ABSTRACT
BACKGROUND: Changes in menstrual bleeding concern many users of the 52 mg Levonorgestrel Intrauterine System. Prescribing information for Levonorgestrel Intrauterine System 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. OBJECTIVE: The objective of the study was to systematically calculate the mean days of bleeding-only, spotting-only, and bleeding and/or spotting experienced by a population of reproductive-aged Levonorgestrel Intrauterine System users with normal regular menses prior to insertion during the first year of use. DATA SOURCES: 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. STUDY ELIGIBILITY CRITERIA: We considered studies that reported data on Levonorgestrel Intrauterine System devices releasing 20 µg 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. STUDY APPRAISAL AND SYNTHESIS METHODS: 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. RESULTS: Among 3403 potentially relevant studies, we included 7 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 Levonorgestrel Intrauterine System insertion. Combined menstrual bleeding and/or spotting days gradually decreased throughout the first year, from 35.6 days (95% confidence interval, 32.2-39.1) during the first 90 day interval to 19.1 (95% confidence interval, 16.6-21.5), 14.2 (95% confidence interval, 11.7-16.8), and 11.7 days (95% confidence interval, 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. CONCLUSION: Our study provides 90 day reference period measures that characterize menstrual patterns for Levonorgestrel Intrauterine System 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 and 6. Accurately establishing expectations with the Levonorgestrel Intrauterine System may improve informed selection and decrease discontinuation.
Subject(s)
Contraceptive Agents, Female , Intrauterine Devices, Medicated , Metrorrhagia , Adult , Female , Humans , Levonorgestrel/therapeutic use , Menstruation , Time FactorsABSTRACT
OBJECTIVE DATA: Amenorrhea is a polarizing noncontraceptive effect of the levonorgestrel intrauterine system. Composite amenorrhea prevalence estimates that summarize all clinical data for the first-year after insertion currently are not available. The purpose of this study was to investigate the validity of existing prevalence estimates by the systematic calculation of amenorrhea measures for a general population of levonorgestrel intrauterine system users and to provide 90-day interval point estimates for the first year of use. STUDY: We identified clinical trials, randomized controlled trials, and randomized comparative trials that were published in English between January 1970 and September 2017 through electronic searches of 12 biomedical and scientific literature databases that included MEDLINE and ClinicalTrials.gov. STUDY APPRAISAL AND SYNTHESIS METHODS: We considered studies that clearly defined amenorrhea per World Health Organization standards (the complete cessation of bleeding for at least 90 days), collected data from written daily bleeding diaries (the gold standard data collection technique on menstrual bleeding changes), and evaluated levonorgestrel intrauterine system devices that released 20 µg of levonorgestrel per day. We assessed study quality using guidelines established by the US Preventive Services Task Force and Cochrane handbook for systematic reviews of interventions. Two reviewers independently conducted all review stages; disagreements were resolved by a third reviewer. Where possible, data were pooled with the use of a random-effects model. RESULTS: Of 2938 potentially relevant studies, we included 9 in our meta-analysis. We calculated amenorrhea prevalence, which was weighted for inter- and intrastudy variance, for 4 90-day intervals and months 0-12. Our results demonstrated few levonorgestrel intrauterine system users (0.2%; 95% confidence interval, 0.0-0.4) experienced amenorrhea during the first 90 days after insertion; however, prevalence increased to 8.1% (95% confidence interval, 6.6-9.7) on days 91-180. Finally, 18.2% (95% confidence interval, 14.9-21.5) of users experienced amenorrhea for at least 1 90-day interval during the first year. Although interstudy heterogeneity limited reliability of days 181-271 and 272-365 measures, prevalence increased from 13.6% (95% confidence interval, 9.3-18.0) to 20.3% (95% confidence interval, 13.5-27.0), respectively. CONCLUSION: Approximately 20% of levonorgestrel intrauterine system users experience amenorrhea during at least 1 90-day interval by the first year after insertion. This composite estimate is consistent with the product labeling and demonstrates that most users do not experience amenorrhea during the first year. These results provide accurate summary measures to facilitate counselling and informed method selection.
