The effects of gender and sex hormones on outcome in rheumatoid arthritis.

Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome. Men, however, are more likely than women to die from extra-articular complications of rheumatoid disease. This chapter discusses the outcome and mortality studies that substantiate these conclusions and then examines the possible mechanisms that may account for them, including the HLA system, seropositivity, compliance, response to therapy and pain threshold. In particular, sex and sex hormones emerge as independent risk factors in rheumatoid disease. The epidemiological evidence points towards a peak age of onset of RA at the time of the menopause in women and towards later in life in men. Premenopausal women may fare better than postmenopausal women with RA. The possible protective effects of the oral contraceptive pill and the dramatic amelioration with pregnancy are well documented. In vivo and in vitro studies have demonstrated that sex hormones interfere with a number of the putative processes involved in the pathogenesis of RA, including immunoregulation, interaction with inflammatory mediators and the cytokine system, and direct effects on cartilage itself. All these observations point towards the importance of gonadal hormones. However, trials on the potential therapeutic use of sex hormones in RA are limited and, as yet, disappointing. Further work is necessary to determine whether the roles of sex hormones are as central protagonists or just supporting cast in the complex arena of rheumatoid disease.