Vitale Cristiana, Cornoldi Alessandra, Gebara Otavio, Silvestri Antonello, Wajngarten Mauricio, Cerquetani Elena, Fini Massimo, Ramires José Antonio F, Rosano Giuseppe M C
Cardiovascular Research Unit Department of Medical Sciences, Fondazione San Raffaele IRCCS-Roma, Tosinvest Sanita, Roma, Italy.
Menopause. 2005 Sep-Oct;12(5):552-8. doi: 10.1097/01.gme.0000172267.24949.70. Epub 2005 Sep 1.
The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy.
We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy.
all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy.
Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.
近期随机研究观察到激素治疗缺乏有益的长期心血管效应以及心血管不良事件的早期发生，这与激素治疗增强的炎症效应有关。
我们评估了不同绝经后疗法对205名绝经后女性治疗前后炎症标志物和内皮功能的影响。
在所有绝经后女性中，单独使用雌激素可使血浆C反应蛋白（CRP）水平升高，但降低包括白细胞介素-6（IL-6）在内的所有其他炎症标志物水平（CRP：升高75%±11%，细胞间黏附分子：降低21%±4%，血管细胞黏附分子：降低15%±6%，E选择素：降低18%±4%，可溶性血栓调节蛋白降低10.5%±3.7%，IL-6降低14%±6%；变化百分比，与基线相比P<0.01）。雷洛昔芬和替勃龙对整体炎症环境无显著影响。在少数患者中，雌激素-孕激素联合用药和替勃龙可使IL-6水平升高，并引起炎症标志物的不利变化（CRP：升高93%±8%，细胞间黏附分子：降低3%±2%，血管细胞黏附分子：降低5%±2%，E选择素：升高6%±2%，可溶性血栓调节蛋白：升高5%±2%，IL-6：升高12%±4%；与基线相比的变化百分比）。IL-6水平升高的患者年龄较大且绝经时间较长。在除IL-6水平升高的患者外的所有患者中，激素治疗可改善内皮功能，而与基线相比，替勃龙和雷洛昔芬对内皮功能无显著改变。治疗期间IL-6水平升高的患者内皮功能恶化。
绝经后激素治疗与血管炎症减轻有关；然而，对于绝经时间较长的患者，绝经后激素治疗可能会增加炎症并恶化内皮功能。这些不利的血管效应可通过IL-6水平升高和内皮功能无改善来检测。
