To assess the 5-year contraceptive efficacy and safety of a levonorgestrel (LNG) 52-mg intrauterine system (IUS) from an ongoing 10-year phase 3 contraceptive trial.
Study investigators enrolled 1,751 nulliparous and parous females aged 16–45 years and desiring contraception to receive a novel LNG 52-mg IUS at 29 centers in the United States, including reproductive health clinics, private offices, and university centers. Participants had scheduled follow-up visits four times during the first year. After year 1, study visits occurred every 6 months, with phone contact at the 3-month point between visits. We assessed the primary outcome of pregnancy rate (Pearl Index) in females aged 16–35 years at enrollment through 60 months. The safety evaluation included all females for their entire duration of participation.
The 1,751 enrollees included 1,600 females aged 16–35 years and 151 aged 36–45 years. Successful IUS placement occurred in 1,714 (97.9%) participants. At the time of the data evaluation, 495 participants finished 5 years and 176 had entered the seventh year of IUS use. Nine pregnancies occurred, six of which were ectopic. The Pearl Indices for years 1 and 5 were 0.15 (95% CI 0.02–0.55) and 0.20 (95% CI 0.01–1.13) pregnancies per 100 women-years, respectively. The cumulative life-table pregnancy rate was 0.92% (0.46–1.82%) through 5 years. Participants aged 16–35 years at enrollment were significantly more likely to report new or worsening acne, dyspareunia, pelvic pain, and dysmenorrhea; participants aged 36–45 years at enrollment were more likely to report new or worsening weight increase. Discontinuation for adverse events occurred in 322 (18.8%) participants, most commonly related to expulsion (n=65 [3.8%]). Only 39 (2.2%) IUS users discontinued as a result of bleeding symptoms. Pelvic infection was diagnosed in 14 (0.8%) participants.
This LNG 52-mg IUS is highly effective and safe over 5 years of use in U.S. females.
A phase 3 study of a levonorgestrel 52-mg intrauterine system in U.S. females shows high 5-year contraceptive efficacy and low hormonal adverse effect rates.
Department of Obstetrics and Gynecology, University of Colorado, Aurora, Colorado; the Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah; the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, Pennsylvania; the Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia; Medicines360, San Francisco, California; and the Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, California.
Corresponding author: Mitchell D. Creinin, MD, University of California, Davis, 4860 Y Street, Suite 2500, Sacramento, CA 95817; email: firstname.lastname@example.org.
Supported by Medicines360.
Financial Disclosure Stephanie B. Teal has served on the Advisory Board for Merck & Co. Her university department receives contraceptive research funding from Bayer HealthCare, Medicines360, Merck & Co, and Sebela. David K. Turok has received speaking honoraria from Allergan and Medicines360. He also served on the Advisory Boards for Allergan, Bayer, Pharmanest, and Teva and has been a consultant for Bioceptive. His university department receives contraceptive research funding from Bayer HealthCare, Cooper Surgical, Medicines360, Merck & Co, Sebela, and Teva. Beatrice A. Chen has served on the Advisory Board for Merck & Co. Her university department receives contraceptive research funding from Medicines360, Merck & Co, and Sebela. Thomas Kimble has received speaking honoraria from Allergan and Merck and is a consultant for Medicines360. His university department receives contraceptive research funding from Allergan, Antiva, Bayer HealthCare, Chemo, Invovio, Medicines360, Mithra, and Sebela. Andrea I. Olariu is a Medicines360 employee. Mitchell D. Creinin has received speaking honoraria from Gedeon Richter and Merck & Co. He has served on the Advisory Boards for Lupin and Merck & Co. He has been a consultant for Estetra, Gedeon Richter, Icebreaker Health, and Medicines360, and his university department receives contraceptive research funding from Daré Bioscience, HRA Pharma, Medicines360, Merck & Co, and Sebela.
Presented in part as a poster at the American College of Obstetricians and Gynecologists' Annual Clinical and Scientific Meeting, April 27–30, 2018, Austin, Texas.
The authors thank the participating investigators and coordinators at the 29 study centers for conduct of the clinical trial and submission of data.
Each author has confirmed compliance with the journal's requirements for authorship.
Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Peer reviews are available at http://links.lww.com/AOG/B227.
Received July 17, 2018
Received in revised form October 15, 2018
Accepted October 18, 2018