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Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis
Melinda Magyari1,2, Nils Koch-Henriksen2,3
1Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Copenhagen, Denmark Melinda.Magyari.01@regionh.dk.
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.
Insights
Women experience more relapses in multiple sclerosis (MS) before menopause, while men show faster disability progression after age 45. These sex differences highlight distinct disease trajectories in MS.
Area of Science:
- Neurology
- Immunology
- Epidemiology
Background:
- Multiple sclerosis (MS) exhibits varied clinical presentations between sexes.
- Understanding these sex-specific differences is crucial for personalized treatment strategies.
Purpose of the Study:
- To quantify sex differences in the activity and severity of multiple sclerosis (MS).
- To investigate how these differences are influenced by disease duration and time since clinical onset.
Main Methods:
- Analysis of a large cohort of Danish citizens diagnosed with relapsing MS since 1996.
- Utilized inverse probability weighting for sex comparisons.
- Employed weighted general linear models for relapse rates and Expanded Disability Status Scale (EDSS) changes.
- Used weighted Cox regression to determine hazard ratios for EDSS endpoints.
Main Results:
- Women had a higher relapse rate ratio (1.16) than men, a difference diminishing after age 50.
- Men showed a faster annualized increase in EDSS (0.07) compared to women (0.05).
- Women had a 1.34 times higher hazard of reaching EDSS 4 and 1.43 times higher hazard of reaching EDSS 6 compared to men.
Conclusions:
- Women exhibit greater inflammatory activity (relapses) pre-menopause, suggesting a role for sex hormones.
- Men are more prone to the neurodegenerative aspects of MS, particularly after age 45.
- Distinct sex-based patterns in MS activity and progression warrant further investigation into underlying mechanisms.
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