Should Low-intensity Extracorporeal Shockwave Therapy Be the First-line Erectile Dysfunction Treatment for Nonresponders to Phosphodiesterase Type 5 Inhibition?
Low-intensity extracorporeal shockwave therapy (LI-ESWT) aims to reverse the underlying aberrant mechanisms that lead to the development of erectile dysfunction (ED) and is unlike other commonly used treatment options such as intracavernosal injection (ICI) and phosphodiesterase type 5 inhibitor (PDE-5i) agents. Therefore, there is substantial interest in this novel treatment modality. In this Clinical Consultation Guide we discuss the evidence for LI-ESWT as first-line therapy for PDE-5i nonresponders.
When considering which patients fall under the umbrella of PDE-5i nonresponders, it is important to recognize that this definition includes a heterogeneous group of men. A 72-year-old diabetic male who has been unresponsive to PDE-5i therapy for several years is different to a 55-year-old male who responds partially to PDE-5i therapy but is unable to have penetrative intercourse. It is therefore essential to consider baseline erectile function as well as patient expectations before treatment. Furthermore, proper counseling regarding optimizing PDE-5i therapy is important to truly consider a patient nonresponsive. Optimization of PDE-5i treatment entails applying sexual stimulation for appropriate nitric oxide release, reducing food intake (which may impair drug absorption), dose escalation as necessary, and repeated attempts. All four currently approved PDE-5i agents have demonstrated equivalent efficacy; however, given that various agents cross-react to other PDE-i drugs, this may lead to a varying side-effect profile and therefore switching agents may be warranted in cases of adverse reactions.
Classical shockwaves are characterized by high peak pressure (100 mPa or higher), a rapid pressure rise (<10 ns), a short duration (<10 ms), and a wide frequency range. Shockwaves used for biomedical purposes are generated in a fluid medium using an electrohydraulic, piezoelectric, or electromagnetic generator. The shockwaves generated are then directed to the target with or without a focusing unit. The effects of LI-ESWT seem to be tissue-dependent and disease-dependent. In animal studies, various effects of LI-ESWT were noted in different animal models of ED. In an animal model of diabetic ED with lower levels of endothelium, smooth muscle, and nNOS nerves, LI-ESWT significantly ameliorated these harmful effects from diabetes and improved nerve-stimulated intracavernous pressure [1]. In an animal model of severe injury to cavernous and pudendal nerves and internal pudendal arteries, LI-ESWT improved intracavernous pressure by enhancing angiogenesis, tissue restoration, and nerve regeneration with activation of Schwann cells and endothelial cells [2]. In an animal model of obesity-associated ED with smooth muscle atrophy, endothelial dysfunction, and lipid accumulation within the corpus cavernosum, LI-ESWT restored penile hemodynamic parameters in obese rats by restoring smooth muscle and endothelium content and reducing lipid accumulation [3]. The mechanism underlying the effect of LI-ESWT appears to be activation of resident stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration [4].
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