Taking the contraceptive pill, particularly for seven or more consecutive years, is linked to a lowered risk of developing rheumatoid arthritis, finds US-Swedish research.
But no significant link was found for breastfeeding – a practice that has been associated with a protective effect – after accounting for various potentially influential factors, the findings from researchers at the Karolinska Institutet, Stockholm, Sweden, Karolinska University Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston show.
Because rheumatoid arthritis is two to three times as common in women as it is in men, it is thought hormonal and reproductive factors may partly explain this gender difference. But the research to date has produced equivocal results.
In a bid to look at these issues in more depth, the researchers looked at the possible link between the development of the disease and use of the Pill and/or breastfeeding among adult women who had had at least one child. They drew on data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA), which included women aged 18 and above, living in a defined area of Sweden between 1996 and 2014.
During this time-frame, 2,809 women were diagnosed with rheumatoid arthritis, and 5,312 women, randomly selected from the general population and matched for age, acted as a comparison group.
Blood samples were taken from all the participants to check for antibodies (ACPA) to rheumatoid arthritis, and the women were quizzed in depth about their contraceptive and reproductive histories; their lifestyle; whether they had breastfed their kids; and their educational attainment.
In all, 2,578 women with arthritis and 4,129 women from the comparison group were included in the final analysis. Of these, 884 with rheumatoid arthritis and 1,949 from the comparison group had breastfed at least one child between 2006 and 2014.
Women who had used an oral contraceptive at any time had a lower risk of developing rheumatoid arthritis than those who had never done so. The risk was 15% lower in current users of the Pill and 13% lower in past users. And the association was significant for women who tested positive for ACPA antibodies, even after taking account of tobacco and alcohol consumption, compared with women who had never used an oral contraceptive.
Nine out of 10 people who test positive for ACPA (anti-citrullinated protein) antibodies will have rheumatoid arthritis, and the presence of these antibodies may indicate more serious disease.
Using the Pill for more than seven years – the average length of use among the study participants – was associated with a 19% lower risk of developing rheumatoid arthritis, and this was the case for those who tested positive and negative for ACPA.
Although a lower risk was also found among women who had breastfed at least one child, this was not significant after potentially influential factors were accounted for.
This is an observational study so no firm conclusions can be drawn about cause and effect, added to which the researchers were unable to glean any information about the dose or type of oral contraceptive the women used. But the number of participants was large, and a wide range of potentially influential factors was looked at, the researchers point out.
Abstract
Objectives: To study whether oral contraceptive (OC) use or breastfeeding (BF) influence the risk of rheumatoid arthritis (RA), stratifying the cases by presence/absence of anticitrullinated protein antibodies (ACPA), and whether these factors interact with known risk factors in the development of ACPA-positive RA.
Methods: Women aged ≥18 years, participants in the population-based case–control Swedish Epidemiological Investigation of RA study (2641 cases/4251 controls), completed an extensive questionnaire regarding OC, BF and potential confounders. We calculated ORs, with 95% CIs, adjusted for age, residential area, smoking and alcohol consumption. Attributable proportion due to interaction (AP) was estimated to evaluate presence of interaction.
Results: Compared with never users, ever and past OC users had a decreased risk of ACPA-positive RA (OR=0.84 (95% CI 0.74 to 0.96); OR=0.83 (95% CI 0.73 to 0.95), respectively). No significant associations were found for ACPA-negative RA. Long duration of OC use (>7 years vs never use) decreased the risk of both ACPA-positive (p=0.0037) and ACPA-negative RA (p=0.0356).
A history of long BF decreased the risk only of ACPA-positive RA in a dose-dependent manner (p=0.0086), but this trend did not remain after adjustments. A significant interaction was observed between the lack of OC use and smoking (AP=0.28 (95% CI 0.14–0.42)) on the risk of ACPA-positive RA. No interactions were found for BF.
Conclusions: OC decreased the risk of RA, especially ACPA-positive RA, where an interaction with smoking was observed. A long duration of OC use decreased the risk of both disease subsets. We could not confirm an association between BF and a decreased risk of either ACPA-positive or ACPA-negative RA.
Authors
Cecilia Orellana, Saedis Saevarsdottir, Lars Klareskog, Elizabeth W Karlson, Lars Alfredsson, Camilla Bengtsson
[link url="https://www.sciencedaily.com/releases/2017/08/170817191007.htm"]BMJ material[/link]
[link url="http://ard.bmj.com/content/early/2017/07/28/annrheumdis-2017-211620"]Annals of Rheumatic Diseases[/link]