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_ant]) alone, and an additional 3 days of GnRH_ant 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_ant + add-back. Before GnRH_ant, 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_ant 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_ant + placebo. There was no effect of vitamin C on FMD in women on GnRH_ant + 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.

在更年期过渡的各个阶段，内皮功能逐渐下降；然而，造成这种下降的机制尚不清楚。我们假设绝经前、围绝经期和绝经后女性内皮功能的差异与雌二醇和氧化应激的差异有关。对 87 名按绝经阶段分类的健康女性（24 名绝经前、17 名围绝经早期和 21 名晚期围绝经期、25 名绝经后）在卵巢激素抑制（促性腺激素释放激素拮抗剂 [GnRH）3 天之前和之后测量了肱动脉血流介导的扩张 (FMD) _ant ]）单独使用，并额外进行 3 天的 GnRH _ant联合经皮雌二醇或安慰剂回加治疗。在 82 名女性中，在 GnRH _ant + add-back 之前和之后测量了急性维生素 C（抗氧化剂）输注期间的 FMD。在 GnRH _ant之前，各组之间的 FMD 不同（ p < 0.005；在绝经阶段各阶段有所减少）。维生素 C 会增加围绝经期晚期和绝经后妇女的 FMD ( p < 0.005)，但不会增加围绝经期前后妇女的 FMD ( p > 0.54)。单独使用 GnRH _ant后，绝经前和围绝经期妇女的 FMD 有所下降（ p < 0.01），但绝经后妇女的 FMD 没有下降，并且通过雌二醇回加，绝经前和围绝经期组的 FMD 恢复至绝经前水平。维生素 C 可以改善服用 GnRH _ant + 安慰剂的绝经前、围绝经期和绝经后女性的 FMD。维生素 C 对使用 GnRH _ant + 雌二醇的女性 FMD 没有影响。这些观察结果支持这样的概念：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。