Women Using IUDs at Greater Risk for Rheumatoid Arthritis

Intrauterine devices (IUDs) may contribute to an increased risk of the development of rheumatoid arthritis (RA) in women, according to a presentation at the American College of Rheumatology Annual Meeting held November 14-19 in Boston.

Researchers from the Studies of Etiology of RA (SERA) project examined the effects of various contraceptive methods on blood levels of RA-related antibodies to citrullinated protein antigens (ACPA). ACPA was tested using anti-cyclic citrullinated peptide (anti-CCP) test, in which elevated anti-CCP levels can be found in the blood several years before RA development.

The pre-clinical period of RA where anti-CCP levels are present is often an indicator of joint disease and RA diagnosis. Recent studies have suggested ACPA may be directly pathogenic and that hormonal factors may make women more susceptible to RA development than men, especially with contraception and pregnancy as major influences.

The researchers observed 976 women without an RA diagnosis, but with a first-degree relative with RA and were therefore classified as an increased risk for future RA based on family history. A blood sample was given at the baseline visit to test for ACPA. A questionnaire was also given to participants, where data about prior contraception use and pregnancy was collected.

The researchers concluded that women using an IUD had statistically significantly increased risk for anti-CCP positivity. Women who used oral contraceptive pills (OCPs) were at a decreased risk of anti-CCP positivity, either currently or in the past. There was no link found between anti-CCP positivity and pregnancy or breastfeeding.

“We think these findings are very exciting and will lead to future studies that improve our understanding of RA development in women,” the study’s lead author Kristen Demourelle, MD, of the University of Colorado Denver, said in a press release. “However, it is important to remember that this study was performed in a group of women already known to be at increased risk for RA. These findings may not apply to the general population, and additional studies of women over a longer period of time are needed to confirm and extend these findings. Furthermore, not all women who were anti-CCP positive had used IUDs.”

In the future, the researchers hope to examine whether OCPs similarly affect women at risk for RA. They specifically want to pinpoint which mechanisms in OCPs play a role in protecting against RA-related autoimmunity and the ACPA factor. They note that IUDs can generate inflammatory responses in the uterus, which they hypothesize may play a role.

“While the mechanisms that link contraceptive factors to ACPA generation are unknown, unlike OCPs, IUDs have been shown to generate endometrial inflammatory responses,” the authors conclude. “Therefore, the association of IUD use and ACPA suggest that IUD-induced endometrial inflammation may be a potential mucosal trigger of RA-related autoantibodies.”