Letter to the Editor

Reply to Zi-Jun Zou, Jia-Yu Liang, Yi-Ping Lu's Letter to the Editor re: Zhihua Lu, Guiting Lin, Amanda Reed-Maldonado, Chunxi Wang, Yung-Chin Lee, Tom. F. Lue. Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis. Eur Urol. In press.

By: Zhihua Lua b, Guiting Lina, Amanda Reed-Maldonadoa, Chunxi Wangb, Yung-Chin Leec and Tom F. Luea

European Urology, Volume 71 Issue 2, February 2017, Pages e59-e60

Published online: 01 February 2017

Abstract Full Text Full Text PDF (155 KB)

Refers to article:

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

Zhihua Lu, Guiting Lin, Amanda Reed-Maldonado, Chunxi Wang, Yung-Chin Lee and Tom F. Lue

Accepted 31 May 2016

February 2017 (Vol. 71, Issue 2, pages 223 - 233)

Refers to article:

Re: Zhihua Lu, Guiting Lin, Amanda Reed-Maldonado, Chunxi Wang, Yung-Chin Lee, Tom F. Lue. Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis. Eur Urol 2017;71:223–33

Zi-Jun Zou, Jia-Yu Liang and Yi-Ping Lu

Accepted 8 August 2016

February 2017 (Vol. 71, Issue 2, pages e57 - e58)

Years of extensive clinical experience in treating thousands of patients with erectile dysfunction (ED), Peyronie's disease (PD), and ED with PD has led us to a thorough understanding of the symptoms, categories, and contributing factors for each of these diseases. To define which subtype of penile functional disease responds best to low-intensity extracorporeal shock wave therapy (LI-ESWT) was not the purpose of this meta-analysis [1]. The purpose of this meta-analysis was to evaluate the currently available clinical trials of LI-ESWT for ED to determine whether or not LI-ESWT improves penile function. In this meta-analysis, we intentionally included all etiologies of ED to determine whether LI-ESWT affects all ED, not just vasculogenic ED.

We showed in animal studies that LI-ESWT increases vascularity, increases the number of progenitor cells in the tissue, and promotes nerve regeneration [2] and [3]. In their correspondence, Zou et al simplified the mechanism of LI-ESWT as being exclusively vasculogenic, which we have established as inaccurate. These authors expressed concerns about our inclusion of the study by Zimmermann et al (reference 14 [1]) in our meta-analysis. Based on our extensive research and understanding of the mechanisms of LI-ESWT, we believe that it is logical that LI-ESWT would improve erectile function in ED associated with both PD and chronic pelvic pain syndrome. We included the study by Zimmermann et al in our meta-analysis [1] because those authors showed that application of LI-ESWT to remote sites may improve penile erectile function. This was unique in that all other studies applied LI-ESWT directly to the penis. We feel that this is a very important distinction that makes this article valuable to our understanding of the clinical impacts of LI-ESWT.

Zou et al also raised concerns about heterogeneity among the studies included in our meta-analysis [1]. We realize there was heterogeneity. There are relatively few studies using LI-ESWT for ED, and the available studies have small sample sizes and heterogeneous populations. Clinical and methodological diversity always occurs in a meta-analysis. As such, we used specific types of statistical analyses to determine the extent to which the results of studies are consistent. We also adopted subgroup analysis to reduce the influence of heterogeneity on the conclusions. We divided the studies into different subgroups according to the patient characteristics provided. We separated the studies into three groups according to the International Index of Erectile Function score for ED (Fig. 3c in our meta-analysis [1]), as the severity of ED may affect the therapeutic effect of LI-ESWT. We also divided the studies into two groups according to different ED etiologies: ED (ED only) and ED plus PD (Fig. 3d in meta-analysis [1]). We agree that outcomes of LI-ESWT may differ depending on the etiology of the ED, and more well-designed randomized clinical trials are needed to clarify this issue, but this was not the purpose of our meta-analysis, nor could this be accomplished through meta-analysis at the current time due to the aforementioned limitations in the available research [4]. The heterogeneity between the studies could not be avoided completely, as many factors, alone or in combination, may contribute to ED, such as older age, hypertension, diabetes, hyperlipidemia, neurologic diseases, and coronary artery disease. Currently, the practical way to decrease the heterogeneity is to use subgroup analysis to reduce confounders, as we did.

Because LI-ESWT is a new technology for ED, randomized controlled trials are limited. Therefore, the major aim of this meta-analysis [1] was to present current data about LI-ESWT for ED, to stimulate more research, and to encourage scientists and clinicians to design high-quality clinical trials that will help identify the real benefits of LI-ESWT and the ideal patient population for treatment.

We caution health care providers that treatment protocols for LI-ESWT are not standardized, and much additional research is needed before LI-ESWT becomes the standard of care.

Conflicts of interest

Tom F. Lue is a consultant for Pfizer, Eli Lilly, and Boston Scientific and chief medical officer and stock holder for AWCT, Inc.

Funding support: This work was supported by the US Army, Navy, Air Force, Department of Veterans Affairs and Office of Health Affairs to support the AFIRM II effort under award W81XWH-13- 2-0052. The US Army Medical Research Acquisition Activity (820 Chandler Street, Fort Detrick, MD 21702-5014, USA) is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Department of Defense.


  • [1] Z. Lu, G. Lin, A. Reed-Maldonado, C. Wang, Y.C. Lee, T.F. Lue. Low-intensity extracorporeal shock wave treatment improves erectile function: a systematic review and meta-analysis. Eur Urol. 2017;71:223-233
  • [2] X. Qiu, G. Lin, Z. Xin, et al. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med. 2013;10:738-746 Crossref
  • [3] H. Li, M.P. Matheu, F. Sun, et al. Low-energy shock wave therapy ameliorates erectile dysfunction in a pelvic neurovascular injuries rat model. J Sex Med. 2016;13:22-32
  • [4] D. Hatzichristou. Low-intensity extracorporeal shock waves therapy (LI-ESWT) for the treatment of erectile dysfunction: where do we stand?. Eur Urol. 2017;71:234-236


a Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA

b Department of Urology, The First Hospital of Jilin University, Changchun, People's Republic of China

c Department of Urology, Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Corresponding author. Department of Urology, University of California, San Francisco, 400 Parnassus Ave., Suite A-630, San Francisco, CA 94143-0738, USA. Tel. +1 415 353 7339; Fax: +1 415 476 3803.

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