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Women younger than 50 who used a levonorgestrel-releasing intrauterine device (IUD) had a significantly higher risk of breast cancer as compared with women who did not use hormonal contraceptives, a Danish registry study showed.

During follow-up of almost 7 years, hormone-releasing IUD use conferred a 40% higher risk of breast cancer. The data showed a trend toward increasing risk with duration of IUD use, reaching 80% among women who reported using the devices for 10-15 years.

The differences translated into excess breast cancer diagnoses that ranged from 14 to 71 per 10,000 users, although a trend analysis proved to be nonsignificant, reported Lina Steinrud Mørch, PhD, of the Danish Cancer Institute in Copenhagen, and co-authors in .

"Given the increase in LNG-IUS [levonorgestrel intrauterine systems] among females at an age with some risk for breast cancer, and its likely long-term use, information about breast cancer risk should accompany discussions about benefits and risks," the authors stated. In a prior study, "the HR [hazard ratio] with short-term LNG-IUS use was similar to that of contraceptive pills (1.2, 95% CI 1.1-1.3)."

But that earlier research could not address the duration of continuous use, and prior studies have not adequately accounted for use of other types of hormonal contraceptives.

The new results add to existing evidence suggesting an association between hormonal contraception and breast cancer, and are consistent with a recent study showing a 29% greater relative risk for breast cancer among BRCA1 carriers who used any type of hormonal contraceptive.

To examine breast cancer risk by duration of LNG-IUS use, Mørch and colleagues queried Danish national healthcare registries to identify first-time users of LNG-IUS, ages 15-49, during 2000-2019. Users of other hormonal contraceptives within the previous 5 years were excluded.

The search identified 78,595 new users of LNG-IUS who were matched to 78,595 non-users of hormonal contraceptives. The study population had a mean age of 38. Mean duration of follow-up was 6.8 years for the entire population, including 5.9 years for the LNG-IUS users and 7.7 years for the non-users.

Baseline characteristics were similar, including parity, age at first delivery, duration of previous hormonal contraceptive use, history of polycystic ovarian syndrome, history of endometriosis, and use of fertility drugs. Continuous use of LNG-IUS averaged 6 years for 95% of devices.

The results showed 1,617 new breast cancer diagnoses, 720 among LNG-IUS users (over 462,261 person-years) and 897 among non-users (over 601,066 person-years). Comparison of the two groups yielded a breast cancer hazard ratio of 1.4 for LNG-IUS users versus the control group (95% CI 1.2-1.5).

An analysis of breast cancer risk by duration of LNG-IUS use versus non-use for the same duration produced hazard ratios of 1.3 for 0-5 years of use, 1.4 for >5-10 years, and 1.8 for >10-15 years. The hazard ratios translated into 14 excess breast cancer diagnoses per 10,000 users for 0-5 years, 29 per 10,000 for >5-10 years, and 71 per 10,000 for >10-15 years. However, a trend analysis yielded a non-significant P-value of 0.15.

The authors acknowledged limitations of the study. Some women might have removed the device before the end of recommended use, potentially leading to underestimation of risk. The results also could have been affected by inability to account for unmeasured confounders.

"Lack of dose-response could indicate low statistical precision or no causal association," they added.

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