Menarche, Motherhood, Menopause: Mapping the Brain's Three Big Rewires

A woman’s reproductive life encompasses several major hormonal transitions, including puberty, pregnancy and postpartum, and menopause. These transitions are accompanied by profound physiological and hormonal changes, but their effects extend beyond the reproductive system. The brain also undergoes substantial structural reorganisation in response to these changing hormonal environments.

Puberty is the first major reproductive transition and is characterised by dramatic increases in sex steroid hormones alongside extensive brain remodelling. Previous longitudinal neuroimaging studies have demonstrated reductions in cortical grey matter during puberty. Menarche-the first menstrual period appears to represent a particularly important point within this developmental window. Indeed, machine-learning approaches have shown that pre- and post-menarcheal status can be distinguished from structural brain imaging, suggesting that the transition to menarche carries a measurable neurobiological signature beyond general age-related brain maturation.

Pregnancy represents another profound hormonal transition and is also associated with structural changes in the brain. Longitudinal studies have shown reductions in grey matter volume during pregnancy, with changes linked to circulating estradiol levels. These changes are particularly prominent in regions involved in the default-mode and theory-of-mind networks, including areas implicated in social cognition and caregiving. They have therefore been proposed to represent adaptive brain remodelling that supports maternal behaviour and mother-infant bonding. Importantly, similar structural changes occur during a second pregnancy, although the present study found that the overall magnitude and pattern of cortical change were not significantly different between first- and second-time mothers.

Menopause presents a strikingly different hormonal and neurobiological transition. Unlike puberty and pregnancy, menopause is characterised by a decline in sex steroid hormones, particularly oestrogen and progesterone. Previous longitudinal research on menopause had been limited largely to the hippocampus, leaving the trajectory of whole-brain cortical grey matter changes unresolved. The present study therefore provides an important advance by examining longitudinal cortical and subcortical structural changes across the menopausal transition within the same analytical framework used for puberty and pregnancy.

Each reproductive transition places different demands on the brain. Puberty involves neurodevelopmental specialisation; pregnancy requires adaptation to maternal caregiving and mother-infant bonding; and menopause involves adaptation to reproductive senescence. Although all three transitions are associated with substantial changes in sex steroid hormones, they may engage both overlapping and distinct patterns of brain remodeling.

To investigate these similarities and differences, researchers compared longitudinal structural MRI data across puberty, pregnancy and menopause using the same FreeSurfer-based morphometric approach. This allowed them to compare the magnitude, spatial distribution and regional specificity of grey matter changes across the three transitions. Crucially, each cohort included stable control groups, allowing the researchers to distinguish changes associated with the reproductive transition from those expected during normal development or ageing.

The three cohorts

The study included three cohorts:

• Puberty (n = 142): 49 girls who remained pre-menarcheal, 34 who transitioned from pre- to post-menarche, and 59 who were already post-menarcheal.
• Pregnancy (n = 110): 40 women transitioning through a first pregnancy, 30 transitioning through a second pregnancy, and 40 nulliparous controls.
• Menopause (n = 843): 49 women who remained premenopausal, 120 women who transitioned from pre- to post-menopause, and 674 women who were already postmenopausal. Women who had undergone bilateral oophorectomy were excluded.
• Controls: stable groups within each cohort provided a reference for normal developmental or age-related change.

Puberty and pregnancy accelerate cortical grey matter reduction

Both puberty and pregnancy were associated with significant reductions in total and cortical grey matter relative to their respective control groups.

Girls transitioning through menarche showed a monthly reduction of approximately 0.13% in total grey matter and 0.16% in cortical grey matter. In contrast, neither the stable pre-menarcheal nor stable post-menarcheal groups showed significant monthly changes in these measures.

A similar pattern was observed during pregnancy. First-time mothers showed approximately 0.12% monthly reductions in total and cortical grey matter, while second-time mothers showed approximately 0.11–0.12% monthly reductions. Nulliparous controls did not show a significant reduction in total or cortical grey matter. Importantly, first- and second-time mothers did not differ significantly from one another, suggesting that the core cortical pattern associated with pregnancy is broadly similar regardless of parity.

The pregnancy-related pattern was particularly prominent in the precuneus, superior temporal sulcus and superior parietal lobule, regions involved in higher-order social cognition and the default-mode and theory-of-mind networks. In first-time mothers, older maternal age was associated with stronger expression of the dominant cortical change pattern; this association was not observed in second-time mothers or nulliparous controls.

The findings therefore suggest that puberty and pregnancy share a broadly similar direction and magnitude of cortical remodelling, although the changes are not identical across the cortex. Indeed, the study found that 67 of 74 cortical regions showed greater decline during both the pubertal and pregnancy transitions compared with their respective controls.

Menopause shows a fundamentally different pattern

The menopausal transition produced a markedly different result. Women transitioning from pre- to post-menopause showed no significant reduction in total or cortical grey matter volume. In contrast, women who remained premenopausal and those who were already postmenopausal both showed the gradual grey matter decline expected with ageing.

This pattern remained unchanged when women using hormone replacement therapy were excluded, and neither age nor parity appeared to account for the findings.

The authors interpret this cautiously. The absence of significant cortical and total grey matter loss during the menopausal transition may indicate an attenuation of the age-related decline that is evident in stable pre- and postmenopausal women. However, because direct group-by-time contrasts were not significant, this interpretation remains preliminary.

Shared and distinct patterns across the three transitions

The regional analyses reveal that the relationship between these reproductive transitions is more nuanced than simply saying that all three produce the same brain changes.

In 34 cortical regions, puberty and pregnancy showed similar patterns of change, while both differed from menopause. These regions were concentrated largely in prefrontal, parietal and temporal association cortices, with additional involvement of occipital regions. This suggests that higher-order association areas may be particularly sensitive to the shared neurobiological effects of puberty and pregnancy.
In another 33 regions, however, there was a clear stepwise pattern: puberty > pregnancy > menopause in the magnitude of grey matter decline. These regions included sensorimotor, cingulate, frontal, temporal and occipital areas.

There were also six regions, predominantly within the insula and central sulcus, in which puberty showed greater decline than both pregnancy and menopause, while pregnancy and menopause did not differ significantly from one another. This suggests that some aspects of pubertal brain remodeling are qualitatively distinct from the changes occurring during pregnancy and menopause.

Overall, more than half of the cortical regions examined showed divergent patterns across the three reproductive transitions. Thus, while puberty and pregnancy share substantial cortical remodelling, they are not identical processes. The brain appears to combine a common pattern of plasticity with transition-specific regional adaptations.

An important overarching observation is that the direction of hormonal change appears to correspond to the direction of structural brain change. Puberty and pregnancy are characterised by increases in sex steroid hormones and are accompanied by accelerated cortical grey matter reduction. Menopause, in contrast, involves declining sex steroid hormones and was associated with an absence of the cortical volume reduction seen in stable ageing groups during the transition itself.

However, it is important not to interpret grey matter reduction as evidence of brain damage or loss of function. Structural MRI measures of grey matter volume cannot, by themselves, establish whether a change represents beneficial adaptation, altered cellular organisation, or another biological process. The authors therefore use the term brain plasticity descriptively, rather than claiming a specific underlying mechanism.

The overall picture is therefore one of dynamic, hormone-sensitive brain remodelling across a woman's reproductive lifespan. Puberty and pregnancy are both associated with accelerated cortical grey matter reduction, with substantial overlap in higher-order association regions but also clear regional differences. Menopause is qualitatively different: rather than accelerating grey matter loss, the transition is characterised by an apparent attenuation of the age-related decline observed in women who remain premenopausal or are already postmenopausal. In this sense, menopause is defined not simply by what changes in the brain, but by what does not change during the transition itself.

Reference

van ’t Hof, S.R., Bos, M.G.N., Straathof, M. et al. Puberty, pregnancy, and menopause show shared and distinct structural changes across the lifespan. Nat Commun 17, 9360 (2026). https://doi.org/10.1038/s41467-026-76755-2