Sex differences in neurological disorders: Insights from ischemic stroke, Parkinson’s disease, and multiple sclerosis

Ischemic stroke, Parkinson's disease (PD), and multiple sclerosis (MS), are neurodegenerative disorders that exhibit significant sex differences in pathophysiology, clinical manifestations, and outcomes. Women are more likely to experience strokes in older age, with estrogen playing dual protective/detrimental roles depending on reproductive age. In PD, men show earlier onset and steadier decline, while women exhibit a protective estrogen-driven advantage and distinct gut-brain axis interactions. MS disproportionately affects women (3:1 ratio), particularly during reproductive years, with sex hormones and X-linked genes modulating autoimmune demyelination. This review synthesizes sex-specific mechanisms across these diseases, emphasizing immune dysregulation, hormonal influences, and emerging roles of the gut microbiome. Key modifiers such as epigenetic factors, microbiome composition, and sex chromosome interactions are discussed to inform personalized therapeutic strategies.