A levonorgestrel 52-mg intrauterine system (IUS) was found to be safe and effective for pregnancy prevention, according to a study published in Obstetrics & Gynecology.
Researchers designed a phase 3 clinical trial to assess the efficacy and safety of a levonorgestrel 52-mg IUS in 1011 nulliparous and 438 parous women aged 16 to 45 years who requested contraception. Women included in the study were healthy, sexually active (≥4 times per month), and with regular menstrual cycles (21-35 days without additional hormone use).
Participants had scheduled follow-up visits at 1, 3, 6, and 12 months following IUS placement; after 12 months, visits occurred at 6-month intervals. IUS presence was confirmed by palpation or direct visualization of the strings; participants with unidentifiable strings underwent transvaginal ultrasonography at that visit and at subsequent annual visits. Participants also completed a diary for the first 2 years for daily recording of other contraceptive use and amount of bleeding per day.
Efficacy and safety data were collected through September 8, 2017; pregnancy rates were evaluated in women aged 16 to 35 years at study entry with successful IUS insertion who had at least one follow-up contact during IUS use. Pregnancy was defined as a conception date beginning on the day of insertion and through 1 week after IUS discontinuation. Pregnancy rates were calculated using the Pearl Index; secondary efficacy outcomes included Pearl Indices over 5 years and life-table pregnancy rates calculated using the Kaplan-Meier method.
At enrollment, 1538 women were aged 16 to 35 years and 146 were aged 36 to 45 years. The 5-year life-table pregnancy rate was 0.92% (95% CI, 0.46%-1.82%). Nine pregnancies occurred in 4 nulliparous and 5 parous women, indicating life-table pregnancy rates of 0.83% (95% CI, 0.28%-2.50%) and 1.26% (95% CI, 0.51%-3.10%), respectively. Six (67%) pregnancies were ectopic, resulting in an ectopic pregnancy rate of 0.13 per 100 woman-years. No pregnancies occurred in IUS users aged 36 to 45 years.
Approximately half of patients experienced amenorrhea or spotting only during the last 90 days of the first year of IUS insertion, and 80% experienced amenorrhea, spotting, or light bleeding only. For participants who reported heavy menstrual flow at baseline, 53 of 145 (36.6%), 53 of 122 (43.4%), and 52 of 102 (51.0%) reported amenorrhea or spotting only at 1, 2, and 3 years, respectively. Similarly, for participants who reported severe menstrual cramping, 26 of 62 (41.9%), 25 of 52 (48.1%), and 21 of 44 (47.7%) reported none or mild cramping at 1, 2, and 3 years, respectively.
Overall, 1041 (66.4%) participants aged 16 to 35 years and 69 (47.3%) participants aged 36 to 45 years discontinued study participation, most frequently for an adverse event (n=293 [18.3%] and n=29 [19.2%], respectively), desire for pregnancy (n=228 [14.5%] and n=4 [2.6%], respectively), lost to follow-up or withdrawal of consent
(n=226 [14.1%] and n=16 [10.6%], respectively), or relocation from a study site (n=102 [6.5%] and n=4 [2.6%], respectively). At least 1 adverse event was noted in 1438 (89.9%) participants aged 16 to 35 years and 136 (90.1%) participants aged 36 to 45 years; of these, 73 (4.2%) were serious, including ectopic pregnancies and 1 ovarian cyst surgical treatment. Overall, 322 (18.8%) of patients discontinued treatment due to an adverse event.
Bleeding symptoms were the most frequent nonadverse events that resulted in IUS discontinuation; however, only 39 (2.2%) reported experiencing bleeding symptoms. Rates of discontinuation for bleeding events were low: 17 of 1714 (1.0%) participants in the first year, 13 of 1401 (0.9%) in the second, 5 of 1149 (0.4%) in the third, 2 of 965 (0.2%) in the fourth, and 2 of 819 (0.2%) participants in the fifth. A total of 7 (0.04%) participants attributed vaginal infection to the IUS and requested removal.
“The LNG 52-mg IUS evaluated in this study is highly effective for contraception through 5 years and has low discontinuation rates for infectious or systemic hormonal adverse events,” the researchers concluded.
Teal SB, Turok DK, Chen BA, Kimble T, Olariu AI, Creinin MD. Five-year contraceptive efficacy and safety of a levonorgestrel 52-mg intrauterine system [published online December 4, 2018]. Obstet Gynecol. doi: 10.1097/AOG.0000000000003034