Effects of Estradiol & Phytoestrogens on Stress Responsivity

焦虑在中年女性中是一种常见但未得到充分研究的主诉，在更年期期间会增加。 过渡。雌激素的变化在更年期过渡期间是戏剧性的，间接数据表明 雌激素，尤其是雌激素受体β在调节焦虑中的潜在作用。的两个子类型 雌激素受体α和β(ER-α和ER-β)似乎与 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)，降低焦虑行为和对包括社会压力在内的离散应激源的反应性 实验动物。这项建议的主要目的是开展第一项研究，以将这些临床前 通过比较和对比植物雌激素、雌二醇和安慰剂对人体的影响进行研究 实验室中的日常焦虑和对中等心理社会压力的反应。另一个主要关注点是 情绪认知和非情绪认知。这一焦点源于雌激素可以影响负面影响的证据。 糖皮质激素对记忆的影响。这些目标将在为期12周的随机安慰剂中实现- 比较三种治疗方法的对照临床试验：1)广泛使用的植物雌激素补充剂(Novasoy(R)) 2)口服雌二醇片(每天1毫克)；以及3)安慰剂(相同的片剂出现两次 每天)在120名处于更年期过渡期的健康妇女中(每组40人)。为了衡量焦虑，女性会 完成基线和整个治疗期间的每日情绪日记。衡量对……的责任感 心理社会压力，特里尔社会压力测试的平行形式，一种广泛使用的实验室感应 涉及意料之外的公开演讲和社会评估恐惧，将被用来诱导温和 治疗前后的心理社会压力。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 中年时期雌激素变化作为中年焦虑和压力症状的一个因素的重要性 女人。阳性发现将为后续研究ER-β激动剂在 女性焦虑症状和精神障碍的治疗。

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.