MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW

提案(改编自申请人的摘要)：绝经后雌激素 替代疗法(ERT)已经成为老年妇女的一种公认的干预措施。 最近发表的心脏与雌激素和孕激素替代疗法 研究(HERS)做出了启动绝经后ERT的艰难决定 这对临床医生来说更加困难。都是小而密的低密度脂蛋白 低密度脂蛋白(LDL)和纤溶酶原激活物抑制物-1(PAI-1)是 随着更年期的增加而增加的冠状动脉疾病(CAD)，可能代表 未来个体冠心病风险的标志物。建议的主要目标是 这项研究是为了调查在整个子宫中出现小而密集的低密度脂蛋白的女性 更年期将选择性地受益于经皮ERT。其作用机制 低密度脂蛋白大小变化的基础也将通过测量肝脏 脂肪酶活性、胆固醇酯转运蛋白(CETP)活性、 甘油三酯水平、体脂分布与肝脂酶基因 启动子的多态，都知道影响低密度脂蛋白的大小。调查人员将 还确定了绝经后出现小而密的低密度脂蛋白的女性是否也 PAI-1升高。这是一种前瞻性的、随机的、非盲目的交叉 两组绝经后妇女口服和透皮ERT的对比试验 从绝经前状态开始就一直被跟踪。二十三个 绝经后的女性在绝经后会出现小而密的低密度脂蛋白 相比之下，23名绝经后女性的低密度脂蛋白水平仍然很高。 他们将被随机分成六个月的透皮或口服ERT疗程 在第二次ERT开始前有六个月的冲洗期 当然了。这项研究将确定是否有更好的方法来 绝经后发生小密度低密度脂蛋白的妇女的ERT亚组 更年期。他们还将阐明这些转变背后的机制。 在低密度脂蛋白大小与口服和经皮ERT。

PROPOSAL (Adapted from the applicant's abstract): Postmenopausal estrogen replacement therapy (ERT) has become an accepted intervention in aging women. The recent publication of the Heart and Estrogen and Progestin Replacement Study (HERS) has made the difficult decision to initiate postmenopausal ERT even more difficult for clinicians. Both small, dense low density lipoprotein (LDL) and plasminogen activator inhibitor Type 1 (PAI-1) are risk factors for coronary artery disease (CAD) that increase with menopause and may represent markers of future individual CAD risk. The primary objective of the proposed study is to investigate whether women who develop small, dense LDL across the menopause will selectively benefit from transdermal ERT. The mechanisms underlying the changes in LDL size will also be studied by measuring hepatic lipase activity, cholesteryl ester transfer protein (CETP) activity, triglyceride (TG) levels, body fat distribution and the hepatic lipase gene promoter polymorphism, all known to affect LDL size. The investigators will also determine whether women who develop small, dense LDL with menopause also have elevated PAI-1. This is a prospective, randomized non-blinded crossover trial comparing oral and transdermal ERT in two groups of postmenopausal women who have been followed since the premenopausal state. Twenty-three postmenopausal women who have developed small, dense LDL with menopause will be compared to 23 postmenopausal women who remain with large, buoyant LDL. They will be randomized to a six-month course of transdermal or oral ERT followed by a six-month washout period before the start of the second ERT course. This study will determine if there is a preferred method of postmenopausal ERT in the subset of women who develop small, dense LDL after menopause. They will also elucidate the mechanisms that underlie the shifts in LDL size with oral and transdermal ERT.