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Current Sexual Health Reports

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01-09-2018 | Male Sexual Dysfunction and Disorders (AW Pastuszak and NK Gupta, Section Editors)

What Is the Future of Erectile Dysfunction Therapy?

Authors: Jeffrey D. Campbell, Uros Milenkovic, Maarten Albersen, Trinity J. Bivalacqua

Published in: Current Sexual Health Reports | Issue 3/2018

Abstract

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.

Summary

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.

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. https://doi.org/10.1097/01.ju.0000164463.19239.19.CrossRefPubMed

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. https://doi.org/10.5489/cuaj.2699.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1111/j.1743-6109.2009.01601.x.CrossRefPubMed

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. https://doi.org/10.1016/j.eururo.2012.05.046.CrossRefPubMed

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. https://doi.org/10.1111/j.1365-2605.2008.00879.x.CrossRefPubMed

• 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. https://doi.org/10.1111/bju.13582. ProtecT trial patient-report outcome data. CrossRefPubMedPubMedCentral

Ryu JK, Suh JK, Burnett AL. Research in pharmacotherapy for erectile dysfunction. Transl Androl Urol. 2017;6(2):207–15. https://doi.org/10.21037/tau.2016.11.17.CrossRefPubMedPubMedCentral

Hawksworth DJ, Burnett AL. Pharmacotherapeutic management of erectile dysfunction. Clin Pharmacol Ther. 2015;98(6):602–10. https://doi.org/10.1002/cpt.261.CrossRefPubMed

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. https://doi.org/10.1016/j.jsxm.2018.01.023.CrossRefPubMed

10.

Murthy SK. Nanoparticles in modern medicine: state of the art and future challenges. Int J Nanomedicine. 2007;2(2):129–41.PubMedPubMedCentral

11.

Quinn JF, Whittaker MR, Davis TP. Delivering nitric oxide with nanoparticles. J Control Release. 2015;205:190–205. https://doi.org/10.1016/j.jconrel.2015.02.007.CrossRefPubMed

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. https://doi.org/10.1111/j.1743-6109.2009.01507.x.CrossRefPubMed

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. https://doi.org/10.1111/jsm.12705.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1016/j.jsxm.2018.03.009.CrossRefPubMed

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. https://doi.org/10.1111/j.1743-6109.2012.02741.x.CrossRefPubMed

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. https://doi.org/10.1111/and.12309.CrossRefPubMed

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. https://doi.org/10.1038/ijir.2014.24.CrossRefPubMed

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.CrossRefPubMed

19.

Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol. 2014;7(2):31–9.PubMedPubMedCentral

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. https://doi.org/10.1016/j.sxmr.2017.07.008. Review of potential mechanism of action of Botox for ED treatment. CrossRefPubMed

21.

Giuliano F, Brock G. Botox for erectile dysfunction. J Sex Med. 2017;14(2):177–8. https://doi.org/10.1016/j.jsxm.2016.12.229.CrossRefPubMed

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.

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.

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. https://doi.org/10.1038/nrurol.2017.119. Review of Li-ESWT. CrossRefPubMed

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. https://doi.org/10.1016/j.eururo.2010.04.004.CrossRefPubMed

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. https://doi.org/10.1111/j.1743-6109.2011.02498.x.CrossRefPubMed

27.

Man L, Li G. Low-intensity extracorporeal shock wave therapy for erectile dysfunction: a systematic review and meta-analysis. Urology. 2017; https://doi.org/10.1016/j.urology.2017.09.011.

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. https://doi.org/10.1016/j.eururo.2016.05.050.CrossRefPubMed

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. https://doi.org/10.1016/j.jsxm.2016.11.001.CrossRefPubMed

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. https://doi.org/10.1590/S1677-5538.IBJU.2016.0245.CrossRefPubMedPubMedCentral

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; https://doi.org/10.1016/j.juro.2018.02.070. Long-term outcome data for Li-ESWT.

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.PubMed

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.

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. https://doi.org/10.1038/nrurol.2012.143.CrossRefPubMed

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. https://doi.org/10.1002/smrj.5.CrossRefPubMed

36.

Albersen M, Lin CS, Lue T. Stem-cell therapy for erectile dysfunction. Arab J Urol. 2013;11(3):237–44. https://doi.org/10.1016/j.aju.2013.05.005.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1016/j.sxmr.2016.11.002.CrossRefPubMed

38.

• Matz EL, Terlecki R, Zhang Y, Jackson J, Atala A. Stem cell therapy for erectile dysfunction. Sex Med Rev. 2018; https://doi.org/10.1016/j.sxmr.2017.12.008. Extensive review of SCT in ED.

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. https://doi.org/10.1016/j.juro.2010.05.088.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1152/ajpheart.00685.2006.CrossRefPubMed

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. https://doi.org/10.1111/j.1464-410X.2003.05057.x.CrossRefPubMed

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.PubMed

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. https://doi.org/10.7556/jaoa.2016.007.CrossRefPubMed

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. https://doi.org/10.1016/j.ebiom.2016.01.024.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1016/j.eururo.2015.09.026. Most rigorously performed human trial of SCT for ED. CrossRefPubMed

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) https://doi.org/10.3390/ijms18081794.

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. https://doi.org/10.21037/tau.2017.09.01.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1089/wound.2016.0699.CrossRef

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. https://doi.org/10.1016/j.eururo.2015.01.012.CrossRefPubMed

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; https://doi.org/10.1007/s11701-017-0719-8. Large human trial using dHACM during radical prostatectomy.

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.

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. https://doi.org/10.1038/aja.2008.37.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1111/j.1743-6109.2012.02881.x.CrossRefPubMed

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. https://doi.org/10.1002/term.1806.CrossRefPubMed

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. https://doi.org/10.4111/icu.2018.59.1.61.CrossRefPubMed

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. https://doi.org/10.1016/j.jsxm.2016.01.017.CrossRefPubMed

57.

McVary A CA, Le B. Induction of novel shape memory alloy penile prosthesis. World Congress of Sexual Medicine; Lisbon, Portugal.February 2018.

58.

• SMSNA Position Statement on Restorative Therapies for ED. http://www.smsna.org/V1/news/433-smsna-position-statement-on-restorative-therapies-for-ed. 2018. Accessed may 2, 2018. Current SMSNA position for restorative therapies for ED.

Title: What Is the Future of Erectile Dysfunction Therapy?
Authors: Jeffrey D. Campbell
Uros Milenkovic
Maarten Albersen
Trinity J. Bivalacqua
Publication date: 01-09-2018
Publisher: Springer US
Published in: Current Sexual Health Reports / Issue 3/2018
Print ISSN: 1548-3584
Electronic ISSN: 1548-3592
DOI: https://doi.org/10.1007/s11930-018-0153-6

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Springer Medicine

What Is the Future of Erectile Dysfunction Therapy?

Abstract

Purpose of Review

Recent Findings

Summary

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Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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