Age-related gray-matter loss pauses in the 120 women who crossed into menopause mid-study
A two-scan study of 1,095 female brains in Nature Communications finds the ordinary adult decline in cortical gray matter flattening through late perimenopause and resuming afterward. Its first author says the implications are hard to state.
The Scientist · Science desk
What happened
- A study published Sept. 8 in Nature Communications compared MRI scans taken at two time points from 1,095 brains spanning puberty, pregnancy and the transition into menopause.
- The gradual adult decline in gray matter leveled off during late perimenopause and resumed in postmenopausal women, with the timing of the pause varying between women but showing up across the group.
- The menopause scans came from the UK Biobank, a database covering 500,000 U.K.-based adults, and the puberty and pregnancy scans came from datasets compiled at Leiden University in the Netherlands.
- Girls entering puberty and women who were pregnant lost gray matter, matching what earlier studies of those two transitions had found.
- The menopause result does not entirely agree with previous research that found distinct reductions in hippocampal gray matter volume during the transition.
Why it matters
- What it limits constraint The study measured structure and not cognition, so it gives a clinician no way either to attribute a midlife memory complaint to volume loss or to rule that out; its first author says the link to cognitive function cannot yet be stated.
- What doesn't add up contradiction A stable cortical total and a shrinking hippocampus can both be true at once, so whether the transition reads as benign depends on which measurement a trial or a clinic adopts as its endpoint.
- Who has to decide decision Anyone treating the menopausal transition as a window of neurodegeneration now needs a measure other than overall cortical gray matter volume to carry that claim.
- What's now possible capability With one two-scan comparison covering puberty, pregnancy and menopause, later work can ask whether the three hormonal transitions differ in mechanism inside a single dataset.
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The plateau rests on 120 women. Each was scanned twice, about 3.5 years apart, and between the two scans each passed the full year without a period that defines menopause [16][17]. That within-person design is why the finding is worth reading. It compares a woman with her own earlier scan, so it does not have to assume that two women of different ages differ only in menopause status.
The reference groups carry that other assumption, and they are lopsided. About 50 women who had not yet had a last period, mean age 51, sit against more than 670 who had, mean age 55.5 [18]. Their mean ages are 4.5 years apart [29].
Add the three menopause groups together and they account for roughly 840 of the study's 1,095 brains [27]. The pregnancy arm is 110: 40 first pregnancies during the study, 30 second pregnancies and 40 women who had never been pregnant [28][22].
"No one had looked at the changes in the whole brain matter in this menopause transition before," said Sophie van 't Hof, a doctoral student in psychiatry at Amsterdam University Medical Center and the study's first author, at a press conference [7][2].
What the scans do not speak to is thinking. Van 't Hof said it is too soon to say whether any specific structural change is linked to cognitive function in menopause [8]. She has made the same point about pregnancy more bluntly: "But what's really important is that gray matter decline is not equal to cognitive complaints" [25]. The losses at puberty and in pregnancy, she said, look to her team like "neural fine-tuning" [24].
The measure here is total cortical gray matter volume, the wrinkled outer layer that contributes to memory, reasoning and movement [1][6]. A total can hold steady while one structure inside it loses volume.
Menopause stage came from what participants reported about their own periods, and the researchers did not confirm it with hormone or other diagnostic tests [20]. So the line between late perimenopause and postmenopause is drawn from recall.
Magdalena Martínez-García, scientific director of maternal health for the Ann S. Bowers Women's Brain Health Initiative, who was not involved in the work, told Live Science by email that "This study provides the first direct longitudinal comparison of brain structural changes across all three major female hormonal transitions" [10][11]. On what follows from it, van 't Hof said: "The exact implications are very difficult at this stage" [9].
What to watch
- A replication that stages menopause with hormone assays instead of self-report would test whether the pause falls where this study puts it.
- A longitudinal hippocampus-specific analysis paired with cognitive testing would show whether the regional and whole-cortex results can both hold.
- Whether the per-woman timing of the pause lines up with when symptoms start.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence58
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- Hype gap+14
- Incentives34
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- [1]
A study published Sept. 8 in the journal Nature Communications examined the brain's gray matter, which mostly includes the wrinkled outer surface of the organ, the cerebral cortex.
- [2]
Sophie van 't Hof is a doctoral student in psychiatry at Amsterdam University Medical Center and the first author on the study.
- [3]
Gray matter declines with age regardless of a person's biological sex, and this gradual decline during adulthood is seen as a normal part of aging.
- [4]
During late perimenopause the brain's gradual decline in gray matter paused, and in postmenopausal women that gradual decline resumed; the exact timing of the pause differed for each woman but it occurred consistently across the group, van 't Hof said.
- [5]
Unlike puberty and pregnancy, the menopausal transition does not appear to be linked to an overall decrease in cortical gray matter volume.
- [6]
Cortical gray matter, the brain's outer wrinkly layer, plays a role in memory, reasoning and movement.
- [7]
"No one had looked at the changes in the whole brain matter in this menopause transition before," said Sophie van 't Hof at a press conference discussing the results.
- [8]
Van 't Hof said it is too soon to say whether any specific structural brain changes or effects are linked to cognitive function in menopause, and that the results beg for further research.
- [9]
"The exact implications are very difficult at this stage," van 't Hof said.
- [10]
"This study provides the first direct longitudinal comparison of brain structural changes across all three major female hormonal transitions," said Magdalena Martinez-Garcia, scientific director of maternal health for the Ann S. Bowers Women's Brain Health Initiative, a brain imaging consortium headquartered at the University of California, Santa Barbara.
- [11]
Martinez-Garcia was not involved in the study and commented to Live Science in an email.
- [12]
As in previous studies, the researchers observed that both the girls entering puberty and the pregnant women lost gray matter.
- [13]
The study included data from 1,095 brains across the three life stages, and each participant's brain was analyzed at two different time points.
- [14]
For the menopause analysis the researchers used data from the UK Biobank, a biomedical database containing information from 500,000 U.K.-based adults, including MRI brain scans.
- [15]
To look at puberty and pregnancy, the researchers pulled from several brain-scan datasets compiled by Leiden University in the Netherlands.
- [16]
The analysis included 120 women who entered menopause during the study: at the first time point they had not gone a full year without a period, and by the second time point about 3.5 years later they had.
- [17]
Menopause is defined as the point at which a full year has elapsed since a person's final period.
- [18]
The 120 transitioning women were compared with about 50 women of average age 51 who had not had their last period yet, and with over 670 women of average age 55.5 who had already had their last period.
- [19]
"This is really fundamental research, and it's really understanding the basic brain mechanisms of the female brain. It's long been overlooked," said van 't Hof.
- [20]
The authors write that the individuals in the study self-reported their stage of menopause, which the researchers did not confirm with hormone or other diagnostic tests.
- [21]
The result does not entirely jibe with previous research finding distinct reductions in gray matter volume in the hippocampus during the menopausal transition.
- [22]
The pregnancy cohort included 40 participants who had a first pregnancy during the study, 30 who had second pregnancies, and 40 women who had never been pregnant as a comparison group.
- [23]
The youngest cohort included participants who had not started menstruating, those who had recently started, and those who had had periods for an average of 19 months.
- [24]
Of the gray-matter declines at puberty and in pregnancy, van 't Hof said: "we actually see it as something positive" and "We see it as neural fine-tuning."
- [25]
"But what's really important is that gray matter decline is not equal to cognitive complaints," van 't Hof said.
- [26]
"I'm not saying that there's no neurobiological basis for this mommy brain, but up until now, we haven't found it," van 't Hof said.
- [27]
The three menopause groups together account for roughly 840 of the study's 1,095 brains; the figure is approximate because the source gives one group as about 50 and another as over 670.
- [28]
The pregnancy arm of the study comprises 110 participants.
- [29]
The two menopause reference groups are 4.5 years apart in mean age.
Sources
2 independent publishers whose own reporting we read for this story.
- livescience.comBrain shrinkage tied to aging 'pauses' as a woman nears menopause, study finds
1 article · September 11, 2026
- scientificamerican.comSomething unique seems to be happening to the brain in menopause
1 article · September 8, 2026
Topics and entities
Topics
- Longitudinal cohort studies
- Neuroimaging
- Women's health research
- Menopause
Entities
- Amsterdam University Medical Center
- Sophie van 't Hof
- Magdalena Martínez-García
- Leiden University
- Nature Communications
- Ann S. Bowers Women's Brain Health Initiative
- UK Biobank