Menopause is the only hormonal transition in a woman’s life that is not associated with a reduction in grey matter or brain volume

This is a high-quality study and is particularly interesting because it analyses, over time, how brain structure changes during three major transitions in a woman’s reproductive life: puberty, pregnancy and the menopause. One of its main strengths is that it does not study these stages in isolation, but instead uses a common analytical methodology and includes stable comparison groups. This allows for a clearer distinction between changes associated with each transition and those that occur simply as a result of development or ageing.

Perhaps the most striking finding is that puberty and pregnancy share certain patterns of brain remodelling, with reductions in cortical grey matter volume across numerous regions, although there are also differences between the two stages. Menopause, on the other hand, shows a different pattern: during the menopausal transition, the significant reduction in cortical grey matter observed in women who remain in stable pre- or post-menopausal stages is not seen. It is important not to interpret the reduction in grey matter observed during puberty and pregnancy as necessarily negative or as ‘brain loss’; these are structural changes that may form part of processes of brain reorganisation and adaptation.

There are, however, some limitations that call for caution. The study lacks comparable hormonal measurements across the three cohorts, so it cannot demonstrate that hormones are directly responsible for the changes observed. Furthermore, puberty and the menopause were defined on the basis of self-reported information regarding menarche and the last menstrual period, and the participants were drawn from independent studies carried out using different MRI teams. This is particularly relevant when interpreting the results relating to the menopause: the fact that no significant reduction in cortical volume is detected during this transition does not mean that the brain ‘does not change’. The authors themselves regard this interpretation as preliminary.

The study opens up a very interesting avenue for understanding the female brain from a life-course perspective, but we still need studies that directly measure hormonal changes and enable us to determine the functional significance of these brain changes and how they may relate to women’s health.

This study assesses changes in the brain associated with three major hormonal and reproductive transitions that occur throughout a woman’s life: puberty, pregnancy and the menopause. Its aim is to identify similarities and differences between these stages. To this end, the authors analyse MRI data from 1,095 participants who underwent scans at two different time points to identify longitudinal changes in their brain volume.

A key feature of the study is that it compares the changes observed during each transition (before and after menarche, pregnancy and the menopause) with those of control women of a similar age who did not undergo that transition during the follow-up period. The results show that, compared with their respective control groups, menarche and pregnancy are associated with a decrease in grey matter volume, whilst the transition to the menopause did not show the same pattern of volume loss. As for the specific regions affected during menarche and pregnancy, the study identifies similar areas of change but also reports that each stage exhibits specific changes.

This is a methodologically sound study that provides evidence of extensive brain remodelling during puberty and pregnancy. However, it should be borne in mind that brain volume is a macroscopic measure that does not allow for the identification of changes at the cellular level or functional alterations. Furthermore, as this is an observational study, it does not allow a causal relationship to be established between hormonal changes and brain changes.

We have known for years that the brain changes during pregnancy and adolescence, and previous studies by the same team had already indicated that both processes follow a similar pattern of change; however, these two stages had never before been compared with the menopause, which remains the great unknown in this field.

That is precisely what this study contributes. It examines puberty, pregnancy and the menopause and analyses them using the same yardstick, within a single study, with stable control groups for each transition. Puberty and pregnancy are more similar than one might expect, as both involve a loss of grey matter in extensive areas of the association cortex (prefrontal, parietal and temporal), as if the brain were ‘pruning’ and reorganising itself in a similar way during both processes. Menopause, however, breaks this pattern. Rather than accelerating this loss, it appears to mitigate it, at least during the transition itself: whilst pre- and post-menopausal women in stable conditions do show a decline in grey matter, the group undergoing the transition does not. This finding is consistent with what we know about sex hormones, which rise during puberty and pregnancy and fall during the menopause, and it opens up an interesting avenue for considering female brain plasticity — understood here in a descriptive, rather than functional, sense — as something that could go in both directions, rather than simply representing a decline.

That said, it is advisable not to draw overly categorical conclusions. Puberty and the menopause were determined by a single question (whether the participant had ever had a period or no longer had one), which excludes situations such as perimenopause. Furthermore, the three datasets have diverse origins; that is, they come from different studies, using different scanning techniques and with widely varying sample sizes. The volume of data on the menopause, drawn from the UK Biobank, is enormous compared with that of the other two categories. The authors themselves are cautious in interpreting the lack of change in the menopause: they point out that it could reflect a slowing of age-related decline, but caution that the direct statistical comparisons did not reach statistical significance and that this interpretation is preliminary. Even with these caveats, it is a necessary study in a highly neglected area, as the female brain across the lifespan remains under-represented in neuroscience. It is worth remembering, however, that these structural changes do not in themselves imply functional improvement or deterioration, and that further research will be needed to understand what they actually mean for cognition or long-term brain health.