THE ROLE OF ANDROGENS IN THE PATHOPHYSIOLOGY OF RHEUMATOID-ARTHRITIS

Androgens exert immunosuppressive activities and their deficiency is s uggested to surely contribute to the pathophysiology of rheumatoid art hritis as well as of other immune-mediated conditions. Evidence is acc umulating to prove that low levels of both gonadal androgens (testoste rone and dihydrotestosterone) and adrenal androgens (dehydroepiandrost erone sulphate) are present and even preexist in both male and female patients affected by rheumatoid arthritis. Cell-specific metabolism of androgens by cells involved in immune reactivity may well represent a natural hormonal means of control over tissue-specific immune respons es. Gonadal androgens in physiological concentrations seem to exert th eir modulatory activities both through a direct influence on cytokine production by activated macrophages (inhibition of IL-1, IL-6 and TNF alpha production) and an indirect influence on cytokine production by activated T cells (inhibition of IL-4, IL-5 and IFN-gamma production). On the other hand adrenal androgens may exert a direct influence on c ytokine production by T cells (increase of IL-2 and IFN-gamma synthesi s). A close relationship between different Female:Male ratios and diff erent sex hormone concentrations is well assessed in rheumatoid arthri tis patients. Androgen replacement therapy at least in male rheumatoid arthritis patients may well represent a sort of biological means of c ontrol of some pathophysiological mechanisms of rheumatoid arthritis.