Combined oral contraceptive treatment for bleeding complaints with the etonogestrel contraceptive implant: a randomised controlled trial

Abstract

Objective: Estimate symptom improvement rate of women with bleeding complaints using the etonogestrel contraceptive implant when started on continuous combined oral contraceptives (COC).

Methods: We conducted a double-blinded randomised controlled trial of women reporting troublesome bleeding related to their etonogestrel contraceptive implant and desiring intervention. Participants received continuous COCs or placebo for four weeks to evaluate self-reported bleeding improvement at four weeks. Participants could continue study treatment or prescribed COCs for another eight weeks if desired. We planned to enroll 130 participants between two sites (80% power to detect a 20% effect size at a 0.05 significance level, with 10% loss to follow up).

Results: We closed the study after enrolling 26 participants due to recruitment futility. All women on COCs and 75% of placebo users reported bleeding improvement at four weeks (p = 0.09), with 92% and 42%, respectively, reporting significant improvement (p = 0.03). The median number of days until bleeding stopped for at least four days in COC and placebo users was 1 day (range 1–9) and 4.5 days (range 1–28), respectively (p = 0.63). Eight (75%) COC and five (42%) placebo users opted to continue study treatment (p = 0.41). Despite bleeding improvement, women who desired implant removal at enrollment were more likely to re-request removal than those who initially considered other interventions (3 of 5 [60%] vs 1 of 17 [6%], p = 0.03).

Conclusion: Although women who have troublesome bleeding while using the contraceptive implant may experience improvement with no treatment over 4 weeks, women using COCs are more likely to report significant improvement.

Clinicaltrials.gov registration number: NCT01963403.

Chinese abstract

目的: 评价用复方口服避孕药（COC）连续治疗依托孕烯植入避孕出血的女性症状改善率。方法: 我们对使用依托孕烯植入避孕后有出血问题并且渴望被干预的女性进行了一项双盲随机对照试验。对参与者采用连续口服四周的COCs或安慰剂来评估四周内自我报告的出血改善情况。参与者可以继续进行研究治疗或如果有意愿可再开八周的口服避孕药。在这两个站点我们计划招募130名参与者（80%的把握度, 0.05的显着性检验水准, 20%的效度, 10%的失访）。结果: 由于招募问题, 在招募到26名参与者后我们结束了这项研究。所有连续口服COCs的女性和75%的服用安慰剂者在四周内都报告有出血改善的情况（ρ= 0.09）, 分别有92%和42%、报告有显著改善（ρ= 0.03）。直到出血停止的中位数天数至少4天, 分别在COC和安慰剂组的时间分别为1天（范围1–9）和4.5天（范围1–28）, （ρ= 0.63）。COC组中的8名（75%）和安慰剂组中5名（42%）女性选择继续研究治疗（ρ= 0.41）。虽然出血都有改善, 但在招募就渴望移除植入物的女性比那些起初考虑其他干预措施的女性更有可能重新要求去除（3/5 [60%] vs1/17 [6%] , ρ= 0.03）。结论: 尽管用植入避孕有出血麻烦的女性不处理超过4周后可能也会有改善, 但用口服避孕药 的女性更可能报告有显著改善。

Keywords:

• Contraception
• implant
• etonogestrel
• bleeding
• combined oral contraceptive

Acknowledgements

We would like to thank Drs. Catherine Cansino, Juliana Melo and Melissa Chen, as well as Ragini Maddipati, the staff of the Family Planning Research Office at the University of California, Davis and the staff of the Division of Clinical Research at Washington University in St. Louis.

Disclosure statement

Dr. Hou serves as a medical advisory board member for Afaxys, Inc. and receives speaking honoraria from Merck & Co. Dr. McNicholas has no disclosures. Dr. Creinin receives speaking honoraria from Allergan and Merck & Co., serves on Advisory Boards for Allergan, Evofem and Merck & Co., and is a consultant for Danco, Estetra, Femasys, HRA Pharma, Icebreaker Health and Medicines360. The Department of Obstetrics and Gynecology, University of California, Davis, receives research funding for contraceptive clinical trials from Contramed, Merck & Co. Medicines360, NIH/NICHD and the Society of Family Planning.

Funding

This study was funded by a Merck Independent Research Grant. The sponsor had no involvement in the research conduct, data analysis or interpretation, or article preparation.