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

Jin-Sung Yuk, Myoung Hwan Kim, Sang Hee Yoon, Gwan Hee Han, Ji Hyun Noh
Obstetrics and gynecology · 2025 · vol. 145(5) , pp. 523–531 · doi:10.1097/AOG.0000000000005881 · PMID:40080821
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⚙ AI-generated summary by claude@2026-06, 2026-06-13 ⓘ

This study found that levonorgestrel-releasing intrauterine system (LNG-IUS) use is associated with increased breast cancer risk, particularly during the initial years of exposure.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-11 · read from full text ⓘ

This retrospective cohort study used Korean National Health Insurance Claims data (2013–2022) to examine whether the duration of levonorgestrel-releasing intrauterine system (LNG-IUS) use is associated with breast cancer incidence among 2,094,029 women aged 30–49 who had initial diagnoses of endometriosis, uterine leiomyomas, or abnormal uterine bleeding (2014–2017), with propensity score matching and Cox proportional hazards models. Among 61,010 women included in the matched cohort, breast cancer incidence was higher in LNG-IUS users (223 vs 154 cases per 100,000 person-years), and LNG-IUS exposure was associated with increased breast cancer risk (HR 1.38, 95% CI 1.192–1.585). Time-stratified analyses suggested particularly elevated risk during the initial years of use, with early-use hazard ratios highest for those with less than 3 years exposure, while later periods showed lower or attenuated estimates. The study is based on claims data and includes only women with those specified baseline diagnoses, which may limit generalizability. This paper is centrally about endometriosis — it analyzes LNG-IUS exposure duration and breast cancer incidence in a cohort of women whose initial diagnoses include endometriosis, alongside leiomyomas and abnormal uterine bleeding.

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Abstract

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

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

Methods

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.

Results

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).

Conclusion

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.

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Condition tags

endometriosis

MeSH descriptors

Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms

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