STRESS, ESTROGEN, OPIOIDS AND ATHEROGENESIS IN WOMEN

描述：冠心病是女性的头号杀手。 在整个一生中，女性患冠心病的风险低于男性 育龄，但绝经年龄前后风险相对较大 女性患冠心病的风险增加，这表明 生殖激素可能会提供一定程度的保护，防止 冠心病的心血管病理生理学。这是 进一步支持的报告表明雌激素替代疗法 可能会防止绝经后冠心病风险激增。在… 目前雌激素在卵巢癌病理生理学中的确切作用 心血管疾病尚不清楚，但对这些疾病有更多的了解 相互作用可以为冠心病提供具体的策略 降低风险。首席调查员之前的工作是 已确定的内源性阿片肽机制可能缓冲 心理应激的病理生理效应。之前的工作由 其他研究表明，更年期剥夺雌激素会破坏阿片类药物。 控制垂体功能，雌激素替代可以恢复这种状态 功能。这些发现表明阿片类药物的作用机制可能与此有关。 雌激素对心脏的保护作用。 拟议研究的目的是检验这种相互作用。 雌激素和阿片类药物与冠心病风险之间的关系。这 将通过比较阿片类药物的效果来实现 纳曲酮拮抗剂对绝经后患者心血管反应性的影响 接受和不接受雌激素替代治疗的女性。一个组合的杂交- 提出了横断面研究和纵向研究相结合的方法。横断面研究 将利用完整的妇女群体进行激素替代，而妇女不会 在纵向研究中激素替代疗法的前情提要， 以前没有接受激素替代治疗的女性将被随机 被分配到三组之一：雌激素替代组，雌激素加雌激素组 黄体酮，或安慰剂。纳曲酮压力测试将在 在三个月的治疗后。如果雌激素减少心血管疾病 压力反应性降低带来的风险，然后绝经后妇女 雌激素替代疗法将显示较小的血压和心脏 心理应激期间的比率变化比不服用雌激素的妇女要高 替代疗法。如果应激反应性的降低是由 通过雌激素促进阿片类药物抑制机制，然后 纳曲酮的预处理应增加雌激素的反应性 替换组，从而拮抗 雌激素。

DESCRIPTION: Coronary heart disease is the number one killer of women. Women enjoy less risk for coronary disease than men throughout their reproductive years, but around the age of menopause the relative risk for coronary heart disease in women increases, suggesting that reproductive hormones may provide some degree of protection from cardiovascular pathophysiology of coronary heart disease. This is further supported by reports suggesting that estrogen replacement therapy may prevent the postmenopausal surge in coronary heart disease risk. At present the precise role of estrogens in the pathophysiology of cardiovascular disease is unclear, but greater understanding of these interactions can provide concrete strategies for coronary heart disease risk reduction. Previous work by the principal investigator has identified endogenous opioid peptide mechanisms that may buffer the pathophysiological effects of psychological stress. Previous work by others has shown that estrogen deprivation of menopause disrupts opioid control of pituitary function, and estrogen replacement can restore this function. These findings suggest that opioid mechanisms may be involved in the cardioprotective role of estrogens. The purpose of the proposed research is to examine the interaction between estrogen and opioids in risk for coronary heart disease. This will be accomplished by comparison of the effects of the opioid antagonist naltrexone on cardiovascular reactivity in postmenopausal women with and without estrogen replacement therapy. A combined cross- sectional and longitudinal study is proposed. The cross-sectional study will utilize intact groups of women on hormone replacement and women not previously on hormone replacement therapy in the longitudinal study, women not previously on hormone replacement therapy will be randomly assigned to one of three groups: estrogen replacement, estrogen plus progestin, or placebo. Naltrexone stress testing will take place before and after three months of therapy. If estrogens reduce cardiovascular risk by reduction of stress reactivity, then postmenopausal women on estrogen replacement therapy will show smaller blood pressure and heart rate changes during psychological stress than women not on estrogen replacement therapy. If the reduction in stress reactivity is mediated via estrogen facilitation of opioid inhibitory mechanisms, then pretreatment with naltrexone should increase reactivity in the estrogen replacement groups, thereby antagonizing the cardiovascular benefits of estrogen.