REDUCTION OF TRIGLYCERIDES IN WOMEN ON HRT

说明(申请人提供)：激素的风险和益处 近年来，替代疗法(HRT)受到越来越多的关注 由于HERS和WHI试验的结果，乳房风险增加 癌症，新疗法，如SERM和降脂药物，双磷酸盐， 以及对激素代谢和疾病的更好理解。我们已经在 几项研究表明，HRT的潜在好处受到生活方式的限制， 辅助因素，特别是体重增加、肥胖和内脏腹部增加 脂蛋白、炎性标志物和脂肪相关代谢改变 雌激素代谢物。我们建议对500名女性进行激素替代治疗的随机试验 两年以上，年龄52-60岁，三年或以上 以测试绝经后腰围、甘油三酯、 高密度脂蛋白、低密度脂蛋白颗粒数、CPR、剧烈饮食运动后的PAI-I、 与健康教育控制相比，会减缓进展或导致 亚临床血管疾病指标的回归。干预措施是 旨在将总脂肪摄入量减少到卡路里的17%，1300公斤 卡路里，并将适度运动增加到每周150-240分钟，以获得 体重减轻了10%。主端点将为20%或 甘油三酯水平至少降低20毫克，腰围减少5厘米 周长，LDLc减少了10%。这将导致变化 在亚临床测量中，包括颈动脉超声，电子束 冠状动脉和主动脉的计算机断层扫描，脉搏波速度，内皮 功能，并测量桡动脉的眼压。脂蛋白的核磁共振波谱， 炎症标志物和雌激素代谢物也将被评估。 因此，这项试验的主要目标是修改 激素替代疗法使用者中的亚临床疾病。

DESCRIPTION (provided by applicant): The risk and benefits of hormone replacement therapy (HRT) have come under increased concern in recent years because of the results of the HERS and WHI trials, the increased risk of breast cancer, new therapies, i.e., SERMs and lipid lowering drugs, bisphosphorates, and better understanding of hormone metabolism and disease. We have shown in several studies that the potential benefits of HRT are limited by lifestyle, cofactors, specifically weight gain, obesity and increased visceral abdominal fat associated metabolic changes in lipoproteins, inflammatory markers and estrogen metabolites. We are proposing a randomized trial of 500 women, on HRT for at least two years, aged 52-60 years, and three or more years postmenopausal to test whether reduction in waist circumference, triglycerides, dense LDLc, number of LDL particles, CPR, PAI-I by aggressive diet exercise, versus a health education control will decrease progression or result in regression of measures of subclinical vascular disease. The intervention is designed to reduce total fat intake to 17 percent of calories, 1300 kilo calories, and increase moderate activity to 150-240 minutes per week to obtain a 10 percent reduction in weight. The primary endpoint will be a 20 percent or at least a 20 mg decrease in triglyceride levels, a 5 cm decrease in waist circumference, and a 10 percent decrease in LDLc. This will result in changes in subclinical measurements including carotid ultrasound, electron beam computer tomography of the coronary and aorta, pulse wave velocity, endothelial function, and tonometry of the radial artery. NMR spectroscopy of lipoproteins, inflammatory markers, and estrogen metabolites will also be evaluated. Therefore, the primary goal of this trial is the modification of measures of subclinical disease among HRT users.