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

Mei Heting; Lu Wenping; Wang Yanan; Zhang Dongni; Wu Xiaoqing; Zhuo Zhli

doi:10.1016/j.heliyon.2023.e14733

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

Heliyon. 2023 Mar 22;9(4):e14733. doi: 10.1016/j.heliyon.2023.e14733. eCollection 2023 Apr.

Authors

Mei Heting¹, Lu Wenping¹, Wang Yanan¹, Zhang Dongni¹, Wu Xiaoqing¹, Zhuo Zhli¹

Affiliation

¹ Guang'anmen Hospital of Chinese Academy of Chinese Medical Sciences, Beijing, 100053, China.

Abstract

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. We conducted an updated meta-analysis (larger sample capacity and including Asian data) to explore whether LNG-IUS can increase the risk of BC.

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.

Keywords: Breast cancer; Intrauterine device; Levonorgestrel intrauterine sustained release system; Meta-analysis; Risk factors; Systematic review.