Evaluation of Cavernosal Oxidative Biomarkers Following Radial Li-ESWT in Vasculogenic Erectile Dysfunction

Radial shockwave therapy improved erectile function in 44% of 48 men with vasculogenic ED, but left cavernosal oxidative stress markers unchanged

Journal: World Journal of Urology | Published: 2026-06-23 | Type: Prospective Study | PMID: 42334469 Authors: Celik M et al. (Ergani State Hospital and Ankara Bilkent City Hospital, Turkey) Funding/COI: Funding not listed; authors declare no conflicts of interest

Summary

Forty-eight men with vasculogenic ED underwent 12 sessions of radial-type low-intensity extracorporeal shockwave therapy (Li-ESWT). Erectile function improved significantly by most measures, but the study's central hypothesis — that Li-ESWT works by reducing cavernosal oxidative stress — found no support. SOD, IMA, glutathione redox status, and thiol-disulfide homeostasis all came back flat. The mechanism, whatever it is, isn't oxidative stress reduction — at least not detectably in cavernosal blood one week after treatment.

Claims

• 43.8% of patients (21/48) achieved clinically meaningful improvement in IIEF-EF at 6 months
• IIEF-EF and Erection Hardness Score (EHS) improved significantly at both 1 and 6 months (p < 0.001)
• Prior PDE5 inhibitor responsiveness independently predicted response to Li-ESWT (OR 5.59, 95% CI 1.24–25.23; p = 0.025) in multivariable logistic regression
• HbA1c (diabetes severity) did not independently predict response
• No significant changes in superoxide dismutase (SOD), ischemia-modified albumin (IMA), or glutathione redox status in cavernosal blood
• Borderline thiol-disulfide changes in unadjusted analyses did not survive correction for multiple comparisons and were not associated with clinical outcomes

Study Quality

Prospective design with three time points (baseline, 1 month, 6 months) and validated outcome measures (IIEF-EF and EHS) is adequate for a pilot-level mechanistic study. Collecting cavernosal blood — rather than peripheral venous blood — to measure oxidative markers is methodologically rigorous; if oxidative changes happen in the corpus cavernosum, this is where you'd see them.

The critical flaw is the absence of a sham control group. Li-ESWT is a non-invasive procedure with a well-documented placebo effect, and roughly 44% improvement in an uncontrolled cohort is clinically uninterpretable without a comparator. The treatment protocol used radial-type (not focused) shockwave delivery, which produces lower energy penetration depth and differs physically from the focused ESWT used in most existing evidence — the authors do not address whether these results are comparable to the focused-device literature.

Red Flags

• No sham or placebo arm. Without a control group, the 43.8% response rate cannot be disentangled from placebo response, regression to the mean, or natural variation
• Radial vs. focused ESWT conflation. Most Li-ESWT evidence is for focused devices; radial devices are physically different. The authors acknowledge this distinction without adequately addressing its implications for generalizability
• Small sample (n = 48). Underpowered for the multivariable regression being attempted
• Biomarker timing. Oxidative markers were measured one week post-treatment. If shockwave-induced mechanotransduction signals are transient, this window may simply be wrong — a null biomarker result doesn't rule out an oxidative mechanism, it only rules out a persistent one
• Funding undisclosed. No manufacturer listed, but absence of disclosure is not the same as absence of support
• Conclusions section appears largely generic, describing animal studies on gene therapy and stem cells unrelated to this paper's scope

Strengths

• Cavernosal blood sampling is methodologically appropriate and underused — most similar studies use peripheral blood
• Multiple oxidative biomarker panels measured simultaneously (SOD, IMA, thiol-disulfide, glutathione)
• Correction for multiple comparisons applied to biomarker analyses — unusual in this literature and scientifically honest
• Multivariable regression identifying prior PDE5i responsiveness as a predictor is a clinically relevant finding that replicates signals from earlier work
• 6-month follow-up with no significant attrition reported

Verdict

This paper asks an interesting mechanistic question — does Li-ESWT work via oxidative stress reduction? — and returns a clean negative answer from a methodologically reasonable measurement site. That honest null finding on mechanism is the most valuable thing here. The clinical efficacy data, however, are nearly uninterpretable without a sham arm: 44% response in 48 unblinded, uncontrolled patients tells you approximately nothing about whether the shockwaves are doing the work. The radial-versus-focused distinction is glossed over, which limits applicability to the broader evidence base. Worth reading for the biomarker methodology; treat the efficacy numbers as hypothesis-generating only.