Many factors, such as genetic susceptibility, age, sex, and sex hormones, influence the incidence and the disease course of multiple sclerosis (MS). MS affects almost three times more women than men, and both factors (advanced age and gender) were associated with worsening disability and more rapid progression of the disease. Moreover, women whose onset of MS symptoms occurred after age 50 are more likely to have a progressive course than women with an earlier onset, and the female/male ratio for individuals in this group is lower than in individuals with onset between ages 18-49. This suggests that the endocrine changes associated with menopause may reduce sexual dimorphism in disease course in later years. However, it remains unclear the role of sex-specific changes in the disease course around age 50, which may represent a key biological transition period for reproductive aging. 551 subjects with MS and no prior chemotherapy exposure were divided into two age cohorts, aged before and after 50. Consistent with prior studies, the authors found that both older age and gender influenced the disease course of MS, with men displaying a more progressive disease and more rapid accumulation of disability as measured by clinical and radiological outcomes. However, they did not find any interaction between age and sex on cross-sectional adjusted clinical or radiological measures, or on 2-year trajectories of decline. The age-related decline was observed both in men and women, suggesting that the change is not driven primarily by changes in female sex hormones.