Intriguing sex differences both in multiple sclerosis (MS) susceptibility and its disease course may offer important insights into MS disease pathophysiology, prevention and treatment. In this review, we first summarize the key sex-related differences in MS risk, heritability and disease progression. One promising hypothesis we explore is whether sexually-dimorphic responsiveness to cultural and environmental changes may explain the observation of an increasing female:male sex ratio in MS. We then review the evidence for hormonal modulation of MS, during such transitions as puberty and pregnancy. Finally, we review sex differences in the non-inflammatory facets of MS. We highlight those research gaps that may point to important sex or sex hormone-mediated mechanistic and therapeutic insights.
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