An Epidemiologic Study of the Role of Exogenous and Endogenous Estrogens in Rheumatoid Arthritis
Etiologic studies of estrogens and rheumatoid arthritis (RA) have shown varying results. The primary objective of this case-control study was to investigate the etiologic role of exogenous and endogenous estrogens in RA, and the secondary to determine whether association estimates for each hormonal exposure differed by time since diagnosis. Cases (n=245) were women, aged 25 to 69, residents of the Greater Toronto Area (GTA), and diagnosed with RA within 10 years of ascertainment. Controls (n=244), matched on age (+/-10 years), were GTA residents attending the Toronto Western Orthopaedic Clinic for an accidental injury. Socio-demographic and health history information were collected in a self-administered questionnaire. Two series of models were examined: the first containing one main hormonal variable, and the second multiple hormonal variables. Hormonal exposures included history of OC use, hormone replacement therapy (HRT) use, pregnancy, live births, breastfeeding and menstruation. Four findings emerged in the first series: (1) current OC users had a strong decreased risk (OR=0.25; 95% CI=0.09, 0.73); (2) HRT use duration and RA were negatively associated (e.g., OR=0.1; 95% CI=0.0, 0.5 for HRT use>5.2 years), (3) parous women who breastfed were at least half as likely to develop RA than non-breastfeeders, and (4) menstrual years and risk of RA were negatively associated. In the second series (adjusted for hormonal exposures and potential confounders), there were two strong negative associations with RA: menstrual years (e.g., OR=0.1, 95% CI=0.01, 0.3 for>36.9 menstrual years), and lifetime weeks of breastfeeding (test for trend chi2df=4=15.62, p