According to the World Health Organization (WHO), in 2021, 57 million people globally were living with dementia.
Of that number, about 65% are women, including postmenopausal women or women who have undergone menopause.
Previous research shows there are several reasons why postmenopausal women face a higher risk of developing dementia than men, including loss of the hormone estrogen, brain structural changes, and co-occurring symptoms of menopause that may lead to a higher dementia risk, such as sleeping issues and metabolic changes.
Past studies on the link between use of hormone replacement therapy (HRT) — estrogen, progesterone, or a combination of the two — and dementia risk have been mixed.
Now, a new study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association finds a potential link between HRT use and a lessened risk for dementia in reportedly the largest study of its kind to date.
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For this study, researchers analyzed medical data from more than 183,000 postmenopausal women in the U.K. Biobank who had been followed for an average of 13 years to determine how many participants developed dementia.
At the study’s conclusion, scientists discovered that women who had taken HRT lowered their dementia risk by about 10% and Alzheimer’s disease risk by 16%, when compared to women who had not taken HRT.
However, researchers found that this lower risk depended on a few factors.
For example, women who started HRT between the ages of 46 and 56 had the greatest reduction in dementia risk.
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And researchers found stronger associations between HRT use and lower dementia risk among women who had surgical menopause rather than natural, or who were carriers of the Alzheimer’s-related gene APOE4.
“Our findings contribute to growing evidence that hormone therapy’s effects on brain health are complex and influenced by individual biological factors,” says Anne-Marie Minihane, PhD, professor of nutrigenomics in the Norwich Medical School at the University of East Anglia in England, and lead author of this study, in a press release.
“While HRT has long been prescribed primarily to relieve menopausal symptoms such as hot flushes and night sweats, this work suggests it may also play a role in long‑term cognitive health for some women.”
— Anne-Marie Minihane, PhD
Medical News Today spoke with Sherry Ross, MD, a board certified OB/GYN and women’s health expert at Providence Saint John’s Health Center in Santa Monica, CA, about this study.
Ross commented that this was an exciting observational study as it looked at a substantial number of women over a long period of time and found an association between starting HRT earlier and a significant reduction in dementia and Alzheimer’s disease, a disease that disproportionately affects women.
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“Gray matter in the brain has been found to have a key role in memory, sensory perception, information processing, emotion regulation, attention, decision making, executive functioning, language, and social cognition,” Ross, who was not involved in this study, explained. “During menopause, gray matter, and all that it does to allow us to function, think, feel, speak, and move normally, can be negatively affected.”
“Starting estrogen early in the menopause transition may minimize these changes from happening and reduce the risk of dementia and Alzheimer’s disease,” she added.
Prudence Hall, MD, an OB/GYN in private practice in Santa Monica, CA, and author of Radiant Again & Forever: Overcome Menopause & Restore Your Radiance, told MNT that a common concern among perimenopausal and menopausal women is brain fog and poor short-term memory.
“At any age, all the way up to 90, women commonly report that HRT has helped their brain function better,” Hall, who likewise was not involved in this study, explained. “I consider hormones to be the body’s software, in a similar way that our computers need software in order to operate. Bioidentical estradiol — the exact same hormone women make — increases blood flow to the brain and improves the connection between neurons.”
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As two-thirds of dementia cases are in women and one-third are in men, Hall said it’s imperative to educate and treat women to prevent this disease specifically.
“Especially in menopause, there is a pronounced increase in dementia, so the major causes of dementia need to be addressed,” she continued. “Sugar damage needs to be lowered, all hormones optimized, and lifestyle changes instituted (during) menopause.”
MNT also spoke with Dung Trinh, MD, an internist for MemorialCare Medical Group and chief medical officer of the Healthy Brain Clinic in Irvine, CA, who was not involved in this study.
Trinh commented that this is an encouraging and clinically interesting study, particularly because it suggests that the relationship between HRT and dementia risk may depend heavily on when HRT is started and on a woman’s individual risk profile.
“At the same time, this was an observational study, so it cannot prove that HRT itself prevented dementia, and I would not recommend starting HRT solely for dementia prevention based on these findings alone.”
— Dung Trinh, MD
For future research, Trinh said he would like to see prospective and ideally randomized studies designed specifically to examine cognitive and dementia outcomes in women starting HRT around the menopausal transition.
“Future research needs to separate different hormone formulations, including estrogen alone versus estrogen plus a progestogen, and compare oral versus transdermal treatment, different doses, and different durations of therapy,” he detailed. “It would also be valuable to study women with natural menopause separately from those with surgical menopause and to stratify participants by APOE genotype and other dementia-risk factors.”
“Ultimately, we need to determine which women might benefit, which type of hormone therapy is most appropriate, and when treatment would need to begin to have the greatest potential effect on brain health,” Trinh added.
