Here’s One Reason Why Women May Have a Higher Alzheimer’s Risk Than Men

Updated: Apr. 23, 2021

New research may help explain why women are more likely to develop Alzheimer's disease than men—and it's not because they live longer.

It’s an unpleasant fact: Women are twice as likely as men to develop Alzheimer’s disease. Researchers have long believed this was because women live longer than men, and Alzheimer’s is a disease of old age. But new research suggests that there may be more to this story—estrogen, the female sex hormone. Women develop Alzheimer’s-related changes in their brains earlier than men do, and these changes begin around menopause as the production of estrogen dramatically declines, reports a new study in Neurology.

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Alzheimer’s disease is a progressive neurological decline that starts with short-term memory loss and other early symptoms. It is the most common cause of dementia. The Alzheimer’s Association points out that more than 5 million Americans age 65 and older are living with Alzheimer’s dementia, and this number is expected to rise to 14 million by 2050. Fully two-thirds of senior citizens with Alzheimer’s are women, the group notes.

What the new research revealed

The recent study included 85 women and 36 men who were not showing any signs of cognitive decline. Participants underwent three types of high-tech brain imaging scans to measure changes in the brain that indicate Alzheimer’s: One scan checked for beta-amyloid proteins, which can clump together and cause the buildup of plaque in the brain. Another gauged the amount of gray and white matter in the brain; when these vital tissues decline, they can indicate advanced disease. The third test tracked how well the brain uses glucose, its energy source.

Menopause was the strongest predictor of higher beta-amyloid loads, lower glucose metabolism, and lower gray and white matter volumes. Women who had had a hysterectomy showed even greater changes than women who entered menopause naturally. A hysterectomy is a surgical procedure that removes part or all of a woman’s reproductive organs. If the ovaries are removed, a woman will go into immediate menopause.

Forty-one percent of participants had a gene that increases risk for Alzheimer’s disease. About half (49 percent) of women were post-menopausal and 16 percent used hormone replacement therapy (HRT).

Does this mean estrogen could lower Alzheimer’s risk?

Also included in the study: Women on estrogen replacement therapy—or, more generally, hormone replacement therapy (HRT). Most were taking the pills to help combat the symptoms of menopause, and these women accounted for about 16 percent of the total volunteers. The researchers discovered the HRT women were less likely to have the brain changes linked to Alzheimer’s. “These findings suggest that the window of opportunity for AD preventive interventions in women is early in the [hormonal] aging process,” the researchers concluded.

For years HRT was widely prescribed to help reduce the signs and symptoms of menopause, including hot flashes, night sweats, and other quality-of-life-robbing menopausal changes. Some research even suggested that HRT could protect the heart and the bones, which led many to think of it as a potential “fountain of youth.”

But this changed when the hormone therapy trial associated with the Women’s Health Initiative (WHI), a large government-run study of older women, was halted early when it was found that use of combination hormones or estrogen alone led to an increased risk of breast cancer, heart disease, stroke, and blood clots.

Don’t sign up for HRT just yet

The newly published findings, however, may eventually tip the scale in favor of estrogen replacement therapy for some women, says Howard Fillit, MD, founding executive director and chief science office of the Alzheimer’s Drug Discovery Foundation in New York City.

“At the time of menopause, which is around age 51, 60 to 80 percent of women complain of memory problems, irritability, and depression, yet the clinical onset of Alzheimer’s takes place around age 75, so there is this 20 to 25 year period during which there is a festering of AD,” he theorizes. This opens up a window of potential opportunity for prevention, he says.

Still, the study is not enough to cause doctors to change their approach to Alzheimer’s, specifically because of its small size and the fact that it was not designed to show whether the decline in estrogen actually caused the brain changes, he says.

It’s too soon to suggest the use of hormone replacement therapy to stave off Alzheimer’s, but there are things to do today that may help mitigate your chances.

female patient sitting on examination table in doctor's officeJose Luis Pelaez/Getty Images

Control what you can

While menopause was the greatest risk factor for developing Alzheimer’s in this study, there are other known risks that can be modified, Dr. Fillit says. These include high blood pressure, diabetes, lack of exercise, and smoking. Taking proactive steps to keep your blood pressure where it should be and to prevent diabetes can help lower risk for Alzheimer’s disease. Regular exercise can help you achieve both of these goals. There are other things you can do to help prevent, delay, or slow down Alzheimer’s disease and dementia, such as socializing and playing brain games.

Keep an eye out for thyroid disease

In the study, thyroid disease was on the list of conditions potentially raising the risk of Alzheimer’s. Work with your doctor to monitor your thyroid function and treat any issues—it could play a role in preventing some of the changes that lead to Alzheimer’s, Dr. Fillit says.

Talk to your doctor about HRT

Some women may reap more benefits than risks if they take estrogen replacement therapy, he says. Regular mammograms and gynecologic exams can identify cancer early in women taking hormones, he says. “If it turns out that one of the benefits of menopausal HRT is preventing these early biomarkers or signs of Alzheimer’s disease, it would be enough to change clinical practice.”

In the future, researchers will be able to use brain scans or blood tests to see if HRT is positively affecting Alzheimer’s risks. “We can see if these changes reverse themselves when women take hormone replacement therapy,” Dr. Fillit says.

“Studies like this help us paint a clearer picture of what may be contributing to the underlying biology of Alzheimer’s disease, and this includes the role of hormones and hormonal changes,” says Keith Fargo, PhD, director of scientific programs & outreach at the Alzheimer’s Association. “However, this study reflects a relatively small number of participants, and individuals should not draw conclusions or make decisions about hormone replacement therapy based on these findings.”

Women with questions about hormone therapy should talk to their physician about potential risks and benefits, Dr. Fargo says.