One size does not fit all: how type of menopause and hormone therapy matters for brain health

Menopause is an inflection point in the ageing trajectory. Independent of chronological age, menopause is associated with the biological ageing of several body systems. In this review, we highlight the importance of considering the influence of menopause - its types, symptoms and interventions - on brain health. Supplementing the loss of ovarian hormones with menopausal hormone therapy (MHT) may be key for supporting the healthy brain ageing of females. MHT has been associated with reduced risk of several neurodegenerative diseases; however, its benefits are not always observed on brain health.

This narrative review highlights often overlooked MHT factors that influence its effects to produce positive or negative effects on brain health, cognition and neurodegenerative disease risk. These factors include the many varieties of MHT, including formulation, administration route and dosing schedule, as well as individual characteristics, particularly the presence of vasomotor symptoms and apolipoprotein ε4 (APOE4) genotype.

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Menopause factors, including age, abruptness and symptoms, influence brain ageing. MHT influences brain health, with transdermal MHT showing more positive effects on brain ageing, but its effectiveness may depend on individual factors such as genotype, reproductive and lifestyle factors.

To develop effective and individualised MHT treatments, further research is needed. Preclinical models must consider the type of human menopause and MHT. To achieve the greatest dementia prevention in females, more menopause education and care is needed that extends beyond 60 years of age, or 10 years postmenopause.