Five-Year Contraceptive Efficacy and Safety of a Levonorgestrel 52-mg Intrauterine System

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This LNG 52-mg IUS is highly effective and safe over 5 years of use in U.S. females. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT00995150. FUNDING SOURCE: Medicines360.