Demyelinating disorders in women: epidemiology, immunology, and clinical implications across MS, NMOSD, and MOGAD

Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-associated disease (MOGAD) are the major types of demyelinating disorders of the central nervous system (CNS). Demyelinating disorders impact women disproportionately and frequently present during reproductive years. These conditions can cause significant neurological disability and psychosocial challenges, especially for women. Because they often present during reproductive years, clinicians frequently manage contraception, pregnancy, and the postpartum period alongside disease control. Sex-specific evidence, therefore, becomes especially important for treatment decisions. Despite this, sex-specific differences in epidemiology, immunopathology, clinical features, and therapeutic response remain inconsistently addressed in both clinical practice and research. In this review, we synthesize current evidence on the factors underlying the female predominance observed in MS, NMOSD, and MOGAD, and discuss the clinical consequences of these findings. We investigate the influence of sex hormones, X-chromosome-mediated immune regulation, and immunological changes associated with pregnancy and the postpartum period, as well as disease-specific mechanisms. We also examine how these factors affect diagnosis, prognosis, therapeutic decision-making, pregnancy management, and quality of life. Finally, we highlight important gaps in knowledge and underscore the necessity for a sex-informed approach to the diagnosis, management, and research of autoimmune demyelinating diseases.