Abstract：
Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.
摘要：
目的：评估绝经后妇女超低剂量雌二醇和地屈孕酮（E0.5mg/D2.5mg）的安全性和耐受性。方法：对来自三项临床研究的数据进行汇总分析，评估了连续超低剂量雌二醇和地屈孕酮对绝经后妇女的影响。参与者接受E0.5mg/D2.5mg或安慰剂13周（双盲，随机化，欧洲研究)，E0.5mg/D2.5mg或安慰剂12周（双盲，随机化，中文学习)，或E0.5mg/D2.5mg，持续52周（开放标签，欧洲研究）。安全性结果包括治疗引起的不良事件（TEAE），治疗引起的严重不良事件（TESAE），由于TEAE而停止治疗，和特殊关注的不良事件（AESI）。结果：总体而言，1027名女性纳入汇总分析(E0.5mg/D2.5mg，n=736；安慰剂，n=291)。E0.5mg/D2.5mg组的平均治疗暴露为288.9天，安慰剂组为86.6天。在E0.5mg/D2.5mg和安慰剂组中，经历≥1TEAE的女性比例相似（50.1％vs49.5％，分别)。TESAE发生在12名（1.6％）接受E0.5mg/D2.5mg的女性和9名（3.1％）接受安慰剂的女性中。在两组中都很少停止研究治疗（E0.5mg/D2.5mg：1.5％；安慰剂：2.4％）。E0.5mg/D2.5mg组的乳房疼痛发生率高于安慰剂组（2.0％vs0.3％），子宫出血（6.5％vs2.4％）。痤疮的发病率，两组之间的高毛囊和体重增加相似。结论：在三项研究中，超低剂量雌二醇加地屈孕酮在绝经后妇女中耐受性良好，与安慰剂相比，TEAE或TESAE没有增加。
