Trauma-Induced Dysregulation of the Hypothalamic–Pituitary–Adrenal and Hypothalamic–Pituitary–Gonadal Axes:

Severe or chronic stress exerts long-lasting effects on human health through persistent dysregulation of neuroendocrine systems. Sustained activation of the hypothalamic–pituitary–adrenal (HPA) axis alters cortisol dynamics, impairs negative feedback regulation, and suppresses the hypothalamic–pituitary–gonadal (HPG) axis. These coordinated disturbances are amplified by epigenetic programming, cholesterol dependent cortisol synthesis, impaired cortisol inactivation via 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), chronic inflammation, and loss of sex-steroid neuroprotection. This review integrates evidence demonstrating how trauma-induced HPA–HPG axis dysregulation contributes to cardiometabolic disease, cancer progression, neurodegeneration, addiction, reproductive dysfunction, and long-term relational and functional impairment across the lifespan.