Study of Women's Health Across the Nation V: Endocrinology/CLASS Laboratory

描述（由申请人提供）：通过准确分析生殖配体来研究更年期过渡的激素动力学特征，对于理解更年期对女性从中年到老年健康的影响至关重要。从根本上说，更年期内分泌学/CLASS实验室组件将检查动态并为SWAN的所有其他项目提供内分泌支架。我们将描述与绝经过渡相关的激素变化，并将其与临床表现精确地联系起来，探索内分泌的新领域，并将激素特征的研究从绝经早期扩展到绝经后期。我们将挑战传统的观念，即更年期过渡仅仅是卵巢雌二醇分泌的减少，以一个更完整和数据驱动的模型，即由动态肝球蛋白系统调节的性类固醇从雌激素主导向雄激素主导的平衡转变。通过SWAN I、II和III，我们在横断面和纵向上都表明：1)性激素结合球蛋白（SHBG）与心血管危险因素、代谢综合征、身体成分、胰岛素和葡萄糖水平的相关性最强；2)雄激素与心血管危险因素、代谢综合征、身体组成、胰岛素和葡萄糖水平以及性功能密切相关；3)促卵泡激素与骨质流失、血管舒缩症状和末次月经时间密切相关；4)肾上腺雄激素分泌的短暂增加与围绝经期晚期雌二醇分泌的下降一致；雌二醇与血管舒缩症状、代谢和止血因子只有适度的关联，但与骨质流失无关。这些发现为以下观点的进化提供了内分泌学上的支持：更年期过渡是一个从雌激素主导状态向雄激素主导状态的综合转变，这种转变的程度与健康风险有关。为了完整地描述绝经过渡期的自然历史，我们将追求以下具体目标：1)将循环A和E1的测量添加到每年测量的T和E2中，以提供更完整的循环雌激素和雄激素总量的估计。我们将计算这四种甾体之间的平衡以及平衡与SHBG的关系，包括横截面和纵向；2)测量SHBG的同型异构体，并将其相对比例与性类固醇水平和种族差异联系起来，包括横断面和纵向；3)确定所测循环肾上腺雄激素与绝经妇女健康状况的关联程度。我们将继续对之前测得的激素进行血清取样。

DESCRIPTION (provided by applicant): Examining the hormonal dynamics that characterize the menopausal transition by accurately assaying reproductive ligands is central to understanding the impact of menopause on women's health from midlife through old age. Fundamentally, the Endocrinology of the Menopause/CLASS Laboratory component will examine the dynamics and provide the endocrinologic scaffolding for all other projects in SWAN. We will characterize the hormonal changes associated with the menopausal transition and precisely relate these to their clinical manifestations, explore new areas of endocrine importance, and extend the study of hormonal characteristics from the early to late postmenopause. We will challenge the traditional concept of the menopausal transition as simply a loss of ovarian estradiol secretion to a more integrated and data driven model of a shift from an estrogen dominant to an androgen dominant balance of sex steroids modulated by a dynamic hepatic globulin system. Through SWAN I, II and III we have shown, both cross-sectionally and longitudinally: 1) sex hormone binding globulin (SHBG) to be most strongly associated with cardiovascular risk factors, metabolic syndrome, body composition, insulin, and glucose levels; 2) androgens to be strongly associated with cardiovascular risk factors, metabolic syndrome, body composition, insulin and glucose levels, and sexual function; 3) follicle stimulating hormone to be strongly associated with bone loss, vasomotor symptoms and timing of the final menstrual period; 4) a transient increase in adrenal androgen secretion coincides with the late perimenopausal drop in estradiol secretion; 5) only modest associations of estradiol with vasomotorsymptoms, metabolic and hemostatic factors but not bone loss. These findings provide endocrinological support for the evolution in thinking of the menopausal transition as an integrated shift from an estrogen dominant to an androgen dominant state with health risks associated with the magnitude of that shift. To characterize completely the natural history of the menopausal transition, we will pursue the following Specific Aims: 1) Add measures of circulating A and E1 to the annually measured T and E2 to provide a more complete estimate of total circulating estrogens and androgens. We shall calculate the equilibrium among these four steroids and the relationship of the equilibrium to SHBG, both cross-sectionally and longitudinally; 2) Measure the isoforms of SHBG and relate the relative proportions to sex steroid levels and ethnic differences, both cross-sectionally and longitudinally; and 3) Determine the degree to which the measured circulating adrenal androgens are associated with health outcomes in women traversing the menopause. We will continue serum sampling of previously measured hormones. RELEVANCE (See instructions): These studies will increase our understanding of the hormonal physiology of the entire menopausal transition and assist in the development of evidence-based paradigms for treating peri- and postmenopausal health concerns.