Bleeding patterns for the Liletta^® levonorgestrel 52 mg intrauterine system

Abstract

Purpose: Evaluate bleeding patterns for the Liletta^® levonorgestrel 52 mg intrauterine system (IUS) using the World Health Organization Belsey definitions.

Material and methods: This prospective multicenter trial evaluates the efficacy and safety of Liletta^® (Clinicaltrials.gov NCT00995150). We evaluated bleeding patterns for 1700 nulliparous and multiparous women using a daily diary completed by participants for the first 2 years and by questionnaire every 3 months thereafter. We assessed amenorrhea rates over 3 years and the proportion of subjects with infrequent, frequent, prolonged and irregular bleeding per 90-day reference period over 2 years for the entire study population as well as comparing nulliparous and parous women and obese and non-obese women.

Results: Amenorrhea rates at 1 and 3 years in levonorgestrel 52 mg IUS users were 19 and 37%, respectively. The infrequent bleeding rate increased from 14% in the first 90 days to 30% at the end of Year 1, and was maintained at the same rate through Year 2. Frequent, prolonged and irregular bleeding declined to low levels by the end of the first year. Discontinuation for bleeding-related complaints occurred in 35 (2.1%, 95% CI 1.3–2.7%) women during the first 36 months; only one subject discontinued for amenorrhea (in Year 2). Outcomes did not vary for nulliparous versus parous or obese versus non-obese women.

Conclusions: Among Liletta users, amenorrhea and infrequent bleeding become more prevalent over time and amenorrhea rates continue to increase after the first year of use. Bleeding patterns do not differ significantly by parity or by obesity-status. Discontinuation for bleeding concerns is uncommon with this product.

Chinese abstract

目的：根据世界卫生组织的Belsey定义, 评估Liletta 52mg左炔诺孕酮宫内缓释系统（IUS））的出血模式。

材料与方法：此前瞻性多中心试验评估了Liletta的疗效和安全性（Clinicaltrials.gov NCT00995150）。我们采用受试者前两年记日记和此后每3个月进行一次问卷调查的方法, 对1700名未生育过的妇女和多胎妇女的出血模式进行评估。评估整个研究人群的3年以上闭经比例, 以及在2年以上的每90天参照期中, 出血过稀、出血过频、出血期过长和不规则出血的受试者比例, 并比对未生育过的妇女和多胎妇女及肥胖和非肥胖妇女进行了比较。

结果：52mg左炔诺孕酮IUS应用者的第1年和第3年闭经比例分别为19%和37%, 月经稀发比例从前90天的14%上升到第1年末的30%, 并且在第2年保持同样的比例。第1年末, 出血过频、出血期过长和不规则出血的比例降到低水平。在前36个月中, 有35名妇女因出血相关不适而停止治疗（2.1%, 95% CI 1.3-2.7%）, 只有1名受试者因闭经而停止治疗（第2年）。经过对比发现, 未生育过的妇女和多胎妇女之间及肥胖和非肥胖妇女之间的结果并无差异。

结论：在Liletta的应用者中, 闭经和月经稀发在用Liletta一段时间后更常见, 且闭经比例在Liletta用一年后持续增加。不同产次和肥胖状态下的出血模式无显著差异。因担忧出血问题而停用本产品的情况不常见。

Keywords:

• Intrauterine device
• intrauterine system
• amenorrhea
• bleeding
• spotting
• Liletta

Acknowledgements

The authors thank the participating investigators and coordinators at the 29 study centers for conduct of the clinical trial and submission of data (investigators funded by Medicines360 to conduct the study).

Disclosure statement

This research is sponsored by Medicines360. The universities for C.A.S., S.B.T., P.D.B., L.M.K. and M.D.C. receive funding from Medicines360 to conduct this research. The university for C.A.S. receives contraceptive research funding from Bayer Healthcare and NIH/NICHD. S.B.T. has served as a consultant for Bayer Healthcare, Allergan, and Merck & Co. The university for S.B.T receives contraceptive research funding from Bayer Healthcare, Contramed, Medicines360, Merck & Co., NIH/NICHD and the Society of Family Planning; the university for L.M.K receives contraceptive research funding from Agile Therapeutics, Contramed and PRA International. A.I.O. is an employee of Medicines360. M.D.C. receives speaking honoraria from Allergan and Gedeon Richter, serves on an Advisory Board for Merck & Co. and is a consultant for Estetra, Gedeon Richter, Icebreaker Health and Medicines360; the university for M.D.C. receives contraceptive research funding from Contramed, Medicines360, Merck & Co., NIH/NICHD and the Society of Family Planning.

Additional information

Funding

The study was funded by Medicines360.