Puberty, pregnancy, and menopause are accompanied by distinct patterns of brain plasticity

A new study indicates that puberty and pregnancy are associated with similar patterns of widespread structural change in the female brain, primarily marked by reductions in gray matter. The research also suggests that the menopausal transition presents a distinctly different pattern characterized by a pause in typical age-related brain changes rather than an acceleration. The findings were published in Nature Communications.

The human brain processes information using gray matter, which is the tissue consisting mainly of nerve cell bodies and branching dendrites. A large portion of this tissue makes up the cerebral cortex, the wrinkled outer layer of the brain responsible for high-level functions like memory, emotion, and perception. Across the lifespan, the female brain typically experiences three major hormonal transitions: puberty, pregnancy, and menopause.

These major life periods involve substantial shifts in sex steroid hormones like estrogen and progesterone. Because these hormones bind to receptors distributed throughout the brain, they can influence the brain’s physical structure. Previous longitudinal brain imaging studies have established that both puberty and pregnancy coincide with distinct structural remodeling. For example, a study covered by PsyPost in 2023 indicated that more advanced pubertal development in adolescent females predicts longitudinal shifts in the size and thickness of the cerebral cortex.

While researchers have extensively documented brain changes related to puberty and pregnancy, the menopausal transition has received far less attention. Previous studies on menopause have mostly examined isolated brain regions or compared different groups of women at a single point in time. It has remained unknown whether these three major life events share a common biological blueprint for brain remodeling or if each involves completely independent changes. The research, led by Sophie R. van ‘t Hof of the Pregnancy Brain Lab at Amsterdam University Medical Center, aimed to compare brain structural changes across all three events.

“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.”

By applying identical analytical methods to longitudinal data from three separate groups of women, the scientists sought to map out shared and distinct patterns of brain plasticity. “What we wanted to know here, although we know both show gray matter reduction, is whether pregnancy is the same as puberty or whether we also see differences,” van ‘t Hof explained.

The scientists analyzed magnetic resonance imaging (MRI) data from 1,095 participants, tracking changes in gray matter volume over time. The analysis was divided into three distinct cohorts representing puberty, pregnancy, and menopause. To isolate changes specifically tied to the hormonal transitions, the researchers included age-matched control groups of participants who were not actively transitioning during the study period.

In the puberty cohort, the researchers analyzed data from 142 girls. Based on self-reports of menarche, or a girl’s first menstruation, participants were categorized into three groups. These included a stable pre-menarche group of 49 girls, a transitioning group of 34 girls, and a stable post-menarche group of 59 girls.

The MRI scans indicated that girls transitioning through menarche experienced accelerated reductions in total and cortical gray matter, shrinking at a rate of 0.13 percent and 0.16 percent per month, respectively. Neither of the stable control groups showed similar monthly changes in cortical volume. In deeper brain regions, known as subcortical structures, the stable pre-menarche group showed a steady volume increase. This growth appeared to halt once girls transitioned through menarche.

The pregnancy cohort included 110 women. This cohort was divided into 40 women transitioning through a first pregnancy, 30 women transitioning through a second pregnancy, and a control group of 40 nulliparous women, meaning they had never given birth. Similar to the puberty group, women transitioning through both first and second pregnancies showed distinct reductions in cortical gray matter volume, shrinking by about 0.12 percent per month. The nulliparous control group did not display these reductions.

The data also indicated that these pregnancy-related changes were largely consistent regardless of whether it was a woman’s first or second child. These findings are in line with research covered by PsyPost in 2024 and in 2025, which found that pregnancy is associated with widespread reductions in cortical gray matter volume.

“As we see increases in sex hormones during puberty and pregnancy, and those changes have been linked in previous work with the gray matter reduction, we wanted to know, during menopause, when sex hormones decrease, what happens to the gray matter?” van ‘t Hof said. “No one had looked at the whole brain changes from pre- to post-menopause before. So that is what we did.”

The menopause cohort utilized data from the UK Biobank, involving 843 women. Participants were categorized based on whether their menstrual periods had stopped. The cohort featured 120 women transitioning from pre-menopause to post-menopause between scans, along with two stable control groups: 49 premenopausal women and 674 postmenopausal women.

The findings in the menopause cohort stood in stark contrast to the other two groups. The stable premenopausal and postmenopausal control groups showed typical aging-related brain shrinkage, losing around 0.025 to 0.033 percent of their cortical gray matter per month. However, women actively transitioning through menopause showed no statistically significant reduction in gray matter volume. Instead of accelerating brain changes, the transition appeared to temporarily pause typical age-related volume loss.

“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.”

“Now what this means is really hard to say,” she noted. “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 findings provide an interesting contrast to prior work. The new data stands in tension with a study covered by PsyPost in 2026, which found that post-menopausal women exhibited reduced gray matter volume compared to pre-menopausal women. It is worth noting that the earlier study compared pre- and post-menopausal women cross-sectionally at a single point in time across specific regions, whereas the new study tracked whole-brain cortical gray matter continuously over time.

When comparing the specific regions of the brain affected across all three cohorts, the researchers found both overlap and divergence. In 34 regions of the cerebral cortex, primarily higher-order areas involved in complex thought and memory, puberty and pregnancy were associated with highly similar rates of gray matter reduction. Other areas of the brain displayed a stepwise pattern.

In 33 regions, primarily related to sensory processing and movement, pubertal transition coincided with the largest gray matter decline. Pregnancy coincided with a moderate decline in these areas, and menopause was associated with the least. A small cluster of brain regions, including areas involved in emotion and internal bodily sensations, showed strong declines only during puberty.

“This is a much-needed piece of work,” Susana Carmona, who was not involved in the study, told PsyPost. “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.”

Carmona, the head of the Neuromaternal Research Group at Instituto de Investigación Sanitaria Gregorio Marañón, chief scientific officer for Maternal Brain Health at the Ann S. Bowers Women’s Brain Health Initiative, and author of A Mother’s Brain: The New Science of the Neuro-Maternal Revolution, noted that these stages have been historically under-researched. “The study corroborates and refines the parallelism between pregnancy and puberty described previously,” she added. “The major novelty is that it incorporates the third transition, menopause, a stage that until relatively recently was not even mentioned.”

As with all research, there are some caveats to consider. “A common misinterpretation that I still hear from journalists now, is that a reduction in gray matter is a bad thing,” van ‘t Hof cautioned. “We don’t know, in some cases it might, in some cases it might not.”

The researchers calculated changes using a monthly rate, which averages out the brain’s structural changes over the period between scans. This approach might smooth over more rapid bursts of brain plasticity that could occur during specific months of pregnancy or puberty. The study also relied on single, self-reported questions to determine the onset of menarche and menopause.

Carmona pointed out that this limits the findings, as puberty and menopause are not as clearly bounded in time as pregnancy. “Menarche is preceded by pubertal changes that are already remodeling the brain and that do not end with the arrival of the first period,” she explained. “And menopause, medically defined as a year without menstruation, comes after several years of perimenopause during which the dialogue between the ovary and the brain is already readjusting to the progressive decline of the ovarian reserve.”

“Capturing such a long, gradual transition with a single self-reported item is difficult, and this is why the menopause part is best read as a valuable first step rather than the last word,” Carmona said.

Additionally, the researchers lacked harmonized data across the three groups regarding hormone levels, stress, or the use of hormonal contraceptives, any of which could influence brain structure.

“The hormonal directionality (an increase in puberty and pregnancy, a decrease in menopause) is inferred from typical endocrine profiles, but is neither measured nor directly related to individual brain change,” Carmona noted. “The next step is to build well-characterized longitudinal databases of the three stages that also gather variables that may be modulating them, such as hormonal variables, pubertal and menopausal staging, and hormonal treatments.”

Finally, the three cohorts were scanned using different MRI machines. To account for this hardware difference, the researchers focused on the relative change between transitioning and control groups within each cohort before making broad comparisons. Even so, variations in scanner hardware can influence precise measurements. Direct numerical comparisons across the different life stages should be interpreted cautiously.

Looking ahead, the research team plans to investigate the downstream effects of these structural shifts. “Our long-term goal differs a bit for each transition phase,” van ‘t Hof explained. “We are really doing the groundwork, fundamental research, and we need to build further on this. For menopause, we are really at the beginning, so we need to know a lot more, using these longitudinal designs with many more variables.”

“For pregnancy, we know the structural brain changes now, they have been replicated several times, and now we really want to know what that means. So we are looking at brain functioning and the link of brain changes with mental health,” she said. “For puberty, the field is a lot more established, and now the group we work with on this paper focuses on social belonging and well-being, and resilience in this group.”

The study, “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.