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cross-sectional analysis by cumulating data (sex, year of birth, age at diagnosis, and MS phenotypes) from unpublished and published studies of the participating centers.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.