Women who go through menopause at younger ages and put off hormone replacement therapy to manage their symptoms may be at increased risk of Alzheimer’s disease, a new study suggests.
“Hormone therapy is the most reliable way to ameliorate severe menopause symptoms, but over the last few decades, there has been a lack of clarity on how hormone therapy affects the brain,” said the senior study author, Rachel Buckley, PhD, an assistant professor of neurology at Harvard Medical School and Massachusetts General Hospital in Boston, in a statement.
Women Already Have a Higher Risk of Alzheimer’s Than Men
To take a closer look at this relationship, researchers examined data on 99 men and 193 post-menopausal women who had no history of cognitive impairment. All participants underwent positron emission tomography (PET) scans to assess levels of tau and beta-amyloid, proteins in the brain that play a role in the development of Alzheimer’s disease.
Female participants provided data on their age at menopause. Researchers characterized people who went through menopause before age 40 as experiencing premature menopause, and people who went through menopause between 40 and 45 as experiencing early menopause. The normal timing of menopause is between 45 and 55 years old, according to the National Institutes of Health (NIH).
For the subset of 98 women who used hormone therapy, researchers examined data on how soon after menopause these women initiated treatment.
Overall, women had higher tau levels than men, the researchers reported April 3 in JAMA Neurology. This finding was expected, the study team noted, because a large body of evidence has long shown women are far more likely to develop Alzheimer’s disease than men.
Scientists also found that women who went through menopause earlier had higher levels of tau and beta-amyloid protein in their brains, even after accounting for genetic risk factors for Alzheimer’s disease and known risk factors for early menopause, such as smoking and surgical removal of the ovaries.
Starting Hormone Therapy Shortly After Early Onset of Menopause May Offer Cognitive Protection
But when researchers also looked at the timing of hormone therapy among women who went through menopause early, there didn’t appear to be increased protein levels when the women started hormones soon after this transition. Among these women, the highest protein levels were seen in participants who waited at least five years before taking hormones.
“We found that the highest levels of tau, a protein involved in Alzheimer’s disease, were only observed in hormone therapy users who reported a long delay between age at menopause onset and their initiation of hormone therapy,” Dr. Buckley said.
One limitation of the study is that most participants were white, and it’s possible the results would have been different for Black or Hispanic women or individuals from other racial or ethnic groups, the study team noted. Another drawback is that researchers relied on participants to accurately recall and report the timing of menopause and hormone therapy initiation, and it’s possible that they didn’t always provide accurate information.
Even so, the findings offer fresh evidence that the link between hormone therapy and dementia established in the landmark Women’s Health Initiative (WHI) study two decades ago may not be the same for every woman who uses hormones, says Victor Henderson, MD, the director of the Alzheimer’s Disease Research Center at Stanford University in California.
“The effects of hormone therapy on dementia risk may depend on the age at which hormone therapy is initiated or on the timing of initiation in relation to menopause, with higher risks with initiation and use at older ages further from menopause,” says Dr. Henderson, who wasn’t involved in the new study.
This should reassure women that they can minimize their dementia risk by taking hormones sooner, Henderson adds. But it shouldn’t lead women without any so-called vasomotor symptoms of menopause — like hot flashes or night sweats — to start hormones simply to promote brain health.
The findings “don’t suggest that women should consider hormone therapy in the absence of moderate-to-severe vasomotor symptoms in the hope of staving off dementia,” Henderson says. “On the other hand, findings are consistent with other evidence that overall benefits of hormone therapy in the perimenopause and early post-menopause are not outweighed by overall risks in otherwise healthy women.”