Gräser T, Rössner P, Schubert K, Müller A, Bönisch U, Oettel M
Department of Medical Research, Jenapharm GmbH and Co. KG, Jena, Germany.
Maturitas. 1997 Dec 15;28(2):169-79. doi: 10.1016/s0378-5122(97)00069-8.
To compare the effect of two sequential hormone replacement regimens differing in the dose of levonorgestrel on climacteric symptoms, bleeding pattern and lipid metabolism in postmenopausal women.
In a multicentre, randomized, double-blind, active-treatment-controlled study, 210 postmenopausal women were assessed at the end of treatment cycles 3 and 6. The high-levonorgestrel group was treated with 2 mg estradiol valerate (days 1-21) sequentially combined with 0.25 mg levonorgestrel (days 12-21). The low-levonorgestrel group received the same estrogen regimen (2 mg estradiol valerate, days 1-21), but levonorgestrel was administered sequentially in a dose of 0.15 mg during the last 12 days of the cycle (days 10-21). Statistical analysis by Student's t-test for dependent variables (measured values versus baseline) and independent variables (differences between groups), and the composite t-test method for comparison of both regimens with respect to efficacy, was performed.
Both groups were statistically comparable. The trial was completed by 137 subjects. Protocol violations occurred in 38 cases. Thirty-five subjects dropped out during the study, 21 of them because of adverse events. Both treatments were equally effective in the treatment of climacteric complaints. There were no clinically significant changes in body weight, blood pressure, haematological tests, and parameters of clinical chemistry. There was a tendency towards a reduction in bleeding intensity in both groups in the second half of the treatment period. The treatment for six cycles with both regimens significantly (P < 0.05) decreased plasma concentrations of triglycerides (significant in the low-levonorgestrel group only), high-density lipoprotein cholesterol, high-density lipoprotein-3-cholesterol, lipoprotein(a) and apolipoprotein A1. In parallel, the serum concentration of total cholesterol increased significantly in both treatment groups, whereas low-density lipoprotein cholesterol increased significantly in the high-levonorgestrel group only. The changes in high-density lipoprotein-2-cholesterol, and apolipoprotein B did not reach statistical significance.
It can be concluded that both sequential combined oral hormone replacement therapy (HRT) regimens were equivalent with respect to efficacy and tolerability in the treatment of women with climacteric complaints. The preparation with the lower dose of progestin showed a tendency towards a less unfavourable influence on the lipid profile.
比较两种左炔诺孕酮剂量不同的序贯激素替代方案对绝经后女性更年期症状、出血模式及脂质代谢的影响。
在一项多中心、随机、双盲、活性药物对照研究中，于治疗周期3和6结束时对210名绝经后女性进行评估。高剂量左炔诺孕酮组接受戊酸雌二醇2mg（第1 - 21天）序贯联合左炔诺孕酮0.25mg（第12 - 21天）治疗。低剂量左炔诺孕酮组接受相同的雌激素方案（戊酸雌二醇2mg，第1 - 21天），但在周期的最后12天（第10 - 21天）序贯给予左炔诺孕酮0.15mg。采用配对t检验对因变量（测量值与基线值）和自变量（组间差异）进行统计分析，并采用复合t检验方法比较两种方案的疗效。
两组在统计学上具有可比性。137名受试者完成了试验。38例出现方案违背情况。35名受试者在研究期间退出，其中21名是因为不良事件。两种治疗方法在治疗更年期症状方面同样有效。体重、血压、血液学检查及临床化学参数均无临床显著变化。在治疗期后半段，两组的出血强度均有降低趋势。两种方案治疗六个周期后，甘油三酯血浆浓度（仅在低剂量左炔诺孕酮组显著降低）、高密度脂蛋白胆固醇、高密度脂蛋白 - 3 - 胆固醇、脂蛋白(a)和载脂蛋白A1均显著降低（P < 0.05）。同时，两个治疗组的总胆固醇血清浓度均显著升高，而仅高剂量左炔诺孕酮组的低密度脂蛋白胆固醇显著升高。高密度脂蛋白 - 2 - 胆固醇及载脂蛋白B的变化未达到统计学显著水平。
可以得出结论，两种序贯联合口服激素替代疗法（HRT）方案在治疗更年期症状的疗效和耐受性方面相当。低剂量孕激素制剂对血脂谱的不良影响较小。
