Overtraining Syndrome and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Athletes: Mechanisms and Diagnostic Uncertainty - a narrative review

Background. Overtraining syndrome (OTS) is a maladaptive state arising from chronic imbalance between training/non-training stress and recovery, historically attributed to dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Despite decades of research, no validated biomarker or diagnostic threshold exists, and the directionality of HPA involvement remains contested.Aim. To critically synthesise evidence on HPA-axis mechanisms in OTS, contrast them with competing pathophysiological hypotheses, and evaluate the diagnostic uncertainty limiting clinical recognition and management.Materials and Methods. Narrative review of peer-reviewed English-language systematic reviews, cross-sectional and longitudinal cohort studies, case series, consensus statements, and mechanistic physiological studies addressing OTS, HPA-axis function, hormonal biomarkers, and related conditions in athletes.Results. Basal cortisol and ACTH are generally unhelpful diagnostically, whereas stimulation-test responses (insulin tolerance test, two-bout exercise protocol) more consistently reveal blunted late hormonal reactivity in overtrained athletes, though findings remain inconsistent across cohorts. The testosterone-to-cortisol ratio, cytokine, glycogen, central-fatigue, autonomic, and gut-brain-axis hypotheses each explain fragments of the clinical picture without unifying explanatory power. Composite instruments (EROS-COMPLETE, EROS-SIMPLIFIED) show promising discrimination in small single-sex cohorts but lack external validation.Conclusions. HPA-axis dysfunction in OTS is real but neither sufficient nor specific as a diagnostic criterion. Progress requires standardised stimulation-testing protocols, sex-inclusive cohorts, and multi-domain composite instruments rather than continued pursuit of a single biomarker.