The Biological Clock Influenced by Burnout, Hormonal Dysregulation and Circadian Misalignment: A Systematic Review.

Burnout is increasingly recognized as both a psychosocial and a chronobiological disorder characterized by endocrine dysregulation and circadian disruption. It arises from chronic occupational stress and manifests through psychological, physical, and physiological symptoms. Although psychosocial determinants are well established, the biological and chronobiological mechanisms, particularly those involving cortisol and melatonin, remain less explored. This systematic review synthesizes current evidence on hormonal and circadian dysregulation in burnout and complements it with exploratory observational data from healthcare professionals. Peer-reviewed studies evaluating endocrine or circadian biomarkers in individuals with burnout were systematically reviewed. In addition, an exploratory observational analysis was carried out among 195 Romanian clinicians using an adapted Maslach Burnout Inventory. Morning salivary cortisol was measured once at 9 a.m. in a small subsample (n = 26) to provide preliminary physiological data. Because only a single time point was obtained, these values were interpreted as indicative of stress-related activation rather than circadian rhythm. Thirty-seven studies met the inclusion criteria. Across the literature, burnout was associated with altered HPA-axis activity, blunted diurnal cortisol variation, and irregular melatonin secretion related to shift work and disrupted sleep-wake cycles. Complementary exploratory data from our Romanian cohort indicated strong correlations between burnout severity, physical symptoms, and higher morning cortisol values among shift-working clinicians. These findings are preliminary and not representative of full circadian profiles. Burnout should be considered both a psychosocial and a systemic disorder influenced by endocrine and circadian dysregulation. Recognizing alterations in cortisol and melatonin as objective indicators may facilitate earlier detection and inform chronobiological interventions such as optimized scheduling, light exposure management, or melatonin therapy. The observational data presented here is preliminary and intended to generate hypotheses; future research should employ repeated cortisol sampling under controlled Zeitgeber conditions to confirm circadian associations.