Postmenopausal hormone replacement therapy for prevention of coronary heart disease

绝经后激素替代疗法预防冠心病

• 批准号: 14571567
• 负责人: WAKATSUKI Akihiko
• 金额: $ 2.11万
• 依托单位: KOCHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571567/
• 关键词: postmenopausal women; transdermal HRT; coronary heart disease; vascular inflammation; エストロゲン補充; 中性脂肪; LDLサイズ

(Objectives) Postmenopausal hormorie replacement therapy(HRT) decreases the incidence of coronary heart disease(CHD). According to the recent studies, however, HRT increased the risk of CHD in postmenopausal women. We previously demonstrated that oral HRT increases vascular inflammatory markers such as C-reactive protein(CRP) concentrations. In the present study, we evaluated whether oral HRT have a pro-inflammatory effect and investigated the effects of transdermal HRT on vascular inflammatory markers.(Methods and Results) Postmenopausal women received no treatment or were treated with 0.625mg oral conjugated equine estrogen daily or with transdermal estradiol(25μg/day,n=15) for 3 months. Oral ERT significantly increased plasma concentrations of CRP, serum amyloid A protein(SAA), and matrix metalloproteinase(MMP)-3, but significantly decreased tissue inhibitor of MMP(TIMP)-1 concentrations by 8.6%. In contrast, transdermal ERT significantly decreased CRP concentrations and tended to increase TIMP-1 concentrations. Oral ERT significantly, decreased p-selectin concentrations, but the concentrations of intercellular adhesion molecule(ICAM-1) and vascular cell adhesion molecule(VCAM-1) did not change significantly. Transdermal ERT, however, significantly decreased all cell adhesion molecule concentrations.(Conclusion) Oral HRT may have a pro-inflammatory effect by increasing vascular inflammatory markers. Oral HRT-induced increases in inflammatory markers and imbalances between MMP and TIMP-1 might be reversed by transdermal administration of estrogen. Because transdermally administered estrogen decreased cell adhesion molecule concentrations, the anti-inflammatory effect of transdermal HRT may actually be responsible for the favorable effect of estrogen on cell adhesion molecule, concentrations in postmenopausal women.

目的绝经后激素替代疗法（HRT）可降低冠心病（CHD）的发病率。然而，根据最近的研究，HRT增加了绝经后妇女冠心病的风险。我们以前证明，口服HRT增加血管炎症标志物，如C-反应蛋白（CRP）浓度。在本研究中，我们评估了口服HRT是否具有促炎作用，并研究了经皮HRT对血管炎症标志物的影响。（方法和结果）15例绝经后妇女不接受任何治疗，或每天口服0.625mg结合雌激素或每天透皮雌二醇（25μg，n=15）治疗3个月。口服ERT显著增加CRP、血清淀粉样蛋白A蛋白（SAA）和基质金属蛋白酶（MMP）-3的血浆浓度，但显著降低MMP组织抑制剂（TIMP）-1浓度8.6%。相反，经皮ERT显著降低CRP浓度，并倾向于增加TIMP-1浓度。口服ERT可显著降低P-选择素浓度，但对细胞间粘附分子（ICAM-1）和血管细胞粘附分子（VCAM-1）浓度无明显影响。然而，经皮ERT显著降低了所有细胞粘附分子的浓度。结论口服HRT可能通过增加血管炎性标志物而发挥促炎作用。口服HRT诱导的炎症标志物增加和MMP和TIMP-1之间的不平衡可能会逆转经皮给药的雌激素。因为经皮给药雌激素降低细胞粘附分子浓度，经皮HRT的抗炎作用实际上可能是雌激素对绝经后妇女细胞粘附分子浓度的有利影响的原因。

项目成果

Wakatsuki A, Okatani Y, Fukaya T: "Effect of transdermal estradiol and oral conjugated equine estrogen on C-reactive protein in retinoid-placebo trial in healthy women"Circulation. (in press).

Wakatsuki A、Okatani Y、Fukaya T：“在健康女性的类维生素A-安慰剂试验中，透皮雌二醇和口服结合马雌激素对 C 反应蛋白的影响”循环。

Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T: "The antiinflammatory properties of medroxyprogesterone acetate."Circulation. 106. e185 (2002)

Wakatsuki A、Okatani Y、Ikenoue N、Fukaya T：“醋酸甲羟孕酮的抗炎特性。”循环。

Wakatsuki A.: "Postmenopausal hormone replacement therapy and cardiovascular disease.(Progress in Hormone Replacement Therapy Research)"Nova Science Publishers, USA(in press).

Wakatsuki A.：“绝经后激素替代疗法和心血管疾病。（激素替代疗法研究进展）”Nova Science Publishers，美国（出版中）。

Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T: "Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women."Circulation.

Wakatsuki A、Okatani Y、Ikenoue N、Fukaya T：“口服结合马雌激素和透皮雌激素替代疗法对绝经后妇女低密度脂蛋白颗粒大小和氧化敏感性的不同影响。”循环。

Wakatsuki A, Okatani Y, Ikenoue N, Shinohara K, Watanabe K, Fukaya T: "Effect of lower dose of oral conjugated equine estrogen on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women."Circulation. 108. 808 (2003)

Wakatsuki A、Okatani Y、Ikenoue N、Shinohara K、Watanabe K、Fukaya T：“低剂量口服结合马雌激素对绝经后妇女低密度脂蛋白颗粒大小和氧化敏感性的影响。”循环。