Association Between Levonorgestrel-Releasing Intrauterine System Exposure Duration and Breast Cancer Incidence

To investigate the association between the duration of levonorgestrel-releasing intrauterine system (LNG-IUS) use and breast cancer risk in Korean women.

A retrospective cohort study was conducted using the Korean National Health Insurance Claims database from 2013 to 2022. A total of 2,094,029 women aged 30-49 years with initial diagnoses of endometriosis, uterine leiomyomas, or abnormal uterine bleeding between 2014 and 2017 were included in the study. Propensity score matching was applied to create balanced cohorts of LNG-IUS users and nonusers. Cox proportional hazards models were used to evaluate the association between LNG-IUS exposure duration and breast cancer incidence.

A total of 61,010 women were included in the study cohort. The incidence rate of breast cancer in LNG-IUS group was 223 cases per 100,000 person-years compared with 154 cases per 100,000 person-years in the non-LNG-IUS group. Use of LNG-IUS was linked to an increased breast cancer risk (hazard ratio [HR] 1.38, 95% CI, 1.192-1.585). Analysis of LNG-IUS use over time suggests that early initiation is associated with an increased risk of breast cancer, which may decrease over time (less than 3 years: early HR 5.40, 95% CI, 4.037-7.216; less than 3 years: late HR 1.04, 95% CI, 0.547-1.994; 3-4.9 years: early HR 3.44, 95% CI; 2.671-4.431; 3-4.9 years: late HR 1.75, 95% CI; 1.12-2.723; 5 years or more: HR 1.77, 95% CI, 1.26-2.479).

The LNG-IUS may be associated with an increased risk of breast cancer among women with abnormal uterine bleeding, endometriosis, or leiomyomas, with the risk being particularly elevated during the initial years of use.