Users of the levonorgestrel-releasing intrauterine system may face an increased risk of breast cancer, with 71 excess cases per 10,000 users after 10 to 15 years of use, similar to patterns observed with oral contraceptives.

In a study of 157,900 women, published in JAMA, data of 78,595 first-time levonorgestrel-releasing intrauterine system (LNG-IUS) users was analyzed and an equal number of matched nonusers. Nationwide Danish registries were used to identify all first-time LNG-IUS users from 2000 to 2019.

After an average follow-up of 6.8 years, investigators found a 40% increased risk of breast cancer among LNG-IUS users aged 15 to 49 years compared with nonusers of hormonal contraceptives. They identified an excess of 14 breast cancer diagnoses per 10,000 users within the first 5 years of use, with the risk continuing but not significantly increasing over longer durations. By 5 to 10 years of use, excess diagnoses rose to 29 per 10,000, and after 10 to 15 years, the excess was 71 per 10,000 users.

Participants who had used other hormonal contraceptives in the 5 years prior to the index date, as well as those with a previous cancer diagnosis or pregnancy at the time of initiation, were excluded. They were followed until the earliest occurrence of breast cancer diagnosis, other cancer diagnosis, pregnancy, postmenopausal hormone therapy initiation, emigration, death, or December 31, 2022. Continuous use was defined as starting from the date of a filled prescription and was tracked until the recommended maximum usage of the device, typically 6 years. 

The average age of participants was 38.3 years. LNG-IUS users were more likely to have had children, with 51% having two children and a mean age at first delivery of 26.4 years. In contrast, nonusers were less likely to have children, with 27% reporting no children and a mean age at first delivery of 26 years.

Limitations included the potential underestimation of breast cancer risk as a result of unmeasured early removal of the LNG-IUS and the lack of a dose-response relationship, which could reflect either low statistical precision or no causal association. Unmeasured confounding factors were not accounted for.

While the absolute breast cancer risk remains low, discussions about LNG-IUS use should include information about this potential risk, especially as usage increases among women in age groups where breast cancer risk is more relevant, concluded study investigators.

They declared having no competing interests.