Effects of Estradiol & Phytoestrogens on Stress Responsivity

雌二醇的作用

• 批准号: 7653502
• 负责人: PAULINE M MAKI
• 金额: $ 49.22万
• 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/7653502
• 关键词: Affect; Aftercare; Age; Agonist; Anxiety; Anxiety Disorders; Behavior; Clinical; 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; public health relevance; response; social; social stress; soy; stem; stressor; trait; treatment duration; trial comparing

DESCRIPTION (provided by applicant): 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 application 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. PUBLIC HEALTH RELEVANCE: The prevalence of anxiety disorders is higher in women compared to men, and increases significantly in women at midlife (after age 45) but not men. Anxiety traits in non-clinical samples are also more common in women than men and worsen during hormonal transitional states, including the menopausal transition. To further our understanding of treatment options for women with anxiety during the menopausal transition, this study aims to test the effects of two widely used menopausal therapies, estradiol and phytoestrogens, on daily anxiety and stress responsivity, and the cognitive effects of daily and provoked stress.

描述（由申请人提供）：焦虑是一种常见的，但在中年妇女的投诉研究不足，并在绝经过渡期增加。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，在介导焦虑的潜在作用。雌激素受体的两种亚型，α和β（ER-α和ER-β），似乎在女性焦虑的表达中起着至关重要的作用。优先靶向ER-β的化合物，包括植物源性雌激素（植物雌激素），在实验室动物中降低焦虑行为和对离散压力（包括社会压力）的反应。本申请的主要目的是通过比较和对比植物雌激素、雌二醇和安慰剂对实验室中日常焦虑和对中度心理社会压力的反应的影响，进行第一项研究，将这些临床前研究转化为人类研究。另一个主要焦点是情绪和非情绪认知。这一关注源于雌激素可以影响糖皮质激素对记忆的负面影响的证据。这些目的将在一项为期12周的随机安慰剂对照临床试验中实现，该试验比较了三种治疗方法：1）广泛使用的植物雌激素补充剂（Novasoy 400，55 mg片剂，每日两次）; 2）口服雌二醇（1 mg/日）;和3）安慰剂（相同外观的片剂，每日两次），用于120名处于绝经过渡期的健康妇女（每组40名）。为了测量焦虑，女性将在基线和整个治疗期间完成每日情绪日记。为了测量对社会心理压力的反应性，将使用Trier社会压力测试的平行形式，这是一种广泛使用的实验室诱导，涉及意外的公开演讲和社会评估恐惧，将用于在治疗前后诱导中度社会心理压力。在这两个实验室会议上，主观压力，皮质醇和情绪记忆表现的措施将在控制条件和心理社会压力条件下获得。这项临床试验的结果将增加关于中年雌激素变化的重要性的关键信息，作为中年妇女焦虑和压力症状的一个促成因素。阳性结果将为ER-β激动剂治疗女性焦虑症状和障碍的后续研究提供依据。 公共卫生相关性：焦虑症的患病率在女性中高于男性，并且在中年女性（45岁以后）中显着增加，但男性则没有。非临床样本中的焦虑特征在女性中也比男性更常见，并且在激素过渡状态（包括绝经过渡期）期间恶化。为了进一步了解绝经过渡期焦虑女性的治疗选择，本研究旨在测试两种广泛使用的绝经治疗方法，雌二醇和植物雌激素，对日常焦虑和压力反应的影响，以及日常和激发压力的认知影响。