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

• Published in: Clinical breast cancer Vol. 21; no. 6; pp. 497 - 508
• Main Authors: Silva, Fabio R., Grande, Antonio Jose, Lacerda Macedo, Ana Cristina, Colonetti, Tamy, Rocha, Marina C., Rodrigues Uggioni, Maria Laura, Silva, Bruno R., da Rosa, Maria Inês
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2021
• Subjects: Breast Neoplasms - chemically induced; Breast Neoplasms - diagnosis; Contraceptive Agents, Female - adverse effects; Female; Humans; Intrauterine Devices, Medicated - adverse effects; Levonorgestrel; Levonorgestrel - adverse effects; LNG-IUS; Risk factor; Risk Factors; Systematic review; Women; Women; Systematic review; LNG-IUS; Levonorgestrel; Risk factor
• ISSN: 1526-8209; 1938-0666
• DOI: 10.1016/j.clbc.2021.03.013

•The primary studies included in this systematic review did not show substantial heterogeneity in the pooled results.•We avoid introducing bias in the analysis, conducting two meta-analyzes separately.•The evidence found does not suggest that LNG-IUS is a risk factor for breast cancer, with evidence of moderate quality. 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.