Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women

Abstract

Objectives To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days’ hormone free), on several coagulation factors and thrombin formation markers.Methods Randomised, open-label, parallel-group comparative study involving healthy women (18–40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months.Results A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [− 18.3 pmol/L] > − 130 pmol/L).Conclusions The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE.Chinese 摘 要 目的 评估口服避孕药91天长周期疗法（150μg左炔诺孕酮[levonorgestrel，LNG]/30μg炔雌醇[ethinylestradiol，EE]84天，10μg EE 7天[治疗1]）与两种21/7常规方案（21天150μg LNG/30μg EE [治疗2]或150μg去氧孕烯[desogestrel，DSG]/30μg EE [治疗3]，两种治疗均有7天的间歇期）对凝血因子和凝血酶形成标记物的影响。方法 关于18-40岁健康女性的随机、开放、平行组对照研究。主要研究终点为治疗6个月后凝血酶原片段F1+2与基线水平的变化。结果 初步分析了187名受试者，治疗6个月后整个人群的F1+2平均水平上升。治疗1与治疗2的变化类似：最小二乘均数变化分别为170 pmol/L和158 pmol/L，但治疗3的变化明显大：最小二乘均数变化为592 pmol/L。治疗1的止血效果与治疗2的相似，但不比治疗3差（95%置信区间下限[ -18.3 pmol/L] ＞ -130 pmol/L）。结论 LNG/EE两种治疗方案对F1+2的影响相似，LNG/EE长周期方案与DSG/EE常规方案相比无差别。