Current Sexual Health Reports

, Volume 10, Issue 3, pp 169–176 | Cite as

What Is the Future of Erectile Dysfunction Therapy?

  • Jeffrey D. CampbellEmail author
  • Uros Milenkovic
  • Maarten Albersen
  • Trinity J. Bivalacqua
Male Sexual Dysfunction and Disorders (AW Pastuszak and NK Gupta, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Male Sexual Dysfunction and Disorders


Purpose of Review

Erectile dysfunction (ED) is a burden for the majority of men during their lifetime. Phosphodiesterase type-5 inhibitors are first-line treatment for men with ED; however, they are limited by on-demand dosing, short-term benefits, and reduced efficacy in difficult to treat populations such as men with diabetes mellitus or ED after radical prostatectomy.

Recent Findings

Novel treatment options that offer a durable, tissue restorative approaches are being explored and potentially offer a long-term solution to this medical affliction. Medical therapies such as nanoparticles and botulinum neurotoxin, new technology including vibratory devices and low-intensity extracorporeal shockwave treatment, and regenerative medicine approaches that are undergoing human clinical trials.


Although preclinical data surrounding novel ED therapies are intriguing, these studies are not yet robust enough to support these endeavors outside of clinical trials and further work is ongoing.


Erectile dysfunction Low-intensity extracorporeal shockwave treatment Phosphodiesterase-5 inhibitors Stem cell therapy Platelet-rich plasma Nanoparticles 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Montague DK, Jarow JP, Broderick GA, Dmochowski RR, Heaton JP, Lue TF, et al. Chapter 1: the management of erectile dysfunction: an AUA update. J Urol. 2005;174(1):230–9. Scholar
  2. 2.
    Bella AJ, Lee JC, Carrier S, Bénard F, Brock GB. 2015 CUA practice guidelines for erectile dysfunction. Can Urol Assoc J. 2015;9(1–2):23–9. Scholar
  3. 3.
    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(4 Pt 1):1362–80. Scholar
  4. 4.
    Ficarra V, Novara G, Ahlering TE, Costello A, Eastham JA, Graefen M, et al. Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol. 2012;62(3):418–30. Scholar
  5. 5.
    Lee DM, O'Neill TW, Pye SR, Silman AJ, Finn JD, Pendleton N, et al. The European male ageing study (EMAS): design, methods and recruitment. Int J Androl. 2009;32(1):11–24. Scholar
  6. 6.
    • Lane A, Metcalfe C, Young GJ, Peters TJ, Blazeby J, Avery KN, et al. Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life. BJU Int. 2016;118(6):869–79. ProtecT trial patient-report outcome data. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ryu JK, Suh JK, Burnett AL. Research in pharmacotherapy for erectile dysfunction. Transl Androl Urol. 2017;6(2):207–15. Scholar
  8. 8.
    Hawksworth DJ, Burnett AL. Pharmacotherapeutic management of erectile dysfunction. Clin Pharmacol Ther. 2015;98(6):602–10. Scholar
  9. 9.
    Hackett G, Kirby M, Wylie K, Heald A, Ossei-Gerning N, Edwards D, et al. British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men-2017. J Sex Med. 2018;15(4):430–57. Scholar
  10. 10.
    Murthy SK. Nanoparticles in modern medicine: state of the art and future challenges. Int J Nanomedicine. 2007;2(2):129–41.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Quinn JF, Whittaker MR, Davis TP. Delivering nitric oxide with nanoparticles. J Control Release. 2015;205:190–205. Scholar
  12. 12.
    Han G, Tar M, Kuppam DS, Friedman A, Melman A, Friedman J, et al. Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction. J Sex Med. 2010;7(1 Pt 1):224–33. Scholar
  13. 13.
    Tar M, Cabrales P, Navati M, Adler B, Nacharaju P, Friedman AJ, et al. Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy. J Sex Med. 2014;11(12):2903–14. Scholar
  14. 14.
    Draganski A, Tar MT, Villegas G, Friedman JM, Davies KP. Topically applied curcumin-loaded nanoparticles treat erectile dysfunction in a rat model of Type-2 diabetes. J Sex Med. 2018;15(5):645–53. Scholar
  15. 15.
    Abdel Aziz MT, Motawi T, Rezq A, Mostafa T, Fouad HH, Ahmed HH, et al. Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction. J Sex Med. 2012;9(7):1815–33. Scholar
  16. 16.
    Abdel Aziz MT, Rezq AM, Atta HM, Fouad H, Zaahkouk AM, Ahmed HH, et al. Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction. Andrologia. 2015;47(6):616–25. Scholar
  17. 17.
    Zaahkouk AM, Abdel Aziz MT, Rezq AM, Atta HM, Fouad HH, Ahmed HH, et al. Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function. Int J Impot Res. 2015;27(1):9–15. Scholar
  18. 18.
    Aoki KR, Guyer B. Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001;8(Suppl 5):21–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol. 2014;7(2):31–9.PubMedPubMedCentralGoogle Scholar
  20. 20.
    • Ghanem H, Raheem AA, AbdelRahman IFS, Johnson M, Abdel-Raheem T. Botulinum neurotoxin and its potential role in the treatment of erectile dysfunction. Sex Med Rev. 2018;6(1):135–42. Review of potential mechanism of action of Botox for ED treatment. CrossRefPubMedGoogle Scholar
  21. 21.
    Giuliano F, Brock G. Botox for erectile dysfunction. J Sex Med. 2017;14(2):177–8. Scholar
  22. 22.
    Campbell JD,De Young L, Radomski S, Alzubaidi R, Brock GB. Intracavernosal injection of botulinum toxin to improve erectile function in older rats. Presented at the Canadian Urological Association Meeting June 2016. Vancouver, BC.Google Scholar
  23. 23.
    Punjani N, Campbell JD, De, Young L, Radomski S, Alzubaidi R, Gros R, Brock GB. An evolving hypohesis on the mechanism and efficacy of intracavernosal injection of Botulinum toxin to improve erectile function: an animal study in aging rats. Presented at the World Congress of Sexual Health February 2018. Lisbon, Portugal.Google Scholar
  24. 24.
    • Fode M, Hatzichristodoulou G, Serefoglu EC, Verze P, Albersen M, Group YAUMsH. Low-intensity shockwave therapy for erectile dysfunction: is the evidence strong enough? Nat Rev Urol. 2017;14(10):593–606. Review of Li-ESWT. CrossRefPubMedGoogle Scholar
  25. 25.
    Vardi Y, Appel B, Jacob G, Massarwi O, Gruenwald I. Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction. Eur Urol. 2010;58(2):243–8. Scholar
  26. 26.
    Gruenwald I, Appel B, Vardi Y. Low-intensity extracorporeal shock wave therapy—a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med. 2012;9(1):259–64. Scholar
  27. 27.
    Man L, Li G. Low-intensity extracorporeal shock wave therapy for erectile dysfunction: a systematic review and meta-analysis. Urology. 2017;
  28. 28.
    Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity extracorporeal shock wave treatment improves erectile function: a systematic review and meta-analysis. Eur Urol. 2017;71(2):223–33. Scholar
  29. 29.
    Clavijo RI, Kohn TP, Kohn JR, Ramasamy R. Effects of low-intensity extracorporeal shockwave therapy on erectile dysfunction: a systematic review and meta-analysis. J Sex Med. 2017;14(1):27–35. Scholar
  30. 30.
    Zou ZJ, Tang LY, Liu ZH, Liang JY, Zhang RC, Wang YJ, et al. Short-term efficacy and safety of low-intensity extracorporeal shock wave therapy in erectile dysfunction: a systematic review and meta-analysis. Int Braz J Urol. 2017;43(5):805–21. Scholar
  31. 31.
    • Kitrey ND, Vardi Y, Appel B, Shechter A, Massarwi O, Abu-Ghanem Y, et al. Low intensity shock wave treatment for erectile dysfunction: how long does the effect last? J Urol. 2018; Long-term outcome data for Li-ESWT.
  32. 32.
    Segal RL, Tajkarimi K, Burnett AL. Viberect penile vibratory stimulation system: evaluation of its erectogenic efficacy. Can J Urol. 2013;20(4):6844–7.PubMedGoogle Scholar
  33. 33.
    Clavell Hernandez J, Wu Q, Zhou X, Nguyen JN, Davis JW, Wang R. Penile vibratory stimulation in penile rehabilitation after radical prostatectomy: a randomized controlled trial. Presented at the World Congress of Sexual Medicine 2018, Lisbon, Portugal MP-319.Google Scholar
  34. 34.
    Hakim L, Van der Aa F, Bivalacqua TJ, Hedlund P, Albersen M. Emerging tools for erectile dysfunction: a role for regenerative medicine. Nat Rev Urol. 2012;9(9):520–36. Scholar
  35. 35.
    Albersen M, Weyne E, Bivalacqua TJ. Stem cell therapy for erectile dysfunction: progress and future directions. Sex Med Rev. 2013;1(1):50–64. Scholar
  36. 36.
    Albersen M, Lin CS, Lue T. Stem-cell therapy for erectile dysfunction. Arab J Urol. 2013;11(3):237–44. Scholar
  37. 37.
    Soebadi MA, Milenkovic U, Weyne E, Castiglione F, Albersen M. Stem cells in male sexual dysfunction: are we getting somewhere? Sex Med Rev. 2017;5(2):222–35. Scholar
  38. 38.
    • Matz EL, Terlecki R, Zhang Y, Jackson J, Atala A. Stem cell therapy for erectile dysfunction. Sex Med Rev. 2018; Extensive review of SCT in ED.
  39. 39.
    Kendirci M, Trost L, Bakondi B, Whitney MJ, Hellstrom WJ, Spees JL. Transplantation of nonhematopoietic adult bone marrow stem/progenitor cells isolated by p75 nerve growth factor receptor into the penis rescues erectile function in a rat model of cavernous nerve injury. J Urol. 2010;184(4):1560–6. Scholar
  40. 40.
    Bivalacqua TJ, Deng W, Kendirci M, Usta MF, Robinson C, Taylor BK, et al. Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol. 2007;292(3):H1278–90. Scholar
  41. 41.
    Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin CS, et al. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int. 2004;94(6):904–9. Scholar
  42. 42.
    Bahk JY, Jung JH, Han H, Min SK, Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010;8(2):150–60.PubMedGoogle Scholar
  43. 43.
    Levy JA, Marchand M, Iorio L, Cassini W, Zahalsky MP. Determining the feasibility of managing erectile dysfunction in humans with placental-derived stem cells. J Am Osteopath Assoc. 2016;116(1):e1–5. Scholar
  44. 44.
    Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, et al. Safety and potential effect of a single intracavernous injection of autologous adipose-derived regenerative cells in patients with erectile dysfunction following radical prostatectomy: an open-label phase I clinical trial. EBioMedicine. 2016;5:204–10. Scholar
  45. 45.
    • Yiou R, Hamidou L, Birebent B, Bitari D, Lecorvoisier P, Contremoulins I, et al. Safety of intracavernous bone marrow-mononuclear cells for postradical prostatectomy erectile dysfunction: an open dose-escalation pilot study. Eur Urol. 2016;69(6):988–91. Most rigorously performed human trial of SCT for ED. CrossRefPubMedGoogle Scholar
  46. 46.
    Campbell JD, Burnett AL. Neuroprotective and nerve regenerative approaches for treatment of erectile dysfunction after cavernous nerve injury. Int J Mol Sci. 2017;18(8)
  47. 47.
    Oottamasathien S, Hotaling JM, Craig JR, Myers JB, Brant WO. Amniotic therapeutic biomaterials in urology: current and future applications. Transl Androl Urol. 2017;6(5):943–50. Scholar
  48. 48.
    Lei J, Priddy LB, Lim JJ, Massee M, Koob TJ. Identification of extracellular matrix components and biological factors in micronized dehydrated human amnion/chorion membrane. Adv Wound Care (New Rochelle). 2017;6(2):43–53. Scholar
  49. 49.
    Patel VR, Samavedi S, Bates AS, Kumar A, Coelho R, Rocco B, et al. Dehydrated human amnion/chorion membrane allograft nerve wrap around the prostatic neurovascular bundle accelerates early return to continence and potency following robot-assisted radical prostatectomy: propensity score-matched analysis. Eur Urol. 2015;67(6):977–80. Scholar
  50. 50.
    • Ogaya-Pinies G, Palayapalam-Ganapathi H, Rogers T, Hernandez-Cardona E, Rocco B, Coelho RF, et al. Can dehydrated human amnion/chorion membrane accelerate the return to potency after a nerve-sparing robotic-assisted radical prostatectomy? Propensity score-matched analysis. J Robot Surg. 2017; Large human trial using dHACM during radical prostatectomy.
  51. 51.
    Epifanova MV, Chalyi ME, Krasnov AO. Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction. Urologiia. 2017;(4):46–8.Google Scholar
  52. 52.
    Ding XG, Li SW, Zheng XM, Hu LQ, Hu WL, Luo Y. The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model. Asian J Androl. 2009;11(2):215–21. Scholar
  53. 53.
    Wu CC, Wu YN, Ho HO, Chen KC, Sheu MT, Chiang HS. The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med. 2012;9(11):2838–48. Scholar
  54. 54.
    Wu YN, Wu CC, Sheu MT, Chen KC, Ho HO, Chiang HS. Optimization of platelet-rich plasma and its effects on the recovery of erectile function after bilateral cavernous nerve injury in a rat model. J Tissue Eng Regen Med. 2016;10(10):E294–304. Scholar
  55. 55.
    Matz EL, Pearlman AM, Terlecki RP. Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions. Investig Clin Urol. 2018;59(1):61–5. Scholar
  56. 56.
    Levine LA, Becher E, Bella A, Brant W, Kohler T, Martinez-Salamanca JI, et al. Penile prosthesis surgery: current recommendations from the international consultation on sexual medicine. J Sex Med. 2016;13(4):489–518. Scholar
  57. 57.
    McVary A CA, Le B. Induction of novel shape memory alloy penile prosthesis. World Congress of Sexual Medicine; Lisbon, Portugal.February 2018.Google Scholar
  58. 58.
    • SMSNA Position Statement on Restorative Therapies for ED. 2018. Accessed may 2, 2018. Current SMSNA position for restorative therapies for ED.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jeffrey D. Campbell
    • 1
    Email author
  • Uros Milenkovic
    • 2
  • Maarten Albersen
    • 2
  • Trinity J. Bivalacqua
    • 1
  1. 1.The James Buchanan Brady Urological Institute and Department of Urologythe Johns Hopkins School of MedicineBaltimoreUSA
  2. 2.Laboratory of Experimental Urology, Department of Development and RegenerationCatholic University of LeuvenLeuvenBelgium

Personalised recommendations