Celik M. et al., 2026: Evaluation of cavernosal oxidative biomarkers following radial Li-ESWT in vasculogenic erectile dysfunction.

Celik M, Polat ME, Ceviz K, Arabaci B, Boyaci Lİ, Ölcucuoglu E, Neselioglu S, Erel O, Yeni E
World J Urol. 2026 Jun 23;44(1):451. doi: 10.1007/s00345-026-06560-5

Abstract

Purpose: Vasculogenic erectile dysfunction (ED) is associated with endothelial dysfunction and oxidative stress. This study evaluated the clinical efficacy of radial-type low-intensity extracorporeal shockwave therapy (Li-ESWT) and its effects on cavernosal oxidative stress biomarkers.

Methods: In this prospective study, 48 men with vasculogenic ED underwent 12 sessions of radial-type Li-ESWT. Erectile function was assessed at baseline, 1 month, and 6 months using the International Index of Erectile Function-Erectile Function domain (IIEF-EF) and Erection Hardness Score (EHS). Cavernosal blood samples were collected before treatment and one week after completion to measure superoxide dismutase (SOD), ischemia-modified albumin (IMA), thiol-disulfide homeostasis, and glutathione redox status.

Results: At 6 months, 43.8% of patients achieved a clinically meaningful improvement in IIEF-EF. Both IIEF-EF and EHS scores improved significantly at 1 and 6 months (p < 0.001). In exploratory multivariable logistic regression analysis, prior PDE5i responsiveness remained independently associated with clinically meaningful improvement (OR 5.59, 95% CI 1.24-25.23; p = 0.025), whereas HbA1c did not retain significance. No significant changes were observed in SOD, IMA, or glutathione redox status. Borderline thiol-disulfide alterations observed in unadjusted analyses did not remain significant after correction for multiple comparisons and were not associated with clinical outcomes.

Conclusion: Radial-type Li-ESWT was associated with clinically meaningful improvements in erectile function in men with vasculogenic ED. However, no robust oxidative biomarker changes were observed in cavernosal blood following treatment.

Comment Jens Rassweiler

Objectives

The study aimed to evaluate two things:

- Clinical efficacy of radial-type low-intensity extracorporeal shockwave therapy in men with vasculogenic erectile dysfunction.

- Biochemical effects of treatment on oxidative stress markers measured directly from cavernosal blood.

Thus, the authors focused on whether Li-ESWT improves erectile function and whether this improvement is accompanied by measurable changes in oxidative stress biomarkers.

Methods

This was a prospective study including 48 men with vasculogenic ED confirmed by penile Doppler ultrasound. All ED medications, including PDE5 inhibitors, were stopped at least one month before treatment and during the early follow-up period.

Patients received 12 sessions of radial-type Li-ESWT (Vibrolith Ortho (ELMED Ltd., Ankara, Turkey) twice weekly. The protocol consisted of: 3 weeks of treatment, a 3-week break, and additional 3 weeks of treatment. Each session included 1,500 shockwaves at 2 Hz with Energy flux density of  0.09 mJ/mm² applied to 5 penile sites: proximal, mid, distal shaft, and both crura.

Outcome Measures

Erectile function was assessed using IIEF-EF domain score and Erection Hardness Score at Baseline, 1 and 6 months after Li-ESWT.

For biochemical outcomes cavernosal blood samples were collected before treatment and one week after completion of treatment. The oxidative stress biomarkers measured included:

• Superoxide dismutase
• Ischemia-modified albumin
• Thiol-disulfide homeostasis
• Glutathione redox status

Results

Clinical efficacy

The study found significant improvement in erectile function after radial Li-ESWT at 6 months:

43.8% of patients achieved clinically meaningful improvement in IIEF-EF score (14,38 to 17,53)  and EHS score (2,00 to 2,57). There was no significant difference between 1-month and 6-month outcomes, suggesting that improvement was maintained during follow-up. These changes were statistically significant.

Predictors of Response

Patients who achieved clinically meaningful improvement were more likely to have been previous responders to PDE5 inhibitors.

HbA1c was lower in responders in univariate analysis, but it did not remain significant after adjustment.

This suggests that patients with preserved PDE5 inhibitor responsiveness may have better underlying endothelial or vascular reserve and may respond more favorably to Li-ESWT.

Oxidative Stress Biomarker Findings

Despite clinical improvement, the study did not find robust biochemical evidence that radial Li-ESWT significantly modified oxidative stress markers in cavernosal blood. No significant changes were observed in:

• Superoxide dismutase
• Ischemia-modified albumin
• Glutathione redox markers

Some borderline changes were seen in thiol-disulfide parameters, including:

• Disulfide/native thiol ratio
• Disulfide/total thiol ratio
• Native thiol/total thiol ratio

However, these findings did not remain statistically significant after correction for multiple comparisons and were not associated with clinical outcomes. Therefore, the authors concluded that the observed erectile improvement was not clearly explained by measurable changes in cavernosal oxidative stress markers.

Discussion

Strengths

A major strength is that oxidative markers were measured from cavernosal blood, not just peripheral blood. This provides a more anatomically relevant assessment of penile oxidative status. The study was conducted prospectively, which improves data consistency and reduces some biases compared with retrospective studies.The authors used well-established erectile function measures.

Limitations

The most important limitation is the absence of a sham-treated control group. This makes it difficult to determine whether the observed clinical improvements were due to:

• True treatment effect
• Placebo effect
• Natural fluctuation in erectile function
• Behavioral changes during study participation

This is especially relevant in ED studies, where placebo responses can be substantial.

Only 48 patients completed the study. This limits statistical power and makes subgroup and regression analyses less reliable. the wide confidence interval for PDE5 inhibitor responsiveness reflects this limitation.

Radial shockwave therapy remains controversial

The device used was radial-type Li-ESWT. Radial pressure wave devices differ from focused or linear shockwave devices because they lack a true focal point and produce different energy characteristics. The literature generally suggests that focused or linear shockwave therapy may have stronger evidence than radial devices. Therefore, the findings should not automatically be generalized to all forms of Li-ESWT. The authors applied 50% of the normally applied shock waves (1500 vs 3000).

Oxidative markers measured only once after treatment

Oxidative stress markers were assessed one week after completion of therapy. It is possible that oxidative changes occur earlier, later, or transiently during treatment.

Repeated sampling during and after therapy might have provided a better picture of oxidative dynamics.

Mechanistic conclusions remain limited

Because oxidative biomarkers did not change significantly, the mechanism of clinical benefit remains uncertain.

Possible alternative mechanisms include:

• Angiogenesis
• Improved endothelial signaling
• Recruitment of progenitor cells
• Neural modulation
• Smooth muscle remodeling
• Placebo-related psychosexual improvement

The study does not directly assess these mechanisms.

Conclusion

This study suggests that radial-type Li-ESWT may improve erectile function in some men with vasculogenic ED, particularly those who previously responded to PDE5 inhibitors.

However, the lack of a sham-control group means the clinical benefit cannot be confidently attributed to the treatment alone.

The biochemical findings are also important. Although oxidative stress is thought to contribute to vasculogenic ED, this study did not show clear evidence that radial Li-ESWT improves erectile function by changing measurable cavernosal oxidative stress markers.

Thus, the study supports possible clinical benefit but does not confirm an oxidative stress-mediated mechanism.

Jens Rassweiler