The Study of Women's Health Across the Nation (SWAN): The Impact of Midlife and the Menopause Transition on Health and Functioning in Early Old Age

全国妇女健康研究 (SWAN)：中年和更年期过渡对早年健康和功能的影响

• 批准号: 10911525
• 负责人: Maria Mori Brooks
• 金额: $ 11.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10911525
• 关键词: Administrative Supplement; Age; Aging; Biological Assay; Data; Estradiol; Estrogen Therapy; Estrone; Genitourinary system; Gonadal Steroid Hormones; Grant; Health; Hormones; Immunoassay; Laboratories; Ligands; Liquid Chromatography; Measurement; Measures; Menopausal Syndrome; Menopause; Menstruation; Methods; Michigan; Perimenopause; Physiological; Postmenopause; Reporting; Sampling; Sampling Studies; Serum; Services; Study of Women' s Health Across the Nation; Technology; Testosterone; Time; Universities; Vagina; Variant; Visit; Woman; biopsychosocial; cohort; detection limit; follow-up; human old age (65+); liquid chromatography mass spectrometry; middle age; tandem mass spectrometry

PROJECT SUMMARY SWAN, the Study of Women's Health Across the Nation, has collected a wealth of biopsychosocial and physiologic data on an inception cohort of 3,302 women, most of whom have adhered to follow-up examinations spanning 25 years. Since the original aims of SWAN were to characterize the menopausal transition in women, sex steroid measurements for estradiol (E2) and testosterone (T) have been a crucial part of the project from the start. In the early years of SWAN, state-of-the-art, highly sensitive, direct immunoassays (IA) for E2 and T were developed by the University of Michigan Central Ligand Assay Satellite Services (CLASS) Laboratories. Liquid chromatography/mass spectrometry (LC-MS/MS)-based technology has now largely supplanted IA for hormone measurement. SWAN has adapted to this change by performing all sex steroid assays using LC-MS/MS from Visit 15 onwards. However, all hormone levels performed on the cohort from the baseline (Visit 0) to Visit 13 have been performed using IA and require reconciliation to LC-MS/MS. The proportion of undetectable samples for both E2 and T has also increased over time as the SWAN sample are now all well past their final menses. Correlation of IA to LC-MS/MS sufficient to allow for conversion of one method to the other for hormones is incomplete due to an inability to resolve the lower limit of detection. In the current SWAN-Aging U19 grant, we have planned to reanalyze E2 and T using a contemporary LC-MS/MS-based technology. We now propose to develop and measure E2 and estrone (E1) using an ultrasensitive LC-MS/MS-based assay that will measure reliably as low as 1 pg/mL E2. This assay will be used subsequently for postmenopausal samples from SWAN. The current administrative supplement proposes 1 new aim, Aim 1: To develop an ultrasensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for E1 and E2 that performs with <15% intra- and inter-assay coefficients of variation (CV) at 2 pg/mL and a LLOQ of 1 pg/mL. Accomplishment of this aim will allow us to maximize the use of SWAN assay data moving forward, which has to date resulted in approximately 100,000 serum sex steroid measurements in women who have traversed the menopause and are now all postmenopausal and over the age of 70, and to determine the true circulating E2 increment that is observed in women reporting use of topical vaginal estrogen for treatment of genitourinary syndrome of menopause (GSM).

项目摘要 SWAN，全国妇女健康研究，收集了大量的 生物心理社会和生理数据的初始队列的3,302名妇女，其中大多数人 坚持了25年的随访检查。由于天鹅最初的目标 描述女性绝经过渡期的特征， 雌二醇（E2）和睾酮（T）从一开始就是该项目的关键部分。在 早期的SWAN，最先进的，高灵敏度，E2和T的直接免疫测定（IA） 由密歇根大学中央配体分析卫星服务（CLASS）开发 Laboratories.基于液相色谱/质谱（LC-MS/MS）的技术 现在在很大程度上取代了IA用于激素测量。SWAN已经适应了这种变化， 从访视15开始，使用LC-MS/MS进行所有性类固醇测定。但所有 从基线（访视0）至访视13对队列进行的激素水平测定， 使用IA进行，需要与LC-MS/MS进行核对。 E2和T的样本也随着时间的推移而增加，因为SWAN样本现在都很好 度过最后一次月经IA与LC-MS/MS的相关性足以允许一个转化 另一种方法用于激素是不完整的，因为无法解决的下限 侦测在目前的天鹅老化U19补助金中，我们计划使用以下方法重新分析E2和T： 基于LC-MS/MS的现代技术。我们现在建议开发和测量E2 和雌酮（E1），使用超灵敏的LC-MS/MS为基础的分析，将可靠地测量， 低至1 pg/mL E2。该测定随后将用于绝经后样本， 天鹅目前的行政补编提出了一个新的目标，目标1： E1的超灵敏液相色谱/串联质谱（LC-MS/MS）测定， E2在2 pg/mL时的试验内和试验间变异系数（CV）<15%， LLOQ为1 pg/mL。实现这一目标将使我们能够最大限度地利用天鹅 分析数据向前发展，迄今为止已导致大约100，000名血清性别 类固醇测量的妇女谁已经走过更年期，现在都 绝经后和70岁以上，并确定真正的循环E2增量， 在报告使用局部阴道雌激素治疗泌尿生殖系统疾病的女性中观察到 绝经综合征（GSM）。

项目成果

Quantifying physical activity across the midlife: Does consideration of perceived exertion matter?

• DOI: 10.1016/j.pmedr.2022.101850
• 发表时间: 2022-08
• 期刊: PREVENTIVE MEDICINE REPORTS
• 影响因子: 2.8
• 作者: Ylitalo, Kelly R.;Karvonen-Gutierrez, Carrie A.;Oh, Minsuk;Sternfeld, Barbara;Stamey, James;Gabriel, Kelley Pettee
• 通讯作者: Gabriel, Kelley Pettee

Migraine with aura.

有先兆的偏头痛。

• DOI: 10.1136/bmj.a745
• 发表时间: 2008
• 期刊: BMJ (Clinical research ed.)
• 作者: Lipton,RichardB;Derby,CarolA
• 通讯作者: Derby,CarolA

Self-Reported Sleep Disturbances over the Menopausal Transition and Fracture Risk: The Study of Women's Health Across the Nation.

• DOI: 10.1002/jbm4.10762
• 发表时间: 2023-08
• 期刊: JBMR PLUS
• 影响因子: 3.8
• 作者: Cauley, Jane A.;Kravitz, Howard M.;Ruppert, Kristine;Lian, Yinjuan;Hall, Martica J.;Harlow, Sioban D.;Finkelstein, Joel S.;Greendale, Gail
• 通讯作者: Greendale, Gail

The effect of starting metformin on bone mineral density among women with type 2 diabetes in the Study of Women's Health Across the Nation (SWAN).

在全国女性健康研究 (SWAN) 中，开始服用二甲双胍对 2 型糖尿病女性骨矿物质密度的影响。

• DOI: 10.1007/s00198-023-06915-3
• 发表时间: 2024
• 期刊: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
• 作者: Solomon,DanielH;Ruppert,Kristine;Cauley,JaneA;Lian,Yinjuan;Altwies,Hallie;Shieh,Albert;Burnett-Bowie,Sherri-AnnM
• 通讯作者: Burnett-Bowie,Sherri-AnnM

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women.

• DOI: 10.1093/humrep/deac028
• 发表时间: 2022-05-03
• 期刊: Human reproduction (Oxford, England)