口服结合马雌激素与经皮雌二醇对自然绝经女性C反应蛋白、其他炎症血清标志物及其他肝脏蛋白的短期影响比较。
A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women.
作者信息
Shifren Jan L, Rifai Nader, Desindes Sophie, McIlwain Marilyn, Doros Gheorghe, Mazer Norman A
机构信息
Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, 670 Albany Street, Boston, MA 02118, USA.
出版信息
J Clin Endocrinol Metab. 2008 May;93(5):1702-10. doi: 10.1210/jc.2007-2193. Epub 2008 Feb 26.
OBJECTIVE
Our objective was to compare the effects of oral vs. transdermal estrogen therapy on C-reactive protein (CRP), IL-6, E- and P-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1, serum amyloid A, transferrin, prealbumin, IGF-I, SHBG, thyroxine-binding globulin (TBG), and cortisol-binding globulin (CBG) in naturally menopausal women.
DESIGN
This was a randomized, open-label crossover clinical trial. A 6-wk withdrawal from prior hormone therapy (baseline) was followed in randomized order by 12-wk oral conjugated equine estrogens (CEEs) (0.625 mg/d) and 12-wk transdermal estradiol (E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both regimens.
RESULTS
A total of 27 women enrolled, and 25 completed both treatment periods. Nine parameters changed significantly during oral CEE (median percent change from baseline; P value): CRP (192%; P <0.001); E-selectin (-16.3%; P = 0.003); P-selectin (-15.3%; P = 0.012); ICAM-1 (-5%; P = 0.015); transferrin (5.3%; P = 0.024); IGF-I (-30.5%; P < 0.001); SHBG (113%; P < 0.001); TBG (38%; P < 0.001); and CBG (20%; P < 0.001). With transdermal E2, only three parameters changed significantly and to a lesser degree: ICAM-1 (-2.1%; P = 0.04); IGF-I (-12.5%; P < 0.001); and SHBG (2.6%; P = 0.042). During oral CEE the intrasubject changes in CRP correlated strongly with the changes in serum amyloid A (r = 0.805; P < 0.001), and were only weakly associated with the changes in SHBG (r = 0.248; nonsignificant), TBG (0.430; P = 0.031), and CBG (r = 0.072; nonsignificant). The log-log relationship between CRP and IL-6 observed at baseline showed a parallel shift during oral CEE, suggesting an amplified hepatic response or a greater sensitivity to IL-6 stimulation.
CONCLUSION
Compared with oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters.
目的
我们的目的是比较口服与经皮雌激素疗法对自然绝经女性的C反应蛋白（CRP）、白细胞介素-6（IL-6）、E-选择素和P-选择素、细胞间黏附分子（ICAM）-1和血管细胞黏附分子-1、血清淀粉样蛋白A、转铁蛋白、前白蛋白、胰岛素样生长因子-I（IGF-I）、性激素结合球蛋白（SHBG）、甲状腺素结合球蛋白（TBG）和皮质醇结合球蛋白（CBG）的影响。
设计
这是一项随机、开放标签的交叉临床试验。在从先前激素治疗中撤药6周（基线）后，随机依次给予12周口服结合马雌激素（CEE）（0.625mg/d）和12周经皮雌二醇（E2）（0.05mg/d），两种治疗方案期间均持续给予口服微粒化孕酮（100mg/d）。
结果
共有27名女性入组，25名完成了两个治疗期。口服CEE期间，9项参数有显著变化（相对于基线的中位变化百分比；P值）：CRP（192%；P<0.001）；E-选择素（-1−6.3%；P = 0.003）；P-选择素（-1−5.3%；P = 0.012）；ICAM-1（-5%；P = 0.015）；转铁蛋白（5.3%；P = 0.024）；IGF-I（-3−0.5%；P<0.001）；SHBG（113%；P<0.001）；TBG（38%；P<0.001）；CBG（20%；P<0.001）。经皮E2治疗时，只有3项参数有显著变化且变化程度较小：ICAM-1（-2.1%；P = 0.04）；IGF-I（-1−2.5%；P<0.001）；SHBG（2.6%；P = 0.042）。口服CEE期间，受试者体内CRP的变化与血清淀粉样蛋白A的变化密切相关（r = 0.805；P<0.001），而与SHBG的变化（r = 0.248；无显著性）、TBG的变化（0.430；P = 0.031）和CBG的变化（r = 0.072；无显著性）仅弱相关。在基线时观察到的CRP与IL-6之间的对数-对数关系在口服CEE期间呈现平行移动，提示肝脏反应增强或对IL-6刺激的敏感性增加。
结论
与口服CEE相比，经皮E2对CRP及其他炎症和肝脏参数的影响极小。
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