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Table of Contents
Vol. 58, No. 1, 2012
Issue release date: December 2011
Section title: Clinical Section / Mini-Review
Free Access
Gerontology 2012;58:3–14
(DOI:10.1159/000329598)

Evaluation and Treatment of Erectile Dysfunction in the Aging Male: A Mini-Review

Albersen M.a, b · Orabi H.a, c · Lue T.F.a
aDepartment of Urology, University of California at San Francisco, San Francisco, Calif., USA; bDepartment of Urology, University Hospitals Leuven, Leuven, Belgium; cDepartment of Urology, Assiut University, Assiut, Egypt
email Corresponding Author

Abstract

Before the 20th century, individuals often did not live beyond the reproductive years, and sexuality of the elderly was not an issue. However, in the current era it is known that as life expectancy improves, both men and women are seeking to preserve their sexuality into old age. While the appreciation of sexuality persists with aging, a decline in sexual activity is typically seen with, and can be attributed to both general health problems as well as specific sexual dysfunctions. Erectile dysfunction is the most frequently diagnosed sexual dysfunction in the older male population. This mini-review provides an overview of contemporary literature concerning epidemiology, pathophysiology, assessment and treatment of erectile dysfunction in the aging male.

© 2011 S. Karger AG, Basel


  

Key Words

  • Aging male
  • Erectile dysfunction
  • Pathophysiology
  • Penis
  • Phosphodiesterase-5 inhibitors

References

  1. Lindau ST, Schumm LP, Laumann EO, Levinson W, O’Muircheartaigh CA, Waite LJ: A study of sexuality and health among older adults in the United States. N Engl J Med 2007;357:762–774.
  2. Smith LJ, Mulhall JP, Deveci S, Monaghan N, Reid MC: Sex after seventy: a pilot study of sexual function in older persons. J Sex Med 2007;4:1247–1253.
  3. NIH Consensus Conference: Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83–90.
  4. Uckert S, Mayer ME, Stief CG, Jonas U: The future of the oral pharmacotherapy of male erectile dysfunction: things to come. Expert Opin Emerg Drugs 2007;12:219–228.
  5. Hatzimouratidis K, Hatzichristou DG: A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs 2005;65:1621–1650.
  6. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB: Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol 1994;151:54–61.
  7. Corona G, Lee DM, Forti G, O’Connor DB, Maggi M, O’Neill TW, et al: Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med 2010;7:1362–1380.
  8. Russell ST, Khandheria BK, Nehra A: Erectile dysfunction and cardiovascular disease. Mayo Clin Proc 2004;79:782–794.
  9. Albersen M, Shindel AW, Lue TF: Sexual dysfunction in the older man. Rev Clin Gerontol 2009;19:237–248.

    External Resources

  10. Ayta IA, McKinlay JB, Krane RJ: The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999;84:50–56.
  11. Laumann EO, Waite LJ: Sexual dysfunction among older adults: prevalence and risk factors from a nationally representative US probability sample of men and women 57–85 years of age. J Sex Med 2008;5:2300–2311.

    External Resources

  12. Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ: Urologic Diseases in America Project. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med 2006;166:207–212.
  13. Lue TF: Erectile dysfunction. N Engl J Med 2000;342:1802–1813.
  14. Albersen M, Shindel AW, Mwamukonda KB, Lue TF: The future is today: emerging drugs for the treatment of erectile dysfunction. Expert Opin Emerg Drugs 2010;15:467–480.
  15. Hannan JL, Blaser MC, Oldfield L, Pang JJ, Adams SM, Pang SC, et al: Morphological and functional evidence for the contribution of the pudendal artery in aging-induced erectile dysfunction. J Sex Med 2010;7:3373–3384.
  16. El-Sakka AI, Yassin AA: Amelioration of penile fibrosis: myth or reality. J Androl 2010;31:324–335.
  17. Rudner XL, Berkowitz DE, Booth JV, Funk BL, Cozart KL, D’Amico EB, El-Moalem H, Page SO, Richardson CD, Winters B, Marucci L, Schwinn DA: Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age. Circulation 1999;100:2336–2343.
  18. Christ GJ, Stone B, Melman A: Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men. Can J Physiol Pharmacol 1991;69:909–913.
  19. Vanhoutte PM: Ageing and endothelial dysfunction. Eur Heart J Suppl 2002;4(suppl A):A8–A17.

    External Resources

  20. Musicki B, Kramer MF, Becker RE, Burnett AL: Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. J Sex Med 2005;2:347–355.
  21. Aversa A, Bruzziches R, Francomano D, Natali M, Gareri P, Spera G: Endothelial dysfunction and erectile dysfunction in the aging man. Int J Urol 2010;17:38–47.
  22. Park CS, Ryu SD, Hwang SY: Elevation of intracavernous pressure and NO-cGMP activity by a new herbal formula in penile tissues of aged and diabetic rats. J Ethnopharmacol 2004;94:85–92.
  23. Wespes E: The ageing penis. World J Urol 2002;20:36–39.
  24. Ferrini MG, Davila HH, Valente EG, Gonzalez-Cadavid NF, Rajfer J: Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media. Cardiovasc Res 2004;61:796–805.
  25. Ferrini M, Magee TR, Vernet D, Rajfer J, Gonzalez-Cadavid NF: Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis. Biol Reprod 2001;64:974–982.
  26. Traish AM, Munarriz R, O’Connell L, Choi S, Kim SW, Kim NN, et al: Effects of medical or surgical castration on erectile function in an animal model. J Androl 2003;24:381–387.

    External Resources

  27. Rogers RS, Graziottin TM, Lin CS, Kan YW, Lue TF: Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res 2003;15:26–37.
  28. Traish A, Kim N: The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med 2005;2:759–770.
  29. Traish AM, Kim N: Weapons of penile smooth muscle destruction: androgen deficiency promotes accumulation of adipocytes in the corpus cavernosum. Aging Male 2005;8:141–146.
  30. Lue TF, Broderick GA: Evaluation and nonsurgical management of erectile dysfunction and premature ejaculation; in Campbell-Walsh Urology ed 9. Amsterdam, Elsevier, 2007.
  31. Jackson G, Rosen RC, Kloner RA, Kostis JB: The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med 2006;3:28–36.
  32. Korfage IJ, Pluijm S, Roobol M, Dohle GR, Schroder FH, Essink-Bot ML: Erectile dysfunction and mental health in a general population of older men. J Sex Med 2009;6:505–512.
  33. Saltzman EA, Guay AT, Jacobson J: Improvement in erectile function in men with organic erectile dysfunction by correction of elevated cholesterol levels: a clinical observation. J Urol 2004;172:255–258.
  34. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A, et al: SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997;23:176–194.
  35. Rosen RC, Lane RM, Menza M: Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol 1999;19:67–85.
  36. Fujisawa M, Sawada K: Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction. Arch Androl 2004;50:255–260.
  37. Bella AJ, Deyoung LX, Al-Numi M, Brock GB: Daily administration of phosphodiesterase type 5 inhibitors for urological and nonurological indications. Eur Urol 2007;52:990–1005.
  38. Shindel AW: Update on phosphodiesterase type 5 inhibitor therapy part 1: recent studies on routine dosing for penile rehabilitation, lower urinary tract symptoms, and other indications (CME). J Sex Med 2009;6:1794–1808.
  39. Konstantinopoulos A, Giannitsas K, Athanasopoulos A, Spathas D, Perimenis P: The impact of daily sildenafil on levels of soluble molecular markers of endothelial function in plasma in patients with erectile dysfunction. Expert Opin Pharmacother 2009;10:155–160.
  40. Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H: Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004;172:658–663.
  41. Giuliano F, Donatucci C, Montorsi F, Auerbach S, Karlin G, Norenberg C, et al: Vardenafil is effective and well-tolerated for treating erectile dysfunction in a broad population of men, irrespective of age. BJU Int 2005;95:110–116.
  42. Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V, et al: Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002;168:1332–1336.
  43. Hatzimouratidis K, Hatzichristou D: Phosphodiesterase type 5 inhibitors: the day after. Eur Urol 2007;51:75–88.
  44. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, et al: Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010;57:804–814.
  45. Ning H, Xin ZC, Lin G, Banie L, Lue TF, Lin CS: Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology 2006;68:1350–1354.
  46. Shindel AW, Xin ZC, Lin G, Fandel TM, Huang YC, Banie L, et al: Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. J Sex Med 2010;7:1518–1528.
  47. Jones RW, Rees RW, Minhas S, Ralph D, Persad RA, Jeremy JY: Oxygen free radicals and the penis. Expert Opin Pharmacother 2002;3:889–897.
  48. Hellstrom WJ, Montague DK, Moncada I, Carson C, Minhas S, Faria G, et al: Implants, mechanical devices, and vascular surgery for erectile dysfunction. J Sex Med 2010;7:501–523.

  

Author Contacts

Maarten Albersen, MD
Laboratory of Experimental Urology, Department of Urology
University Hospitals Leuven, Herestraat 49
BE–3000 Leuven (Belgium)
Tel. +32 16 34 69 30, E-Mail Maarten.albersen@uzleuven.be

  

Article Information

Received: November 29, 2010
Accepted: May 25, 2011
Published online: September 7, 2011
Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 1, Number of References : 48

  

Publication Details

Gerontology (International Journal of Experimental, Clinical, Behavioural and Technological Gerontology)

Vol. 58, No. 1, Year 2012 (Cover Date: December 2011)

Journal Editor: Wick G. (Innsbruck)
ISSN: 0304-324X (Print), eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Before the 20th century, individuals often did not live beyond the reproductive years, and sexuality of the elderly was not an issue. However, in the current era it is known that as life expectancy improves, both men and women are seeking to preserve their sexuality into old age. While the appreciation of sexuality persists with aging, a decline in sexual activity is typically seen with, and can be attributed to both general health problems as well as specific sexual dysfunctions. Erectile dysfunction is the most frequently diagnosed sexual dysfunction in the older male population. This mini-review provides an overview of contemporary literature concerning epidemiology, pathophysiology, assessment and treatment of erectile dysfunction in the aging male.

© 2011 S. Karger AG, Basel


  

Author Contacts

Maarten Albersen, MD
Laboratory of Experimental Urology, Department of Urology
University Hospitals Leuven, Herestraat 49
BE–3000 Leuven (Belgium)
Tel. +32 16 34 69 30, E-Mail Maarten.albersen@uzleuven.be

  

Article Information

Received: November 29, 2010
Accepted: May 25, 2011
Published online: September 7, 2011
Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 1, Number of References : 48

  

Publication Details

Gerontology (International Journal of Experimental, Clinical, Behavioural and Technological Gerontology)

Vol. 58, No. 1, Year 2012 (Cover Date: December 2011)

Journal Editor: Wick G. (Innsbruck)
ISSN: 0304-324X (Print), eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Article / Publication Details

First-Page Preview
Abstract of Clinical Section / Mini-Review

Received: 11/29/2010 10:26:03 AM
Accepted: 5/25/2011
Published online: 9/7/2011
Issue release date: December 2011

Number of Print Pages: 12
Number of Figures: 1
Number of Tables: 1

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Lindau ST, Schumm LP, Laumann EO, Levinson W, O’Muircheartaigh CA, Waite LJ: A study of sexuality and health among older adults in the United States. N Engl J Med 2007;357:762–774.
  2. Smith LJ, Mulhall JP, Deveci S, Monaghan N, Reid MC: Sex after seventy: a pilot study of sexual function in older persons. J Sex Med 2007;4:1247–1253.
  3. NIH Consensus Conference: Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83–90.
  4. Uckert S, Mayer ME, Stief CG, Jonas U: The future of the oral pharmacotherapy of male erectile dysfunction: things to come. Expert Opin Emerg Drugs 2007;12:219–228.
  5. Hatzimouratidis K, Hatzichristou DG: A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs 2005;65:1621–1650.
  6. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB: Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol 1994;151:54–61.
  7. Corona G, Lee DM, Forti G, O’Connor DB, Maggi M, O’Neill TW, et al: Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med 2010;7:1362–1380.
  8. Russell ST, Khandheria BK, Nehra A: Erectile dysfunction and cardiovascular disease. Mayo Clin Proc 2004;79:782–794.
  9. Albersen M, Shindel AW, Lue TF: Sexual dysfunction in the older man. Rev Clin Gerontol 2009;19:237–248.

    External Resources

  10. Ayta IA, McKinlay JB, Krane RJ: The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999;84:50–56.
  11. Laumann EO, Waite LJ: Sexual dysfunction among older adults: prevalence and risk factors from a nationally representative US probability sample of men and women 57–85 years of age. J Sex Med 2008;5:2300–2311.

    External Resources

  12. Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ: Urologic Diseases in America Project. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med 2006;166:207–212.
  13. Lue TF: Erectile dysfunction. N Engl J Med 2000;342:1802–1813.
  14. Albersen M, Shindel AW, Mwamukonda KB, Lue TF: The future is today: emerging drugs for the treatment of erectile dysfunction. Expert Opin Emerg Drugs 2010;15:467–480.
  15. Hannan JL, Blaser MC, Oldfield L, Pang JJ, Adams SM, Pang SC, et al: Morphological and functional evidence for the contribution of the pudendal artery in aging-induced erectile dysfunction. J Sex Med 2010;7:3373–3384.
  16. El-Sakka AI, Yassin AA: Amelioration of penile fibrosis: myth or reality. J Androl 2010;31:324–335.
  17. Rudner XL, Berkowitz DE, Booth JV, Funk BL, Cozart KL, D’Amico EB, El-Moalem H, Page SO, Richardson CD, Winters B, Marucci L, Schwinn DA: Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age. Circulation 1999;100:2336–2343.
  18. Christ GJ, Stone B, Melman A: Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men. Can J Physiol Pharmacol 1991;69:909–913.
  19. Vanhoutte PM: Ageing and endothelial dysfunction. Eur Heart J Suppl 2002;4(suppl A):A8–A17.

    External Resources

  20. Musicki B, Kramer MF, Becker RE, Burnett AL: Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. J Sex Med 2005;2:347–355.
  21. Aversa A, Bruzziches R, Francomano D, Natali M, Gareri P, Spera G: Endothelial dysfunction and erectile dysfunction in the aging man. Int J Urol 2010;17:38–47.
  22. Park CS, Ryu SD, Hwang SY: Elevation of intracavernous pressure and NO-cGMP activity by a new herbal formula in penile tissues of aged and diabetic rats. J Ethnopharmacol 2004;94:85–92.
  23. Wespes E: The ageing penis. World J Urol 2002;20:36–39.
  24. Ferrini MG, Davila HH, Valente EG, Gonzalez-Cadavid NF, Rajfer J: Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media. Cardiovasc Res 2004;61:796–805.
  25. Ferrini M, Magee TR, Vernet D, Rajfer J, Gonzalez-Cadavid NF: Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis. Biol Reprod 2001;64:974–982.
  26. Traish AM, Munarriz R, O’Connell L, Choi S, Kim SW, Kim NN, et al: Effects of medical or surgical castration on erectile function in an animal model. J Androl 2003;24:381–387.

    External Resources

  27. Rogers RS, Graziottin TM, Lin CS, Kan YW, Lue TF: Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res 2003;15:26–37.
  28. Traish A, Kim N: The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med 2005;2:759–770.
  29. Traish AM, Kim N: Weapons of penile smooth muscle destruction: androgen deficiency promotes accumulation of adipocytes in the corpus cavernosum. Aging Male 2005;8:141–146.
  30. Lue TF, Broderick GA: Evaluation and nonsurgical management of erectile dysfunction and premature ejaculation; in Campbell-Walsh Urology ed 9. Amsterdam, Elsevier, 2007.
  31. Jackson G, Rosen RC, Kloner RA, Kostis JB: The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med 2006;3:28–36.
  32. Korfage IJ, Pluijm S, Roobol M, Dohle GR, Schroder FH, Essink-Bot ML: Erectile dysfunction and mental health in a general population of older men. J Sex Med 2009;6:505–512.
  33. Saltzman EA, Guay AT, Jacobson J: Improvement in erectile function in men with organic erectile dysfunction by correction of elevated cholesterol levels: a clinical observation. J Urol 2004;172:255–258.
  34. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A, et al: SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997;23:176–194.
  35. Rosen RC, Lane RM, Menza M: Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol 1999;19:67–85.
  36. Fujisawa M, Sawada K: Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction. Arch Androl 2004;50:255–260.
  37. Bella AJ, Deyoung LX, Al-Numi M, Brock GB: Daily administration of phosphodiesterase type 5 inhibitors for urological and nonurological indications. Eur Urol 2007;52:990–1005.
  38. Shindel AW: Update on phosphodiesterase type 5 inhibitor therapy part 1: recent studies on routine dosing for penile rehabilitation, lower urinary tract symptoms, and other indications (CME). J Sex Med 2009;6:1794–1808.
  39. Konstantinopoulos A, Giannitsas K, Athanasopoulos A, Spathas D, Perimenis P: The impact of daily sildenafil on levels of soluble molecular markers of endothelial function in plasma in patients with erectile dysfunction. Expert Opin Pharmacother 2009;10:155–160.
  40. Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H: Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004;172:658–663.
  41. Giuliano F, Donatucci C, Montorsi F, Auerbach S, Karlin G, Norenberg C, et al: Vardenafil is effective and well-tolerated for treating erectile dysfunction in a broad population of men, irrespective of age. BJU Int 2005;95:110–116.
  42. Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V, et al: Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002;168:1332–1336.
  43. Hatzimouratidis K, Hatzichristou D: Phosphodiesterase type 5 inhibitors: the day after. Eur Urol 2007;51:75–88.
  44. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, et al: Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010;57:804–814.
  45. Ning H, Xin ZC, Lin G, Banie L, Lue TF, Lin CS: Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology 2006;68:1350–1354.
  46. Shindel AW, Xin ZC, Lin G, Fandel TM, Huang YC, Banie L, et al: Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. J Sex Med 2010;7:1518–1528.
  47. Jones RW, Rees RW, Minhas S, Ralph D, Persad RA, Jeremy JY: Oxygen free radicals and the penis. Expert Opin Pharmacother 2002;3:889–897.
  48. Hellstrom WJ, Montague DK, Moncada I, Carson C, Minhas S, Faria G, et al: Implants, mechanical devices, and vascular surgery for erectile dysfunction. J Sex Med 2010;7:501–523.