The neuroanatomy of menopause

Sex hormones are known to affect brain structure. Given that menopause is marked by a significant decline in female sex hormones, there might be structural brain alterations around menopause. The aim of this article is to provide a narrative review on what we know today with respect to links between brain anatomy and menopause, while also considering potential effects of menopausal hormone therapy (MHT). The review is focused on neuroimaging studies analyzing the macro-anatomy or micro-anatomy of the human brain as based on structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI). Out of the 32 studies reviewed here, 22 studies revealed at least some findings that suggest beneficial effects of estrogen. However, overall, findings are rather mixed pointing to both beneficial and adverse effects (or to no effects at all). The nature of the effects seemed to be unrelated to the spatial scales applied, the morphometric measures obtained, and the brain tissues targeted. Nevertheless, there were some intriguing effects in terms of the study design: Cross-sectionally, there seemed to be a trend for beneficial effects in small-scale studies and for adverse effects in large-scale studies. Longitudinally, there seemed to be a trend for beneficial effects in purely observational studies and for beneficial as well as adverse effects in controlled clinical trials. With particular respect to MHT, early treatment (short after the onset of menopause) might be more beneficial than later treatment. However, overall, data are insufficient to draw final conclusions and further research is required.