ESR2 and Arthritis: Synovial cells of RA joints have both estrogen receptors, ER-α and ER-β, with higher density of ER-β, which is usually upregulated under hypoxic and inflammatory circumstances such as arthritis.17Studies in animal models have shown that the use of selective ER-β estrogens may have a repressive effect in the transcription of proinflammatory genes16; this has led to the attempt to use them in the treatment of RA, unfortunately with negative results.18