The therapeutic effect and mechanism of low-intensity pulsed ultrasound for erectile dysfunction

As an emerging therapeutic option for erectile dysfunction (ED), low-intensity pulsed ultrasound (LIPUS) has attracted increasing attention. The therapeutic effect of LIPUS is comparable to low-intensity extracorporeal shockwave therapy. However, the underlying mechanism of LIPUS remains unclear. We summarized the current literature to assess the efficacy of LIPUS for ED and elucidate the biological effects caused by LIPUS in different ED models. Preliminary clinical studies demonstrate that LIPUS is beneficial for ED with varying degrees of severity, and its therapeutic effect can be enhanced when combined with phosphodiesterase 5 inhibitors. Basic researches have shown that LIPUS can treat ED resulting from type 1 diabetes mellitus, cavernous nerve injury, or cavernosa injury. The underlying mechanisms involve upregulating endothelial and neuronal nitric oxide synthase expression, increasing smooth muscle and endothelium content, inhibiting cavernosal fibrosis mediated by the transforming growth factor-β1/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β1/Smad/CTGF) pathway, and ameliorating oxidative stress via microtubule-associated protein 1 light chain 3 (LC3)- and Parkin-dependent mitophagy in type 1 diabetic ED. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), activated by LIPUS, contribute to the recovery of neurogenic ED. Furthermore, the survival and secretion function of Schwann cells are improved by LIPUS through activating tropomyosin receptor kinase B/protein kinase B/cyclic adenosine monophosphate-response element-binding protein (TrkB/Akt/CREB) pathway, thereby accelerating cavernous nerve repair. LIPUS is a safe and effective treatment modality for ED, which can restore the pathological changes in corpus cavernosum via multiple pathways. The long-term efficacy of LIPUS needs further investigation.