Neuro-endocrine Insights into MS: Exploring the Role of HPA Axis and Sex Hormones

Multiple sclerosis (MS) is a complex autoimmune disease characterized by chronic inflammation and neurodegeneration within the central nervous system. Over the years, researchers have increasingly recognized the significance of neuroendocrine changes and sex hormone alterations in the pathogenesis and clinical course of MS. The neuroendocrine system, encompassing the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis, plays a crucial role in regulating immune responses, inflammation, and tissue repair. Moreover, sex hormones, including estrogen and testosterone, exert profound effects on immune function, neuroprotection, and neuroplasticity, thereby influencing disease susceptibility, course, and progression. This review summarizes the current understanding of neuroendocrine changes observed in MS, focusing on alterations in HPA axis activity, dysregulation of cortisol levels, and disturbances in stress response mechanisms. Furthermore, it explores the impact of sex hormone fluctuations in MS, discussing the protective effects of estrogen and potential influences of testosterone on disease activity. Further investigations are warranted to unravel the underlying mechanisms and explore targeted interventions that could positively impact the lives of individuals affected by MS.