Extended-cycle versus conventional treatment with a combined oral contraceptive containing ethinylestradiol (30 μg) and levonorgestrel (150 μg) in a randomized controlled trial

Abstract

The objective was to assess efficacy and safety of a combined oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in an extended-cycle vs. a conventional-cycle regimen. This first European randomized, active controlled, open, prospective, parallel-group trial was conducted in 48 German gynecological centers. 1,314 healthy, sexually active women aged 18–35 years were randomized. With an unadjusted PI of 0.483 (upper 95% CI: 1.237), the extended-cycle regimen fulfilled the contraceptive efficacy of EE/LNG, the requirements of the European Medicines Agency. The mean total number of bleeding days per year was significantly lower in the extended-cycle vs. the conventional-cycle regimen. Analyses of bleeding patterns showed a reduced total number of bleeding/spotting days per year in the extended-cycle vs. the conventional-cycle regimen. Cycle-associated complaints and AE were comparable in both groups. Both regimens were very well accepted. The extended-cycle regimen of EE/LNG was effective and well tolerated resulting in a lower number of bleeding days and a favorable bleeding pattern compared to the conventional-cycle regimen.

摘要

目的是评价含乙炔雌二醇 (EE) 和左炔诺孕酮 (LNG) 的复方口服避孕药在延长周期和常规周期方案中的有效性和安全性。这是欧洲首次在48个德国妇科中心进行的随机、主动对照、开放、前瞻性、平行组试验。1314名年龄在18-35岁之间的健康、性活跃的女性被随机分组。未调整的PI为0.483 (95%CI上限：1.237), 延长周期方案达到了欧洲药品管理局要求的EE/LNG的避孕效果。与常规周期方案相比, 延长周期方案每年的平均总出血天数显著减少。出血模式分析显示, 与常规周期方案相比, 延长周期方案每年的出血/点状出血总天数减少。两组与周期相关的症状和AE具有可比性。两种方案均被广泛接受。与常规周期方案相比, EE/LNG的延长周期方案有效并且耐受性好, 导致出血天数减少, 出血模式良好。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Oral contraceptives
• extended-cycle regimen
• ethinylestradiol
• levonorgestrel
• bleeding patterns

Acknowledgments

Angelika Thomas and Rhoda Wismer provided medical writing assistance in the preparation of the manuscript, all authors critically revised the manuscript.

Disclosure statement

JN received a grant by Meda Pharma (A Mylan Company) and Rottapharm Madaus, KS, AS, SG, IW had support from Meda Pharma (A Mylan Company) for the submitted work; outside the submitted work, authors had financial relationships in the previous three years with following organizations that might have an interest in the submitted work: PH received lectures and advisory fees from Rottapharm Madaus, Gedeon Richter, Exeltis, Bayer-Jenapharm, MSD, DR. KADE/BESINS Pharma, JN received personal fees from Gedeon Richter Pharma, DR. KADE/BESINS Pharma and MSD, KS received support for lectures, travel expenses and publications from KADE Besins, Gedeon Richter Pharma, Bayer-Jenapharm, MSD, Hexal, Exeltis and Mylan and acted as a consultant for Gedeon Richter Pharma, MSD and Exeltis, AS received support for lectures, travel expenses from DR. KADE/BESINS Pharma, Gedeon Richter Pharma, Bayer-Jenapharm, MSD, Exeltis and Mylan and acted as a consultant for Gedeon Richter Pharma, MSD and Exeltis, SG is an employee of Meda Pharma (A Mylan Company), IW received support for lectures, travel expenses from DR. KADE/BESINS Pharma, Gedeon Richter Pharma, Bayer-Jenapharm, MSD, Exeltis; no other relationships or activities that could appear to have influenced the submitted work.

Trial registration: 2012-004762-18 (EudraCT No).

Additional information

Funding

The study was financially supported by Madaus GmbH.