Testosterone deprivation or androgen receptor inhibition effect on endothelial glycocalyx injury in prostate cancer.

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Background: Endothelial glycocalyx, which coats the luminal surface of vascular endothelial cells, plays a pivotal role in maintaining vascular homeostasis by regulating thrombogenicity, modulating inflammatory responses, and preserving endothelial barrier integrity. Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSIs) are associated with cardiovascular risk in prostate cancer. However, their effects on endothelial glycocalyx integrity, an early determinant of endothelial dysfunction, remain unknown. We investigated whether ARSIs or ADT induce endothelial glycocalyx injury. Methods: In this retrospective study, 43 patients initiating ARSIs (enzalutamide, abiraterone acetate, apalutamide, or darolutamide) and 39 patients initiating ADT (LHRH agonists, GnRH antagonists, or combined androgen blockade) were analyzed. Plasma hyaluronan levels, a validated biomarker of endothelial glycocalyx injury, were measured before and 1 month after treatment initiation using enzyme-linked immunosorbent assay. Paired comparisons were performed using the Wilcoxon signed-rank test. Results: Plasma hyaluronan levels did not significantly change after ARSI initiation (mean 260 vs 270 ng/mL, P = 0.724). In contrast, ADT initiation was associated with a significant increase in hyaluronan levels (mean 238 vs 420 ng/mL, P = 0.009). No significant differences in plasma hyaluronan changes were observed between LHRH agonists and GnRH antagonists ( P = 0.816). Conclusions: Short-term ARSI therapy did not impair endothelial glycocalyx integrity, whereas ADT was associated with significant glycocalyx injury. These findings suggest that testosterone deprivation, rather than direct androgen receptor inhibition, may contribute to endothelial dysfunction during prostate cancer treatment.