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Everyone who menstruates and lives long enough experiences menopause in one form or another. Yet despite that, research into what happens during this natural cessation of menstruation and why is limited. Scientists know that menopause can cause a myriad of neurological symptoms, from hot flashes to poor sleep to depression. But what is going on in people’s brain during this period is still murky. Now, new research offers clues to a link between menopause and changes in the brain’s gray matter, as well as anxiety and depression.

Using brain scans from 10,873 people in the U.K., the researchers found that postmenopausal participants showed lower volumes of gray matter in the entorhinal cortex and hippocampus, which are involved in storing and retrieving memories, and in the anterior cingulate, which is involved in emotional regulation.

The researchers also looked at whether hormone replacement therapy (HRT), a frontline but still rarely prescribed treatment for symptoms of menopause, might ameliorate some of these changes.

Barbara Sahakian, a psychiatry professor at the University of Cambridge and an author of the study, explains that she and her colleagues theorized HRT might influence people’s experiences, tamping down their neurological symptoms, for instance. “That was the hypothesis,” she says, “but it didn’t seem to pan out completely that way.”

They found that people who were treated with HRT for menopause showed lower volumes of gray matter in some areas of the brain than those who did not receive HRT. The HRT group also showed higher rates of anxiety and depression—importantly, Sahakian says their work doesn’t find that HRT treatment causes brain changes or menopause symptoms. Previous research suggests HRT prescribed during the run-up to menopause and early postmenopause can reduce anxiety, depending on the kind of HRT and dose, in at least some women. And a subsequent analysis found that participants who were prescribed HRT were more likely to have reported anxiety and depression before HRT treatment, the study explains.

It’s unclear what kind of hormone therapy the participants received, says Roberta Brinton, director of the Center for Innovation in Brain Science at the University of Arizona, who was not involved in the study. “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,” she says.

Sahakian and her colleagues didn’t have access to the participants’ treatment regimens or what dose of HRT they were taking, which could also muddy the findings. “They are good questions,” she agrees. “They are important. But I think the basic findings still hold, independent of that.”

One potential benefit of HRT that did emerge from the data was its beneficial effect on psychomotor slowing, or the tendency for reaction times to slow with age. Without HRT, postmenopausal women had slower reaction times in a card-matching speed game than those who were premenopausal. But study participants who were treated with HRT had similar reaction times to participants who hadn’t gone through menopause.

This indicated that the HRT may be protective for psychomotor slowing postmenopause,” Sahakian says.

She hopes the results will serve as a basis for future studies on the brain and aging, including menopause’s potential role in Alzheimer’s syndrome and dementia. Women are more likely than men to develop Alzheimer’s, although it’s not totally clear why. Women’s tendency to live longer may play a role, but a growing number of researchers, including Sahakian, wonder if menopause might, too. Indeed, the brain areas singled out in this study are also often among those affected by Alzheimer’s disease.

A next step would be to look more deeply at what’s happening in the brains of the study participants to try and figure out what, exactly, is causing decreases in brain volume—whether it’s stress, hormones, or something else.

In the meantime, Sahakian recommends people who are experiencing menopause focus on behaviors that are known to improve brain health—exercising, sleeping well, keeping your mind active, eating healthy, and maintaining a positive social network.

“If women would try to do those things, particularly during the menopause, then that would put them in the best possible shape to get through it well,” she says.

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