Sex hormones and risks of rheumatoid arthritis and developmental or environmental influences

Sex hormone relationships for onset risks of rheumatoid arthritis (RA) were analyzed in a nested case-control study, derived from a large community-based prospective cohort. A self-reported history of RA in a first-degree relative, heavy cigarette smoking, and positive rheumatoid factor (RF) were confirmed predictors of subsequent RA onset in this data set. In the 11 premenopausal onset cases, lower serum dehydroepiandrosterone sulfate levels were observed as was an imbalance in serum IL-1beta to IL-1ra levels; the latter was not observed in the 43 controls (CNs). In the 18 male cases, significantly higher serum cortisol was observed in the six cases with positive family history versus the 12 with a negative history. To the contrary, a small minority of the male cases had combined low serum cortisol and testosterone, which was not observed in the 72 CNs. Significant gender dimorphism was observed between the sex hormones and serum log RF titers as well as in the correlations of serum log testosterone and estradiol. Principal component analysis of multiply-imputed data sets extracted four uncorrelated components, which provided concordant neuroendocrine immune relationships to the previously investigated univariate and multivariate analyses. The literature on developmental and environmental influences on sex hormones and risks of RA was reviewed.