Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.
The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.
Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).
The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.
Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).
Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).
Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.
The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.