Menopause Symptom Clusters: Refocusing Therapeutics

描述（由申请人提供）：尽管女性在更年期过渡期间会经历一系列症状，但大多数研究都集中在个体症状上，如潮热。该研究将范式从关注个体症状转变为关注症状群（SCs）。重新分析西雅图中年妇女健康研究（P50 NR02323, R01 NR04141, P30 NR04001, P30 ES07033）中500多名参与者的症状和遗传多态性、内分泌生物标志物、症状易感因素和社会行为风险因素的数据，并进行长达19年的纵向随访，将使我们能够实现这些目标：1)利用潜在分类分析确定生殖晚期、绝经早期和晚期过渡阶段以及绝经后早期的流行症状群；2)确定妇女从一个更年期过渡阶段到下一个更年期过渡阶段时症状群的一致性；3)遗传多态性、内分泌生物标志物、症状易感因素、社会行为危险因素和更年期相关因素与症状聚类、幸福感和症状干扰结果的关联检验模型；4)对对照临床试验进行系统综述，确定症状作为次要治疗效应和不良反应，为我们提供治疗症状群的方法；5)综合实证分析和系统综述的结果，制定新的症状群管理方案，在未来的可行性研究中进行测试。一个跨学科的科学顾问委员会，包括国家老龄研究所资助的MS-FLASH临床试验研究人员，将为我们的研究团队提供一个即时分享我们的结果的机会，以便为症状群管理方法的设计以及他们正在进行的研究提供信息，包括症状群和相关机制的辅助研究的产生。

DESCRIPTION (provided by applicant): Although women experience clusters of symptoms during the menopausal transition, most research focuses on individual symptoms such as hot flashes. The proposed study shifts the paradigm from focusing on individual symptoms to symptom clusters (SCs). Re-analyzing data on symptoms and genetic polymorphisms, endocrine biomarkers, symptom vulnerability factors and sociobehavioral risk factors from over 500 participants in the Seattle Midlife Women's Health Study (P50 NR02323, R01 NR04141, P30 NR04001, P30 ES07033) with longitudinal follow-up spanning up to 19 years will allow us to achieve these aims: 1) identify prevalent symptom clusters during the late reproductive stage, early and late menopausal transition stages, and early postmenopause using latent class analysis; 2) determine the consistency of symptom clusters as women change from one menopausal transition stage to the next; 3) test models linking genetic polymorphisms, endocrine biomarkers, symptom vulnerability factors, social-behavioral risk factors and menopause-related factors to symptom clusters, and outcomes of well-being and symptom interference; 4) conduct a systematic review of controlled clinical trials to identify symptoms as secondary treatment effects and adverse effects that will inform us about therapies for symptom clusters and 5) synthesize results of the empirical analyses and systematic review to develop novel symptom cluster management protocols to be tested in future feasibility studies. An interdisciplinary scientific advisory board including National Institute on Aging-funded MS-FLASH clinical trials investigators will provide our research team an opportunity for immediate sharing of our results in order to inform design of symptom cluster management approaches as well as their ongoing studies, including the generation of ancillary studies of symptom clusters and related mechanisms. PUBLIC HEALTH RELEVANCE: The results of this study will help clinicians and women, themselves, identify symptoms that cluster together and that may have different causes. Knowing which cluster of symptoms a woman has may help her clinician recommend the treatment or treatments that are most likely to work best for her. Using some of the genetic and hormone tests, as well as information about the woman's history, such as stressful experiences she has had, may help understand what causes some of her symptoms and may help her and her clinician decide on the best treatment available for her.