Meta-Analysis of Breast Cancer Risk in Levonorgestrel-Releasing Intrauterine System Users

To map and assess evidence regarding use of the levonorgestrel-releasing intrauterine system (LNG-IUS) and its association with breast cancer, we conducted a systematic review and meta-analysis. A search strategy was developed using the terms "Levonorgestrel-releasing," "LNG-IUS," "intrauterine system," and "breast cancer. The electronic databases searched were MEDLINE, Embase, Cochrane Library, Latin American & Caribbean Health Sciences Literature, and Google Scholar for studies published until August 2020. We included observational studies: prospective or retrospective cohort, case-control, and cross-sectional. A total of 494 studies were identified, 294 studies were evaluated by title and abstract, and 262 were excluded because they did not meet the inclusion criteria. A total of 32 studies were read in full, and 24 were excluded. Thus, eight studies were included in the systematic review. The meta-analysis included four studies (two cohort and two case-control studies). Two subgroup analyses were performed for different study designs. The estimated relative risk for the two cohort studies (144,996 cases), with moderate-quality evidence, was 0.93 (95% confidence interval [CI], 0.840-1.03). The odds ratio estimated for the two case-control studies (5556 cases and 35987 controls), with moderate-quality evidence, was 1.07 (95% CI, 0.91-1.26). Evidence of an increased risk of breast cancer was not observed in levonorgestrel-releasing intrauterine system users.