Puberty, pregnancy and menopause are three of the biggest hormonal transitions in the female lifespan.
They occur at very different ages and involve very different biological circumstances, but they all expose the brain to major changes in reproductive hormones.
New research suggests that the brain does not respond to all three transitions in the same way.
A longitudinal MRI study published in Nature Communications on 8 September 2026 compared structural brain changes across puberty, pregnancy and menopause using the same analytical framework in 1,095 participants.
The researchers found broad similarities between puberty and pregnancy, including accelerated reductions in cortical grey-matter volume relative to their respective control groups. Menopause followed a different pattern.
Rather than showing an accelerated decline, women transitioning through menopause showed little to no significant total or cortical grey-matter loss over the study interval, even though stable premenopausal and postmenopausal groups did.
The result suggests that hormonal transitions across the lifespan may share some features of brain plasticity while still engaging distinct forms of structural reorganisation.
The study compared three hormonal transitions using the same approach
One difficulty in comparing puberty, pregnancy and menopause is that they are usually studied separately.
Different research groups may use different scanners, different brain-processing pipelines and different statistical methods, making direct comparisons difficult.
Sophie R. van ’t Hof and colleagues addressed this by analysing longitudinal structural MRI data across all three life stages using a common framework.
The final sample included 142 participants in the puberty cohort, 110 in the pregnancy cohort and 843 in the menopause cohort.
Each cohort included a transition group and comparison groups that remained in a relatively stable reproductive stage during the same period.
This allowed the researchers to separate transition-related changes from the ordinary developmental or ageing changes that would be expected to occur anyway.
Puberty was associated with measurable cortical grey-matter reduction
In the puberty cohort, the key comparison involved girls who moved from pre-menarche to post-menarche during the study period.
This group showed significant monthly reductions in both total grey-matter volume and cortical grey-matter volume.
The researchers reported an average monthly change of approximately −0.13% in total grey matter and −0.16% in cortical grey matter in the pre-to-post menarche group.
Stable pre-menarche and stable post-menarche comparison groups did not show the same pattern over the corresponding intervals.
The result supports earlier evidence that puberty is not only a hormonal event but also a period of substantial structural brain remodelling.
Pregnancy showed a surprisingly similar overall pattern
The pregnancy cohort included women scanned before and after a first pregnancy, women scanned before and after a second pregnancy and a nulliparous control group.
Both first-time and second-time mothers showed significant reductions in total and cortical grey-matter volume across the study interval.
The monthly rates were similar in magnitude to those observed during puberty, at roughly −0.11% to −0.12% for total and cortical grey matter.
The nulliparous comparison group did not show the same significant cortical pattern.
This is notable because puberty and pregnancy are separated by years or decades and occur in very different contexts, yet both involve large increases and fluctuations in reproductive hormones.
The similarities suggest that some aspects of cortical remodelling may be reused by the brain during different hormonally intense periods of life.
The similarities were not uniform across the brain
Puberty and pregnancy did not produce identical brain changes.
When the researchers compared individual cortical regions, they found both convergence and divergence.
Some prefrontal, parietal and temporal association regions showed broadly similar patterns across puberty and pregnancy.
But more than half of the cortical regions examined showed significant differences between the two transitions.
In several sensorimotor and cingulate regions, the decline followed a stepwise pattern: the strongest reduction appeared during puberty, followed by pregnancy, with menopause showing the least decline.
The picture is therefore not that pregnancy simply repeats puberty.
Instead, the two transitions appear to share part of a broader cortical-remodelling signature while preserving substantial regional differences.
Menopause did not follow the same trajectory
The menopause cohort produced the most unexpected result.
The researchers compared women who moved from premenopausal to postmenopausal status between scans with groups that remained stably premenopausal or stably postmenopausal.
The transitioning group did not show a significant reduction in total or cortical grey-matter volume across the interval.
By contrast, both stable comparison groups showed significant reductions.
This made menopause qualitatively different from puberty and pregnancy.
The transition was characterised less by accelerated structural loss than by an apparent attenuation of the decline seen in the surrounding age groups.
That does not mean menopause leaves the brain unchanged. The researchers still identified regional differences, but the overall pattern was far less pronounced than the remodelling observed during puberty and pregnancy.
Grey-matter reduction does not automatically mean damage
The phrase “grey-matter loss” can sound alarming, but it should not be interpreted as evidence that puberty or pregnancy damages the brain.
Changes in MRI-measured grey-matter volume can reflect many biological processes, including changes in synaptic organisation, dendritic structure, glial cells, blood flow, myelination and the boundaries between grey and white matter.
During development, reductions in cortical grey-matter volume are often part of normal maturation rather than degeneration.
Pregnancy-related structural changes have also been interpreted in previous research as a form of adaptive neuroplasticity rather than injury.
The current study is therefore about patterns of reorganisation, not about ranking one hormonal life stage as healthier or more damaging than another.
Pregnancy-related changes may support social and caregiving functions
Previous pregnancy research has repeatedly identified structural changes in brain regions involved in social cognition.
These include areas associated with understanding other people, interpreting social information and responding to emotionally meaningful cues.
That has led researchers to propose that some pregnancy-related remodelling may help prepare the brain for caregiving and parent-infant interaction.
The new paper does not directly test maternal behaviour, but it places those pregnancy changes into a much broader lifespan context.
By showing overlap with puberty, the study suggests that major endocrine changes may recruit some common plasticity mechanisms even when the behavioural demands of the life stage are very different.
Hormones are a plausible link, but the study does not prove the mechanism
Puberty, pregnancy and menopause all involve major shifts in sex steroid hormones, particularly oestrogens and progesterone.
Receptors for these hormones are widely distributed throughout the brain, making hormonal change a plausible contributor to structural plasticity.
The direction of hormonal change also differs across the three transitions.
Puberty and pregnancy generally involve substantial increases or surges in reproductive hormones, whereas menopause involves a long-term decline.
The fact that puberty and pregnancy shared more of their structural pattern than menopause is therefore biologically suggestive.
However, the study was not designed to prove that a specific hormone directly caused each MRI change.
Age, life stage, reproductive history and other physiological processes differ substantially across the cohorts and may also contribute.
The menopause finding challenges a simple ageing explanation
Menopause occurs during a period when age-related brain changes are already underway.
If the menopausal transition simply accelerated normal ageing, the transitioning group might have been expected to show greater cortical decline than women whose menopausal status remained stable.
That is not what the researchers observed.
The stable premenopausal and postmenopausal groups showed measurable total and cortical grey-matter reductions, while the transition group did not.
This suggests that menopause may involve a temporary or distinct pattern of brain plasticity that cannot be described simply as faster structural ageing.
Exactly why this occurs remains unclear and will require studies that combine repeated brain imaging with more detailed hormone measurements.
The study has important limitations
Although the total sample was large, the three cohorts were very different in size.
The menopause cohort contained 843 participants, compared with 142 in the puberty cohort and 110 in the pregnancy cohort.
The groups also came from different studies and were scanned on different MRI systems.
The researchers used the same analytical methods across cohorts to improve comparability, but this cannot remove every difference between datasets.
Menopause status was based on self-report in the UK Biobank cohort, and the study did not assess gender identity. The paper uses female-related terminology because the reproductive transitions examined are tied to biological sex and the cohorts were recruited on that basis.
The work also focuses on brain structure rather than directly testing memory, mood, cognition or day-to-day functioning.
Structural differences should therefore not be translated automatically into claims about behaviour or mental performance.
Why the comparison matters
Most neuroscience studies focus on one life stage at a time.
This can make it easy to treat puberty, pregnancy and menopause as unrelated biological events.
By placing all three within one analytical framework, the new study shows that the female brain may move through several distinct periods of large-scale plasticity across the lifespan.
Some of those periods appear to reuse similar forms of cortical remodelling, while others follow a different trajectory.
The broader implication is that adult brain structure is not static between adolescence and old age.
Major reproductive transitions may be accompanied by measurable reorganisation decades apart.
The next question is what these structural changes actually do
The study establishes that the patterns differ, but it cannot yet explain all of their functional consequences.
Future work will need to connect structural MRI changes with cognition, emotion, behaviour and hormonal measurements collected at the same time.
Researchers will also need to determine how long the changes persist and whether individual differences in hormone exposure, reproductive history or hormone therapy alter the pattern.
For now, the clearest finding is that three major hormonal transitions do not leave the brain on one simple trajectory.
Puberty and pregnancy share parts of a cortical-remodelling signature, while menopause appears to represent a different form of brain plasticity altogether.
Source Information
Study Title: Puberty, pregnancy, and menopause show shared and distinct structural changes across the lifespan
Authors: Sophie R. van ’t Hof, Marieke G. N. Bos, Milou Straathof, Eveline A. Crone and Elseline A. Hoekzema
Journal: Nature Communications
Published: 8 September 2026
Sample: 1,095 participants across puberty, pregnancy and menopause cohorts, including 142 participants in the puberty analyses, 110 in the pregnancy analyses and 843 in the menopause analyses.
Method: Structural MRI data were analysed across longitudinal reproductive-transition cohorts to compare changes in total and regional grey matter during puberty, pregnancy and the menopausal transition.
Main finding: Puberty and pregnancy both showed accelerated cortical grey-matter reductions relative to control groups, with overlapping and distinct regional patterns, while the menopausal transition showed a qualitatively different profile characterised by little or no significant total or cortical grey-matter loss.
DOI: 10.1038/s41467-026-76755-2
