Prolonged Use of the Etonogestrel Implant and Levonorgestrel Intrauterine Device - Two Years Beyond FDA-Approved Duration

Abstract

The subdermal contraceptive implant, and the 52mg levonorgestrel intrauterine device (IUD) are currently FDA-approved for three and five years of use respectively. Limited available data has suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. Objective To evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device (IUD) in women using the method for two years beyond the current FDA-approved duration. Study Design We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel IUD for a minimum of 3 and 5 years, respectively (started IUD in 2007 or later or implant in 2009 or later). Demographic and reproductive health histories, as well as objective body mass index (BMI) were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rates, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using chi-square test and Fisher Exact test, and compared serum ENG levels stratified by body mass index using the Kruskal-Wallis test. Results Implant users (n=291) have contributed 444.0 women-years of follow-up. There have been no documented pregnancies in implant users during the two years of post-expiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (one-sided %97.5 confidence interval (CI) 0–1.48) per 100 woman years at four years and 0 (one-sided %97.5 CI 0–2.65) per 100 women years at five years. Among 496 levonorgestrel IUD users, 696.9 women-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the levonorgestrel IUD is calculated as 0.25(%95 CI 0.04–1.42) per 100 women year; failure rate during the seventh year is 0.43 (%95 CI 0.08–2.39) per 100 women years. Among implant users with serum etonogestrel results, the median etonogestrel level at the time of method expiration was 207.7 pg/mL (range 63.8–802.6 pg/mL), 166.1 pg/mL (range 67.9 25.0 – 470.5 pg/mL) at the end of the fourth year, and 153.0 pg/mL (range 72.1–538.8 pg/mL) at the end of the fifth year. Median ENG levels were compared by BMI at each time point and a statistical difference was noted at the end of four years of use with overweight women having the highest serum ENG (195.9 pg/ml: range 25.0–450.5) when compared to normal (178.9 pg/ml: range 87.0–463.7) and obese (137.9 pg/ml: range 66.0–470.5) women (p=0.04). Conclusion This study indicates that the contraceptive implant and 52-mg hormonal IUD continue to be highly effective for at least two additional years of use. Serum etonogestrel evaluation demonstrates median levels remain above the ovulation threshold of 90pg/ml for women of in all BMI classes.