shockwave- and cell-based regenerative therapies in the treatment of ED

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Abstract: Erectile dysfunction (ED) is both a common and complex disease process. Existing ED treatments do not always achieve adequate results. There is clinical interest in employing regenerative therapies, including low-intensity extracorporeal shockwave therapy (Li-ESWT), platelet-rich plasma (PRP), and stem cell therapy (SCT), in the treatment of ED as an adjunct or alternative treatments. Here, we present evidence for emerging shockwave- and cell-based regenerative therapies for the treatment of ED following a thorough review of the existing PubMed literature pertaining to Li-ESWT, PRP, and SCT in relation to the treatment of ED. Li-ESWT causes microtrauma in tissue that hypothetically upregulates angiogenesis and recruits stem cells. Several large-scale systematic reviews and meta-analyses have reported that Li-ESWT improved ED in humans. Additionally, evidence has commenced showing that Li-ESWT may be effective against two recognized and complex etiologies of ED: diabetic and neurogenic. PRP delivers an autologous sample rich in growth factors to damaged tissue. Animal model studies have demonstrated improved erectile function recovery as well as preservation of cavernous nerve axons. Studies with PRP in humans are limited. SCT utilizes the regenerative potential of stem cells for the healing of damaged tissue. In the treatment of ED, SCT has been used in the setting of diabetic and post-prostatectomy ED. Results of human studies are varied, although SCT treatments did result in increased erectile rigidity with some patients recovering the ability to achieve penetration. While these regenerative therapies show potential to augment the current treatment regimen for ED, there is a paucity of evidence to support the safety and efficacy of these treatments. Further research is necessary to define the role of these alternative therapies in the treatment of ED.





Introduction

Erectile dysfunction (ED) is defined as a man’s continuous (⩾3months) inability to attain and/or maintain a penile erection sufficient for satisfactory sexual intercourse.1
Though a common condition in men over 40years old, evidence suggests increasing prevalence in younger men.2 Many risk factors (e.g., obesity, hypertension) and comorbidities (e.g., cardiovascular) may contribute to the development of ED.3–5 The American Urological Association (AUA) states that the clinical workup for ED should include several constituents, including medical and psychosocial elements.6

Since 1998, phosphodiesterase type 5 inhibitors (PDE5i) have been used as a mainstay of initial treatment for ED.7 Though generally safe for ED treatment, PDE5i may be ineffective or they may have side effects that make them less desirable to certain patients.8,9 Additional treatment options for ED exist, including vacuum erection devices, intracavernosal vasoactive injections, and penile prosthetics.3,10 The AUA states that patients should be informed of all non-contraindicated treatment modalities for ED as potential first-line therapies, regardless of invasiveness or irreversibility.6 Even with multiple treatment options available for ED, some patients continue to have suboptimal outcomes. Therefore, additional treatments are being investigated, including regenerative therapies. Regenerative therapies aim to restore function via replacement or regeneration of human cells, tissues, or organs. Regenerative therapies for the treatment of ED include low-intensity extracorporeal shockwave therapy (Li-ESWT), platelet-rich plasma (PRP), and stem cell therapy (SCT) (Table 1).




*Low-intensity extracorporeal shockwave therapy

*Platelet-rich plasma

*Stem cell therapy




Conclusion


Despite advancements in the understanding of ED, there remains a need for better treatments of this common and often complex condition. Traditional therapies (e.g., lifestyle changes, PDE5i, vacuum erection device, intracavernous vasoactive injections, penile prostheses) are effective, although some patients do not achieve an adequate response to these therapies or are unwilling or unable to undergo such treatment. Novel regenerative therapies have revealed promise as alternative or adjunctive therapies in the treatment of ED. The current body of research to support the use of these methods is limited. In general, these therapies have demonstrated limited side effect profiles, but data on their efficacy is also lacking. Due to this paucity of data, these treatments are not recommended for ED outside of experimental environments. Thus, we recommend these treatments be utilized only for patients with refractory ED who are willing to undergo experimental treatment for their ED. Of the regenerative therapies reviewed herein, Li-ESWT is the treatment with the strongest evidence for its usage. However, additional research highlighting the safety and efficacy of LiESWT, PRP, and SCT is necessary before these regenerative therapies are included in the standard repertoire of ED treatments. It is possible that the further elucidation of the pathophysiology behind ED will allow for clinicopathologically targeted therapies for treatment. This could allow these experimental therapies to be targeted to specific patient populations, such as those with neurogenic or diabetes-associated ED.
 

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Table 1. Shockwave- and cell-based regenerative therapies for ED.
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