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

多发性硬化（MS）是中枢神经系统的慢性炎性脱髓鞘疾病，是青年至中年成人残疾的第二大原因。易感性和病程似乎都受到激素因素的影响，包括女性性别、排卵年龄、怀孕和可能的哺乳期。MS主要影响育龄期女性，在月经初潮前和绝经后MS的发病率很低，并且在妊娠期间和可能在纯母乳喂养期间疾病显著改善。 虽然专家将怀孕的保护作用归因于高雌激素水平，但朗格古尔德博士和我的研究结果表明，无排卵可能是关键。在本提案中，我们将测试口服避孕药（也会诱导无排卵）或更长的无排卵总年数是否会降低MS的风险。本提案的目的是研究终身使用OC的MS风险，并检查症状发作前3-5年使用OC的效果。此外，我们假设并计划调查，更长的累积状态的无排卵（月经初潮后期，多胎妊娠，更长的OC使用）降低MS的风险。实现这些目标可能会导致重要的见解激素影响MS的病理生理学。我们将实现这些目标，利用巨大的研究资源和专业知识，在南加州大学和凯撒永久南加州。这些目标的实现将使我能够扩大德国MS和妊娠登记，以解决激素因素在MS易感性中的作用，并加强我在预后研究方面的技能。

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.