Demyelinating disorders of the central nervous system (CNS) — including multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) — exhibit striking sex-specific differences in epidemiology, pathophysiology, clinical course, and treatment response. The female-to-male (F:M) ratio varies substantially across these conditions: approximately 3:1 in MS, up to 9:1 in AQP4-NMOSD, and close to 1:1 in MOGAD. While the higher prevalence of MS and AQP4-NMOSD in women is well recognized, many sex- and gender-related issues remain underreported or insufficiently addressed in both research and clinical practice.

This Research Topic aims to highlight and critically evaluate these overlooked aspects in women with demyelinating disorders across the lifespan. Topics of interest include, but are not limited to:

• Clinical presentation and progression: Sex-related differences in onset patterns, relapse rates, progression risk, and comorbidity profiles in women compared to men.

• Hormonal influences: The role of reproductive milestones (menarche, pregnancy, postpartum period, menopause) and hormone-related interventions (contraceptives, hormone replacement therapy, assisted reproduction) on disease activity, progression, and recovery.

• Personalized therapy considerations: Sex-specific pharmacokinetics, efficacy, and safety profiles of disease-modifying therapies, including the impact of pregnancy planning, breastfeeding, and fertility preservation on treatment strategies.

• Psychosocial and quality-of-life factors: Gender-related disparities in healthcare access, mental health burden, work productivity, and social participation in women with demyelinating disorders.

• Comorbidity landscape: Underrecognized autoimmune, psychiatric, and metabolic comorbidities disproportionately affecting women, and their implications for prognosis and management.

• Mechanistic insights: Immunological, genetic, and neuroendocrine mechanisms underlying sex differences in CNS demyelination.

By integrating perspectives from basic science, clinical neurology, neuroimmunology, epidemiology, and patient-reported outcomes research, this collection will provide a comprehensive framework for recognizing and addressing the specific needs of women with demyelinating disorders. Contributions are welcomed in the form of original research, systematic reviews, meta-analyses, and perspectives that advance understanding of this critical yet often underexplored area.

Please note: to be considered for this collection, the first or last author should be a researcher who identifies as a woman.

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Underecognized Issues in Women with Demyelinating Disorders