Comparative studies on the interplay of testosterone, estrogen and progesterone in collagen induced arthritis in rats

Rheumatoid arthritis (RA) is a sexually dimorphic autoimmune disorder exhibiting a higher disease prevalence and severity among females. This study was carried out to understand the role of the major sex hormones viz., testosterone, estrogen and progesterone on the severity in arthritis. The interplay of the sex hormones was studied in a rat model of collagen induced arthritis (CIA). The parameters used for analyzing the disease severity included paw volume, radiology, histopathology of joint, markers for bone turnover, cytokine profile, levels of pain mediator (prostaglandin E(2)) and immune response to type II collagen. Arthritis induction to castrated and ovariectomised rats resulted in enhanced inflammation thereby indicating the importance of sex hormones. Treatment with physiological doses of dihydrotestosterone and estrogen attenuated the inflammation, with estrogen exhibiting higher potency. Progesterone was not shown to have any significance in disease modification; however, when progesterone was administered in combination with estrogen, the protective effects of estrogen were noticed to decrease.