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Background and purpose Birth cohort effects have greatly shaped long-term trends in multiple sclerosis ( MS). This study examined whether birth cohort effects have also determined trends in the sex ratio. Methods Age−period−cohort analyses were applied to Swiss mortality data, 1901−2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C. Results Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex-specific birth cohort estimates were not congruent. Conclusion The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex-specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors. [ABSTRACT FROM AUTHOR]