The Metabolic Pathway of Cortisol in Chronic Stress: A Systematic Literature Review

Chronic stress is a pervasive factor in modern life, exerting a profound influence on human physiology far beyond psychological distress. This report provides an in-depth systematic review of the literature on the metabolic pathways of cortisol in the context of chronic stress. The central premise is that prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in chronic hypercortisolemia, fundamentally disrupts metabolic homeostasis. This disruption is a key etiological factor in the development of a cluster of pathologies, including insulin resistance, muscle atrophy, and metabolic syndrome. This review synthesizes current research, outlines key molecular and cellular mechanisms, and identifies critical gaps in the literature. The evidence demonstrates that cortisol's catabolic effects on protein and glucose metabolism are not isolated events but are deeply interconnected, forming a synergistic pathway that drives metabolic deterioration. A key finding is the bidirectional nature of the relationship, where metabolic state can, in turn, modulate the stress response, creating a self-perpetuating cycle of dysfunction. The report concludes by highlighting the urgent need for standardized stress measurement and long-term longitudinal studies to better understand the temporal relationship between chronic stress and the onset of metabolic disease. Keywords: Cortisol, Chronic Stress, Protein Metabolism, Glucose Regulation, Insulin Resistance, Systematic Review