Levonorgestrel intrauterine system and breast cancer risk: An updated systematic review and meta-analysis of observational studies.

Objectives: Levonorgestrel intrauterine sustained release system (LNG-IUS) is an intrauterine hormonal contraceptive device. Breast cancer (BC) was the most common type of cancer in women in the world in 2020. The relationship between LNG-IUS and BC is controversial Study design: We performed a thorough review of peer-reviewed publications from January 2005 through November 2022 using combinations of search terms for BC risk and LNG-IUS in the PubMed, Cochrane, Embase, Science Direct, and Web of Science databases. Studies reporting BC risk estimates among users of LNG-IUS were included according to the PRISMA criteria. Two authors independently evaluated all studies identified from the databases using Endnote software, and a third author resolved disagreements. The quality of evidence was evaluated using the Newcastle‒Ottawa Scale (NOS). A funnel plot was generated to assess publication bias. Results: We identified 3029 studies; 12 studies were included in our systematic review, and 6 studies involving 261,221 women were included in our meta-analysis. Two subgroup analyses were performed for different study designs. A total of 190,475 women were included in the meta-analysis of cohort studies, and the results were RR = 0.80 (95% CI 0.57-1.11, Z = 1.33, P = 0.18 > 0.05). The meta-analysis of the case‒control studies included 70,746 women, and the results were OR = 1.38 (95% CI 0.98-1.94, Z = 1.85, P = 0.06 > 0.05). Conclusions: Evidence of an increased risk of BC was not observed among LNG-IUS users. Implications: There are inconsistencies in existing studies that prevent us from confirming whether LNG-IUS can increase the risk of BC. Our updated meta-analysis preliminarily suggested that LNG-IUS did not increase the risk of BC, providing evidence for more clinically safe use and thus providing a better choice for contraception.