Sex differences in the development, treatment, and prognosis of multiple sclerosis in Switzerland.

Introduction
There has been growing recognition of potential differences in disease course and presentation between men and women with MS. This study examined sex differences in MS using data collected at study entry in the Swiss Multiple Sclerosis Cohort (SMSC).Methods
A cross-sectional analysis of the data from 1541 SMSC participants (June 2012-February 2022) with persons with relapsing-remitting MS or Clinically Isolated Syndrome (named relapsing type) and progressive MS including persons with Primary Progressive Multiple Sclerosis (PPMS) and Secondary Progressive Multiple Sclerosis (SPMS) was performed. Sociodemographic and clinical characteristics, disease history, and severity indicators were examined, focusing on sex differences within progressive and relapsing MS types, and comparing these MS types. Statistical analyses included Mann-Whitney U tests and chi-squared tests for group comparisons. Multivariate linear regression models were constructed to examine the independent association of sex with Expanded Disability Status Scale (EDSS) scores, adjusting for age, disease duration, treatment category, recent relapse, and body mass index (BMI).Results
Women represented 65.8% of the cohort (1,014/1,541). BMI was significantly lower in women than in men in the relapsing type and SPMS (relapsing: p < 0.001; SPMS: p = 0.001; PPMS: p = 0.86). Age at first symptoms differed by sex depending on MS type: women were younger in the relapsing group (29.7 vs. 31.4 years, p = 0.036), while men were younger in PPMS (42.3 vs. 47.7 years, p < 0.001), with no difference in SPMS (p = 0.5). In univariate analysis, men showed a trend toward higher disability levels at study entry in the relapsing type (p = 0.058), but no significant sex differences in EDSS were observed in progressive forms. In multivariate analysis, female sex showed a trend toward lower EDSS scores in relapsing MS after adjusting for clinical factors (β = -0.13, 95% CI: -0.26 to 0.005, p = 0.059) but was not associated with EDSS in PPMS (β = -0.09, p = 0.802) or SPMS (β = + 0.09, p = 0.816).Conclusion
This study identified sex differences in disease distribution, BMI and EDSS at their entry in the SMSC. These findings underscore the complexity of sex differences in MS and highlight the importance of prospective longitudinal studies with standardized severity assessments to clarify sex-specific disease trajectories and inform personalized treatment strategies.