Sex hormones play a significant role in the development and severity of rheumatoid arthritis (RA), experimentation with a pre-clinical model of the disease has shown.
Women are significantly more likely to develop RA than are men, suggesting that sex hormones, such as estrogen and testosterone, influence the risk for the condition.
Although this association is intuitive, data supporting it are scarce, say Rengarajulu Puvanakrishnan (Central Leather Research Institute, Chennai, India) and fellow researchers.
Puvanakrishnan and colleagues therefore studied the effects of treatment with various sex hormones on rats with collage-induced arthritis.
The authors report in the journal Bone that castration and ovariectomy both significantly increased the severity of arthritis, as measured by paw volume, radiologic joint assessment, joint histopathology, bone turnover markers, inflammatory cytokine levels, and concentrations of pain mediators such as prostaglandins.
Other findings also demonstrated the influence of reproductive hormones on RA severity; specifically, the researchers found that inflammation associated with castration or ovariectomy could be significantly lessened by treatment with physiologic doses of testosterone or estrogen. Of the two hormones, estrogen administration led to the greater decreases in inflammation.
Animals were not given testosterone, which can be converted to estrogen once administered, but dihydrotestosterone, which cannot be aromatized. In this way, the authors were able to confirm the observed effects of testosterone.
The authors also showed that progesterone had no discernible effect on RA symptoms but did lessen the protective effects of estrogen.
The authors note that estrogen can reduce inflammation by suppressing the activity of tumor-necrosis factor (TNF)-α. They add that estosterone can also reduce inflammation either by directly decreasing TNF-α levels, or by encouraging the production of interleukin-10, which suppresses the activity of TNF-α.
The researchers stress that theirs is the first study to individually test the effects of various sex hormones on RA symptoms and the first to show that progesterone attenuates the protective effects of estrogen in this disease.