Mijatovic V, Kenemans P, Netelenbos J C, Peters-Muller E R, van Kamp G J, Voetberg G A, van de Weijer P H, van der Mooren M J
Department of Obstetrics and Gynecology, University Hospital, Vrije Universiteit, Amsterdam, The Netherlands.
J Clin Endocrinol Metab. 1997 Nov;82(11):3543-7. doi: 10.1210/jcem.82.11.4357.
Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Serum Lp(a) concentrations increase after menopause, and postmenopausal estrogen replacement appears to decrease Lp(a) levels. In a randomized, double blind study, we examined the effects of 6-month treatment with daily 17 beta-estradiol (E2; 2 mg, orally) continuously combined with one of four dosages [2.5 mg (n = 41), 5 mg (n = 38), 10 mg (n = 38), and 15 mg (n = 20)] of dydrogesterone on fasting serum Lp(a) concentrations in 137 healthy postmenopausal women. At baseline, no significant differences were noted among the four treatment groups. During the study period of 6 months the median serum Lp(a) concentration decreased significantly from 128 mg/L (range, 5-1660) to 110 mg/L (range, 1-1530) in the total population, corresponding to a reduction of 13% (P < 0.001). The percent changes in serum Lp(a) correlated positively with the percent changes in serum E2 at 3 as well as 6 months of therapy (r = 0.38; P < 0.001 and r = 0.35; P < 0.001, respectively). A dose response of dydrogesterone on serum Lp(a) was not found. In addition, serum lipids and (apo)lipoproteins improved significantly in all four treatment groups. In conclusion, oral E2 continuously combined with dydrogesterone has beneficial effects on the lipid and lipoprotein profile and is effective in lowering Lp(a) concentrations in postmenopausal women.
脂蛋白(a)[Lp(a)]是动脉粥样硬化的独立危险因素。绝经后血清Lp(a)浓度升高,而绝经后雌激素替代治疗似乎可降低Lp(a)水平。在一项随机双盲研究中,我们检测了137名健康绝经后女性每日口服2mg 17β-雌二醇(E2)连续6个月联合四种剂量[2.5mg(n = 41)、5mg(n = 38)、10mg(n = 38)和15mg(n = 20)]的地屈孕酮对空腹血清Lp(a)浓度的影响。基线时,四个治疗组之间未观察到显著差异。在6个月的研究期间,总人群中血清Lp(a)浓度中位数从128mg/L(范围5 - 1660)显著降至110mg/L(范围1 - 1530),相当于降低了13%(P < 0.001)。治疗3个月及6个月时,血清Lp(a)的变化百分比与血清E2的变化百分比呈正相关(r分别为0.38;P < 0.001和0.35;P < 0.001)。未发现地屈孕酮对血清Lp(a)有剂量反应。此外,所有四个治疗组的血脂和(载)脂蛋白均有显著改善。总之,口服E2联合地屈孕酮对脂质和脂蛋白谱有有益影响,且能有效降低绝经后女性的Lp(a)浓度。