Alzheimer's disease affects women more frequently, with approximately two-thirds of those diagnosed being female. The reasons for this disparity are not fully understood; it might be due to women generally living longer, or it could stem from social or genetic factors. However, recent research is highlighting a potential contributing factor: menopause.

During menopause, the ovaries cease egg production, and the generation of estrogen, a crucial hormone for female reproductive health, declines. Evidence suggests that this significant drop in estrogen levels may impact how our brains age.

"A leading hypothesis is that this steep decrease in estrogen may, in some way, contribute to differences in brain aging," including an increased susceptibility to developing Alzheimer's, explains Jennifer Bruno, a cognitive neuroscientist at Stanford University.

A new study conducted by Bruno and her colleagues, published in Neurology, offers further insight into the potential connection between menopause and dementia. The researchers examined two extensive datasets, comprising the records of 21,462 patients. Notably, for one of these datasets, nearly 3,000 individuals had generously donated their brains for scientific study after their passing.

The findings revealed that patients who underwent estrogen-only hormone therapy for menopause showed a reduced likelihood of exhibiting symptoms of memory loss or cognitive decline, and a lower incidence of dementia diagnoses. Among the brains donated for research, those belonging to individuals who had taken estrogen were less prone to displaying the neurobiological indicators of Alzheimer's disease, such as beta-amyloid plaques or tau protein tangles.

The study's authors, including co-author Jacob Shaw, a psychiatry resident at Massachusetts General Hospital/McLean, took into account various confounding factors such as age, race, a history of hypertension, and other characteristics. The second dataset, analyzing living patients, also indicated a reduction in Alzheimer's-related biomarkers among those who had used estrogen.

It is important to note that this study establishes an association between estrogen-only hormone therapy and a decreased risk of dementia; it does not conclusively prove that this therapy prevents or treats dementia.

Hadi Hosseini, a neuroscientist at Stanford University and the study's senior author, suggests that other factors might be involved. He posits that women who received estrogen-only hormone therapy could have been healthier overall, had better access to healthcare, or other undisclosed elements could have played a role.

Another limitation is the absence of information regarding the specific reasons each patient was prescribed estrogen-only therapy. Currently, this treatment is primarily recommended for menopausal symptoms in women who have had hysterectomies, due to a heightened cancer risk. However, the datasets used in this study did not include hysterectomy records.

Complicating matters further, some previous research has indicated that other hormonal therapies, including combined progestin and estrogen treatments, might be linked to an increased risk of dementia, though the reasons for this remain unclear.

The authors emphasize the need for more comprehensive research into the intricate relationship between menopause, estrogen, and dementia. This includes conducting long-term studies that monitor patients as they age. "It sets the stage for future randomized controlled trials," stated Bruno.

English Translation:

Estrogen-Only Hormone Therapy Could Lower Risk of Alzheimer’s

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 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. 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. Currently, estrogen-only therapy is primarily recommended for menopause treatment in women who have undergone hysterectomies because of an increased risk of cancer, 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 progestin 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.