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

描述(由申请人提供)：通过准确地分析生殖配体来检查表征更年期转变的激素动力学，是了解更年期对女性从中年到老年健康的影响的核心。从根本上说，更年期/班级实验室的内分泌学部分将检查动力学，并为天鹅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的特征，并将这些变化与其临床表现精确地联系起来，探索内分泌重要的新领域，并将激素特性的研究从绝经早期扩展到晚期。我们将挑战传统的更年期转变概念，将其简单地视为卵巢雌激素分泌的丧失，以更完整和数据驱动的模型从雌激素主导转变为雄激素主导的性类固醇平衡，由动态的肝脏球蛋白系统调节。通过SWAN I、II和III的横断面和纵向研究，我们已经证明：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、胰岛素和血糖水平最相关；2)雄激素与心血管危险因素、代谢综合征、身体成分、胰岛素和血糖水平以及性功能密切相关；3)卵泡刺激素与骨质丢失、血管运动症状和末次月经时间密切相关；4)肾上腺雄激素分泌短暂增加，与围绝经期晚期雌二醇分泌下降一致；5)雌二醇与血管舒缩症状、代谢和止血因素之间只有适度的相关性，但与骨丢失无关。这些发现为绝经期转变的思维进化提供了内分泌学支持，认为绝经期转变是从雌激素主导状态向雄激素主导状态的综合转变，这种转变的大小与健康风险相关。为了完整地描述绝经过渡的自然历史，我们将追求以下具体目标：1)将循环A和E_1的测量添加到每年测量的T和E_2中，以提供更完整的循环雌激素和雄激素总量的估计。我们将计算这四种类固醇之间的平衡，以及平衡与SHBG的关系，包括横断面和纵向；2)测量SHBG的异构体，并将其相对比例与性别类固醇水平和种族差异进行横向和纵向关联；以及3)确定所测量的循环肾上腺雄激素与更年期妇女健康结局的关联程度。我们将继续对以前测量的激素进行血清采样。 相关性(见说明)：这些研究将增加我们对整个更年期转变的荷尔蒙生理学的理解，并有助于开发治疗围绝经期和绝经后健康问题的循证范例。

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.