Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Bldg. L15 Rm 8111, 12631 East 17th Ave., Mail Stop B179, Aurora, CO, 80045, USA.
Veterans Affairs Eastern Colorado Geriatric Research, Education and Clinical Center, Denver, CO, USA.
Geroscience. 2020 Dec;42(6):1699-1714. doi: 10.1007/s11357-020-00236-7. Epub 2020 Aug 8.
Endothelial function declines progressively across stages of the menopause transition; however, the mechanisms contributing to this decline are unknown. We hypothesized that differences in endothelial function among pre-, peri, and postmenopausal women are related to differences in estradiol and oxidative stress. Brachial artery flow-mediated dilation (FMD) was measured in 87 healthy women categorized by menopause stage (24 premenopausal, 17 early and 21 late perimenopausal, and 25 postmenopausal) before and after 3 days of ovarian hormone suppression (gonadotropin releasing hormone antagonist [GnRH]) alone, and an additional 3 days of GnRH with concurrent transdermal estradiol or placebo add-back treatment. In 82 women, FMD during acute vitamin C (antioxidant) infusion was measured before and after GnRH + add-back. Before GnRH, FMD was different among groups (p < 0.005; reduced across stages of menopause). Vitamin C increased FMD in late peri- and post- (p < 0.005) but not pre- or early perimenopausal women (p > 0.54). After GnRH alone, FMD decreased in pre- and peri- (p < 0.01), but not postmenopausal women, and was restored to premenopausal levels by estradiol add-back in the pre- and perimenopausal groups. Vitamin C improved FMD in pre-, peri-, and postmenopausal women on GnRH + placebo. There was no effect of vitamin C on FMD in women on GnRH + estradiol. These observations support the concept that the decline in endothelial function across the menopause transition is related to the loss of ovarian estradiol. The decline in estradiol may alter redox balance, thereby increasing oxidative stress and impairing endothelial function.
血管内皮功能随着绝经过渡阶段的进展而逐渐下降；然而，导致这种下降的机制尚不清楚。我们假设，绝经前、绝经中和绝经后妇女之间的内皮功能差异与雌二醇和氧化应激的差异有关。在 87 名健康女性中，根据绝经阶段（24 名绝经前、17 名早期和 21 名晚期绝经中、25 名绝经后）进行分类，在单独使用促性腺激素释放激素拮抗剂（GnRH）抑制卵巢激素 3 天前后，以及在 GnRH 联合透皮雌二醇或安慰剂添加治疗的另外 3 天，测量肱动脉血流介导的扩张（FMD）。在 82 名女性中，在 GnRH 加添加物前后测量了急性维生素 C（抗氧化剂）输注期间的 FMD。在 GnRH 之前，FMD 在各组之间存在差异（p < 0.005；随着绝经过渡阶段的进展而降低）。维生素 C 增加了晚期绝经中和绝经后（p < 0.005）但不是早期绝经中和绝经前（p > 0.54）女性的 FMD。单独使用 GnRH 后，FMD 在绝经前和绝经中减少（p < 0.01），但在绝经后女性中没有减少，并且在绝经前和绝经中组中，雌二醇添加物恢复到绝经前水平。在 GnRH + 安慰剂组中，维生素 C 改善了绝经前、绝经中和绝经后女性的 FMD。维生素 C 对 GnRH + 雌二醇女性的 FMD 没有影响。这些观察结果支持这样的概念，即绝经过渡期间内皮功能的下降与卵巢雌二醇的丧失有关。雌二醇的下降可能会改变氧化还原平衡，从而增加氧化应激并损害内皮功能。
