What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis?

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease and has a female predominance of around 3:1. The relationship between sex hormones and RA has been of great interest to researchers ever since Philip Hench's observations in the 1930's regarding spontaneous disease amelioration in pregnancy. Extensive basic scientific work has demonstrated the immunomodulatory actions of sex hormones but this therapeutic potential has not to date resulted in successful clinical trials in RA. Epidemiological data regarding both endogenous and exogenous hormonal factors are inconsistent, but declining estrogen and/or progesterone levels in the menopause and post-partum appear to increase the risk and severity of RA. This review assimilates basic scientific, epidemiological and clinical trial data to provide an overview of the current understanding of the relationship between sex hormones and RA, focusing on estrogen, progesterone and androgens.