During the past few years, there has been increasing interest in the proposition that, when it comes to rheumatoid arthritis (RA), sex really matters. Suddenly, articles on sex and gender differences in RA abound in the scientific literature as well as the lay press. Most importantly, these articles advance the idea that the course of RA is significantly worse in women when compared with men.
The implications of this idea are profound and affect both clinical care and scientific research. This view that RA is worse in women than in men may seem surprising to clinical rheumatologists who have seen progressive disability in patients of both sexes. Correspondingly, clinical rheumatologists have seen impressive treatment responses and also spontaneous remissions in men as well as women. Nevertheless, news about differences between women and men in the course of disease seems “hot” and inevitably attracts fanfare and attention. As this review will argue, it should also attract careful scrutiny and perhaps skepticism.
Not surprisingly, reports indicating differences in the course and outcomes of RA according to sex (as well as other unexpected influences) appear to gain more attention than reports indicating the absence of an effect. Ten years ago, a study from the Mayo Clinic compared 55 male patients to 110 female patients with a similar disease duration of at least 10 years.1 This study showed that erosive disease was more prevalent and developed earlier in men than in women. The investigators suggested that this finding, along with others in the study, might help “assess the prognosis and tailor the treatment of the individual patient.” This suggestion was seen by some members of the rheumatology community as a reflection of an old-fashioned treatment approach of “go low, go slow” that should be abandoned. A modern treatment strategy with early and aggressive therapies was suggested to apply equally both sexes.2
By contrast, male sex was recently shown to be a major predictor of remission in early RA.3,4 Analyses of RA differences include studies indicating higher disease activity and poorer functional status in women when compared with men.3–7 Some recent studies have also suggested that men have better responses to treatment with biologic agents than women.5–7 On the other hand, men have been shown to experience more adverse effects, particularly serious infections, during biologic treatments.8,9
There are obvious differences between the sexes concerning the prevalence, age at onset, and autoantibody production in RA.10 The prevalence of RA differs between sexes, primarily among menstruating women. Although the majority of patients with RA are middle-aged women, generally greater than 70% in any RA cohort, RA can nonetheless occur at any age in both sexes. Furthermore, sex differences are seen in biologic factors (e.g., hormones) or behavioral factors (e.g., smoking) that may influence susceptibility to and the phenotype of RA.11,12