Anovulation and multiple sclerosisThe cumulative effect of anovulation (menarche, oral contraceptive use, pregnancy) on the risk of multiple sclerosis

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Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system and the second leading cause of disability in young to middle-aged adults. Both susceptibility and disease course appear to be influenced by hormonal factors including female sex, ovulatory age, pregnancy and likely lactation. MS predominantly affects women in their childbearing years, the onset of MS is rare prior to menarche and after menopause, and the disease is significantly ameliorated during pregnancy and possibly during exclusive breastfeeding. While experts attributed the protective effects of pregnancy to high estrogen levels, Dr. Langer-Gould`s and my findings suggest that anovulation may be the key. In this proposal we will test whether oral contraceptives - which also induce anovulation - or longer total anovulatory years reduce the risk of MS. The aims of this proposal are to investigate the risk to develop MS considering the lifetime OC use and to examine the effect of OC use in the 3-5 years prior to symptom onset. Furthermore we hypothesize and plan to investigate that a longer cumulative state of anovulation (late menarche, multiple pregnancy, longer OC use) reduces the risk of MS. Accomplishment of these aims could lead to important insights into hormones influence the pathophysiology of MS. We will accomplish these goals by utilizing the tremendous research resources and expertise available at University of Southern California and Kaisers Permanente Southern California. Accomplishment of these goals will allow me to expand the German MS and pregnancy registry to address the role of hormonal factors in MS susceptibility and strengthen my skills in prognostic research.