The increasing incidence and prevalence of female multiple sclerosis-A critical analysis of potential environmental factors

Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two women for every man with a diagnosis of MS, recent serial cross-sectional assessments provide compelling evidence for an increase of the female to male sex ratio in patients with relapsing-remitting MS over the last decades. An understanding of this phenomenon might provide key insights into the pathogenesis of the disease but also may have implications for health-care strategies and further research efforts.We review possible etiologies for the gender disparity in MS, and we discuss possible underlying causes. We determined that the biologically most plausible explanations for a disproportional increase of MS among women in some population may be the role of vitamin D in MS pathogenesis. Decreased sun exposure may be a critical factor in diminished vitamin D levels in many recent cohort studies. Vitamin D insufficiency or deficiency has been shown to affect T cell differentiation and regulation, which may affect cellular immune responses against autoantigens and pathogens that have been associated with the etiology of MS. Vitamin D also appears to impact B cell activation and differentiation, another cell type that has been implicated in the inflammatory cascade underlying CNS autoimmune disease.