Cognitive decline is well recognized during ageing but is often accelerated in women after menopause. Studies have shown that there are significant gender differences in brain ageing with significantly greater changes in brain structure, function and metabolism between females and males. Estrogens exert protective effects on neuronal cells in culture but the exact underlying mechanism for their neuroprotective effect in humans is not completely understood. Estrogens have been shown to affect the nervous system in many different ways: via binding to estrogen receptors (ERs) but also via multiple pathways. The results of small randomized trials and larger observational studies suggest a beneficial effect of estrogen therapy on cognitive function in symptomatic postmenopausal women. However, the results of the Women's Health Initiative Study (WHIMS) do not support this, at least not in women over the age of 65. Alzheimer's disease (AD) is two to three times more common in women than in men. Based on currently available data, routine therapeutic use of estrogens in women with AD is not justified but it may have a role in the prophylaxis of AD. The existing evidence supports the use of HRT only in women with menopausal symptoms for a few years following menopause.