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Contraceptive Choices Affect RA-Specific Autoantibodies in Women at Risk for RA

The choice of contraception for women at increased risk of rheumatoid arthritis (RA) may affect detectable levels of autoantibodies, specific to RA, in the blood, a new study has found. Women who had used an intrauterine device (IUD) were almost 3 times more likely to test positive for autoantibodies related to RA.

The diagnosis of rheumatoid arthritis is not based on blood tests alone, but certain tests that measure nonspecific inflammatory markers or disease-specific autoantibodies are helpful in determining an accurate diagnosis. For example, most people with RA will test positive for rheumatoid factor (RF). Those that do not test positive for RF, up to a third of people with RA, may be diagnosed with sero-negative RA.

Autoimmunity in rheumatoid arthritis is often characterized by the presence of autoantibodies directed against citrullinated protein/peptide antigens (ACPAs) specific to RA that are detected with an anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) test. In those already diagnosed with RA, the presence of serum ACPAs predicts a more erosive disease course.

ACPAs can also be detected in the serum of healthy individuals years before clinical onset of RA. According to a recent study presented at the annual meeting of the American College of Rheumatology in Boston, MA, the choice of contraception in women at increased risk for RA may affect serum ACPA positivity.

In the Studies of the Etiology of RA (SERA) project, 1243 first degree relatives (FDR) of probands with RA who are enrolled are women. Sonia Khatter, from the University of Colorado School of Medicine in Aurora, and colleagues studied female FDRs who at their baseline visit had serum ELISA testing for ACPA and a contraceptive and pregnancy history taken (n=336). All subjects were free from clinical manifestations (or symptoms) of inflammatory arthritis at the time of serum testing. Only one subject was randomly selected per family, so the final analysis included 297 FDRs.

In this group of women with increased risk of RA, researchers found that after adjustment for age, race, and smoking, prior use of the oral contraceptive pill (OCP) was associated with a decreased risk of serum ACPA positivity (odds ratio, 0.34). These results align with previous studies that found an association between OCP use and decreased risk of rheumatoid factor (RF) positivity. In contrast, researchers found an increased risk for ACPA positivity in women who had a history of intrauterine device (IUD) use (odds ratio, 2.68).

It is not known what mechanisms are in play that link contraceptive factors to the development of ACPAs; however, Khatter et al (2014) note that unlike OCPs, IUDs have been shown to generate endometrial inflammatory responses. Therefore, the association of IUD use and ACPA positivity suggest that IUD-induced endometrial inflammation may be a potential mucosal trigger of RA-related antibodies.

This study revealed no significant correlations between ACPA positivity and pregnancy or breastfeeding. First degree relatives who were ACPA+ were slightly older than those who were ACPA-. The mechanisms by which OCPs could protect against RA and IUD use could increase risk for RA-related autoimmunity warrant further study.


This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Khatter S, Parish MC, Feser ML, et al. Contraceptive Factors Are Associated with Serum Antibodies to Citrullinated Protein Antigens in Women at Elevated Risk For Future Rheumatoid Arthritis [abstract]. In: Proceedings of the Annual Meeting of American College of Rheumatology; 2014 Nov 14-19; Boston, MA. 2014. ACR/ARHP 2014 Program Book; Page 142; Abstract Number: 2921. Accessed at
  2. Ossipova E, Cerqueira CF, Reed E, et al. Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint. Arthritis Research & Therapy. 2014;16:R167. doi:10.1186/ar4683. Accessed at


  • Rheannon Hart
    5 years ago

    This is very interesting, Lisa, thanks for posting it. I have honestly wondered if my IUD triggered my RA. I know you have to have the genetics, first and foremost, but environmental factors can “switch” your RA “on”. A year before I started experiencing RA symptoms, I had an IUD put in, before that, I relied solely on condoms (non hormonal, non intrusive, and effective). But, they can be a bit of a pain and I was in a monogamous relationship, so I had a non-hormonal IUD put in. That was 5 years ago; I was diagnosed 4 years ago. I actually just had my IUD removed a couple of months ago because I was an emotional wreck, for a week, every month, and I wanted to see if the IUD was causing it. Since the removal, I haven’t had any of the crazy emotions that I had before. So, I’m SO glad I had the thing removed, but now, I wish I would never have had it installed.

  • Lisa Emrich author
    5 years ago

    Hi Rheannon,

    I’m so glad that you are doing much better now. For years, before and after onset of RA and MS, I relied on condoms as well. Last year, I finally explored the option of IUD so that I wouldn’t have to worry about the risk of pregnancy as someone taking methotrexate. My experience has been positive. The IUD (Mirena) is hormonal and I have actually stopped having periods, but I will still sometimes experience cycle-related symptoms such as tender, swollen breasts.

    If I didn’t already have RA, and if I knew that it seemed to run in my family, and if I were aware of this research, I might not have chosen to go the IUD route. It would be interesting to see research that explored IUD use and diagnosis of RA, not just increased antibodies which are known to be associated with RA. Then it would be easier to infer a potentially causal or more closely associated relationship.

    I hope that you continue to feel better, Rheannon, without the crazy emotions you had before, and that your RA behaves itself.


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