The pathology of rheumatoid arthritis (RA) is ameliorated during pregnancy and deteriorated after delivery. Thus, female sex hormones could be involved in the pathogenesis of RA. However, the effects of estrogen and progesterone on the development and progression of RA have been unclear. In this study, we analyzed the effects of female hormones on the pathogenesis of RA by performing ovariectomy (OVX) and hormone implantation in the SKG mouse model of human RA. OVX mice showed severe arthritis and cartilage destruction with increased serum levels of TNF-alpha and IL-6, when compared with sham-operated mice. In contrast, estrogen-treated mice exhibited remarkable suppression of arthritis, with no bone erosion, little synovial hyperplasia and little infiltration of immune cells. Moreover, serum levels of TNF-a. and IL-6 were decreased. In progesterone-treated mice, mild synovial hyperplasia and no immune cell infiltration were observed, with decreased serum levels of IL-6. These results suggest that female hormones, estrogen and progesterone, can play roles in the remission of RA. (c) 2013 Elsevier Inc. All rights reserved.