Metabolic Syndrome as Women Undergo Menopausal Transition: A Multi-Ethnic Study

描述(由申请人提供)：年轻女性的心血管疾病(包括中风)的发病率比男性低得多。然而，随着中年女性过渡到绝经后，她们失去了这种“心血管保护”，而心血管疾病在绝经后比女性一生中的任何其他阶段都更常见。代谢综合征(METS)是5种代谢异常的聚集性，是心血管疾病和2型糖尿病的主要预测因子。甲硫氨酸被临床诊断为具有5种成分中的任何一种，并且至少有3种。在绝经过渡期(MT)，甲胎蛋白的发生率增加。其原因尚不清楚，但这可能是由于MT期间雄激素相对于雌激素过多所致。该提案的目标是确定大都会星座成员在MT过程中星座如何演变的基本方面，MT是女性生命中关键的5至10年生物阶段。反过来，这是为了确定定制的方法，以预防甲硫氨酸早期和相关的心血管疾病和糖尿病，在MT期间有效的干预策略。该提案结合了我们对中年女性更年期和性激素的看法的转变，即METS发生率的增加可能更多地是由于MT中雄激素的增加(而不是雌激素丢失)。我们最初的假设是，绘制中年时甲硫氨酸的星座和满足的甲硫氨酸成分的数量，将为研究MT、其变化的性激素以及女性CV保护的丧失提供一个窗口。如果正确，这将把我们的临床重点转移到针对中年和绝经后早期女性特有的甲硫氨酸星座和相关的心血管疾病和糖尿病的激素策略的个体化。目的1.描述5个种族/民族的女性在经历MT时发生METS的时间满足的METS成分的特征。目的2.确定激素和炎症因素在中年妇女接受MT时预测METS星座的进程。我们提出了一项有效的研究，分析了美国最大的MT研究--全国妇女研究(SWAN)--的独特的、现有的纵向数据，这是一个由3302名妇女组成的多种族队列。我们的长期目标是通过在中年实施个性化的预防策略来防止老年女性心血管疾病的急剧增加。我们的这两个目标都与这个更广泛的目标直接相关。这些措施将影响6000多万中年和老年美国女性。

DESCRIPTION (provided by applicant): Young women have much lower rates of cardiovascular disease (CVD, including stroke) than men. However, as midlife women transition to post-menopause, they lose this 'cardiovascular protection,' and CVD is most common in post-menopause than any other stage of a woman's lifespan. Metabolic Syndrome (MetS) is a clustering of 5 metabolic abnormalities and is a major predictor of CVD and type 2 diabetes. MetS is clinically diagnosed as having any, and at least, 3 of the 5 components. MetS occurrence increases during the menopausal transition (MT). Reasons for this are unclear; however this may be due to androgen excess, relative to estrogen, during the MT. The proposal's goal is to establish basic aspects of how the constellations of the MetS components evolve during the course of the MT, a key 5- to 10-year biological stage in a woman's lifespan. In turn, this is intended to identify customized ways of preventing MetS early and related CVD and diabetes, with effective intervention strategies during the MT. The proposal incorporates a shift in our thinking of menopause and sex hormones in midlife women, namely, that the increase in MetS occurrence may be due more to androgen gain (and less to estrogen loss), in the MT. Our starting hypothesis is that mapping the constellations of MetS components, and the number of MetS components satisfied, in the midlife will provide a window into bridging the MT, its changing sex hormones, and loss of CV protection in women. If correct, this would shift our clinical focus to individualize hormone strategies against characteristic MetS constellations and related CVD and diabetes in midlife and early post-menopausal women. Aim 1. To characterize the constellations of MetS components satisfied over time in women, of 5 race/ethnicities, who develop MetS as they undergo the MT. Aim 2. To determine the hormonal and inflammatory factors that predict the course of MetS constellations in midlife women as they undergo the MT. We propose an efficient study that analyzes unique, existing longitudinal data from the largest U.S. study of the MT, the Study of Women Across the Nation (SWAN), a multi-ethnic cohort of 3302 women. Our long-term objective is to prevent the dramatic increase in CVD in older women by implementing, in midlife, individualized preventative strategies. Both our aims bear directly on this wider objective. These would impact 60+ million midlife and older U.S. women.