One promising research direc¬tion is to determine the role of metabolic control on the neuroprotective actions of oestradiol, as the hormone may exert sustained protective and reparative actions by maintaining metabolic homeostasis in the brain115. Acting on mitochondria, oestradiol regulates glucose metabolism, glycolysis and the tricarboxylic acid cycle-coupled oxidative phosphorylation and ATP generation in neurons115. In addition, the hormone regulates whole-body metabolism by acting on adipose tissue, the pan¬creas and the hypothalamus115,138. Substantial evidence supports an influence of metabolic alterations on chronic neurodegenerative diseases and cognitive impairment. Therefore, further studies should determine whether the metabolic control exerted by oestradiol is a princi¬pal component of its long-term neuroprotective actions.