A new international study reveals that puberty and pregnancy trigger similar widespread reductions in cortical gray matter, while the menopausal transition appears to pause rather than accelerate age-related brain changes. The research, conducted by Sophie R. van ’t Hof and colleagues at Amsterdam University Medical Center, analysed brain scans from three distinct female life stages to map shared and unique patterns of brain plasticity. The work draws on cohorts from the UK Biobank and involved more than a thousand participants overall, with each group representing puberty, pregnancy and menopause.
Gray matter, the brain tissue rich in nerve cell bodies and dendrites, forms much of the cerebral cortex, the seat of memory, emotion and perception. Hormonal shifts during puberty, pregnancy and menopause are known to influence the brain’s structure because sex hormones such as estrogen and progesterone interact with receptors throughout the brain. Earlier longitudinal imaging has shown puberty and pregnancy coincide with structural remodeling, including reductions in gray matter. The new study extends this by comparing all three major hormonal transitions.
The research also echoes previous work noted in PsyPost in 2023, which linked more advanced pubertal development with longitudinal changes in cortical size and thickness. It also confirms later signals that pregnancy is associated with widespread cortical gray matter reductions. By applying the same analysis across three separate cohorts, the team sought to determine whether puberty, pregnancy and menopause share a common brain-remodeling blueprint or reflect distinct processes.
“What we saw in our previous work was that there was a similar gray matter loss during puberty and pregnancy,” van ’t Hof told PsyPost. “That was interesting, as when we found the gray matter reduction during pregnancy, people often assumed it as something bad.”
“But during puberty, when this also happens, this is an optimization of the brain,” she continued. “That shifted the field to also adopt ‘neural fine-tuning’ during pregnancy, now the main hypothesis of our lab, that the brain changes during pregnancy are not inherently bad, but adaptive.”
The team applied identical analytical methods to longitudinal MRI data from 1,095 participants, forming three cohorts to represent puberty, pregnancy and menopause. To isolate hormone-driven changes, they included age-matched control groups not undergoing transitions during the study period.
The puberty cohort comprised 142 girls, divided based on self-reported menarche into three groups: a stable pre-menarche group of 49, a transitioning group of 34, and a stable post-menarche group of 59. Scans showed accelerated reductions in total and cortical gray matter during menarcheal transition—0.13 percent and 0.16 percent per month respectively. The stable control groups did not display similar monthly cortical changes, while a regionally deeper set of structures (subcortical) in the pre-menarche group showed growth that halted once menarche occurred.
The pregnancy cohort included 110 women, split into 40 transitioning through a first pregnancy, 30 through a second, and 40 nulliparous controls. Like puberty, both first- and second-pregnancy groups showed cortical gray matter reductions of around 0.12 percent per month, with the nulliparous group showing no such changes. The data indicated these pregnancy-related shifts were largely consistent whether it was a first or subsequent pregnancy.
For menopause, the UK Biobank provided data on 843 women, with 120 transitioning from premenopause to postmenopause between scans and two control groups: 49 premenopausal and 674 postmenopausal women. In contrast to puberty and pregnancy, the menopause cohort did not exhibit a statistically significant reduction in gray matter during transition. Instead, the researchers observed a pause in the typical age-related cortical decline.
“During the whole adult life, the gray matter decreases a little bit, that is known,” van ’t Hof pointed out. “This is also what we saw in our control groups. However, during menopause, we saw a pause in the decrease. So that follows the same theoretical line as sketched here above, a decrease in sex hormones leads to the opposite. Not an increase in gray matter, but a pause in the decrease.”
Regarding what these findings mean, van ’t Hof conceded: “Now what this means is really hard to say. For puberty and pregnancy we have more hypotheses, brain changes seem to have a specific function. But for menopause we don’t know yet. We are the first study to look at the brain this way during menopause, so we need a lot more research, linking it to hormones, to cognition, to mental health etc. before we can say anything about what this pause in brain change means.”
The menopause results stand in contrast to a separate cross-sectional study described by PsyPost in 2026, which suggested post-menopausal women show reduced gray matter relative to pre-menopausal peers. The current study, which tracks whole-brain cortical gray matter across time, stresses that the differences may reflect methodological variation—longitudinal tracking versus single-timepoint regional comparisons.
When examining regional patterns, the researchers found both overlap and divergence. In 34 cortical regions—generally associated with higher-level thinking and memory—puberty and pregnancy showed very similar gray matter reduction rates. In 33 regions tied to sensory processing and movement, puberty produced the largest declines, pregnancy a moderate level, and menopause the least. A small cluster linked to emotion and bodily awareness showed pronounced declines only during puberty.
Susana Carmona, who heads the Neuromaternal Research Group in Madrid and was not involved in the study, lauded the work. “This is a much-needed piece of work,” she said. “Sophie van ’t Hof, Elseline Hoekzema and colleagues have carried out a study that had long been awaited: a study comparing the three neuroendocrine transitions that most women go through over the course of their lives: puberty, pregnancy and menopause.”
She noted the study aligns with the idea of parallels between puberty and pregnancy but emphasized menopause as a novel inclusion. “The major novelty is that it incorporates the third transition, menopause, a stage that until relatively recently was not even mentioned.”
Both researchers and commentators cautioned against simplistic readings. van ’t Hof warned against assuming that gray matter reduction is inherently negative and highlighted the study’s methodological limitations. The team used a monthly rate to quantify changes, which could smooth over rapid bursts of brain plasticity, and relied on self-reported onset dates for menarche and menopause. Carmona pointed out that puberty and menopause are not as clearly bounded in time as pregnancy, limiting the precision of timing in the study.
She also noted that the three cohorts were scanned on different MRI machines, so the researchers focused on within-cohort contrasts rather than direct cross-cohort numerical comparisons. She urged caution in broad interpretation and called for future work that includes hormone measurements and more harmonised data across all three transitions.
Looking ahead, the team intends to explore the downstream consequences of these structural shifts. van ’t Hof said the goals differ by transition: further work on menopause is at an early stage and will require longitudinal data with more modulators such as hormonal profiles; for pregnancy, researchers plan to link brain changes with mental health and functioning; and for puberty, the team will investigate social belonging, well-being and resilience among adolescents.
The study, titled Puberty, pregnancy, and menopause show shared and distinct structural changes across the lifespan, was authored by Sophie R. van ’t Hof, Marieke G. N. Bos, Milou Straathof, Eveline A. Crone, and Elseline A. Hoekzema.
