Oral Contraceptives May Cut Rheumatoid Arthritis Risk

Diana Swift

August 23, 2017

Oral contraceptive (OC) use appears to reduce the risk of developing rheumatoid arthritis (RA) by 13%, according to a Swedish population-based case-control study published online August 18 in the Annals of the Rheumatic Diseases.

The study, conducted by Cecilia Orellana, PhD, from the Karolinska Institute's Institute of Environmental Medicine in Stockholm, and colleagues, found no significant protective effect from breast-feeding. However, they did see a nonsignificant trend toward a dose-response protective effect with longer duration of breast-feeding.

The investigators found an inverse relationship between any oral contraceptive use and developing RA, especially RA that is positive for anticitrullinated protein antibodies (ACPA), which may signal greater disease severity. Ever-users had a 13% decreased risk of developing RA overall compared with women who never used OC (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.78 - 0.97).

Current OC users had a 15% lower risk (OR, 0.85; 95% CI, 0.68 - 1.06), which was not statistically significant; those taking OCs for more than the median use of 7 years had a 19% lower risk (OR, 0.81; 95% CI, 0.71 - 0.92), which was significant.

The association with ever and past OC use was not significant for ACPA-negative RA, but remained significant for ACPA-positive RA after adjustment for smoking duration and alcohol consumption (OR, 0.84 [95% CI, 0.74 - 0.96]; and OR, 0.83 [95% CI, 0.73 - 0.95], for ever and past OC use, respectively).

The researchers observed an interaction between OC never-use and smoking that suggested greater RA risk in never-users than ever-users. "The significant interaction between lack of OC use and smoking indicates that the risk of ACPA-positive RA associated with smoking is higher among women who never used OCs than among those who did," they explain. "However, since both smoking and the use of OC have been linked to an increased predisposition to venous thrombotic events (VTE), women with a history of VTEs (especially if they smoke) might be recommended not to use OC by their physician."

The researchers add, "All of these findings together support the notion of RA as two different disease entities with different risk factors patterns."

Swedish Epidemiological Investigation of Rheumatoid Arthritis Cohort

The investigators analyzed data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA), which included women aged 18 years and older from 1996 to 2014. The average age at inclusion in the study was about 51 years, and the median average duration of oral contraception in users was 7 years.

Blood samples were collected to check for RA antibodies such as ACPA and rheumatoid factor (RF). Among patients, 66.5% had ACPA-positive RA. Detailed questionnaires probed participants' contraception use, parity, breast-feeding, education levels, and lifestyle.

The EIRA cohort included 2809 women diagnosed with RA and 5312 age-matched controls randomly selected from the general population. The authors included 2578 patients with RA and 4129 controls from the EIRA cohort. Of those, 884 in the RA group and 1949 controls had breast-fed at least one child during 2006 to 2014.

Study Limitations

Study limitations included the researchers' lack of detailed information about OCs, including preparations and doses, the authors write. In addition, cause and effect cannot be determined, as the study was observational in nature.

"Further research is required to explore the biological mechanisms behind our findings and whether hormonal factors have different impact on the ACPA-subsets of RA," the researchers conclude.

This study was supported by the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav V's 80-Year Foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative 1-supported BTCure project, and the National Institutes of Health. The authors have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online August 18, 2017. Full text

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