Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future
Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future
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DOI：
10.1097/gme.0b013e3182843aad
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发表时间：
2013-03-01
影响因子：
2.7
通讯作者：
Appt, Susan E.
中科院分区：
文献类型：
--
作者：
Clarkson, Thomas B.;Melendez, Giselle C.;Appt, Susan E.
目的：这项工作的目的是审查临床前/临床心血管研究，导致随机试验的风险和好处的绝经后激素治疗（HT），病理生物学基础的时间假说，和子集分析的随机试验，往往支持的时间假说;阐述实验数据，可能会告知最近的试验结果;并总结关于多早是足够早的HT开始的证据。方法：这项工作采用解释性文献综述。结果：临床前和大型观察性研究提供了当时被认为是令人信服的证据，即HT提供了防止进展的保护。冠状动脉粥样硬化这些发现促使三项随机、安慰剂对照、前瞻性试验来确定HT的风险和益处。没有任何证据表明HT对先前存在的冠状动脉粥样硬化有任何有益作用。猴子研究提供了明确的证据，表明HT仅在手术绝经后不久使用时才能有效减缓冠状动脉粥样硬化的进展，如果雌激素治疗延迟至斑块变得复杂，则益处丧失。这一现象被称为“时间假说”，并寻求其翻译成绝经后妇女的证据，在子集分析的数据，从妇女健康倡议和新计划的前瞻性trials.Conclusions：目前的数据都支持和不支持的时间假说。然而，有证据表明，雌激素在围绝经期过渡期或绝经早期给药对心血管系统无害，当给予几年治疗绝经期症状时，可能会减缓动脉粥样硬化的进展，减少绝经后心血管疾病的负担，这似乎是令人信服的。
Objective: This work aims to review preclinical/clinical cardiovascular studies that led to randomized trials of the risks and benefits of postmenopausal hormone therapy (HT), the pathobiological basis for the timing hypothesis, and subset analyses of randomized trials that tend to support the timing hypothesis; to elaborate experimental data that might inform the results of recent trials; and to summarize evidence regarding how early is early enough for the initiation of HT.Methods: This work used interpretive literature review.Results: Preclinical and large observational studies provided what was considered at the time to be convincing evidence that HT provided protection against progressing coronary artery atherosclerosis. Those findings prompted three randomized, placebo-controlled, prospective trials to determine the risks and benefits of HT. None provided any evidence that HT had any beneficial effects on preexisting coronary artery atherosclerosis. Monkey studies provided clear evidence that HT was effective in slowing the progression of coronary artery atherosclerosis only when administered soon after surgical menopause and that benefit was lost if estrogen therapy was delayed until the plaques had become complicated. The phenomenon was referred to as the "timing hypothesis," and evidence for its translation into postmenopausal women was sought in subset analyses of data from the Women's Health Initiative and from newly planned prospective trials.Conclusions: Current data are both supportive and not supportive of the timing hypothesis. However, evidence indicating that estrogens administered in the perimenopausal transition or early in menopause are not harmful to the cardiovascular system and, when given for a few years for the treatment of menopausal symptoms, may slow the progression of atherosclerosis and reduce the postmenopausal cardiovascular disease burden seems convincing.