Biological sex-related factors are associated with the risk of developing multiple sclerosis (MS), with contemporary incident cases occurring among female individuals at a 3-fold higher rate than among male individuals. Although specific genes on the X chromosome may play a modest role in MS susceptibility and severity,1,2 reproductive factors, including sex steroid hormone production and pregnancy, have long been recognized to alter the disease course in MS.3 Onset of pediatric MS becomes prominent at approximately age 13 years, just after children enter puberty.4 Girls typically present at least 2 years after menarche, and the minority of girls with prepubertal onset may experience increased relapse rate in the perimenarche period.5 On the other hand, pregnancy suppresses relapse activity, with the second and third trimesters having a more potent effect than the first trimester.6 The predominant estrogen of pregnancy, estriol, may be associated with relapse suppression,7 but a number of other biological changes in pregnancy could also mediate or play a role in this outcome. Other hormonal changes in pregnancy include high levels of progesterone, which has the capacity to modulate immune function in ways that fosters tolerance of the fetus, underpins changes in the expression of a number of immunologically important genes, and precipitates a general shift from a helper T cell 1 (TH1) to helper T cell 2 (TH2) phenotype.3,7-10
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Graves JS. Do Pregnancies Forestall the Onset of MS? JAMA Neurol. 2020;77(12):1484–1485. doi:10.1001/jamaneurol.2020.3332
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