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

多发性硬化症(MS)是一种慢性炎症性中枢神经系统脱髓鞘疾病，是导致中青年残疾的第二大原因。易感性和病程似乎都受到荷尔蒙因素的影响，包括女性性别、排卵年龄、怀孕和可能的哺乳期。多发性硬化症主要影响育龄妇女，在月经初潮之前和绝经后发生多发性硬化症的情况很少见，在怀孕期间和可能在纯母乳喂养期间，这种疾病显著改善。虽然专家将怀孕的保护作用归因于高雌激素水平，但兰格-古尔德博士和我的研究结果表明，无排卵可能是关键。在这项建议中，我们将测试口服避孕药--也会导致无排卵--或更长的总无排卵年限是否会降低MS的风险。这项建议的目的是调查考虑终生OC使用的MS的风险，并检查在症状出现前3-5年使用OC的效果。此外，我们假设并计划研究更长时间的累积无排卵状态(月经初潮晚、多胎、使用OC时间更长)可降低多发性硬化的风险。实现这些目标可能导致对激素影响多发性硬化病理生理学的重要洞察。我们将利用南加州大学和南加州凯撒永久大学的大量研究资源和专业知识来实现这些目标。这些目标的实现将使我能够扩大德国多发性硬化症和妊娠登记，以解决激素因素在多发性硬化症易感性中的作用，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.