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 天鹅是全国妇女健康的研究，已经收集了很多 关于3,302名妇女的成立队列的生物心理社会和生理数据，其中大多数 遵守25年的后续考试。由于天鹅的最初目的 是为了表征女性的更年期过渡，性类固醇测量 从一开始，雌二醇（E2）和睾丸激素（T）一直是该项目的关键部分。在 天鹅的早期，最先进的，高度敏感的直接免疫测定（IA） 由密歇根大学中央配体测定卫星服务（类）开发 实验室。液相色谱/质谱（LC-MS/MS）的技术具有 现在，主要取代了IA的激素测量。天鹅已经适应了这种变化 从访问开始时，使用LC-MS/MS进行所有性类固醇测定。但是，一切 从基线（访问0）到访问13的同类中进行的激素水平已经 使用IA进行，并需要核对与LC-MS/MS。无法检测到的比例 E2和T的样品随着时间的流逝也有所增加，因为天鹅样品现在都很好 超越了他们的最后月经。 IA与LC-MS/MS的相关性足以允许转化一个 由于无法解析下限 检测。在当前的天鹅U19赠款中，我们计划使用E2和T进行重新分析 现代LC-MS/MS的技术。我们现在建议开发和测量E2 使用基于LC-MS/MS的超敏化测定法，将可靠地测量为 低至1 pg/ml E2。此测定将随后用于从中的绝经后样本 天鹅。当前的行政补充提出了1个新目标，目标1：开发一个 E1和 E2在2 pg/mL时进行<15％的变异（CV）内和测定间系数 1 pg/ml的LLOQ。实现这一目标将使我们能够最大化天鹅的使用 测定数据向前发展，迄今已导致大约100,000个血清性别 经过更年期的女性的类固醇测量 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器的女性中观察到 更年期综合征（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

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)

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