Section on Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27157-1040, USA.
Menopause. 2013 May;20(5):540-7. doi: 10.1097/GME.0b013e31827461e0.
The aim of this study was to determine the effects of estrogen therapy (ET) on carotid artery inflammation when initiated early and late relative to surgical menopause.
Female cynomolgus macaques consuming atherogenic diets were ovariectomized and randomized to control or oral estradiol (E2; human equivalent dose of 1 mg/d micronized E2) initiated at 1 month (early menopause, n = 24) or 54 months (late menopause, n = 40) after ovariectomy. The treatment period was 8 months. Carotid artery expression of the markers of monocyte/macrophages (CD68 and CD163), dendritic cells (CD83), natural killer cells (neural cell adhesion molecule-1), and interferon-γ was significantly lower in E2-treated animals in the early menopause group but not in the late menopause group (P < 0.05). In contrast, carotid artery transcripts for T-cell markers (CD3, CD4, CD8, and CD25), interleukin-10, type I collagen, monocyte chemoattractant protein-1, matrix metalloproteinase-9, and tumor necrosis factor-α were lower in E2-treated monkeys regardless of menopausal stage (P < 0.05).
ET initiated soon after menopause inhibits macrophage accumulation in the carotid artery, an effect that is not observed when E2 is administered after several years of estrogen deficiency. No evidence for pro-inflammatory effects of late ET is observed. The results provide support for the timing hypothesis of postmenopausal ET with implications for the interpretation of outcomes in the Women's Health Initiative.
本研究旨在确定雌激素治疗（ET）对手术绝经后早期和晚期开始的颈动脉炎症的影响。
食用动脉粥样硬化饮食的雌性食蟹猴被卵巢切除术，并随机分为对照组或口服雌二醇（E2；人用等效剂量 1mg/d 微粒化 E2），分别于卵巢切除后 1 个月（早期绝经，n=24）或 54 个月（晚期绝经，n=40）开始。治疗期为 8 个月。早期绝经组 E2 治疗的动物颈动脉中单核细胞/巨噬细胞（CD68 和 CD163）、树突状细胞（CD83）、自然杀伤细胞（神经细胞黏附分子-1）和干扰素-γ的标志物表达显著降低，但晚期绝经组则没有（P<0.05）。相比之下，无论绝经阶段如何，E2 治疗的猴子颈动脉中的 T 细胞标志物（CD3、CD4、CD8 和 CD25）、白细胞介素-10、I 型胶原、单核细胞趋化蛋白-1、基质金属蛋白酶-9 和肿瘤坏死因子-α 的转录物均较低（P<0.05）。
绝经后早期开始 ET 可抑制颈动脉中巨噬细胞的积累，而在雌激素缺乏数年后给予 E2 则观察不到这种作用。没有证据表明晚期 ET 具有促炎作用。结果为绝经后 ET 的时间假说提供了支持，对理解妇女健康倡议的结果具有启示意义。
