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。