两项 3 期临床试验的汇总分析评估了含有雌三醇/屈螺酮的新型复方口服避孕药对健康女性出血模式的影响。

Pooled analysis of two phase 3 trials evaluating the effects of a novel combined oral contraceptive containing estetrol/drospirenone on bleeding patterns in healthy women.

机构信息

Department of Obstetrics and Gynecology, University of Florida College of Medicine- Jacksonville, Jacksonville, FL, USA.

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh/Magee-Womens Research Institute, Pittsburgh, PA, USA.

出版信息

Contraception. 2022 Dec;116:29-36. doi: 10.1016/j.contraception.2022.07.010. Epub 2022 Aug 1.

DOI:10.1016/j.contraception.2022.07.010

PMID:35921872

Abstract

OBJECTIVE

To evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen.

STUDY DESIGN

We pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m. Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes.

RESULTS

We included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event.

CONCLUSION

E4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns.

IMPLICATIONS STATEMENT

Most estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive.

摘要

目的

评估含有雌三醇（E4）15 毫克/屈螺酮（DRSP）3 毫克的新型复方口服避孕药在 24/4 天方案中的出血模式。

研究设计

我们汇总了两项平行、开放标签、13 个周期的 3 期临床试验的出血数据，这些试验招募了年龄在 16 至 50 岁、体重指数（BMI）≤35kg/m²的参与者。参与者在每日日记中报告阴道出血/点滴。对于这项出血分析，我们纳入了至少有一个可评估周期的参与者。我们计算了计划出血/点滴发作的平均频率和出血/点滴发作的中位持续时间，并评估了治疗依从性、BMI 和最近使用激素避孕药对出血/点滴结局的影响。

结果

我们纳入了 3409 名参与者，共 33815 个周期。87.2%至 90.4%的参与者/周期出现计划出血/点滴，中位持续时间为 4 至 5 天。无计划出血/点滴从第 1 周期的 27.1%下降到第 2 周期的 20.6%，从第 5 周期开始下降到≤17.5%。大多数（66.5%）无计划出血/点滴发作仅为点滴出血。6.8%至 7.8%的使用者/周期没有出现任何计划或无计划的出血/点滴。漏服一颗或多颗活性药物会导致无计划出血/点滴的发生率更高（调整后的优势比[aOR]2.13[95%置信区间 1.68-2.70]）和无计划出血/点滴的发生率更高（aOR 2.36[1.82-3.07]）。BMI≥30kg/m 的参与者报告更多的计划出血/点滴缺失（aOR 1.68[1.37-2.05]）。转换使用者和起始使用者报告无计划出血/点滴的发生率相似（aOR 0.94[0.83-1.07]）和计划出血/点滴缺失的发生率相似（aOR 1.00[0.85-1.19]）。3%的参与者因与出血相关的不良事件而停药。