Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis - Beyond the Abstract

As scientists and clinicians, we must always contemplate the next step in treatment for our patients.  On the horizon for the treatment of erectile dysfunction (ED) is low-intensity extracorporal shock wave treatment (Li-ESWT), also known as low-  energy shock wave therapy or treatment (LESWT). Li-ESWT is rapidly developing into an ostensibly viable treatment option for ED patients. With 14 studies including 833 patients from 2005 to 2015, and multiple ongoing clinical trials, it seems that both clinicians and patients are eager to embrace this technology. 
Despite this overwhelming enthusiasm, several critical questions remain to be answered before the wide-spread application of this treatment modality.  First and foremost, the mode of action still needs to be determined and the safety of treatment established.  Next, the most efficacious settings (energy settings, anatomic targets of treatment, treatment schedule and duration) have yet to be fully ascertained.  Finally, long term surveillance studies are needed to determine the possible adverse effects of LI-ESWT treatment on cell growth and to determine the possible consequences on coexistent subclinical conditions, such as prostate malignancy and benign prostatic hyperplasia. 

Li-ESWT presents a non-invasive method of up-regulating endogenous mesenchymal stem cells (MSC) [1]. Additionally, in a rat model of pelvic neurovascular injury, Li-ESWT-induced endogenous progenitor cell recruitment and Schwann cell activation coincided with angiogenesis, tissue regeneration, and nerve generation  [2]. In human cardiovascular patients, Li-ESWT has demonstrated to have an angiogenesis-promoting effect believed to involve upregulation of vascular endothelial growth factor (VEGF) [3].  Li-ESWT has been shown to markedly improve erectile function in patients with organic ED [4] through down-regulating receptors for advanced glycation end products [5] and through recruitment of endogenous mesenchymal stem cells[6]. 

Proving that physicians are eager for new options for ED patients, Li-ESWT has been discussed, though not endorsed, in the first-line therapy section of the European Association of Urology recommendations for ED (https://uroweb.org/wp-content/uploads/14-Male-Sexual-Dysfunction_LR.pdf).  

By utilizing this non-invasive method, if we are successful, we will be able to potentially mitigate or eliminate the safety and methodological concerns about stem cell acquisition, preparation, and delivery and also reduce or eliminate the need for expensive and invasive medical and surgical therapies for ED in some patients.  As with stem cell therapies, the underlying mechanisms of therapeutic ultrasound and the biological effects it has on the human body remain to be thoroughly investigated, and additional well-designed rigorous studies are needed to further define the mechanism of action, safety profile, and efficacy of treatment. 

Written by: Amanda B Reed-Maldonado, Guiting Lin and Tom F Lue
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.

Bibliography:

1. Xin Z, Lin G, Lei H, Lue TF, Guo Y. Clinical applications of low-intensity pulsed ultrasound and its potential role in urology. Transl Androl Urol. 2016;5(2):255-266.

2. Li H, Matheu MP, Sun F, et al. Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model. J Sex Med. 2016;13(1):22-32.

3. Wang W, Liu H, Song M, Fang W, Yuan F. Clinical Effect of Cardiac Shock Wave Therapy on Myocardial Ischemia in Patients With Ischemic Heart Failure. J Cardiovasc Pharmacol Ther. 2016;21(4):381-387.

4. 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):243-248.

5. Liu J, Zhou F, Li GY, et al. Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats. Int J Mol Sci. 2013;14(5):10661-10673.

6. Qiu X, Lin G, Xin Z, et al. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med. 2013;10(3):738-746.

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