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Alzheimer’s disease disproportionately affects women—around two thirds of the people who develop it are female. Why that is the case isn’t totally clear. It may be because women tend to live longer than men or perhaps because of social or genetic factors. But emerging research points to another potential risk factor: menopause.

During menopause, the ovaries stop producing mature eggs, and the production of estrogen, a sex hormone critical to female reproductive health, slows. Research hints that this precipitous drop in estrogen may affect how our brains age.

“One of the prevailing hypotheses is that this sharp decline in estrogen may somehow contribute to differences in brain aging,” including the likelihood of developing Alzheimer’s, says Jennifer Bruno, a cognitive neuroscientist at Stanford University.

Now a new study by Bruno and her colleagues that was published in Neurology on Wednesday provides another clue to the possible link between menopause and dementia.

The researchers analyzed two datasets that included a total of 21,462 patient records; for one of the datasets, nearly 3,000 people had donated their brains for science when they died. Overall, patients who took estrogen-only hormone therapy for menopause were less likely to display signs of memory loss or cognitive decline or to be diagnosed with dementia.

In the nearly 3,000 patients who donated their brains to science, the brains of those who took estrogen were less likely to show neurobiological hallmarks of Alzheimer’s disease, such as beta-amyloid plaques or tangles of tau protein. The researchers accounted for confounding factors such as age, race, history of hypertension and other traits, notes Jacob Shaw, a study co-author and psychiatry resident at Massachusetts General Hospital/McLean Hospital. The other dataset also showed a drop in Alzheimer’s-related biomarkers in living patients who took estrogen.

Importantly, the study surfaces an association between estrogen-only hormone therapy and a lower risk of dementia—it doesn’t prove that estrogen-only therapy prevents or treats dementia.

There may be other factors at play, says Hadi Hosseini, a neuroscientist at Stanford University and the study’s senior author. It could be that women who took estrogen-only hormone therapy were healthier overall than those who did not or had better access to health care, or something else could have been involved, he says.

Another limitation is that the research team didn’t have access to information about why each of the patients had been taking estrogen-only therapy. Because it is associated with an increased risk of endometrial cancer, estrogen-only therapy is primarily recommended for menopause treatment in women who have undergone hysterectomies, but the datasets in this study didn’t include hysterectomy records.

Another complication is that some past research suggests that other hormonal therapies, including a combination of the sex hormone progesterone and estrogen, may be associated with a higher risk of dementia. It’s not totally clear why.

More research into the relationship between menopause, estrogen and dementia—including long-term studies that track patients as they age—is needed, the authors say. “It sets the stage for the future randomized controlled trials,” Bruno says.

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