Naessen T, Rodriguez-Macias K, Lithell H
Department of Women's and Children's Health, Section for Obstetrics and Gynecology, University Hospital, SE-751 85 Uppsala, Sweden.
J Clin Endocrinol Metab. 2001 Jun;86(6):2757-62. doi: 10.1210/jcem.86.6.7524.
To determine whether ultra-low doses of estradiol (E(2)) affect the serum lipid profile in elderly women, we analyzed changes in serum lipids and lipoproteins in 70 healthy women, 60 yr and older, randomly assigned to parenteral E(2) (7.5 microg per 24 h) delivered by a vaginal ring (Estring; Pharmacia-Upjohn, Malmö, Sweden) or no treatment for 12 months. Baseline serum estrone sulfate (E1S), but not E(2) or serum FSH, was negatively associated with serum total cholesterol (P = 0.026), low-density lipoprotein (LDL) cholesterol (P = 0.053), and apolipoprotein B levels (P = 0.023). Compared with no treatment, Estring treatment yielded nonsignificant increases within the normal postmenopausal range in serum E1S (+16%) and E(2) (+13%), but significantly reduced serum LDL cholesterol by 7.6% (-0.32 mmol/L; 95% confidence interval, -0.58, -0.07; P = 0.014) and LDL to high-density lipoprotein (HDL) ratio by 7.3% (-0.19 mmol/L; 95% confidence interval, -0.44, -0.06; P = 0.030). In Estring users values were significantly reduced in total cholesterol (by 4%), LDL cholesterol (by 7%), LDL to HDL ratio (by 7%), and apolipoprotein B (by 4%), and significantly increased in serum HDL triglyceride (by 25%) but not triglycerides. No significant changes were found in the untreated group. There was a significant interaction between age and both baseline serum E(2)/sex hormone-binding globulin (P = 0.006) and sex hormone-binding globulin (P = 0.009) and a marginal interaction between age and E1S (P = 0.083) with regard to effects on changes in LDL cholesterol levels during Estring treatment. We conclude that ultra-low doses of E(2), which previously were considered to have only local effects, may improve serum lipid profile in elderly women with a pattern and magnitude similar to that reported after conventional estrogen doses or first-generation lipid-lowering agents. The reduction in LDL cholesterol tended to be greater with a combination of high age and low baseline levels of biologically active estrogens.
为了确定超低剂量的雌二醇（E₂）是否会影响老年女性的血清脂质谱，我们分析了70名60岁及以上健康女性的血清脂质和脂蛋白变化，这些女性被随机分配接受经阴道环（Estring；Pharmacia-Upjohn，瑞典马尔默）给予的肠胃外E₂（每24小时7.5微克）或不接受治疗，为期12个月。基线血清硫酸雌酮（E1S）而非E₂或血清促卵泡激素与血清总胆固醇（P = 0.026）、低密度脂蛋白（LDL）胆固醇（P = 0.053）和载脂蛋白B水平（P = 0.023）呈负相关。与不治疗相比，Estring治疗使血清E1S（+16%）和E₂（+13%）在绝经后正常范围内有非显著增加，但血清LDL胆固醇显著降低7.6%（-0.32毫摩尔/升；95%置信区间，-0.58，-0.07；P = 0.014），LDL与高密度脂蛋白（HDL）的比率显著降低7.3%（-0.19毫摩尔/升；95%置信区间，-0.44，-0.06；P = 0.030）。在使用Estring的人群中，总胆固醇（降低4%）、LDL胆固醇（降低7%）、LDL与HDL的比率（降低7%）和载脂蛋白B（降低4%）的值显著降低，血清HDL甘油三酯显著升高（升高25%），但甘油三酯无显著变化。未治疗组未发现显著变化。在Estring治疗期间，年龄与基线血清E₂/性激素结合球蛋白（P = 0.006）、性激素结合球蛋白（P = 0.009）之间存在显著交互作用，年龄与E1S之间存在边缘交互作用（P = 0.083），涉及对LDL胆固醇水平变化的影响。我们得出结论，超低剂量的E₂以前被认为仅具有局部作用，可能会改善老年女性的血清脂质谱，其模式和幅度与常规雌激素剂量或第一代降脂药物治疗后报道的相似。随着年龄增长和生物活性雌激素基线水平降低，LDL胆固醇的降低往往更大。
