Age is also an important factor to take into consid¬eration in future research on neuroprotective oestradiol signalling, as ageing per se, or age after menopause, is known to affect the response of the brain to the hor¬mone. Animal studies121,132–134 and clinical observa¬tions11,135,136 suggest that hormonal therapy has a window of opportunity in the perimenopausal period during which it may reduce cognitive decline. Several studies have addressed the question on whether age or prolonged ovarian hormone deprivation affect the neuroprotective actions of oestradiol. For example, the neuroprotective action of the hormone on experimental stroke in young female mice is impaired in aged female mice, probably because the decrease in IGF1 plasma lev¬els with ageing alters the cross-talk between ERα and IGF1R112. However, high physiological doses of oestra¬diol are able to protect the brain of aged rats from global cerebral ischaemia137. Further studies are therefore nec¬essary to determine in more detail how ageing affects the neuroprotective signalling mechanisms elicited by oestradiol.