Lateralized Veno-Occlusive Dysfunction in Peyronie's Disease: Bilateral Corporal Hemodynamic Discrepancy Revealed by Dynamic Penile Doppler Ultrasonography in Men With and Without Erectile Dysfunction

Technical Summary: Lateralized Veno-Occlusive Dysfunction in Peyronie's Disease

Problem Statement
Peyronie's disease (PD) is a fibroproliferative disorder of the tunica albuginea associated with a significant vascular burden, where erectile dysfunction (ED) affects up to 54% of patients through mechanical and haemodynamic mechanisms. While penile Doppler ultrasonography (PDU) is the reference standard for assessing penile haemodynamics, existing literature has not directly compared bilateral inter-corporal parameters between PD patients with and without ED. Specifically, it remains unknown whether the two corpora cavernosa exhibit asymmetric haemodynamic behavior in PD and whether such discrepancies correlate with ED status or the laterality of penile curvature. Given that PD plaques are anatomically asymmetric (commonly left-sided or dorsal), there is a clinical gap in understanding if ipsilateral fibrosis causes side-specific veno-occlusive impairment.

Methodology
This retrospective cohort study was conducted at a quaternary academic centre in Montreal, Canada, reviewing data from January 2010 to June 2023.

• Cohort: From an initial screen of 208 men with PD, 189 were retained for analysis (102 with ED, 87 without). After exclusions for uninterpretable data, 167 patients (94 with ED, 73 without) underwent haemodynamic analysis.
• Classification: ED was defined using the Sexual Health Inventory for Men (SHIM/IIEF-5) with a cutoff of ≤21, or via treating physician documentation. Doppler parameters were explicitly excluded from ED classification to maintain group independence.
• Protocol: All patients underwent PDU using a high-frequency linear transducer after a standardized intracavernosal injection of 10 µg prostaglandin E1. Measurements were taken bilaterally for Peak Systolic Velocity (PSV), End-Diastolic Velocity (EDV), and Resistive Index (RI) by a single senior operator to eliminate inter-observer variability.
• Statistical Analysis: Continuous variables were reported as medians with interquartile ranges (IQR) and bootstrapped 95% confidence intervals. Between-group comparisons utilized the Mann-Whitney U test, while within-group bilateral symmetry was assessed via the Wilcoxon signed-rank test. Multivariable ordinary least squares regression was employed to explore independent predictors of left RI, controlling for age, diabetes mellitus (DM), and smoking.

Key Results

• Demographics: The ED group was significantly older (median 64.1 vs. 60.4 years, p=0.022) and had a significantly higher prevalence of diabetes mellitus (31.4% vs. 9.2%, p<0.001) compared to the non-ED group.
• Haemodynamic Discrepancies:
  • Arterial Inflow: Bilateral PSV was significantly reduced in the ED group (Right: 24.0 vs. 29.0 cm/s, p=0.004; Left: 26.0 vs. 30.2 cm/s, p=0.018).
  • Venous Occlusion: The most significant finding was a sharp separation in Left RI. Men with ED had a median Left RI of 0.86 (95% CI 0.80–0.90), whereas men without ED had a median of 1.00 (95% CI 0.90–1.00) (p=0.001; r=0.30). Left EDV was also significantly higher in the ED group (3.0 vs. 1.0 cm/s, p=0.024), indicating impaired venous trapping.
  • Bilateral Symmetry: No significant bilateral asymmetry was detected within either group for any parameter. However, the no-ED group showed a borderline tendency toward higher Left RI relative to Right RI (p=0.101).
• Subgroup Analysis by Curvature: The difference in Left RI between ED and non-ED groups was statistically significant only in patients with left-sided curvature (0.9 vs. 1.0, p=0.018, r=0.34). No significant differences were found in right-sided or dorsal/unspecified curvature subgroups.
• Regression Modeling: A multivariable model explained 5.5% of the variance in Left RI. ED status showed a trend-level association with reduced Left RI (β=−0.047, p=0.078), though it did not reach statistical significance as an independent predictor in this model.

Significance and Claims
The paper claims to be the first to characterize bilateral corporal haemodynamic asymmetry in PD patients stratified by ED status. The primary finding is that PD patients with established ED harbor a measurable bilateral haemodynamic asymmetry, most clearly expressed as a reduced Left RI. This pattern is consistent with ipsilateral plaque-mediated veno-occlusive dysfunction, where fibrosis stiffens the tunica albuginea, preventing the compression of emissary veins and leading to persistent venous drainage.

The authors argue that these findings support a modification to clinical practice: bilateral RI recording should be routine during PDU in PD patients. The study demonstrates that relying solely on right-sided assessment or averaging bilateral values could miss the principal haemodynamic signal, particularly in patients with left-sided curvature. This information is presented as critical for pre-surgical vascular risk stratification and patient counselling regarding grafting, plication, or prosthesis implantation.

The paper modestly concludes that while the observed asymmetry is likely driven by local plaque mechanics, the possibility that subclinical haemodynamic asymmetry in men without ED may predict future erectile impairment remains an open question requiring prospective multicentre follow-up. The authors acknowledge limitations including the retrospective design, potential misclassification of ED status due to reliance on clinician documentation, and the lack of data on plaque volume and treatment history.