Ball Jacob D, Chen Xinguang
Department of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, 2004 Mowry Road, CTRB #4228, Gainesville, FL 32610 USA.
Glob Health Res Policy. 2016 Jul 30;1:9. doi: 10.1186/s41256-016-0009-4. eCollection 2016.
Reducing disease risk for women after menopause is global health issue. A major portion of the Women's Health Initiative (WHI) consisted of two clinical trials involving 161,809 post-menopausal women aged 50-79 that tested the effect of hormone replacement therapy (HRT) on reducing cardiovascular disease and other secondary outcomes. Previous analyses of the data reveal that HRT should not be recommended for post-menopausal women, but show potential benefits for younger women. Thus, there may be a critical period just prior to or during the early stages of menopause where HRT could be both safe and beneficial.
Menopause marks the beginning of a process of non-reversible reduction in estrogen by which estrogen levels decline progressively, followed by a reduction in estrogen receptors. This results in periods of hormone-receptor imbalances, exacerbating the effects of lower serum estrogen and is considered the primarily endocrinal source of menopause symptoms. Eventually a hormone-receptor balance is achieved at a lower level.Here, we purport that the negative outcomes from WHI trials were primarily due to the fact preventive HRT was initiated in women who had already achieved hormone-receptor equilibrium at lower hormonal levels.
We argue for further HRT clinical trials in women at varying stages of menopause, including pre-menopause and early menopause, and in women from different countries. Variation across countries and subgroups in how women experience menopause and perceive menopause symptoms suggest that biocultural differences should be considered in both study design and measurement approaches to test the effectiveness of HRT. Particularly, we recommend longitudinal studies to assess changes in hormonal level over time, and to detect the "most effective period" for HRT to reduce health risk for women going through the whole menopause period.
降低绝经后女性的疾病风险是一个全球性的健康问题。女性健康倡议（WHI）的一项主要内容包括两项临床试验，涉及161,809名年龄在50 - 79岁的绝经后女性，试验旨在测试激素替代疗法（HRT）对降低心血管疾病及其他次要结局的效果。此前对这些数据的分析表明，不建议为绝经后女性使用HRT，但对年轻女性可能有潜在益处。因此，在绝经前或绝经早期可能存在一个关键时期，此时HRT既安全又有益。
绝经标志着雌激素不可逆减少过程的开始，在此过程中雌激素水平逐渐下降，随后雌激素受体减少。这会导致激素 - 受体失衡期，加剧血清雌激素水平降低的影响，被认为是绝经症状的主要内分泌来源。最终在较低水平实现激素 - 受体平衡。在此，我们认为WHI试验的负面结果主要是由于预防性HRT是在已经在较低激素水平实现激素 - 受体平衡的女性中开始的。
我们主张针对处于不同绝经阶段（包括绝经前和绝经早期）的女性以及来自不同国家的女性开展进一步的HRT临床试验。不同国家和亚组的女性在经历绝经和感知绝经症状方面存在差异，这表明在研究设计和测量方法中都应考虑生物文化差异，以测试HRT的有效性。特别是，我们建议进行纵向研究，以评估激素水平随时间的变化，并检测HRT降低处于整个绝经阶段女性健康风险的“最有效时期”。
