Sexual disparities in the incidence and course of MS

• There is a 3:1 female:male ratio in multiple sclerosis and this may be increasing.
• Disease progression, brain atrophy, and cognitive impairment may be worse in men.
• Sex hormones have complex inflammatory and neuroprotective effects.
• Sex hormones may interact with other disease modulators, such as vitamin D.
• Little is known about sex differences in treatment response or epigenetic changes.

Multiple sclerosis (MS) affects three times more women than men and this ratio appears to be increasing. However male patients experience increased disease progression, brain atrophy, and cognitive impairment. Gonadal hormones may modulate these sex differences. For example, female puberty heralds an increased risk of MS, and during pregnancy disease activity is milder, with an increased risk of postpartum relapses. Gonadal hormones likely have complex and inflammatory and neuroprotective effects, and may interact with other disease modulators, such as vitamin D. Sex differences in the heritability of disease susceptibility genes implicate a role for epigenetic modification. Many questions remain, including the impact of sex on treatment response and epigenetic changes, and the modulatory potential of hormonal treatments. This article summarizes what is known about sexual dimorphism in MS onset and course, as well as potential interactions between sex and other factors influencing MS pathogenesis, incidence and severity.