Levonorgestrel-Releasing Intrauterine Systems linked to Increased Breast Cancer Risk: JAMA

"Users of the levonorgestrel-releasing intrauterine system faced a higher risk of breast cancer compared to nonusers, with this risk increasing further with the number of years of use," the researchers wrote.

The use of levonorgestrel-releasing intrauterine systems (LNG-IUSs) has been on the rise, becoming the preferred hormonal contraceptive among Danish premenopausal women over 30. However, the association between LNG-IUS use and breast cancer risk remains uncertain. While some studies have indicated an increased risk of breast cancer among LNG-IUS users, these studies did not specifically address the duration of continuous use or adequately consider other hormonal contraceptive methods.

In light of this, Lina Steinrud Mørch, Cancer and Medicine, The Danish Cancer Institute, Copenhagen, Denmark, and colleagues aimed to evaluate the breast cancer risk associated with prolonged LNG-IUS use while accounting for other hormonal exposures.

For this purpose, the researchers conducted a nationwide study utilizing data from Danish registries, focusing on 78,595 first-time initiators of levonorgestrel-releasing intrauterine systems at doses of 52 mg, 19.5 mg, and 13.5 mg between 2000 and 2019. They matched women using the intrauterine system with those who did not use hormonal contraceptives, following all participants until the diagnosis of breast cancer, other cancers, pregnancy, initiation of postmenopausal hormone therapy, emigration, death, or December 2022.

The study revealed the following findings:

• During a mean follow-up of 6.8 years, 1,617 participants had a breast cancer diagnosis, of whom 720 were levonorgestrel-releasing intrauterine system users.
• Levonorgestrel-releasing intrauterine system users had an increased risk for breast cancer compared with hormonal contraceptive nonusers (HR = 1.4).
• Breast cancer risk increased along with years of use for women who used levonorgestrel-releasing intrauterine systems for 0 to 5 years (HR = 1.3), more than 5 to 10 years (HR = 1.4), and more than 10 to 15 years (HR = 1.8).
• Per 10,000 users, the increased breast cancer risk corresponding to years of use resulted in an excess of 14 breast cancer diagnoses for 0 to 5 years, 29 diagnoses for more than 5 to 10 years, and 71 diagnoses for more than 10 to 15 years.

The researchers noted, “While the absolute risk of breast cancer is low among young women, the study identified an excess risk of 14 cases per 10,000 females. Importantly, this risk did not increase with the duration of levonorgestrel-releasing intrauterine system use. Given the rising use of levonorgestrel-releasing intrauterine systems among women at an age where there is some risk for breast cancer, and the likelihood of long-term use, discussions about the benefits and risks must include information regarding breast cancer risk.”

Reference:

Mørch LS, Meaidi A, Corn G, Hargreave M, Wessel Skovlund C. Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems. JAMA. Published online October 16, 2024. doi:10.1001/jama.2024.18575