How Do Menopause and a Treatment to Manage Its Symptoms Affect the Brain and Mental Health?

New research suggests an association between menopause and anxiety, depression and shrinkage in certain brain regions—which hormone replacement therapy might not mitigate

Margherita Bassi | Daily Correspondent

January 28, 2026

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When a person stops menstruating, typically around age 45 to 55, they might endure hot flashes, mood swings and sleep issues. Someone going through menopause can also experience cognitive decline, finding it hard to concentrate or remember things, for example.

To treat such symptoms, some people use hormone replacement therapy (HRT). It supplies them with additional estrogen, a sex hormone that the body makes less of after menopause. But how this treatment, as well as menopause, affects the brain and mental health has remained unclear.

A new analysis involving nearly 125,000 participants hints at an association between menopause and certain mental health and sleep problems, in addition to shrinkage in specific brain regions. What’s more, HRT may not mitigate these effects, although it seems to slow some aspects of cognitive decline, according to a study published January 27 in the journal Psychological Medicine.

“To our knowledge, this is the first study to investigate the effects of menopause and HRT on mental health, cognition and brain structure in a very large sample of women,” the study authors write in the paper.

The researchers relied on data from the U.K. Biobank, a cohort study with roughly half a million participants from the United Kingdom who were recruited from 2006 to 2010. For the new analysis, they included information from female participants who were pre-menopausal, post-menopausal and had taken HRT or post-menopausal and hadn’t used the medication. A subset of them, about 11,000 individuals, also had brain scan data.

The participants’ self-reported questionnaires revealed more depression and anxiety, as well as poorer sleep, in post-menopausal individuals compared with those who were pre-menopausal. People who were no longer menstruating also showed decreased volumes of gray matter—a tissue comprising nerve cell bodies that helps with mental functions—in certain brain regions important for emotion and memory.

Post-menopausal participants who had taken HRT showed worse sleep and mental health symptoms and more brain region shrinkage than those who hadn’t used the treatment, the team found. Neither the therapy nor menopause affected cognitive measures of memory.

Still, HRT-takers did seem to gain one cognitive benefit. Their reaction times, assessed through a fast-paced card-matching game, were quicker than those of post-menopausal participants who didn’t use the treatment—and were on par with those of individuals still menstruating. (Reaction times tend to slow with age.)

But the researchers don’t know which HRTs or doses the participants received, Roberta Brinton, a neuroscientist at the University of Arizona Health Sciences who was not involved with the study, tells Scientific American’s Jackie Flynn Mogensen. “The type of and treatment regimen of menopausal hormone therapy is a critical factor in the efficacy, or lack thereof, for neurological [and] brain-related functions.”

Study co-author Barbara Sahakian, a neuroscientist at the University of Cambridge in England, acknowledges the critiques. “But I think the basic findings still hold, independent of that,” she tells the outlet.

Additionally, the study authors note that their analysis suggests that participants who used HRT possibly had worse baseline mental health—and therefore sought the medication to help—than the other post-menopausal group. While the researchers don’t know whether the individuals on HRT would have experienced more severe mental health problems without it, the treatment isn’t considered effective for anxiety or depression, they write in the paper.

The brain regions implicated in the study may also provide key insights into Alzheimer’s disease, which women are twice as likely to develop as men. The results suggest that menopause is associated with less gray matter volume in areas including the entorhinal cortex and hippocampus, which are important for learning and memory, Sahakian says on the BBC’s “Global News Podcast.”

“Those are two of the first areas to be affected by the changes that we see in Alzheimer’s disease,” she says. “So it does seem that the menopause might make the female brain more vulnerable.”

Margherita Bassi | Read More

Margherita Bassi is a freelance journalist and trilingual storyteller. Her work has appeared in publications including BBC Travel, Discover magazine, Live Science, Atlas Obscura and Hidden Compass.