STRESS, ESTROGEN, OPIOIDS AND ATHEROGENESIS IN WOMEN

描述：冠心病是女性的头号杀手。 女性在其一生中患冠状动脉疾病的风险低于男性。 生育年龄，但在绝经年龄前后的相对风险 女性冠心病发病率增加，这表明， 生殖激素可以提供一定程度的保护， 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， 可以防止绝经后冠心病风险的激增。 在 介绍雌激素在乳腺癌病理生理学中的确切作用， 心血管疾病是不清楚的，但更多的了解这些 相互作用可以为冠心病提供具体的策略 减少风险。 首席研究员之前的工作 确定的内源性阿片肽机制，可能缓冲 心理应激的病理生理学效应。 之前的工作 其他研究表明，绝经期雌激素缺乏会干扰阿片类药物， 控制垂体功能，雌激素替代可以恢复这一点 功能 这些发现表明阿片机制可能参与 雌激素的心脏保护作用。 本研究的目的是检验 雌激素和阿片类药物之间的关系 这 将通过比较阿片类药物 拮抗剂纳洛酮对绝经后妇女心血管反应性的影响 有和没有雌激素替代疗法的女性。 一个组合的十字架- 建议进行纵向和横向研究。 横断面研究 将使用激素替代的完整女性群体， 之前在纵向研究中使用激素替代疗法， 以前没有接受激素替代疗法的妇女将被随机 分为三组：雌激素替代，雌激素+ 或者安慰剂。 纳洛酮压力测试将在 经过三个月的治疗如果雌激素降低心血管 风险的减少压力反应，然后绝经后妇女对 雌激素替代疗法将显示较小的血压和心脏 在心理压力下的变化率比不服用雌激素的女性高 替代疗法如果压力反应性的降低是通过 通过雌激素促进阿片抑制机制，然后 纳洛酮预处理可增加雌激素的反应性， 替代组，从而拮抗心血管益处， 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.