Haines C J, Chung T K, Masarei J R, Tomlinson B, Lau J T
Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, New Territories.
Atherosclerosis. 1996 Jan 26;119(2):215-22. doi: 10.1016/0021-9150(95)05650-5.
Lipoprotein(a) (Lp(a)) is an independent marker of cardiovascular disease which is relatively unresponsive to treatment with most of the commonly prescribed lipid lowering drugs. Concentrations of Lp(a) increase after the menopause, and the primary aim of this study was to determine whether combined hormone replacement therapy was effective in lowering levels of Lp(a) in postmenopausal women. An open longitudinal study was conducted among 42 women who had undergone a spontaneous menopause and were attending the outpatient clinic of the Prince of Wales Hospital, Hong Kong. All subjects were treated with 2 mg oral estradiol daily and 5 mg medroxyprogesterone acetate for 12 days each calendar month. Fasting blood samples for lipoprotein measurement were taken before the commencement of treatment and at 6 and 12 months. Lp(a) levels showed a skewed distribution with a median value before treatment of 9.45 mg/dl (range 1.47-95.62 mg/dl). After 6 months, there was a reduction to 7.70 mg/dl (1.12-72.59 mg/dl) (P < 0.01), and after 12 months the median concentration was 7.14 mg/dl (0.63-69.23 mg/dl) (P < 0.001 0-12 months). There were also significant reductions in the concentrations of apo B from 116.13 to 111.62 mg/dl and LDL-C from 3.02 to 2.74 mmol/l (P < 0.05), plus a lowering of TC of borderline significance. Apo A-I increased from 162.56 to 173.35 mg/dl (P < 0.01), but there were no significant changes in HDL-C or the HDL-C subfractions. TC, LDL-C, apo B and TG concentrations were higher and HDL-C and HDL2-C concentrations were lower when blood was sampled during combined treatment with estrogen and progesterone than when estrogen was being taken alone. Levels of Lp(a) were also lower during the estrogen only phase of treatment, but none of these differences were statistically significant. This study demonstrates that combined cyclical hormone replacement therapy is effective in reducing concentrations of Lp(a). The trend towards a more atherogenic lipid profile during the combined phase of treatment suggests that attention should be given to the timing of blood sampling in future studies of this nature.
脂蛋白(a)[Lp(a)]是心血管疾病的一个独立标志物，对大多数常用降脂药物治疗反应相对不敏感。绝经后Lp(a)浓度会升高，本研究的主要目的是确定联合激素替代疗法是否能有效降低绝经后女性的Lp(a)水平。对42名自然绝经且在香港威尔士亲王医院门诊就诊的女性进行了一项开放性纵向研究。所有受试者每月口服2毫克雌二醇和5毫克醋酸甲羟孕酮，各服用12天。在治疗开始前以及治疗6个月和12个月时采集空腹血样用于脂蛋白测定。Lp(a)水平呈偏态分布，治疗前中位数为9.45毫克/分升(范围1.47 - 95.62毫克/分升)。6个月后降至7.70毫克/分升(1.12 - 72.59毫克/分升)(P < 0.01)，12个月时中位数浓度为7.14毫克/分升(0.63 - 69.23毫克/分升)(P < 0.001，0至12个月)。载脂蛋白B浓度也从116.13显著降至111.62毫克/分升，低密度脂蛋白胆固醇从3.02降至2.74毫摩尔/升(P < 0.05)，总胆固醇有临界显著降低。载脂蛋白A - I从162.56升高至173.35毫克/分升(P < 0.01)，但高密度脂蛋白胆固醇或高密度脂蛋白胆固醇亚组分无显著变化。与仅服用雌激素时相比，雌激素和孕激素联合治疗期间采血时总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B和甘油三酯浓度更高，高密度脂蛋白胆固醇和高密度脂蛋白2 - C浓度更低。仅使用雌激素治疗阶段Lp(a)水平也较低，但这些差异均无统计学意义。本研究表明，周期性联合激素替代疗法可有效降低Lp(a)浓度。联合治疗阶段血脂谱更具致动脉粥样硬化倾向这一趋势表明，在今后此类研究中应关注采血时间。
