@article {Magyari716, author = {Melinda Magyari and Nils Koch-Henriksen}, title = {Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis}, volume = {93}, number = {7}, pages = {716--722}, year = {2022}, doi = {10.1136/jnnp-2022-328994}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective To quantify sex differences in activity and severity of multiple sclerosis (MS) and how it depends on disease duration and time since clinical onset.Methods All Danish citizens with onset of relapsing MS since 1996 who have received disease-modifying therapy have been followed with annual or biannual control visits with mandatory notification of the Danish Multiple Sclerosis Registry. Men and women were compared by the inverse probability of being female. Relapse rates and changes in the Expanded Disability Status Scale (EDSS) scores were analysed with weighted general linear models, and we used weighted Cox regression for HRs between men and women for different EDSS endpoints.Results We included 3028 men and 6619 women. The weighted female:male relapse rate ratio was 1.16 (95\% CI: 1.10 to 1.22) but after age 50 years, the difference disappeared. The annualised increase in EDSS was 0.07 in men (95\% CI: 0.05 to 0.08) and 0.05 in women (95\% CI: 0.04 to 0.06); p=0.017. With women as reference, the HR for reaching EDSS 4 was 1.34 (95\% CI: 1.23 to 1.45; p\<0.001), and for reaching EDSS 6 it was 1.43 (95\% CI: 1.28 to 1.61; p\<0.001). The diagnostic delay did not differ significantly between the sexes.Conclusion Women have more inflammatory disease activity in terms of relapses than men up to the age of menopause indicating that sex hormones may play a role. Men are more subject to the neurodegenerative component of MS than women, particularly after the age of 45 years.All data relevant to the study are included in the article or uploaded as supplemental information. The data underlying this article cannot be shared publicly due to data protection regulation. Data are accessible to authorised researchers after application to the Danish Health Data Authority and the board of the Danish Multiple Sclerosis Registry.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/93/7/716}, eprint = {https://jnnp.bmj.com/content/93/7/716.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }