Effects of Estradiol & Phytoestrogens on Stress Responsivity

雌二醇的作用

• 批准号: 8274899
• 负责人: PAULINE M MAKI
• 金额: $ 48.54万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-16 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274899
• 关键词: Affect; Aftercare; Age; Agonist; Anxiety; Anxiety Disorders; Behavior; Clinical Trials; Cognition; Cognitive; Controlled Clinical Trials; Data; Disease; Emotional; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Female; Fright; Glucocorticoids; Hormonal; Hot flushes; Human; Hydrocortisone; Investigation; Laboratories; Laboratory Animals; Measures; Mediating; Memory; Menopausal Symptom; Menopause; Moods; Oral; Performance; Phytoestrogens; Placebo Control; Placebos; Plants; Prevalence; Psychosocial Stress; Public Speaking; Randomized; Relative (related person); Role; Sampling; Stress; Symptoms; Tablets; Testing; Translating; Trier Social Stress Test; Woman; biological adaptation to stress; diaries; human ESR1 protein; indexing; men; middle age; preclinical study; psychosocial; response; social; social stress; soy; stem; stressor; trait; treatment duration; trial comparing

Anxiety is a common, but understudied complaint in midlife women, and increases during the menopausal transition. Changes in estrogen are dramatic during the menopausal transition, and indirect data suggest a potential role for estrogen, particularly estrogen receptor beta, in mediating anxiety. Two subtypes of the estrogen receptor, alpha and beta (ER-alpha and ER-beta), appear to be critically involved in the expression of anxiety in females. Compounds that preferentially target ER-beta, including plant-derived estrogens (phytoestrogens), lower both anxiety behaviors and responsivity to discrete stressors, including social stress, in laboratory animals. The primary aim of this proposal is to carry out the first study to translate these preclinical studies to humans by comparing and contrasting of the effects of phytoestrogens, estradiol, and placebo on daily anxiety and responses to moderate psychosocial stress in the laboratory. Another major focus is emotional and non-emotional cognition. This focus stems from evidence that estrogen can affect the negative impact of glucocorticoids on memory. These aims will be accomplished in a 12-week randomized placebo- controlled, clinical trial comparing three treatments: 1) a widely used phytoestrogen supplement (Novasoy(R) 400, 55 mg tablet twice daily); 2) oral estradiol (1 mg/daily); and 3) placebo (identical appearing tablets twice daily) in 120 healthy women in the menopausal transition (40 per group). To measure anxiety, women will complete daily mood diaries at baseline and throughout the treatment period. To measure responsivity to psychosocial stress, parallel forms of the Trier Social Stress Test, a widely used laboratory induction that involves unanticipated public speaking and social evaluative fear, will be used to induce moderate psychosocial stress before and after treatment. At both laboratory sessions, measures of subjective stress, cortisol, and emotional memory performance will be obtained during a control condition and during the psychosocial stress condition. The results from this clinical trial will add critical information about the importance of estrogen changes at midlife as a contributing factor for anxiety and stress symptoms in midlife women. Positive findings would provide a rationale for subsequent investigations of ER-beta agonists in the treatment of anxiety symptoms and disorders in women.

焦虑是一种常见的，但研究不足的投诉，在中年妇女，并增加在更年期 过渡在绝经过渡期雌激素的变化是戏剧性的，间接数据表明， 雌激素，特别是雌激素受体β在调节焦虑中的潜在作用。的两个亚型 雌激素受体α和β（ER-α和ER-β）似乎与以下表达密切相关： 女性的焦虑优先靶向ER-β的化合物，包括植物来源的雌激素 （植物雌激素），降低焦虑行为和对离散压力源的反应，包括社会压力， 实验室动物该提案的主要目的是开展第一项研究，将这些临床前研究转化为 通过比较和对比植物雌激素、雌二醇和安慰剂对人类的影响， 日常焦虑和对实验室中等心理社会压力的反应。另一个重点是 情绪和非情绪认知。这种关注源于雌激素可以影响消极的证据 糖皮质激素对记忆的影响这些目标将在为期12周的随机安慰剂治疗中实现- 对照，临床试验比较三种治疗：1）广泛使用的植物雌激素补充剂（Novasoy（R） 400，55 mg片剂，每日两次）; 2）口服雌二醇（1 mg/每日）;和3）安慰剂（相同外观的片剂，两次 每天）在120名健康妇女在绝经过渡期（40/组）。为了测量焦虑，女性会 在基线和整个治疗期间完成每日情绪日记。为了测量对 心理社会压力，特里尔社会压力测试的平行形式，广泛使用的实验室诱导， 涉及意外的公开演讲和社会评价的恐惧，将被用来诱导温和的 治疗前后的心理压力在两次实验室会议上，主观压力的测量， 皮质醇和情绪记忆表现将在控制条件下和在 心理社会压力状况这项临床试验的结果将增加关于 中年雌激素变化作为中年焦虑和压力症状的一个促成因素的重要性 妇女阳性结果将为ER-β激动剂的后续研究提供依据。 治疗妇女的焦虑症状和障碍。