ESTROGEN AND PROGESTIN IN HEART DISEASE

这项赠款提案是对RFA 87-HL-06-H的回应 绝经后雌激素/孕激素干预。在它里面我们 建议对150名绝经后患者进行随机、 前瞻性、三因素析因、可能加倍的盲法研究 设计。需要解决的问题是雌激素的使用(目前与 无)、给药途径(口服还是经皮)、剂量 (低与高)和孕激素联合治疗 (出席与缺席)。患者将在基线和 每隔6个月治疗一次，疗程为3年。终点为 评估的是内分泌(血清雌二醇、雌酮、硫酸雌酮、 和甲羟孕酮水平)、心血管(胸部 疼痛问卷、静息EKG、运动应激EKG、 铊闪烁照相)、血脂(循环总胆固醇、 甘油三酯、低密度脂蛋白、高密度脂蛋白、高密度脂蛋白2/高密度脂蛋白3亚组分、载脂蛋白B、E、A- 1、A-2和Apo E表型)、凝血(血浆纤维蛋白原、 凝血因子VII、抗凝血酶III活性、纤维蛋白原D-二聚体、纤维蛋白 降解产物、纤维蛋白肽A和高分子量 纤维蛋白原)、高血压(红细胞阳离子转运、血浆肾素 活性、正常和高相对分子质量肾素底物，以及 醛固酮)，骨骼(血钙、磷、肌酐，中期- PTH，25(OH)和1，25(OH)维生素D，碱性 磷酸酶、骨钙素；尿钙、羟脯氨酸和 肌酐；双光子测量腰椎和股骨颈骨量 吸光度测定法)、子宫内膜(标准组织学评估， 计算机化数字成像和雌激素受体定位)， 胆囊(超声)和乳房(体检和 乳房X光摄影)。 这些研究将全面评估激素的影响 在据信与心脏病有关的终点进行替换， 以及这种形式的其他建议的好处和风险 心理治疗。

This grant proposal is in response to RFA 87-HL-06-H Postmenopausal Estrogen/Progestin Interventions. In it we propose to study 150 postmenopausal patients using a randomized, prospective, three-way factorial, possibly doubled blind study design. Issues to be addressed are estrogen usage (present versus absent), route of administration (oral versus transdermal), dosage (low versus high) and combination therapy with a progestin (present versus absent). Patients will be studied at baseline and at 6-month intervals for 3 years on therapy. End points to be assessed are endocrine (serum estradiol, estrone, estrone sulfate, and medroxyprogesterone acetate levels), cardiovascular (chest pain questionnaire, resting EKG, exercise stress EKG, and thallium scintigraphy), lipids (circulating total cholesterol, triglycerides, LDL, HDL, HDL2/HDL3 subfractions, Apo B, E, A- 1, A-2, and Apo E phenotyping), coagulation (plasma fibrinogen, factor VII, antithrombin III activity, fibrinogen D-dimer, fibrin degradation products, fibrinopeptide A, and high molecular weight fibrinogen), hypertension (red cell cation transport, plasma renin activity, normal and high molecular weight renin substrate, and aldosterone), skeleton (serum calcium, phosphate, creatinine, mid- segment PTH, 25(OH) and 1,25(OH) vitamin D, alkaline phosphatase, and osteocalcin; urinary calcium, hydroxyproline and creatinine; and lumbar and femoral neck bone mass by dual photon absorptiometry), endometrium (standard histological assessment, computerized digital imaging and estrogen receptor localization), gallbladder (ultrasound) and breast (physical examination and mammography). These studies will comprehensively assess the impact of hormone replacement on end points believed to be related to heart disease, as well as other proposed benefits and risks of this form of therapy.