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（CVD，包括中风）发病率远低于男性。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CVD在绝经后比女性生命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，是CVD和2型糖尿病的主要预测因子。MetS在临床上被诊断为具有5种组分中的任何一种，并且至少具有3种。在绝经过渡期（MT），MetS的发生率增加。其原因尚不清楚;然而，这可能是由于MT期间雄激素相对于雌激素过量。该提案的目标是建立MetS组成部分的星座如何在MT过程中演变的基本方面，MT是女性生命中关键的5至10年生物学阶段。反过来，这是为了确定定制的方法来预防代谢综合征早期和相关的心血管疾病和糖尿病，在MT期间的有效干预策略。该提案纳入了我们对中年女性更年期和性激素的看法的转变，即在MT中，MetS发生率的增加可能更多地是由于雄激素获得（而不是雌激素损失）。我们的初始假设是，在中年绘制MetS组分的星座图，以及满足的MetS组分的数量，将为弥合MT、其变化的性激素和女性CV保护的丧失提供一个窗口。如果正确的话，这将使我们的临床重点转移到针对中年和绝经后早期妇女特征性MetS星座和相关CVD和糖尿病的个体化激素策略。目标1.描述5个种族/民族的女性在接受MT时发生MetS的MetS组分随时间推移的满意度。目标2.确定激素和炎症因素，预测中年妇女接受MT时MetS星座的进程。我们提出了一个有效的研究，分析独特的，现有的纵向数据，从美国最大的MT研究，全国妇女研究（SWAN），一个多种族队列的3302名妇女。我们的长期目标是通过在中年实施个性化的预防策略来预防老年妇女CVD的急剧增加。我们的两个目标都直接关系到这个更广泛的目标。这将影响6000多万中年和老年美国妇女。 公共卫生相关性：代谢综合征（MetS）是CVD和2型糖尿病的主要预测因子，并且可以表现为具有5个风险成分中至少3个的几个星座之一，例如高血压和大腰围。代谢综合征更常发生在经历绝经过渡期的女性中，绝经过渡期是女性生命中关键的5至10年生物学阶段。这项研究旨在显著提高我们对40多岁和50岁出头的女性如何随着时间的推移发展MetS和激素变化以及绝经过渡期间导致MetS风险增加的其他因素的理解。有了这个更好的理解，我们打算最终预防MetS的妇女谁是高风险，由于其过渡到绝经后的可识别和可修改的特征。这可能会影响数以千万计的中年妇女及其家庭，她们在剩余的生命中面临近三分之一的发展MetS的机会。

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. PUBLIC HEALTH RELEVANCE: The Metabolic Syndrome (MetS) is the major predictor for both CVD and type 2 diabetes, and can manifest as having one of several constellations of at least 3 of 5 risk components, such as high blood pressure and large waist girth. MetS occurs more often in women undergoing the menopausal transition, a key 5- to 10-year biological stage in a woman's lifespan. This study seeks to enhance significantly our understanding of how women in their 40s and early 50s, over time, develop MetS and hormonal changes and other factors during the menopausal transition that contribute to their increased risk of MetS. With this better understanding, we intend to ultimately prevent MetS in women who are high risk due to identifiable and modifiable characteristics of their transition to post-menopause. This potentially impacts tens of millions of midlife women and their families who face a nearly 1 in 3 chance of developing MetS in their remaining lifetime.