Key TakeawaysResearch has long suggested a link between the use of hormone therapy during menopause and the risk of developing dementia.A new meta-analysis of more than 50 studies aims to make sense of conflicting research.People who used estrogen-only hormone therapy when they started experiencing menopausal symptoms were better protected against Alzheimer’s disease and dementia, according to the analysis.

Key Takeaways

Research has long suggested a link between the use of hormone therapy during menopause and the risk of developing dementia.A new meta-analysis of more than 50 studies aims to make sense of conflicting research.People who used estrogen-only hormone therapy when they started experiencing menopausal symptoms were better protected against Alzheimer’s disease and dementia, according to the analysis.

Nearly two-thirds of the people who develop Alzheimer’s diseaseare women. For decades, researchers have sought to understand whether the loss of estrogen duringmenopausecould be a major reason and whetherhormone therapycould decrease women’s risk for dementia.

In a meta-analysis published last week, a team of researchers sought to make sense of the existing data on the link between menopause hormone therapy and dementia and to see if they pointed to an overall trend.They included six randomized control trials and 45 observational reports, accounting for the experiences of more than 6 million women.

The researchers found that hormone therapy can help protect against Alzheimer’s disease development in women who take estrogen hormone therapy in midlife, or as close as possible to the onset of menopause.

However, the protective benefit was notable for women who took estrogen-only therapy, which is typically reserved for people who have their ovaries or uterus removed. People who have a uterus areoften recommendedto take combination hormone therapy—estrogen and progestogen—to protect against uterine cancer. But this therapy doesn’t seem to reduce dementia risk.

“Our findings further reinforce this stance, suggesting that for women who are eligible, considering hormone therapy after surgery could not only alleviate menopausal symptoms but also potentially safeguard cognitive health in later years,” saidLisa Mosconi, PhD,one of the authors of the study and associate director of the Alzheimer’s Prevention Program and director of the Women’s Brain Initiative at Weill Cornell Medicine.

“It’s essential, however, for every woman to engage in comprehensive discussions with her healthcare providers to understand the benefits and risks unique to their individual circumstances,” Mosconi added.

The current evidence isn’t yet enough to suggest that clinicians should prescribe hormones to prevent Alzheimer’s disease, according to Mosconi.

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Wading Through Conflicting Data

Years of research have shown conflicting data on whether hormone therapy can benefit or damage long-term cognition. Mosconi said that her team sought to clear up confusion and locate trends in the study results.

When researchers did a follow-up study in 2017, they found that women who were on estrogen-only therapy had a 26% lower risk of dying from Alzheimer’s disease.

That number can sound promising, saidPauline Maki, PhD,a professor of brain and cognitive sciences at the University of Illinois Chicago and an expert in women’s cognitive and behavioral health.

But when it was published, Maki ran a calculation called a “number needed to treat.” She found that 2,004 women would need to take estrogen to prevent a single case of death from dementia. Given the small, but non-zero,risk of complicationswith hormone therapy, she said the data may not be strong enough to recommend it for all women.

“What are the risks you are accumulating among those 2,004 women? Breast cancer, the rare stroke—it’s not a net neutral decision to go on these products to prevent dementia,” Maki told Verywell.

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Case-control studies from Finland,Taiwan,and the United Kingdomindicated that long-term or high-dose usages of systemic hormone therapy, especially estrogen-plus-progestogen, can increase the risk for Alzheimer’s disease overall.

Maki said that the meta-analysis researchers highlighted numbers from sub-analysis in those studies but didn’t adequately note the overall risk findings. If they had, the conclusions in the meta-analysis may have been tempered.

“Meta-analyses produce results depending on which studies are chosen to be included, and I think there were some decisions made for this meta-analysis that I wouldn’t have made,” Maki said. “I’m very, very cautious. I don’t think the data shows any clear sign.”

Observational studies can also present problems, she added. It’s possible that people who have access to hormone therapy are also the people who have the time and resources to best tend to their sleep hygiene, diet, and other factors that are known to reduce dementia risk.

Conversely, people who read about the potential benefits of hormone therapy for dementia may be more likely to seek hormones if they’re already experiencing memory problems. Either way, those observational studies can lead to skewed results.

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The researchers of the meta-analysis wrote that part of the reason WHIM study may have found hormone therapy to increase dementia risk is that it enrolled women who were in their mid-60s and were likely beyond the point of benefitting from hormone therapy.

To study how hormone therapy taken during perimenopause and early post-menopause relates to the development of Alzheimer’s disease, researchers would have to follow participants for decades, from their 40s to their 70s. Keeping track of patients for that period, ensuring data is collected consistently, and paying for such a long-term study can be logistically challenging. Besides, Mosconi said, denying one group a potentially beneficial treatment for that long poses ethical challenges.

Mosconi said her team is enrolling participants in a clinical trial to study how hormone therapy in midlife affects whether a person develops biological markers of Alzheimer’s disease.

“With advanced brain imaging techniques, we can detect Alzheimer’s-related changes in the brain long before clinical symptoms emerge,” Mosconi said. “If menopause hormone therapy can prevent or even halt the progression of these Alzheimer’s-related lesions, it would offer compelling evidence of its preventative potential.”

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Known Ways to Prevent Dementia

While scientists continue to probe whether estrogen therapy during menopause directly relates to dementia risk, there is mounting evidence that treating hot flashes and night sweats can protect brain tissue.

Black womentend to experience hot flashes that persist for a decade after their last period and are 50% more likely to experience vasomotor symptoms than White women. For those women who experience more severe and long-term hot flashes, Maki said hormone therapy could protect cognition in the long run.

“For which women is menopause a risk factor? We think it’s the women—and there’s a lot of them—who continue to have these really bad symptoms that affect the white matter in their brain and their memory functioning,” Maki said.

According to the CDC, certain conditions including obesity, diabetes, and depression are linked to Alzheimer’s risk. Managing those conditions in mid-life can slow long-term cognitive decline.

“Women should do the hard work if they want to prevent Alzheimer’s disease, which is they need to maintain their heart health. They need to engage in aerobic exercise. They need to have really good sleep hygiene, which is hard if you’re a midlife woman,” Maki said.

Women can also reduce their alcohol consumption, avoid smoking, challenge themselves cognitively, and avoid head injuries during perimenopause and throughout the menopausal transition to help avert dementia.

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What This Means For YouEach person’s experience in menopause is different. Talk with a provider about whether hormone therapy may be helpful for you and for guidance on how to prevent your risk for dementia. You can find a list of menopause-aware providers on theNorth American Menopause Society website.

What This Means For You

Each person’s experience in menopause is different. Talk with a provider about whether hormone therapy may be helpful for you and for guidance on how to prevent your risk for dementia. You can find a list of menopause-aware providers on theNorth American Menopause Society website.

7 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Nerattini M, Jett S, Andy C, et al.Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia.Front Aging Neurosci, 2023;15:1260427. doi:10.3389/fnagi.2023.1260427Manson JE, Aragaki AK, Rossouw JE, et al.Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials.JAMA. 2017;318(10):927-938. doi:10.1001/jama.2017.11217Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al.Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study.BMJ. 2019;364:l665. doi:10.1136/bmj.l665Sung YF, Tsai CT, Kuo CY, et al.Use of hormone replacement therapy and risk of dementia: a nationwide cohort study.Neurology. 2022;99(17):e1835-e1842. doi:10.1212/WNL.0000000000200960Vinogradova Y, Dening T, Hippisley-Cox J, et al.Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases.BMJ. 2021;374:n2182. doi:10.1136/bmj.n2182Thurston RC, Wu M, Chang YF, et al.Menopausal vasomotor symptoms and white matter hyperintensities in midlife women.Neurology. 2023;100(2):e133-e141. doi:10.1212/WNL.0000000000201401Centers for Disease Control and Prevention.Dementia risk reduction.

7 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Nerattini M, Jett S, Andy C, et al.Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia.Front Aging Neurosci, 2023;15:1260427. doi:10.3389/fnagi.2023.1260427Manson JE, Aragaki AK, Rossouw JE, et al.Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials.JAMA. 2017;318(10):927-938. doi:10.1001/jama.2017.11217Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al.Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study.BMJ. 2019;364:l665. doi:10.1136/bmj.l665Sung YF, Tsai CT, Kuo CY, et al.Use of hormone replacement therapy and risk of dementia: a nationwide cohort study.Neurology. 2022;99(17):e1835-e1842. doi:10.1212/WNL.0000000000200960Vinogradova Y, Dening T, Hippisley-Cox J, et al.Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases.BMJ. 2021;374:n2182. doi:10.1136/bmj.n2182Thurston RC, Wu M, Chang YF, et al.Menopausal vasomotor symptoms and white matter hyperintensities in midlife women.Neurology. 2023;100(2):e133-e141. doi:10.1212/WNL.0000000000201401Centers for Disease Control and Prevention.Dementia risk reduction.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Nerattini M, Jett S, Andy C, et al.Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia.Front Aging Neurosci, 2023;15:1260427. doi:10.3389/fnagi.2023.1260427Manson JE, Aragaki AK, Rossouw JE, et al.Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials.JAMA. 2017;318(10):927-938. doi:10.1001/jama.2017.11217Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al.Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study.BMJ. 2019;364:l665. doi:10.1136/bmj.l665Sung YF, Tsai CT, Kuo CY, et al.Use of hormone replacement therapy and risk of dementia: a nationwide cohort study.Neurology. 2022;99(17):e1835-e1842. doi:10.1212/WNL.0000000000200960Vinogradova Y, Dening T, Hippisley-Cox J, et al.Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases.BMJ. 2021;374:n2182. doi:10.1136/bmj.n2182Thurston RC, Wu M, Chang YF, et al.Menopausal vasomotor symptoms and white matter hyperintensities in midlife women.Neurology. 2023;100(2):e133-e141. doi:10.1212/WNL.0000000000201401Centers for Disease Control and Prevention.Dementia risk reduction.

Nerattini M, Jett S, Andy C, et al.Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia.Front Aging Neurosci, 2023;15:1260427. doi:10.3389/fnagi.2023.1260427

Manson JE, Aragaki AK, Rossouw JE, et al.Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials.JAMA. 2017;318(10):927-938. doi:10.1001/jama.2017.11217

Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al.Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study.BMJ. 2019;364:l665. doi:10.1136/bmj.l665

Sung YF, Tsai CT, Kuo CY, et al.Use of hormone replacement therapy and risk of dementia: a nationwide cohort study.Neurology. 2022;99(17):e1835-e1842. doi:10.1212/WNL.0000000000200960

Vinogradova Y, Dening T, Hippisley-Cox J, et al.Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases.BMJ. 2021;374:n2182. doi:10.1136/bmj.n2182

Thurston RC, Wu M, Chang YF, et al.Menopausal vasomotor symptoms and white matter hyperintensities in midlife women.Neurology. 2023;100(2):e133-e141. doi:10.1212/WNL.0000000000201401

Centers for Disease Control and Prevention.Dementia risk reduction.

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