Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
Curr Opin Cardiol. 2013 Jul;28(4):411-6. doi: 10.1097/HCO.0b013e32836205e7.
Observational studies have shown benefit of hormone therapy, particularly estrogen, in women who begin treatment in the perimenopausal/early postmenopausal period, whereas randomized controlled trials of such therapy in older postmenopausal women have reported harm. These apparently paradoxical findings have led to the 'timing hypothesis' which proposes that estrogen signaling is altered in older women, converting vasoprotective to vasotoxic effects. We reviewed recent literature on age-dependent effects of hormones (particularly estrogen) on the vasculature of women and the fundamental cellular/molecular mechanisms responsible for those effects.
Observational studies have shown that early menopause is associated with adverse cardiovascular disease outcomes and that starting hormone therapy in the perimenopausal period reduces these outcomes. Mechanistic studies have shown that estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and vascular smooth muscle cells isolated from young women but that these vasoprotective mechanisms are lost in women who are aged and/or deprived of estrogen for prolonged periods of time.
The vasoprotective effects of estrogen are age-dependent and disappear with aging and/or estrogen deprivation. Future studies designed to preserve the vasoprotective effects of estrogen in older women are needed and may lead to innovative approaches to improving women's cardiovascular health.
观察性研究表明，激素治疗（特别是雌激素）对围绝经期/绝经早期开始治疗的女性有益，而此类治疗在老年绝经后女性中的随机对照试验则报告存在危害。这些明显矛盾的发现导致了“时间假说”，该假说提出，雌激素信号在老年女性中发生改变，将血管保护作用转化为血管毒性作用。我们回顾了近期关于激素（特别是雌激素）对女性血管的年龄依赖性影响以及这些影响的基本细胞/分子机制的文献。
观察性研究表明，早期绝经与不良心血管疾病结局相关，而在围绝经期开始激素治疗可降低这些结局。机制研究表明，雌激素可调节年轻女性动脉和血管平滑肌细胞中损伤诱导的炎症、生长因子表达和氧化应激，但在年龄较大和/或长期缺乏雌激素的女性中，这些血管保护机制丧失。
雌激素的血管保护作用具有年龄依赖性，随着年龄的增长和/或雌激素的缺乏而消失。需要进行旨在保留老年女性雌激素的血管保护作用的未来研究，这可能会为改善女性心血管健康带来创新方法。
