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Low intensity shockwave therapy in combination with phosphodiesterase-5 inhibitors is an effective and safe treatment option in patients with vasculogenic ED who are PDE5i non-responders: a multicenter single-arm clinical trial

International Journal of Impotence Research volume 33, pages 634–640 (2021)Cite this article

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Abstract

Low-intensity shockwave therapy (Li-ESWT) has been shown to be an effective and safe treatment for vasculogenic erectile dysfunction (ED). We aim to evaluate the effectiveness and safety of LiESWT in treating patients affected from vasculogenic ED who did not respond to oral treatment with Phosphodiesterase 5 inhibitors (PDE5-i). It is a multicentric open-label prospective study, in a cohort of patients non-responders to PDE-5i. Li-ESWT was performed in an outpatient setting by using the following schedule: 3000 shockwaves with an energy of 0.25 mJ/mm2 and a frequency of 4–6 Hz, twice a week for 3 weeks. International Index of Erectile Function, Erection Hardness Score and Sexual Quality of Life-Male questionnaires, and penile doppler ultrasound (PDU) are the outcome measurements. The Student t-test or Wilcoxon signed-rank test were applied to compare variables, with results considered statistically significant at p < 0.05. 106 (97.2%) completed treatment and performed follow-up visit after 4 weeks. At follow up visit, the mean IIEF-EF increased by 8.6 points (13.47 ± 4.61 vs 22.07 ± 5.27; p < 0.0001). A clinically significant improvement of IIEF-EF was achieved in 75 patients (70.7%). An EHS score ≥ 3, sufficient for a full intercourse, was reported by 72 patients (67.9%) at follow-up visit. 37 (34.9%) patients reported a full rigid penis (EHS = 4) after treatment. Li-ESWT treatment was also able to improve quality of life (SQOL-M: 45.56 ± 8.00 vs 55.31 ± 9.56; p < 0.0001). Li-ESWT significantly increased mean PSV (27.79 ± 5.50 vs 41.66 ± 8.59; p < 0.0001) and decreased mean EDV (5.66 ± 2.03 vs 1.93 ± 2.11; p < 0.0001) in PDU. Combination of Li-ESWT and PDE5-i represents an effective and safe treatment for patients affected from ED who do not respond to first line oral therapy.

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Fig. 1: Study Schedule.

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References

  1. 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.

    Article  CAS  Google Scholar 

  2. Dong JY, Zhang YH, Qin LQ. Erectile dysfunction and risk of cardiovascular disease: meta-321 analysis of prospective cohort studies. J Am Coll Cardiol. 2011;58:1378.

    Article  Google Scholar 

  3. Raheem OA, Su JJ, Wilson JR, Hsieh TC. The Association of Erectile Dysfunction and Cardiovascular Disease: a systematic critical review. Am J Mens Health 2017;11:552–63.

    Article  Google Scholar 

  4. Hatzimouratidis K, Giuliano F, Moncada I, Muneer A, Salonia A, Verze P, Guidelines on male sexual dysfunction. Edition presented at the EAU Annual Congress Barcelona. EAU Guidelines Office, Arnhem, The Netherlands, 2019.

  5. Hatzimouratidis K, Hatzichristou DG. A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs. 2005;65:1621–50.

    Article  CAS  Google Scholar 

  6. Gruenwald I, Shenfeld O, Chen J, Raviv G, Richter S, Cohen A, et al. Positive effect of counseling and dose adjustment in patients with erectile dysfunction who failed treatment with sildenafil. Eur Urol. 2006;50:134–40.

    Article  Google Scholar 

  7. Hatzimouratidis K, Moysidis K, Bekos A, Tsimtsiou Z, Ioannidis E, Hatzichristou D. Treatment strategy for “nonresponders” to tadalafil and vardenafil: a real-life study. Eur Urol. 2006;50:126–32.

    Article  CAS  Google Scholar 

  8. Arcaniolo, D, Autorino, R, Balsamo, R, De Sio, M. Optimum use of second line treatment option for erectile dysfunction. Pract Tips Urol. 2016;157–77. https://doi.org/10.1007/978-1-4471-4348-2_17.

  9. 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;9:259–64.

    Article  Google Scholar 

  10. Fode M, Hatzichristodoulou G, Serefoglu EC, Verze P, Albersen M. Low-intensity shockwave therapy for erectile dysfunction: is the evidence strong enough? Nat Rev Urol. 2017;14:593–606.

    Article  CAS  Google Scholar 

  11. Olsen AB, Persiani M, Boie S, Hanna M, Lund L. Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction? A prospective, randomized, double-blind, placebo-controlled study. Scand J Urol. 2015;49:329–33.

    Article  Google Scholar 

  12. Sokolakis I, Hatzichristodoulou G. Clinical studies on low intensity extracorporeal shockwave therapy for erectile dysfunction: a systematic review and meta-analysis of randomised controlled trials. Int J Impot Res. 2019;31:177–94.

    Article  Google Scholar 

  13. Sokolakis I, Dimitriadis F, Teo P, Hatzichristodoulou G, Hatzichristou D, Giuliano F. The basic science behind low-intensity extracorporeal shockwave therapy for erectile dysfunction: a systematic scoping review of pre-clinical studies. J Sex Med. 2019;16:168–94.

    Article  Google Scholar 

  14. Fisher AB, Chien S, Barakat AI, Nerem RM. Endothelial cellular response to altered shear stress. Am J Physiol Lung Cell Mol Physiol. 2001;281:L529–33.

    Article  CAS  Google Scholar 

  15. Liu T, Shindel AW, Lin G, Lue TF. Cellular signaling pathways modulated by low-intensity 355 extracorporeal shock wave therapy. Int J Impot Res. 2019;31:170–6.

    Article  CAS  Google Scholar 

  16. Kitrey ND, Vardi Y, Appel B, Shechter A, Massarwi O, Abu-Ghanem Y, et al. Penile low intensity 357 shock wave treatment is able to shift PDE5i nonresponders to responders: a double-blind, sham controlled study. J Urol. 2016;195:1550.

    Article  Google Scholar 

  17. Bechara A, Casabé A, De Bonis W, Ciciclia PG. Twelve-month efficacy and safety of low intensity shockwave therapy for erectile dysfunction in patients who do not respond to phosphodiesterase type 5 inhibitors. Sex Med. 2016;4:e225.

    Article  Google Scholar 

  18. Tsai CC, Wang CJ, Lee YC, Kuo YT, Lin HH, Li CC, et al. Low-intensity extracorporeal shockwave therapy can improve erectile function in patients who failed to respond to phosphodiesterase type 5 inhibitors. Am J Mens Health. 2017;11:1781–90.

    Article  Google Scholar 

  19. Patel P, Fode M, Lue T, Ramasamy R. Should low-intensity extracorporeal shockwave therapy be the first-line erectile dysfunction treatment for nonresponders to phosphodiesterase type 5 inhibition? Eur Urol Focus. 2019;5:526–8.

  20. 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;49:822–30.

    Article  CAS  Google Scholar 

  21. 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;54:346–51.

    Article  CAS  Google Scholar 

  22. Mulhall JP, Goldstein I, Bushmakin AG, Cappelleri JC, Hvidsten K. Validation of the erection hardness score. J Sex Med. 2007;4:1626–34.

    Article  Google Scholar 

  23. Abraham L, Symonds T, Morris MF. Psychometric validation of a sexual quality of life questionnaire for use in men with premature ejaculation or erectile dysfunction. J Sex Med. 2008;5:595–601.

    Article  Google Scholar 

  24. Sikka SC, Hellstrom WJ, Brock G, Morales AM. Standardization of vascular assessment of erectile dysfunction: standard operating procedures for duplex ultrasound. J Sex Med. 2013;10:120.

    Article  Google Scholar 

  25. Chung E, Cartmill R. Evaluation of clinical efficacy, safety and patient satisfaction rate after low intensity extracorporeal shockwave therapy for the treatment of male erectile dysfunction: an Australian first open-label single-arm prospective clinical trial. BJU Int. 2015;115(Suppl 5):S46–9.

    Article  Google Scholar 

  26. Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol. 2011;60:1010.

    Article  Google Scholar 

  27. Hatzichristou DG. Sildenafil citrate: lessons learned from 3 years of clinical experience. Int J Impot Res. 2002;14(Suppl 1):S43–52.

    Article  Google Scholar 

  28. Lakin MM, Montague DK, VanderBrug Medendorp S, Tesar L, Schover LR. Intracavernous injection therapy: analysis of results and complications. J Urol. 1990;143:1138–41.

    Article  CAS  Google Scholar 

  29. Yuan J, Hoang AN, Romero CA, Lin H, Dai Y, Wang R. Vacuum therapy in erectile dysfunction—science and clinical evidence. Int J Impot Res. 2010;22:211–9.

    Article  CAS  Google Scholar 

  30. 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;58:243–8.

    Article  Google Scholar 

  31. 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;71:223–33.

    Article  Google Scholar 

  32. Kalyvianakis D, Memmos E, Mykoniatis I, Kapoteli P, Memmos D, Hatzichristou D. Low-intensity shockwave therapy for erectile dysfunction: a randomized clinical trial comparing 2 treatment protocols and the impact of repeating treatment. J Sex Med. 2018;15:334–45.

    Article  Google Scholar 

  33. Fojecki GL, Tiessen S, Osther PJS. Effect of linear low-intensity extracorporeal shockwave therapy for erectile dysfunction-12-month follow-up of a randomized, double-blinded, sham-controlled study. Sex Med. 2018;6:1–7.

    Article  Google Scholar 

  34. Kalyvianakis D, Hatzichristou D. Low-intensity shockwave therapy improves hemodynamic parameters in patients with vasculogenic erectile dysfunction: a triplex ultrasonography-based sham-controlled trial. J Sex Med. 2017;14:891–7.

    Article  Google Scholar 

  35. La Vignera S, Calogero AE, Cannizzaro MA, Condorelli R, Noto Z, Vicari E. Tadalafil and modifications in peak systolic velocity (Doppler spectrum dynamic analysis) in the cavernosal arteries of patients with type 2 diabetes after continuous tadalafil treatment. Minerva Endocrinol. 2006;31:251–61.

    PubMed  Google Scholar 

  36. Xuan XJ, Bai G, Zhang CX, Xu C, Lu FD, Peng Y, et al. The application of color Doppler flow imaging in the diagnosis and therapeutic effect evaluation of erectile dysfunction. Asian J Androl. 2016;18:118–22.

    Article  CAS  Google Scholar 

  37. 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;200:167–70.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Urology, University Federico II, Naples, Italy

    Alessandro Palmieri & Paolo Verze

  2. Department of Urology, University Vanvitelli, Naples, Italy

    Davide Arcaniolo

  3. San Giacomo Hospital, Monopoli, Bari, Italy

    Fabrizio Palumbo

  4. Department of Urology, University of Trieste, Trieste, Italy

    Giovanni Liguori

  5. Urology Unit, Nuovo San Giovanni di Dio Hospital, Florence, Italy

    Nicola Mondaini

  6. Department of Urology, University of Turin, Turin, Italy

    Marco Falcone

  7. Urology Unit, Ospedale di Circolo di Varese, Varese, Italy

    Fabrizio Idelfonso Scroppo

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

    Andrea Salonia

  9. Department of Urology, Santa Chiara Regional Hospital, Trento, Italy

    Tommaso Cai

  10. Department of Urology, University of Florence, Florence, Italy

    Andrea Cocci

  11. Department of Urology, University Vanvitelli, Naples, Italy

    Marco De Sio

  12. Urology Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy

    Danilo Di Trapani

  13. S. Giovanni Calibita Fatebenefratelli, Rome, Italy

    Attilio Guerani

  14. Villa Sofia—CTO Hospital, Palermo, Italy

    Emilio Italiano

  15. Urology Unit, Ospedale di Circolo di Varese, Varese, Italy

    Francesco Marone

  16. Department of Urology, Santa Chiara Regional Hospital, Trento, Italy

    Irene Tamanini

  17. Department of Urology, University of Turin, Turin, Italy

    Massimiliano Timpano

  18. Department of Urology, University of Perugia, Perugia, Italy

    Alessandro Zucchi

Authors
  1. Alessandro Palmieri
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  2. Davide Arcaniolo
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  4. Paolo Verze
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Consortia

SIA-Low intensity shock wave for Erectile Dysfunction (LED) Study Group

  • Andrea Cocci
  • , Marco De Sio
  • , Danilo Di Trapani
  • , Attilio Guerani
  • , Emilio Italiano
  • , Francesco Marone
  • , Irene Tamanini
  • , Massimiliano Timpano
  •  & Alessandro Zucchi

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Correspondence to Tommaso Cai.

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A list of SIA-Low intensity shock wave for Erectile Dysfunction (LED) Study Group members and their affiliations appears at the end of the paper.

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Palmieri, A., Arcaniolo, D., Palumbo, F. et al. Low intensity shockwave therapy in combination with phosphodiesterase-5 inhibitors is an effective and safe treatment option in patients with vasculogenic ED who are PDE5i non-responders: a multicenter single-arm clinical trial. Int J Impot Res 33, 634–640 (2021). https://doi.org/10.1038/s41443-020-0332-7

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