Low-intensity extracorporeal shockwave therapy (Li-ESWT) is thought to treat erectile dysfunction (ED) by stimulating neovascularization and nerve regeneration as demonstrated in animal models by histologically increased angiogenesis and neuronal-related growth factors, though corresponding human studies are limited.
We hypothesized that Li-ESWT results in appreciable increases in growth factors in human tissues, and in this proof-of-concept study we aimed to determine whether markers for neovascularization and nerve regeneration can be detected in the corporal blood of men following Li-ESWT treatment.
Patients were prospectively enrolled in a clinical trial of Li-ESWT for ED. Patients received 12 bi-weekly Li-ESWT treatments of 0.2 mJ/mm2 at 5 Hz, 1500 shocks delivered per treatment, with follow up at 1-2 weeks, 4-6 weeks, 3 months, and 6 months post-treatment. Cavernosal penile blood samples were obtained prior to treatment and at each visit post-treatment. The concentrations of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and brain-derived neurotropic factor (BDNF) in penile plasma samples were measured using enzyme-linked immunosorbent assay with specific commercial kits, following the protocols provided by the manufacturer.
eNOS, nNOS, VEGF, and BDNF were detectable and demonstrated changes in cavernosal plasma samples following Li-ESWT treatment.
Twenty-five patients completed all five study visits. Mean patient age was 63. Mean baseline International Index of Erectile Function-Erectile Function score prior to treatment was 14.24 (±1.21). Corporal plasma samples were analyzed for eNOS, nNOS, VEGF, and BDNF using the enzyme-linked immunosorbent assay. Levels of eNOS, nNOS, and VEGF showed an upward trend following treatment but did not reach significance. BDNF levels were noted to decrease.
Corporal blood aspirates may function as surrogates for histological studies to understand effects of Li-ESWT at the tissue level in humans.
To our knowledge, this is first the molecular study in human tissues to attempt to quantify neurogenesis and neovascularization in penile tissue following Li-ESWT for ED. Although our sample size is small, we believe this represents a promising first step in understanding the effect of Li-ESWT at a tissue level in men.
The clinical significance of our findings is currently unknown, but markers of neovascularization and neurogenesis are detectable in corporal plasma and may change following Li-ESWT. ClinicalTrials.gov ID NCT04720755.
Sexual medicine. 2026 Jan 22*** epublish ***
Skye Coffey, Vy Nguyen, Ashley N Matthew, Bridget S Kastelberg, Maria E Teves, Mina Ghatas, Adam P Klausner, Ryan P Smith, Sarah C Krzastek
School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States., Department of Urology, Virginia Commonwealth University, Richmond, VA 23298, United States., Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, United States., Department of Urology, University of Virginia, Charlottesville, VA 22309, United States.