The critical period hypothesis: can it explain discrepancies in the oestrogen-cognition literature?

Although there is compelling evidence from small randomised controlled trials and cross-sectional studies indicating that oestrogen helps to protect against cognitive ageing in women, the findings of the large, Women's Health Initiative Memory Study failed to support the earlier findings. The attempt to resolve these discrepancies led to the formulation of the Critical Period Hypothesis which holds that oestrogen has maximal protective benefits on cognition in women when it is initiated closely in time to a natural or surgical menopause but not when treatment is begun decades after the menopause. This article reviews the evidence from basic neuroendocrinology, from animal behavioural studies and from human studies that supports the critical period hypothesis. In view of the promise of this hypothesis and its considerable clinical implications, a direct test of its validity is warranted.