Can Hormone Therapy Raise Your Risk for Alzheimer’s?

This new study suggests that hormone therapy might lower—or at least not raise—your dementia risk if you take it in midlife. For older women, the study found some signs that the medication might raise it.

The findings don’t resolve the debate. But it did look at 50 prior studies and give one of the most thorough answers for what we know now. 

Younger women who started taking estrogen-only hormone therapy during perimenopause or early menopause had a 32% reduced risk of developing dementia compared with women not taking anything, concluded the study, which was published online in Frontiers in Aging Neuroscience. Women in that same life stage taking combination therapy—estrogen plus another hormone, progestogen—also had a reduced risk, but it wasn’t considered statistically significant. 

For older women who started taking hormone therapy more than 10 years post menopause, the study found some indications that taking combination hormone therapy might raise the risk of developing dementia. The signs weren’t strong enough to be conclusive. 

The study was a meta-analysis, which means it analyzed prior studies rather than conducting a new investigation. The majority of them were observational studies, which have some limitations, researchers say. 

Parsing the findings

Pauline Maki, a professor of psychiatry, psychology and obstetrics/gynecology at the University of Illinois Chicago, says that earlier studies indicated that hormone therapy might help reduce the risk of dementia. The more recent research shows the opposite trend, with a small but meaningful increase in risk, she says. 

The meta-analysis included both older and newer studies. 

Maki speculates that the change wasn’t necessarily because of the hormone therapy itself, but might be because of declines in women’s overall health. More women today have diabetes, obesity and other metabolic conditions that might raise the risk of dementia.

Women shouldn’t go on hormone therapy just because they think it could lower their dementia risk, says Dr. Stephanie Faubion, director of Mayo Clinic Women’s Health and medical director of the Menopause Society. However, she and other doctors recommend hormone therapy for symptoms such as hot flashes or disturbed sleep, which might also help improve memory or attention.

The latest findings were in line with other research that has suggested that starting hormone therapy early in the menopause transition might help both in treating common menopausal symptoms, as well as lowering the risk of some long-term health conditions. 

“I’m fairly confident in these findings that women who take hormone therapy around the age of menopause do a lot better,” says Rachel Buckley, an assistant professor of neurology at Massachusetts General Hospital in Boston.

Guarding against dementia

Perimenopause is the time leading up to menopause, often starting in your 40s, and can range from several years to more than a decade. Menopause happens when a woman hasn’t had a menstrual cycle in a year; the average age in the U.S. is 51.

The lifetime risk of developing Alzheimer’s is nearly twice as high in women compared with men. In the U.S., about two-thirds of people living with Alzheimer’s are women.

Doctors have long believed the main explanation was that women lived longer. But other research suggests that the estrogen loss that occurs during menopause might also play a role, says Lisa Mosconi, senior author of the new study and an associate professor in the department of neurology at Weill Cornell Medicine, where she is also director of the Alzheimer’s Prevention Program and Women’s Brain Initiative.

The new study’s finding that the strongest protection against dementia risk comes from estrogen-only hormone therapy during perimenopause or early menopause is tricky. That’s because estrogen-only therapy is typically used only in women who have had hysterectomies to remove their uterus.

Other women usually take estrogen in combination with oral progestogen to reduce the risk of uterine cancer. Researchers are trying to come up with new hormone therapy treatments that would reduce this risk without needing to take progestogen, but they are still in development. 

“It is really the progestin part of that hormone therapy that is driving the risk,” says Roberta Brinton, a professor of pharmacology, neuroscience and neurology at the University of Arizona in Tucson and co-author on the study.