Role of puberty in multiple sclerosis risk and course

•The incidence of MS increases at puberty.•Exposure to risk factors during adolescence is associated with multiple sclerosis.•Key changes in the immune, endocrine and nervous system occur during puberty.•Clinical features of MS differ in pre- and post-pubertal children.•Puberty may be a key risk period for the development of multiple sclerosis.

Multiple sclerosis (MS) overwhelmingly presents during the reproductive years, and is more common in females than males. The sexual dimorphism observed in post-pubertal cases is absent in pre-pubertal cases, suggesting that puberty is a key risk period for development of disease, particularly in females. Research has identified several risk factors for MS that occur during the adolescent, or post-pubertal reproductive years, which are associated with clinical presentations later in life. These observations necessitate examination of the biological changes associated with puberty, their interactions with MS risk factors, and potential effects on disease immunopathogenesis. Pediatric and adolescent presentations of MS provide a unique opportunity to study the effects of neuroendocrine changes occurring during puberty and its effect on disease development and disease course. Reviewed is the relationship of MS risk factors and puberty, and differences in disease presentation of pre- and post-pubertal children with MS. Further avenues of research are discussed.