Effects of an extended flexible regimen of an oral contraceptive pill containing 20 μg ethinylestradiol and 3 mg drospirenone on menstrual-related symptoms: a randomised controlled trial

Abstract

Objectives: The aim of the study was to assess the efficacy for menstrual-related symptoms of an extended flexible regimen of an oral contraceptive pill containing 20 μg ethinylestradiol and 3 mg drospirenone in comparison with a 24/4 d cyclical regimen of the same formulation.

Methods: This randomised, non-inferiority, open-label, multicentre study was conducted in women aged 18–39 years. Their menstrual-related symptoms were assessed using the Penn Daily Symptom Rating (DSR17). Participants were randomised to use an extended flexible regimen of 20 μg ethinylestradiol and 3 mg drospirenone (EE/DRSP_e.flex), comprising 168 consecutive days with a 4-d hormone-free interval (HFI, allowing for management of unexpected bleeding) or a conventional 24/4 cyclical regimen of the same pill (EE/DRSP_24/4). The primary measure of efficacy was the percentage change in DSR17 total score from baseline to cycle 6. The secondary measures of efficacy were the percentage changes in DSR17 total score from baseline after each 28-d interval throughout the entire study and in the scores for individual DSR17 symptoms.

Results: The primary analysis demonstrated that EE/DRSP_e.flex was not inferior to EE/DRSP_24/4 (Mean DSR17 score 9.1; 95% confidence interval (CI) − 2.5, 20.6; p = 0.123). Analysis at intervals throughout the entire evaluation period showed greater reduction in DSR17 total score for EE/DRSP_e.flex than for the 24/4 regimen (p < 0.001). The decreases in individual scores for the symptoms ‘poor coordination’ and ‘depression/feeling sad/down or blue’ were greater for the extended flexible regimen than for the cyclical regimen (p < 0.05).

Conclusion: The extended flexible regimen was not inferior to the 24/4 cyclical regimen in terms of the primary endpoint. It significantly improved symptoms in the interval analysis, and the effects on specific DSR17 symptoms, compared with the cyclical regimen.

Chinese abstract

目的：本研究的目的是评估含20μg炔雌醇和3mg屈螺酮的口服避孕药扩展灵活方案与配方相同的24/4天的周期性方案相比, 治疗月经相关症状的效果。

方法：本研究是18-39岁女性参加的随机、非低级、开放和多中心的研究。参加者的月经相关症状用宾夕法尼亚每日症状评分（DSR17）进行评估。参加者随机分为两组, 一组为含有20μg炔雌醇和3mg屈螺酮的口服避孕药扩展灵活方案(EE/DRSPe.flex), 168天连续用药, 停药4天（HFI, 考虑到对意外出血的处理）, 另一组用同样药物传统的24/4天周期性方案(EE/DRSP24/4)。治疗效果的基本评定方法是从基础值到第六个周期的DSR17总评分的百分率的变化。第二个评定方法是整个研究中从基础值到每28天间期的的DSR17总评分和个体的DSR17症状评分的百分率变化。

结果：基本分析结果显示(EE/DRSP24/4)方案的治疗效果不差于EE/DRSP24/4 方案（DSR17评分均值9.1, 95%可信区间(CI)-2.5, 20.6; p = 0.123）。整个评估周期间隔的分析显示EE/DRSPe.flex方案DSR17总评分明显低于24/4周期方案(p < 0.001)。症状的个体评分扩展灵活方案”协调不良”, ”沮丧/情感悲伤/沮丧或者悲哀”评分明显低于周期性的方案(p < 0.05).

结论：扩展灵活方案的效果在基本终末点不差于24/4周期性的方案。和周期性方案相比, 此方案明显改善, 特别的DSR17症状, 间隔期的症状的效果

Keywords:

• Combined oral contraceptives
• drospirenone
• extended regimen
• low-dose oral contraceptive
• premenstrual symptoms

Disclosure statement

Achilles Machado Cruz is a medical consultant with Libbs Farmacêutica Ltda. The other authors have no potential conflicts of interest to disclose.

Funding

Libbs Farmacêutica Ltda (Brazil) provided funding and material support for this research (protocol number LB0901).