AbstractFemales live longer than males. We have shown that this could be in part due to the higher levels of oestrogens in females, which protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. However, the low concentration of oestrogens makes it unlikely that they exhibit significant antioxidant capacity in the organism. Our results show that physiological concentrations of oestrogens activate the expression of manganese superoxide dismutase and glutathione peroxidase by oestrogen receptors and the mitogen-activated protein kinase and nuclear factor kappa B pathway. Moreover, when considering oestrogen replacement therapy, it is of utmost importance to take into account when to start the therapy after menopause. We have shown that only early-onset administration of oestrogen replacement therapy is effective on oestrogen deprivation associated with oxidative and metabolic stress. This is due to a change in oestrogen receptor distribution after oestrogen deprivation. Oestrogens are also involved in inflammatory processes. Their role on inflammation is very complex, because their effects are different depending on the doses and also on the oestrogen receptor distribution.