The Journal of Sexual Medicine, 5, 946–953.

    Article  CAS  PubMed  Google Scholar 

  65. Prince, W. T., Campbell, A. S., & Tong, W. (2006). SLx-2101, a new long-acting PDE5 inhibitor: Preliminary safety, tolerability, PK and endothelial function effects in healthy subjects. The Journal of Sexual Medicine, 3, 29–30.

    Google Scholar 

  66. Paick, J. S., Ahn, T. Y., Choi, H. K., et al. (2008). Efficacy and safety of mirodenafil, a new oral phosphodiesterase type 5 inhibitor, for treatment of erectile dysfunction. The Journal of Sexual Medicine, 5, 2672–2680.

    Article  PubMed  Google Scholar 

  67. Hatzimouratidis, K., & Hatzichristou, D. G. (2008). Looking to the future for erectile dysfunction therapies. Drugs, 68, 231–250.

    Article  CAS  PubMed  Google Scholar 

  68. Rosenthal, B. D., May, N. R., Metro, M. J., Harkaway, R. C., & Ginsberg, P. C. (2006). Adjunctive use of AndroGel (testosterone gel) with sildenafil to treat erectile dysfunction in men with acquired androgen deficiency syndrome after failure using sildenafil alone. Urology, 67, 571–574.

    Article  PubMed  Google Scholar 

  69. Shabsigh, R. (2003). Hypogonadism and erectile dysfunction: The role for testosterone therapy. International Journal of Impotence Research, 15(Suppl 4), S9–S13.

    Article  CAS  PubMed  Google Scholar 

  70. Shabsigh, R., Kaufman, J. M., Steidle, C., & Padma-Nathan, H. (2004). Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. Journal d’Urologie, 172, 658–663.

    CAS  Google Scholar 

  71. Shabsigh, R., Kaufman, J. M., Steidle, C., & Padma-Nathan, H. (2008). Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. Journal d’Urologie, 179, S97–S102.

    CAS  Google Scholar 

  72. Raina, R., Agarwal, A., Zaramo, C. E., Ausmundson, S., Mansour, D., & Zippe, C. D. (2005). Long-term efficacy and compliance of MUSE™ for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis. International Journal of Impotence Research, 17, 86–90.

    Article  CAS  PubMed  Google Scholar 

  73. Lue, T. F., & Broderick, G. A. (2007). Evaluation and nonsurgical management of erectile dysfunction and premature ejaculation. In A. Wein, L. R. Kavoussi, A. C. Novick, A. W. Partin, & C. A. Peters (Eds.), Wein: Campbell-Walsh Urology. Philadelphia: Saunders Elsevier.

    Google Scholar 

  74. Lue, T. F., Giuliano, F., Montorsi, F., et al. (2004). Summary of the recommendations on sexual dysfunctions in men. The Journal of Sexual Medicine, 1, 6–23.

    Article  PubMed  Google Scholar 

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  1. Department of Surgery, Division of Urology, Duke University Medical Center, 1112C Green Zone, Duke Hospital South, DUMC, Durham, NC, 27710, USA

    Craig F. Donatucci

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Correspondence to Craig F. Donatucci .

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  1. Feinberg School of Medicine, Department of Urology, Northwestern University, East Chicago Avenue 303, Chicago, 60611-3008, Illinois, USA

    Kevin T. McVary

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McNamara, E.R., Donatucci, C.F. (2011). Oral Therapy for Erectile Dysfunction. In: McVary, K. (eds) Contemporary Treatment of Erectile Dysfunction. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-60327-536-1_8

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