Objective To assess the effect of reproductive factors, especially hormone replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of rheumatoid arthritis (RA) and the presence of anti-cyclic citrullinated peptide (CCP) antibodies in women included in the ESPOIR cohort (early arthritis cohort).
Methods 568 patients were included in the analyses, which were performed using logistic regression.
Results HRT reduced the risk of RA due to the HLA-DRB1 *01 and/or *04 alleles from OR 1.88 (95% CI 1.32 to 2.68, p<0.000) for HLA-DRB1 *01 and/or *04 alleles alone to OR 1.07 (95% CI 0.51 to 2.26, p=0.85) in women with HLA-DRB1 *01 and/or *04 alleles who received HRT. One explanation might be the protective effect of HRT on the presence of anti-CCP antibodies (OR 0.43, 95% CI 0.24 to 0.77, p<0.006). Other reproductive factors such as the number of pregnancies, menopause and age at menopause, age at menarche and a history of pregnancy with poor outcome were not associated with the diagnosis of RA and the presence of anti-CCP antibodies.
Conclusion HRT may reduce the risk of RA due to HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP antibodies.
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Funding An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Abbott and Wyeth also supported the ESPOIR cohort study.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Lapeyronnie University Hospital, Montpellier, France.
Provenance and peer review Not commissioned; externally peer reviewed.