Saarto T, Blomqvist C, Ehnholm C, Taskinen M R, Elomaa I
Department of Oncology, Helsinki University Central Hospital, Finland.
J Clin Oncol. 1996 Feb;14(2):429-33. doi: 10.1200/JCO.1996.14.2.429.
To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen.
Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy.
Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%).
These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.
评估新型抗雌激素药物托瑞米芬是否具有与他莫昔芬相似的抗动脉粥样硬化作用。
49例绝经后淋巴结阳性乳腺癌患者被随机纳入一项试验,比较他莫昔芬和托瑞米芬对血清脂蛋白的影响。他莫昔芬剂量为每日20 mg,托瑞米芬剂量为每日60 mg,口服3年。在抗雌激素治疗12个月前后,测量血清载脂蛋白(apo)A-I、A-II和B、脂蛋白(a)[Lp(a)]、胆固醇、甘油三酯、高密度脂蛋白(HDL)胆固醇、低密度脂蛋白(LDL)胆固醇、促卵泡激素(FSH)、黄体生成素(LH)和雌二醇的浓度。
两种抗雌激素药物均显著降低血清总胆固醇和LDL胆固醇以及apo B水平。然而,两组中HDL胆固醇对治疗的反应明显不同。托瑞米芬使HDL水平升高14%,而他莫昔芬使其降低5%(P = .001)。因此,托瑞米芬组的胆固醇与HDL比值和LDL与HDL比值下降幅度均大于他莫昔芬组(分别为P = .008和P = .03)。托瑞米芬还使apo A-I水平升高(P = .00007)以及apo A-I与A-II比值升高(P = .018)。他莫昔芬和托瑞米芬均显著降低Lp(a)浓度(变化分别为34%和41%)。
这些结果提供了积极证据,表明托瑞米芬具有抗动脉粥样硬化特性,能够改善所有与冠心病(CHD)风险增加相关的脂蛋白。