Alzheimer’s dementia is generally more prevalent in women than in men, and doctors believe that one reason why is the sudden drop in estrogen after menopause, which can affect the brain.
A new study published in Neurology seems to support this theory. Researchers analyzed the health records of more than 5,000 older women with hysterectomies who had died and had an autopsy of their brains. Those who had received estrogen-only hormone therapy at menopause had 35% lower odds of having the hallmarks of Alzheimer’s disease, including amyloid plaques, in their brains compared to women who did not receive estrogen.
By including the autopsy findings, the results “lend objectivity to the outcome measures,” says Jennifer Bruno, an instructor in psychiatry at Stanford University and one of the co-authors of the study. “Previous studies used cognitive decline or clinical ratings of dementia, which are important for understanding how women are progressing through life, but are not definitive diagnoses of Alzheimer’s and therefore not objective.”
Earlier studies of hormone therapy and Alzheimer’s have led to mixed results, with some suggesting a reduced risk of the neurodegenerative disorder and others finding no benefit or an increased risk. The landmark Women’s Health Initiative hormone-therapy trial, whose initial results were released in 2002, raised a lot of concern about the safety of hormone therapy; it found that the treatment increased women's risk of breast cancer and dementia, while showing no benefit for reducing the risk of Alzheimer's. But the study included women who were post-menopausal and used a different type of hormone replacement therapy, making it hard to generalize the results to women taking hormones during menopause.
The women in the new study were prescribed estrogen only, and not the combination of estrogen and progesterone that is more commonly used to treat menopausal symptoms. Progesterone is prescribed to protect the uterus, but women who have had a hysterectomy, like those in the study, can safely be prescribed estrogen. This population provides a good way to study the effects of estrogen itself, since researchers believe it’s the hormone with more wide-ranging effects on the body, including in the brain.
Hadi Hosseini, an associate professor of psychiatry at Stanford and co-author of the study, says the results don’t establish a cause-and-effect link between estrogen and Alzheimer’s disease, but they do provide a reason to further study the role of the hormone in the neurodegenerative disease. “Previous studies," including the Women's Health Initiative, "showed that hormone therapy—estrogen plus progesterone—had a negative effect on Alzheimer’s disease risk and memory outcomes," he says. "These data are bringing awareness to the fact that maybe we need to reconsider some of the previous findings, since we can now look properly at Alzheimer’s disease outcomes, different formulations of hormone therapy, different times of initiating the therapy, and different durations of use.”
While the current study did not detail when the women began using estrogen, which formulation they took, or how long they remained on estrogen around menopause, future studies should be designed to take these factors into account, says Bruno. The current findings could serve as a foundation for two types of additional studies: a trial that follows women in perimenopause (the time just before menopause) and through menopause to monitor changes in biomarkers for Alzheimer’s disease in the blood and spinal fluid, as well as in brain images. Such objectively based studies could shed more light on what role estrogen therapy can play in preventing Alzheimer’s.
Studying what types of hormone treatments women use, when they start therapy, and how long they remain on the hormones and how that affects their later Alzheimer’s risk could also be useful, says Bruno. “The Women’s Health Initiative was a big study that didn’t address things properly and put a cloud over prescribing [hormone] therapies,” she says. “We want to remove the cloud and reopen dialogue to think about how we can, from a research perspective, further understand the potentially powerful mechanism of [how these hormones] can help with memory and Alzheimer’s disease.”