Hsia Judith, Otvos James D, Rossouw Jacques E, Wu LieLing, Wassertheil-Smoller Sylvia, Hendrix Susan L, Robinson Jennifer G, Lund Bernedine, Kuller Lewis H
Department of Medicine, George Washington University, Washington, DC, USA.
Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1666-71. doi: 10.1161/ATVBAHA.108.170431. Epub 2008 Jul 3.
The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case-control substudy.
We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P).
Postmenopausal hormone therapy-induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials.
妇女健康倡议（Women's Health Initiative）随机激素试验意外地显示早期冠状动脉事件有所增加。为了解释这一发现，我们在一项病例对照子研究中检查了脂蛋白颗粒浓度及其与激素治疗的相互作用。
我们将16608名子宫完整的绝经后妇女随机分为两组，一组每天服用0.625毫克结合雌激素加2.5毫克醋酸甲羟孕酮，另一组服用安慰剂；将10739名既往有子宫切除术的妇女随机分为两组，一组每天服用0.625毫克结合雌激素，另一组服用安慰剂。在354名发生早期冠状动脉事件的妇女及其匹配对照中，于基线和第1年通过核磁共振波谱法测量脂蛋白亚类。绝经后激素治疗可提高高密度脂蛋白胆固醇及其颗粒浓度，并降低低密度脂蛋白胆固醇（LDL-C；与安慰剂相比，所有P<0.001）。相比之下，单用雌激素或雌激素加孕激素均未降低低密度脂蛋白颗粒浓度（LDL-P）。
绝经后激素治疗引起的LDL-C降低并未伴随对LDL-P的有益影响。这一发现可能解释了在随机激素试验中雌激素缺乏冠状动脉保护作用的原因。
