Age-dependent variation of female preponderance across different phenotypes of multiple sclerosis: A retrospective cross-sectional study

Introduction Multiple sclerosis (MS) is an autoimmune disease of the CNS, which predominantly affects women. Studies investigating the sex distribution in MS are sparse. We aim to analyze the female-to-male ratio (F/M ratio) in different MS phenotypes in association with age at diagnosis and year of birth. Methods We performed a retrospective cross-sectional analysis by cumulating data (sex, year of birth, age at diagnosis, and MS phenotypes) from unpublished and published studies of the participating centers. Results Datasets of 945 patients were collected. The overall F/M ratio was 1.9:1.0 and female preponderance was present in all phenotypes except for primary progressive MS (PPMS), in which men were predominantly affected (F/M ratio: 0.5:1.0). Female preponderance declined with increasing age at diagnosis and was no longer present in relapsing-remitting MS (RRMS) patients > 58 years of age. Conclusion Our data demonstrate an age dependency of female preponderance in MS except for PPMS. This could be influenced by the lifecycle of sex hormone secretion in women. In PPMS, a male preponderance was observed in all age-groups, which might point to pathophysiological mechanisms being less influenced by sex hormones.