Menstrual bleeding and spotting with the Levonorgestrel Intrauterine System (52 mg) during the first-year post-insertion: a systematic review and meta-analysis.

Changes in menstrual bleeding concern many users of the 52 mg Levonorgestrel Intrauterine System (LNG-IUS). Prescribing information for LNG-IUS devices describe an overall decrease in bleeding and spotting days over time; however, estimates derived from a variety of existing clinical data are currently unavailable.To systematically calculate the mean days of bleeding-only, spotting-only and bleeding and/or spotting experienced by a population of reproductive-aged LNG-IUS users with normal regular menses prior to insertion during the first-year of use.We identified clinical trials, including randomized controlled trials and randomized comparative trials, as well as cohort studies published in English between January 1970 and November 2018 through searching 12 biomedical and scientific literature databases including MEDLINE and ClinicalTrials.gov.We considered studies that reported data on LNG-IUS devices releasing 20 mcg of levonorgestrel per day, collected daily menstrual bleeding data for at least 90 consecutive days, defined bleeding and spotting per World Health Organization standards, and evaluated participants with normal regular menses prior to insertion.We assessed study quality using established guidelines. Two reviewers independently conducted all review stages and rated the quality of evidence for each article; any disagreements were resolved by a third. Where possible, we pooled data using a random-effects model.Among 3,403 potentially relevant studies, we included seven in our meta-analysis. We calculated the mean days of bleeding-only, spotting-only and bleeding and/or spotting for the first four 90-day intervals after LNG-IUS insertion. Combined menstrual bleeding and/or spotting days gradually decreased throughout the first year, from 35.6 days (95% CI 32.2, 39.1) during the first 90-day interval to 19.1 (95% CI 16.6, 21.5), 14.2 (95% CI 11.7, 16.8), and 11.7 days (95% CI 9.7, 13.7) in the second, third, and fourth intervals. Measures for bleeding-only and spotting-only days similarly decreased throughout the first year, with the greatest decreases occurring between the first and second intervals.Our study provides 90-day reference period measures that characterize menstrual patterns for LNG-IUS users with normal regular menses prior to insertion during the first year of use. Our findings provide broader generalizability and more detail than patterns described in the prescribing information. These findings quantify an overall decrease in menstrual bleeding days with longer duration of use, with the greatest decrease occurring between months 3-6. Accurately establishing expectations with the LNG-IUS may improve informed selection and decrease discontinuation.