Background Rheumatoid arthritis (RA) is a chronic inflammatory disease, with female predominance. Hormonal factors, such as breast-feeding history, use of Oral Contraceptives (OC) and menopausal age, have been suggested to influence the risk of RA[1-3]. The underlying mechanisms and their impact on disease progression are unknown.
Objectives To investigate if recognised hormonal predictors of RA influence the severity of RA.
Methods One hundred and thirty-four incident RA cases, identified by four different local and national registers, which participated as healthy volunteers in a community-based health survey between 1991-1996, were included. By a retrospective structural review of the medical records, information on use of disease modifying anti-rheumatic drugs (DMARDs) including biological treatment, radiographic erosions, rheumatoid factor (RF) status and anti-citrullinated protein antibody (ACPA) status as well as Health Assement Questionnaire (HAQ) data were collected. The variables were added to the SPSS TwoStep Cluster Analysis in order to reveal natural groupings of RA severity.
The analyzed hormonal predictors included breastfeeding history (stratified into never breastfed, 1-12 months of cumulative breast feeding or >12 months of cumulative breast feeding), history of OC use (stratified into never used, 1-5 years or >5 years of use) and menopausal age (early menopause ≤45 years or normal/late menopause (>45 years))
Results The median duration from enrolment in the health survey to RA diagnosis was 5.5 years, and age at baseline was 45-73 years. Mean age at RA diagnosis was 63.4 years, 72% were RF positive, and 28% received biological treatment during the follow-up. Three clusters were identified: one with severe RA, one with mild/moderate RF-positive RA and one with mild/moderate RF-negative RA. In the group with severe RA, all patients had been treated with biological treatment, 89% were RF positive, 85% had ever had erosions and the mean HAQ score after 5 years was 1.17. In the mild/moderate RF positive and RF negative clusters, no one had received biologics, 56% and 52% had erosions, respectively, and mean HAQ scores after 5 years were 0.74 and 0.88. There was a significant difference (p=0.005) in the distribution of these clusters between patients with early menopause and those with menopause after 45 years of age. Patients with a history of early menopause were less likely to develop severe RA (16% vs 35%) and more likely to develop a mild/moderate RF negative phenotype (58% vs 20%). There was no major difference in RA severity depending of OC use or history of breast-feeding.
Conclusions Early menopause predicts a milder form of RA. Hormonal changes may influence pathways that are distinct from those leading to severe, progressive disease.
Pikwer M, Bergstrom U, Nilsson JA, et al. Breast feeding, but not use of oral contraceptives, is associated with a reduced risk of rheumatoid arthritis. Ann Rheum Dis 2009;68:526-30.
Karlson EW, Mandl LA, Hankinson SE, et al. Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses’ Health Study. Arthritis Rheum 2004;50:3458-67.
Merlino LA, Cerhan JR, Criswell LA, et al. Estrogen and other female reproductive risk factors are not strongly associated with the development of rheumatoid arthritis in elderly women. Semin Arthritis Rheum 2003;33:72-82.
Disclosure of Interest None Declared
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