Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, 750 Republican St, Seattle WA 98109, USA.
Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, 101 Manning Drive, Chapel Hill, NC 27599, USA.
J Clin Lipidol. 2021 Jan-Feb;15(1):151-161.e0. doi: 10.1016/j.jacl.2020.11.009. Epub 2020 Nov 24.
The cardiovascular (CV) safety of estrogen replacement therapy (ERT) in perimenopausal women remains uncertain. Although exogenous estrogens increase HDL cholesterol (HDL-C), estrogen-mediated effects on alternative metrics of HDL that may better predict CV risk are unknown.
To determine the effects of transdermal ERT on HDL composition and cholesterol efflux capacity (CEC), as well as the relationships between these metrics and CV risk factors.
Fasting plasma samples were analyzed from 101 healthy, perimenopausal women randomized to receive either transdermal placebo or transdermal estradiol (100 μg/24 h) with intermittent micronized progesterone. At baseline and after 6 months of treatment, serum HDL CEC, HDL particle concentration, HDL protein composition, insulin resistance and brachial artery flow-mediated dilatation (FMD) were measured.
No difference between groups was found for change in plasma HDL-C (p = 0.69). Between-group differences were found for changes in serum HDL total CEC [median change from baseline -5.4 (-17.3,+8.4)% ERT group versus +5.8 (-6.3,+16.9)% placebo group, p = 0.01] and ABCA1-specific CEC [median change from baseline -5.3 (-10.7,+6.7)% ERT group versus +7.4 (-1.5,+18.1)% placebo group, p = 0.0002]. Relative to placebo, transdermal ERT led to reductions in LDL-C (p < 0.0001) and insulin resistance (p = 0.0002). An inverse correlation was found between changes in serum HDL total CEC and FMD (β = -0.26, p = 0.004).
Natural menopause leads to an increase in serum HDL CEC, an effect that is abrogated by transdermal ERT. However, transdermal ERT leads to favorable changes in major CV risk factors.
围绝经期女性使用雌激素替代疗法（ERT）的心血管（CV）安全性仍不确定。虽然外源性雌激素可增加高密度脂蛋白胆固醇（HDL-C），但雌激素对可能更好地预测 CV 风险的 HDL 替代指标的影响尚不清楚。
确定经皮 ERT 对 HDL 组成和胆固醇流出能力（CEC）的影响，以及这些指标与 CV 危险因素之间的关系。
分析了 101 名健康、围绝经期妇女的空腹血浆样本，这些妇女被随机分为接受经皮安慰剂或经皮雌二醇（100μg/24 小时）联合间歇性米诺孕素治疗。在基线和治疗 6 个月后，测量血清 HDL CEC、HDL 颗粒浓度、HDL 蛋白组成、胰岛素抵抗和肱动脉血流介导的舒张（FMD）。
两组间血浆 HDL-C 的变化无差异（p=0.69）。两组间血清 HDL 总 CEC 的变化存在差异[从基线到治疗的中位数变化-5.4（-17.3，+8.4）%ERT 组与+5.8（-6.3，+16.9）%安慰剂组，p=0.01]和 ABCA1 特异性 CEC[从基线到治疗的中位数变化-5.3（-10.7，+6.7）%ERT 组与+7.4（-1.5，+18.1）%安慰剂组，p=0.0002]。与安慰剂相比，经皮 ERT 可降低 LDL-C（p<0.0001）和胰岛素抵抗（p=0.0002）。血清 HDL 总 CEC 的变化与 FMD 呈负相关（β=-0.26，p=0.004）。
自然绝经导致血清 HDL CEC 增加，经皮 ERT 可消除这一影响。然而，经皮 ERT 可导致主要 CV 危险因素的有利变化。
