OBJECTIVE: To evaluate the efficacy and safety of two low-dose levonorgestrel intrauterine contraceptive systems.
METHODS: Nulliparous and parous women aged 18−35 years with regular menstrual cycles (21−35 days) requesting contraception were randomized to 3 years of treatment with one of two levonorgestrel intrauterine contraceptive systems: 13.5 mg total content or 19.5 mg total content. The primary outcome was the pregnancy rate, calculated as the Pearl Index.
RESULTS: Overall, 1,432 and 1,452 women in the 13.5 mg intrauterine contraceptive system and 19.5 mg intrauterine contraceptive system groups, respectively, had a placement attempted and were included in the full analysis set to evaluate efficacy and safety. Mean (standard deviation) age was 27.1 (4.8) years; 39.2% were nulliparous. Over the 3-year study period, 0.33 pregnancies per 100 women-years (95% confidence interval [CI] 0.16–0.60) were observed with the 13.5 mg intrauterine contraceptive system compared with 0.31 per 100 women-years (95% CI 0.15–0.57) with the 19.5 mg intrauterine contraceptive system. Kaplan-Meier estimates for that period were 0.009 and 0.010, respectively. At least partial expulsions occurred in 4.56% and 3.58% and discontinuation rates resulting from a reported adverse event occurred in 21.9% and 19.1%, respectively. Ten of the 20 pregnancies were ectopic. Serious adverse events included six cases of pelvic inflammatory disease and one partial uterine perforation.
CONCLUSIONS: Both lower-dose levonorgestrel intrauterine contraceptive systems were highly effective for 3 years of use and generally well tolerated.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00528112.
LEVEL OF EVIDENCE: I
Levonorgestrel intrauterine contraceptive system 13.5 mg (total content) and levonorgestrel intrauterine contraceptive system 19.5 mg (total content) are small, lower-dose intrauterine contraceptive systems that are highly effective for up to 3 years of use and generally well tolerated.
Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California; the Sexual Health Clinic (Family Federation of Finland), Väestöliitto, Helsinki, Finland; the Department of Obstetrics and Gynecology, Foothills Hospital, University of Calgary, Calgary, Alberta, Canada; Bayer Pharma AG, MülleBerlin, Germany; Bayer HealthCare Pharmaceuticals, Montville, New Jersey; and the Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Corresponding author: Anita Nelson, MD, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90405; e-mail: email@example.com.
Funded by Bayer HealthCare Pharmaceutical Medical. Writing support provided by Sonya Haslam of Chameleon Communications, funded by Bayer HealthCare.
The authors thank the participating investigators and coordinators at the 138 study centers for counselling and enrollment identification of patients, conduct of the clinical trial, and submission of data. The authors also thank Pia Rautiainen and Teija Tervomaa for their management and oversight of the conduct of the study to ensure the quality and consistency of the resulting data.
Presented as a poster at the annual meeting of the American Society of Reproductive Medicine, October 20−24, 2012, San Diego, California.
Financial Disclosure: Dr. Nelson has received honoraria for serving on speakers’ bureaus and advisory boards for Bayer HealthCare. Her clinic has received grant funding for conduct of this Phase III study from Bayer HealthCare. Dr. Apters' institution has received grants from Bayer Healthcare pharmaceuticals for conduct of Phase II and Phase III trials on 13.5 mg levonorgestrel intrauterine contraceptive system (LNG-IUS) and 19.5 mg LNG-IUS . He has also taken part in advisory boards and is currently a speaker for Bayer Healthcare, Merck, and Pfizer. Dr. Hauck has received grants for conduct of Phase II and Phase III clinical trials on 13.5 mg LNG-IUS and 19.5 mg LNG-IUS. He has served on advisory boards and is currently a speaker for Merck, Bayer Healthcare, and Pfizer. Dr. Schmelter and Ms. Rybowski are full-time employees of Bayer Pharma AG. Dr. Rosen is a full-time employee of Bayer HealthCare Pharmaceuticals. Dr. Gemzell-Danielsson occasionally serves on advisory boards and has been an invited speaker at scientific meetings for Bayer AG, MSD/Merck, HRA Pharma, ExcelGyn, and Gideon Richter on an ad hoc basis. Her institution has received grants for conducting Phase II and Phase III clinical trials on 13.5 mg LNG-IUS and 19.5 mg LNG-IUS . Dr. Hauck has received honoraria for serving on advisory boards for Bayer HealthCare and his clinic has received research grants from Bayer HealthCare.