Serum Ferroptosis-Related Proteins ACSL4, SLC7A11, and GPX4 Are Associated With Erectile Dysfunction Severity

To investigate the diagnostic value of circulating ferroptosis-related markers in erectile dysfunction (ED) and identify independent risk factors for disease occurrence and severity.

A total of 204 participants were enrolled, including 102 ED patients and 102 healthy controls. Clinical data and psychometric scores (IIEF-5, EHS, HAMD-17, HAMA-14, PSQI) were assessed. Serum glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4) were quantified by ELISA. Group comparisons, correlation analyses, receiver operating characteristic (ROC) curves, and univariate and multivariate logistic regression were performed.

Compared with controls, ED patients exhibited significantly lower GPX4 and SLC7A11 and higher ACSL4 levels, with greater changes in severe ED. GPX4 and SLC7A11 correlated positively with erectile function and negatively with depression, anxiety, and sleep disturbance, whereas ACSL4 showed opposite associations. ROC analyses demonstrated good diagnostic performance of GPX4 (AUC = 0.841), SLC7A11 (AUC = 0.867), and ACSL4 (AUC = 0.859), with excellent accuracy when combined (AUC = 0.958). Logistic regression identified GPX4 and SLC7A11 as protective factors and ACSL4 as a risk factor for ED. In severe ED, PSQI was an independent risk factor, whereas GPX4 and SLC7A11 were independent protective factors.

Circulating ferroptosis-related markers, particularly in combination, provide strong diagnostic value for ED and reflect disease severity. GPX4, SLC7A11, and ACSL4 may serve as promising biomarkers and potential therapeutic targets for ED management.