Assessment and supplementation of antioxidant amines in male infertility-are we approaching clinical implementation?

Male infertility remains unexplained in a substantial proportion of cases, despite extensive clinical and biological investigations. Oxidative stress has emerged as a central pathophysiological mechanism underlying impaired sperm function, yet current diagnostic and therapeutic strategies inadequately capture the complexity of redox regulation within the male reproductive tract. In this narrative review, we revisit both the historical foundations and recent advances supporting a pivotal role for a specific class of metabolites: polyamines (spermine, spermidine, and putrescine) and carnitine, which we propose to collectively term antioxidant amines. These compounds are present at exceptionally high concentrations in seminal plasma, tightly regulated by androgen-dependent and metabolic pathways, and critically involved in redox homeostasis, mitochondrial function, chromatin stabilization, and sperm maturation. We synthesize evidence from classical biochemical studies, contemporary metabolomics, and translational research linking antioxidant amine imbalance to altered semen parameters and male subfertility. Importantly, we highlight recent analytical advances that now make the targeted quantification of these metabolites technically feasible in clinical laboratories using routinely available liquid chromatography-mass spectrometry (LC-MS) platforms. Beyond their diagnostic potential, we critically discuss experimental and clinical data on antioxidant amine supplementation, emphasizing both their therapeutic potential and the need for balanced dosing strategies to avoid deleterious effects associated with excess exposure. Altogether, this review positions antioxidant amines at the crossroads of pathophysiology, laboratory medicine, and clinical intervention in male infertility. By integrating historical insights with modern analytical and translational perspectives, we argue that antioxidant amines are finally ready to move from overlooked metabolites to actionable biomarkers and therapeutic targets in reproductive medicine.