Oral contraceptive use reduces RA risk
The use of oral contraceptives reduces the risk of developing rheumatoid arthritis (RA), especially ACPA*-positive RA, according to the Swedish EIRA** study.
Responses from 6,892 women aged ≥18 years (2,641 cases and 4,251 controls) were gathered to evaluate lifestyle and environmental exposures including oral contraceptive use, breastfeeding, and potential confounders. Sixty-six percent of the cases were ACPA-positive. [Ann Rheum Dis 2017;76:1845-1852]
Compared with never users, ever and past oral contraceptive users had a decreased risk of developing RA overall (odds ratios [ORs], 0.87 for both) and ACPA-positive RA (OR, 0.84 and 0.83 for ever and past users, respectively).
Additionally, longer oral contraceptive use (>7 years) was found to be associated with a decreased risk of RA overall (OR, 0.81; p=0.0014) and ACPA-positive (OR, 0.80; p=0.0037) and ACPA-negative RA (OR, 0.82; p=0.0356) compared with never use, which further reflects the inverse relationship between oral contraceptive use and the subsequent development of RA, said the researchers.
Moreover, there was a significant interaction between smoking and the lack of oral contraceptive use, showing a more pronounced risk among smokers who have never used oral contraceptives (AP***=0.28). This finding validates smoking as a risk factor for ACPA-positive RA. [Rheum Dis Clin North Am 2012;38:405-426; Ann Rheum Dis 2011;70:508-511; Rheumatology 2012;51:499-512].
However, as smoking and oral contraceptive use have been linked to an increased odds of venous thrombotic events (VTE), women who smoke and have a history of VTEs might have been recommended against the use of oral contraceptives, the researchers pointed out. “We can therefore not exclude the possibility that our findings … merely reflect that women [who smoke], who have an increased RA risk, do not receive [oral contraceptive] prescription as often.”
Overall, these findings may provide useful information on certain mechanisms involved in the development of RA which, although one of the most common autoimmune diseases, has a complex pathophysiology involving an interplay of genetic and environmental factors. [Lancet 2009;373:659-672]
While the findings are consistent with previous studies, [J Rheumatol 2004;31:207-213; Ann Rheum Dis 2001;60:934-939] these also contradicted other trials showing a protective effect of oral contraceptive use on the risk of RA when seropositivity was taken into account. [J Rheumatol 2004;31:207-213; Scand J Rheumatol 2010;39:454-460; Arthritis Res Ther 2006;8:R133].
Further trials are therefore warranted to validate these contradictory results and to investigate the biological mechanisms that could elucidate these findings and determine whether hormonal factors influence the RA ACPA subsets, said the researchers.