Estrogens, osteoarthritis and inflammation.

Estrogens participate in several biological processes through different molecular mechanisms. Their final actions consist of a combination of both direct and indirect effects on different organ and tissues. Estrogen may have pro- and anti-inflammatory properties depending on the situation and the involved tissue. In general, acute loss of estrogens increases the levels of reactive oxygen species and activates nuclear factor-κB and pro-inflammatory cytokine production, indicating their predominant anti-inflammatory properties. Furthermore, pro-inflammatory cytokine expression has been shown to be attenuated by estrogen replacement. Osteoarthritis and cardiovascular disease are two of the more prevalent diseases once menopause is established, which has suggested the link between estrogens and both processes. In addition, deletion of estrogen receptors in female mice results in cartilage damage, osteophytosis and changes in the subchondral bone of the joints suggesting that estrogens have a protective role on the maintenance of joint homeostasis. Furthermore, in spite of the negative effect of estrogen replacement reported in 2002 by the Women's Health Initiative study, several works published afterwards have explored the potential protective effect of estrogen supplementation in animal models and have postulated that these actions may justify a beneficial role of estrogens in different diseases where inflammation is the major feature. In this review, we will analyze the effects of estrogens on certain pathological situations such as osteoarthritis, some autoimmune diseases and coronary heart disease, especially in postmenopausal women.