Levonorgestrel‐releasing intrauterine system and breast cancer risk: A systematic review and meta‐analysis

Introduction Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta‐analysis of the literature on the risk of breast cancer development in women using the 52‐mg levonorgestrel‐releasing intrauterine system (LNG‐IUS). Material and methods We performed a thorough review of peer‐reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG‐IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG‐IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random‐effects model (owing to high study heterogeneity) meta‐analysis of seven suitable studies, stratified by the age distribution of patients (