A recent study by Rebecca Keith and coworkers from the National Jewish Health, Denver, CO, US, published in Arthritis and Rheumatism, provides further experimental evidence that testosterone deficiency might play a role in the development of arthritis.
It is well known that sex hormones are involved in the pathogenesis of rheumatoid arthritis (RA). In addition, a progressive RA associated interstitial lung disease occurs in nearly 10% of RA patients but little is known about its pathogenesis.
Previous research suggests that androgenic deficiencies, particularly of gonadal origin in males, may contribute to RA, while supplemental testosterone has been shown to improve RA symptoms in both postmenopausal women and men with low levels of testosterone. Yet, it is not quite clear whether low testosterone levels precede the development of RA. A recent population-based case-control study, however, indicates that low levels of testosterone are predictive of rheumatoid factor (RF)-negative RA (Pikwer M et al., Ann Rheum Dis. 2013 Apr 3. Epub ahead of print).
In the study of Keith et al., a surgical orchiectomy approach was used to prospectively investigate the effects of testosterone on the development of arthritis, interstitial lung disease, and autoantibody formation in SKG mice. The authors report that female SKG mice developed arthritis and interstitial pneumonia with more rapid onset and with increased prevalence and severity as compared to male SKG mice.The removal of testosterone increased both lung and joint disease in male mice, creating a phenotype that is intermediate between that of intact males and that of females.
The authors conclude that testosterone is protective against the development of arthritis and lung inflammatory disease, and that this might be related, at least in part, to the ability of testosterone to modulate the development of antibodies against citrullinated proteins.