Sex hormones and rheumatoid arthritis: cause or effect relationships in a complex pathophysiology?

Sex hormones are believed to contribute to the risk of rheumatoid arthritis (RA) because of the disease's female preponderance, especially during the child-bearing years, and because of the dramatic improvements seen during pregnancy. Available controlled data on serum dehydroepiandrosterone sulfate (DHEAS), testosterone (T) and estradiol (E2) in RA patients not treated with glucocorticoids are summarized. Hypotheses of sex hormone contributions to RA are tested by judgemental criteria for the causes or determinants of disease. Available data support hypoandrogenicity in RA patients, especially among premenopausal females and males. Limited prospective studies in women and therapeutic trials of testosterone therapy in men further support a role of sex hormones in RA. Interactions of sex hormones and glucocorticoids are also believed to be important and deserve priority in future research.