A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: Effect on mood, cognition and quality of life
A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: Effect on mood, cognition and quality of life
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DOI：
10.1016/j.neurobiolaging.2004.12.012
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Flicker, L
中科院分区：
文献类型：
--
作者：
Almeida, OP;Lautenschlager, NT;Flicker, L
几项观察性研究的结果表明，使用雌激素替代品与更好的情绪，认知功能和生活质量有关。这些发现与实验室研究结果一致，这些研究表明雌激素促进神经元发芽，增强大脑中的胆碱能活性，降低大脑和血浆中的P-淀粉样蛋白水平，增加5-羟色胺突触后反应性和去甲肾上腺素的周转，并抑制单胺氧化酶活性。然而，来自妇女健康倡议对照试验的结果表明，激素替代（雌激素加孕酮）不仅未能改善情绪，认知和生活质量，而且还增加了患痴呆症的风险。目前，关于无对抗性雌二醇替代疗法（ERT）对认知能力下降风险增加的女性（70岁及以上）心理健康结局的影响的信息有限。我们设计了目前的随机、双盲、安慰剂对照试验来澄清这个问题。115名妇女被随机分配到雌二醇治疗组（n = 58;每天2毫克）或安慰剂组，共治疗20周。本研究中关注的结局包括基线和第20周之间贝克抑郁量表（BDI）评分的变化，以及生活质量评分（通过SF-36测量）和认知功能（CAMCOG、区组设计、面孔记忆、加州言语学习测试（CVLT）和言语流畅性（VF））的变化。19名接受雌二醇治疗的女性和10名接受安慰剂治疗的女性在试验期间停止使用药物，最常见的原因是不良反应（OR = 4.11，95% CI = 1.29-15.37）。意向治疗分析显示，活性药物组和安慰剂组在任何结果测量中对治疗的反应均无差异（p>0.05）。一项单独的分析仅限于完成20周试验的妇女，得出了类似的阴性结果。这项试验的结果表明，使用相对高剂量的无对抗性雌激素替代品20周与认知功能，情绪和生活质量的显着变化无关。需要设计其他更有效和更安全的干预措施，以改善老年妇女的精神状态和生活质量。(C)2005年爱思唯尔公司All rights reserved.
The results of several observational studies suggest that the use of estrogen replacement is associated with better mood, cognitive function and quality of life. Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting, enhances cholinergic activity in the brain, decreases brain and plasma levels of P-amyloid, increases serotonin postsynaptic responsivity and the turnover of noradrenaline, and inhibits monoamine oxidase activity. However, the findings from the Women's Health Initiative controlled trial showed that hormone replacement (estrogen plus progestin) not only failed to improve mood, cognition and quality of life but also increased the risk of dementia. At present, there is limited information about the effect of unopposed estradiol replacement therapy (ERT) on the mental health outcomes of women at increased risk of cognitive decline (aged 70 years and over). We designed the present randomized, double-blind, placebo-controlled trial to clarify this issue. One hundred and fifteen women were randomized to treatment with estradiol (n = 58; 2 mg per day) or placebo for a total period of 20 weeks. The outcomes of interest in this study included changes in the Beck Depression Inventory (BDI) scores between baseline and week 20, as well as changes in quality of life scores (as measured by the SF-36) and cognitive function (CAMCOG, Block Design, Memory for Faces, California Verbal Learning Test (CVLT) and verbal fluency (VF)). Nineteen women treated with estradiol and 10 of those treated with placebo discontinued the use of the medication during trial, most frequently due to adverse reactions (OR = 4.11, 95% CI = 1.29-15.37). Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures (p>0.05). A separate analysis restricted to women who completed the 20-week-trial produced similar negative results. The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function, mood and quality of life. Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women. (C) 2005 Elsevier Inc. All rights reserved.