目的:评价雌四醇(E4)15mg/屈螺酮(DRSP)3mg在日本子宫内膜异位症患者中24周循环给药的有效性和安全性。
方法:24周,多中心,随机化,双盲,安慰剂对照,平行组研究。
方法:共有162名诊断为子宫内膜异位症的日本妇女。
方法:参与者被随机分配到E4/DRSP组或安慰剂组。在E4/DRSP组中,参与者每天口服1片包含E415mg和DRSP3mg,共24天,然后是一片安慰剂片,持续4天,无激素间隔,构成一个周期方案。安慰剂组的参与者每天一次服用一片安慰剂片剂,持续28天。在整个确诊期持续治疗6个周期(24周)。
方法:在确认研究期结束时,从基线到六个治疗周期,最严重的盆腔疼痛(下腹部和背部疼痛)的视觉模拟评分变化。
结果:E4/DRSP显示,从基线到六周期治疗结束,最严重的盆腔疼痛(-33.2mm)的平均视觉模拟评分发生变化。组间差异显著(-8.5mm,双侧95%置信区间:-16.1至-0.9mm),显示优于安慰剂(p=0.028)。响应速率,视觉模拟量表评分从基线降低≥30%和≥50%,E4/DRSP组大于安慰剂组:53.2%对29.6%(p=0.004)和36.4%对12.3%(p<0.001)。客观的妇科检查结果(死角硬化,骨盆压痛,限制的子宫活动度)通过E4/DRSP治疗显着改善,稳定和恶化参与者的比例明显低于安慰剂组。E4/DRSP减少了子宫内膜瘤的大小,提高了生活质量,基于生活质量相关问卷和全球印象评分。E4/DRSP治疗未观察到安全性问题。E4/DRSP组和安慰剂组之间止血参数超出参考范围的参与者比例几乎没有差异。
结论:E4/DRSP可有效治疗子宫内膜异位症相关性疼痛并改善妇科表现。E4/DRSP可能是安全的,子宫内膜异位症治疗的新选择可能降低血栓栓塞事件的风险.
OBJECTIVE: To evaluate the efficacy and safety of 24-week cyclic administration of
estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.
METHODS: A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
METHODS: Twenty-five study centers in Japan.
METHODS: A total of 162 Japanese women diagnosed with endometriosis.
METHODS: Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period.
METHODS: Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period.
RESULTS: Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain (-33.2 mm) from baseline to the end of the 6-cycle treatment. The between-group difference was significant (-8.5 mm; 2-sided 95% confidence interval, -16.1 to -0.9 mm), showing superiority to placebo. The responder rates, ≥30% and ≥50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group.
Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life-related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.
CONCLUSIONS: Estetrol/drospirenone effectively treats endometriosis-associated pain and improves gynecological findings.
Estetrol/drospirenone may be a safe, new option for endometriosis treatment with a potentially decreased risk of thromboembolic events.
BACKGROUND: jRCT2011210027.