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

全国妇女健康研究五：内分泌/CLASS实验室

• 批准号: 8462184
• 负责人: DANIEL S MCCONNELL
• 金额: $ 31.63万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8462184
• 关键词: Address; Adrenal Glands; Age; Aging; Androgens; Area; Biological Assay; Blood specimen; Body Composition; Cardiovascular Diseases; Cardiovascular system; Characteristics; Chicago; Clinic Visits; Clinical; Cognitive; DEXA; DNA; DNA Library; Data; Death Records; Degenerative polyarthritis; Development; Disease; Drops; Emotional; Endocrine; Endocrinology; Epidemic; Equilibrium; Equipment and supply inventories; Estradiol; Estrogens; Evaluation; Event; Evolution; Feedback; Follicle Stimulating Hormone; Fracture; Funding; Gait; Genomics; Globulins; Glucose; Goals; Gonadal Steroid Hormones; Health; Hemostatic Agents; Hepatic; Hip region structure; Hormonal; Hormonal Change; Hormones; Hospital Records; Instruction; Insulin; Knee; Laboratories; Ligands; Link; Lymphocyte; Measures; Menopausal Status; Menopausal Symptom; Menopause; Menstruation; Metabolic; Metabolic syndrome; Michigan; Modeling; Natural History; Obesity; Older Population; Outcome; Ovarian; Participant; Perimenopause; Physical Function; Physiological; Physiology; Postmenopause; Prevalence; Process; Protein Isoforms; Protocols documentation; Relative (related person); Reproductive Periods; Research Personnel; Resources; Risk; Roentgen Rays; Saliva; Sampling; Serum; Sex Functioning; Sex Hormone-Binding Globulin; Site; Speed; Staging; Steroids; Symptoms; System; Technology; Telephone; Thinking; Time; Ultrasonography; Urine; Vasomotor; Vertebral column; Walking; Whole Blood; Woman; Women' s Health; bone loss; cardiovascular risk factor; cognitive function; cohort; disability; disabling disease; ethnic difference; evidence base; experience; functional decline; grasp; interest; middle age; morphometry; muscle strength; prevent; psychosocial; repository; reproductive; scaffold; spine bone structure

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.

描述（由申请人提供）：通过准确测定生殖配体来检查表征绝经过渡期的激素动力学，对于了解绝经对中年至老年妇女健康的影响至关重要。从根本上说，更年期/CLASS实验室组成部分的内分泌学将检查动态，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期相关的激素变化，并将其与临床表现精确地联系起来，探索内分泌重要性的新领域，并将激素特征的研究从绝经早期扩展到晚期。我们将挑战绝经过渡期的传统概念，即仅仅是卵巢雌二醇分泌的损失，以一个更综合的和数据驱动的模型，即由动态肝球蛋白系统调节的性类固醇从雌激素为主转变为雄激素为主的平衡。通过SWAN I、II和III，我们已经在横截面和纵向上显示：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密切相关; 2）雄激素与心血管危险因素、代谢综合征、身体成分、胰岛素和葡萄糖水平以及性功能密切相关; 3）促卵泡激素与骨丢失、血管紧张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雌二醇分泌的晚期围月经期下降相一致; 5）雌二醇与血管运动症状、代谢和止血因素仅适度相关，但与骨丢失无关。这些研究结果提供了内分泌学的支持，认为绝经过渡期是一个综合的转变，从雌激素占主导地位的雄激素占主导地位的状态与健康风险的变化幅度。为了完整地描述绝经过渡期的自然史，我们将追求以下具体目标：1）将循环A和E1的测量值添加到每年测量的T和E2中，以提供对总循环雌激素和雄激素的更完整的估计。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，包括横截面和纵向：2）测量SHBG的亚型，并将其相对比例与性类固醇水平和种族差异相关，包括横截面和纵向;和3）确定所测量的循环肾上腺雄激素与经历绝经期的妇女的健康结果相关的程度。我们将继续对先前测量的激素进行血清采样。 相关性（参见说明）：这些研究将增加我们对整个绝经过渡期的激素生理学的理解，并有助于发展以证据为基础的治疗绝经期和绝经后健康问题的范例。