Rheumatoid arthritis: a female challenge

Rheumatoid arthritis (RA) is two-to three-fold more frequent in women than in men and a strong association with sex hormones has been demonstrated. There is strong evidence that autoimmunity is under genetic control, and genes in sexual chromosomes can play a role in supporting the female prevalence. On the other hand, it is widely accepted that sex hormones - estrogens in particular - may regulate the immune response by favoring the survival of forbidden autoreactive clones and ultimately the prevalence of autoimmunity in women. Accordingly, estrogens have been suggested to be associated with the development of RA. Pregnancy in RA women is a common situation and most pregnant patients experience a remission. This has been closely related to a switch from Th1 to Th2 immune responses and to a decreased production of proinflammatory cytokines, at least in part supported by the changes of the hormonal profile in pregnancy. Pregnancy planning is required in RA in order to avoid unwanted complications. In particular, the need to control the disease requires safe use of antirheumatic drugs both during the pregnancy itself and in the breastfeeding period. Hormonal treatment for contraception is contraindicated in the case of positivity for antiphospholipid antibodies owing to the increased thrombophilic risk. Similarly, replacement hormonal treatment in postmenopausal women with RA to control osteoporosis is no longer recommended as a result of its ability to increase the cardiovascular risk closely associated with RA itself.