Effects of Estradiol & Phytoestrogens on Stress Responsivity

雌二醇的作用

• 批准号: 8072596
• 负责人: PAULINE M MAKI
• 金额: $ 48.6万
• 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/8072596
• 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; 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）：焦虑是一种常见但对中年妇女的投诉，并在更年期过渡期间增加。在更年期过渡期间，雌激素的变化是戏剧性的，间接数据表明雌激素，尤其是雌激素受体β在介导焦虑中的潜在作用。雌激素受体Alpha和beta（ER-Alpha和Er-Beta）的两个亚型似乎与女性焦虑表达至关重要。优先针对ER-BETA的化合物，包括植物来源的雌激素（植物雌激素），降低了实验室动物中对离散压力源（包括社会压力）的焦虑行为和对离散压力源的反应。该应用的主要目的是通过比较和对比植物雌激素，雌二醇和安慰剂对每日焦虑的影响以及对实验室中等心理压力的反应，将这些临床前研究转化为人类。另一个主要重点是情感和非情感认知。这种重点源于证据表明雌激素会影响糖皮质激素对记忆的负面影响。这些目标将在比较三种治疗方法的12周随机安慰剂控制的临床试验中完成：1）每天两次使用广泛使用的植物雌激素补充剂（Novasoy（R）400，55 mg片剂）； 2）口服雌二醇（每天1毫克）； 3）安慰剂（每天两次出现两次）在绝经期的120名健康女性中（每组40个）。为了衡量焦虑，妇女将在基线和整个治疗期间完成每日情绪日记。为了衡量对社会心理压力的反应，Trier社会压力测试的平行形式是一种广泛使用的实验室归纳，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的社会心理压力。在两个实验室会议上，将在对照条件和社会心理压力条件下获得主观压力，皮质醇和情绪记忆表现的度量。该临床试验的结果将增加有关中年雌激素变化的重要性的关键信息，这是中年女性焦虑和压力症状的促成因素。积极的发现将为随后对ER-BETA激动剂的调查在治疗女性焦虑症状和疾病时提供基本原理。 公共卫生相关性：与男性相比，女性的焦虑症患病率更高，中年女性（45岁以后）但男性的患病率显着增加。在女性中，非临床样本中的焦虑特征也比男性更为普遍，在激素过渡状态（包括绝经过渡）期间恶化。为了进一步了解在更年期过渡期间对焦虑症的治疗选择的理解，本研究旨在测试两种广泛使用的更年期疗法，雌二醇和植物雌激素，对日常焦虑和压力反应性的影响，以及日常的认知作用和日常压力。