MsFLASH: Living a Healthy Menopause

 描述（由申请人提供）：这是一个新的应用程序从更年期策略：寻找持久的答案症状和健康（MsFLASH）临床试验网络。到2014年底，该网络将完成4项临床试验，在约1000名40-62岁患有血管痉挛（VMS）和其他更年期症状的妇女中测试7种干预措施。在新的申请中，我们建议对更年期的一个相对研究不足的领域-阴道健康和性功能进行一项大型多中心试验。预计到2022年，65岁以上的美国女性人数将增加一倍，约40%的女性将出现令人烦恼的阴道症状，75%的女性可能会出现阴道干燥，高达40%的女性可能会出现性交疼痛。为了解决这个巨大的，未充分研究的问题，我们在具体目标#1中建议在45-70岁的绝经后妇女中进行一项3臂，随机，对照，双盲临床试验。我们将评估超低剂量阴道雌二醇（Vagifem 10 mcg）、非激素亲水性非处方性阴道凝胶（Replens）和安慰剂在降低阴道症状（干燥、瘙痒、刺激或疼痛）综合评分方面的有效性。次要目的包括评估性功能，生活质量， 泌尿生殖道萎缩和阴道和血液标本的生物储存库的建立。在一部分女性中，我们还将检查治疗反应是否与以下因素相关：a）绝经后阴道微生物组; B）阴道粘膜炎症; c）生殖激素谱。对绝经后阴道症状相关机制的深入研究将使用最先进的微生物技术对纵向收集的生物标本进行分析，并将指导未来的转化研究。具体目标#2解决了许多中年妇女及其提供者的常见问题：a）由于治疗安全性和有效性的数据变化迅速，有时相互矛盾，更年期症状管理决策可能具有挑战性;和B）缺乏帮助妇女充分了解各种更年期治疗方案的个性化决策辅助工具。为了翻译和传播我们对绝经后阴道健康的研究结果，除了先前对血管扩张、睡眠、情绪和疼痛症状的试验结果外，我们建议开发和试点测试一种全面的、最先进的、量身定制的多媒体材料，旨在促进有症状的妇女及其提供者做出明智的绝经决策。中年妇女和保健提供者在这一进程的每个阶段的参与都已纳入。该申请是新颖的和变革性的：1）提出了第一个充分把握度的，双盲的，安慰剂对照的激素和非激素治疗绝经后阴道症状的试验; 2）提供了第一个多媒体更年期决策辅助工具，包括围绕所有可用疗法的最新证据。这些目标是为了改变老年妇女可获得的证据基础和资源，以便在中年及以后航行。

 DESCRIPTION (provided by applicant): This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. By the end of 2014, the network will have completed 4 clinical trials testing 7 interventions in approximately 1000 women ages 40-62 with vasomotor (VMS) and other menopause symptoms. In the new application, we propose to conduct a large multicenter trial on a relatively understudied area of menopause - vaginal health and sexual function. The number of US women over age 65 is expected to double by 2022 and approximately 40% will experience bothersome vaginal symptoms, 75% may have vaginal dryness and up to 40% may experience pain with intercourse. To address this vast, understudied problem, we propose in Specific Aim #1 to conduct a 3-arm, randomized, controlled, double-blind, clinical trial among postmenopausal women ages 45-70. We will evaluate the effectiveness of ultra-low dose vaginal estradiol (Vagifem 10 mcg), non-hormonal hydrophilic non-prescriptive vaginal gel (Replens) and placebo in reducing a composite score of vaginal symptoms (dryness, itching, irritation or soreness). Secondary aims include evaluation of sexual function, quality of life, and genitourinary atrophy and the creation of a biorepository of vaginal and blood specimens. In a subset of women, we will also examine whether treatment response is related to: a) the postmenopausal vaginal microbiome; b) vaginal mucosal inflammation; and c) reproductive hormone profiles. The in-depth focus on the mechanisms associated with postmenopausal vaginal symptoms will use state of the art microbiologic techniques on longitudinally collected biologic specimens and will guide future translational studies. Specific Aim #2 addresses common problems for many midlife women and their providers: a) menopausal symptom management decisions can be challenging, due to rapidly changing and sometimes contradictory data on treatment safety and efficacy; and b) individualized decision aids to help women feel fully informed about various menopausal treatment options are lacking. To translate and disseminate our findings on postmenopausal vaginal health, in addition to findings from prior trials on vasomotor, sleep, mood and pain symptoms, we propose to develop and pilot test a comprehensive, state-of- the-art, tailored, multi-media materials aimed at facilitating informed menopausal decision-making for symptomatic women and their providers. Involvement of midlife women and healthcare providers at every stage in the process has been incorporated. This application is novel and transformative for: 1) proposing the first adequately powered, double-blind, placebo-controlled trial of hormonal and non-hormonal treatments for postmenopausal vaginal symptoms; and 2) for providing the first, multi-media menopause decision aid that encompasses the latest evidence surrounding all available therapies. These aims are geared to transforming the evidence-base and resources available to aging women for navigating midlife and beyond.