Brain shrinkage tied to aging 'pauses' as a woman nears menopause, study finds

The brain undergoes dramatic changes during puberty and pregnancy, but during menopause, the organ's structure remains remarkably stable, a new study suggests.

The research, published Sept. 8 in the journal Nature Communications, examined the brain's gray matter, which mostly includes the wrinkled outer surface of the organ, called the cerebral cortex. Past studies have found that the volume of gray matter shrinks markedly during puberty and pregnancy, likely reflecting a fine-tuning of neural circuits during those periods.

There's also a gradual decline in gray matter during adulthood that's seen as a normal part of aging, said study co-author Sophie van't Hof, a doctoral student in psychiatry at Amsterdam University Medical Center. However, during the transition leading up to menopause, that gradual loss of gray matter levels off temporarily, the study found.

"This study provides the first direct longitudinal comparison of brain structural changes across all three major female hormonal transitions," said Magdalena Martínez-García, 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.

"I really appreciate the effort that went into finding and curating such an impressive longitudinal dataset of the female brain," Martínez-García, who was not involved in the study, told Live Science in an email.

Declines in puberty and pregnancy

For their analysis, the researchers gathered data from the UK Biobank, a biomedical database that contains information from 500,000 U.K.-based adults. That data includes MRI scans of people's brains, which the team used to study brain changes in menopause.

To look at puberty and pregnancy, the researchers pulled from several brain-scan datasets that had been compiled by Leiden University in the Netherlands.

In all, the study included data from 1,095 brains across the three life stages. They analyzed each participant's brain at two different time points, examining how each person's brain changed over time and how it compared to others' brains.

The youngest cohort included participants who hadn't started menstruating yet, as well as those who'd recently started and those who'd already had periods for an average of 19 months. The pregnancy cohort included 40 who'd had their first pregnancy during the study and 30 who'd had second pregnancies, as well as 40 women who'd never been pregnant, as a point of comparison.

As in previous studies, the researchers observed that both the girls entering puberty and the pregnant women lost gray matter. But scientists don't necessarily see these declines in gray matter at puberty and pregnancy as negative.

It’s a hypothesis, but "we actually see it as something positive," van't Hof said. "We see it as neural fine-tuning."

During puberty, that gray-matter loss is thought to be a normal part of the brain's development into adulthood. Its function in pregnancy is not well understood, van't Hof noted, but the evidence to date doesn't suggest that it contributes to "mommy brain" — the brain fog and forgetfulness some women can experience postpartum.

"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. "But what's really important is that gray matter decline is not equal to cognitive complaints."

Stability in menopause

The analysis included 120 women who entered menopause during the study. At the first time point, these women had not gone a full year without a period, but by the second time point about 3.5 years later, they had. Menopause is defined as the point at which a full year has elapsed since a person's final period.

The researchers compared these women to two other groups: about 50 women (average age 51) who had not had their last period yet and over 670 women (average age 55.5) who had already had their last period.

During late perimenopause — the final stages of the transition to menopause — the brain's gradual decline in gray matter paused, van't Hof said. Then, in postmenopausal women, that gradual decline of gray matter resumed. The exact timing of that pause differed for each woman, but it occurred consistently across the group, van't Hof noted.

The most striking finding was the lessening of the "ongoing age-related decline in brain volume during the transition into and out of menopause, compared with the more stable premenopausal and postmenopausal groups," Martínez-García said. This is an "interesting finding that adds to our understanding of how dynamic the female brain can be across the lifespan."

Factors such as whether participants had taken hormone replacement therapy for menopause and the number of children they had given birth to did not have a measurable impact on the results, the study authors noted.

In general, complaints of brain fog are widespread just before, during and after menopause, van't Hof said. This could be attributed to declining hormone levels and sleep disruptions.

"We have no clue if there's a neurological basis [for that brain fog], because, again, this is the first study to look at it," she said, adding that more studies are still needed to learn more.

"As with any study, there are some limitations to consider, but overall, I think the methods and conclusions are well supported by the data available," Martínez-García said. Both Martiniz-Garcia and van’t Hof said that they hope other researchers build on these findings to deepen scientists’ understanding of female neurobiology at every stage of life.

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