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

基本信息

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
项目类别：
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

项目摘要

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).

项目概要 SWAN（全国妇女健康研究）收集了丰富的资料 3,302 名女性的初始队列的生物心理社会和生理数据，其中大多数坚持了25年的跟踪检查。由于SWAN的最初目标为了描述女性更年期过渡的特征，性类固醇测量雌二醇 (E2) 和睾酮 (T) 从一开始就是该项目的重要组成部分。在 SWAN 的早期阶段，针对 E2 和 T 的最先进、高灵敏度的直接免疫测定 (IA) 由密歇根大学中央配体检测卫星服务 (CLASS) 开发实验室。基于液相色谱/质谱 (LC-MS/MS) 的技术现在在激素测量中很大程度上取代了 IA。 SWAN 已适应这一变化从第 15 次访视开始，使用 LC-MS/MS 进行所有性类固醇测定。然而，所有从基线（访问 0）到访问 13 对队列进行的激素水平已使用 IA 进行并需要与 LC-MS/MS 协调。无法检测到的比例随着时间的推移，E2 和 T 的样本也有所增加，因为 SWAN 样本现在一切正常过了最后一次月经。 IA 与 LC-MS/MS 的相关性足以允许转换一个由于无法确定激素的下限，另一种方法是不完整的检测。在当前的 SWAN-Aging U19 资助中，我们计划使用基于现代 LC-MS/MS 的技术。我们现在建议开发和测量E2 和雌酮 (E1)，使用基于超灵敏 LC-MS/MS 的检测，可可靠地测量 E2 低至 1 pg/mL。该测定随后将用于绝经后样本天鹅。目前的行政补充提出了 1 个新目标，目标 1：制定超灵敏液相色谱/串联质谱 (LC-MS/MS) 测定 E1 和 E2 在 2 pg/mL 时具有 <15% 的测定内和测定间变异系数 (CV)，并且 LLOQ 为 1 pg/mL。实现这一目标将使我们能够最大限度地利用 SWAN 化验数据不断推进，迄今为止已产生约 100,000 例血清性别对已经历更年期且现在处于更年期状态的女性进行类固醇测量绝经后和 70 岁以上，并确定真实的循环 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更年期综合症（GSM）。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.)
影响因子：
0
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.