There is no strong evidence that replenishing hormones after menopause is linked to dementia, according to a sweeping meta-analysis.
The systematic review is the most rigorous investigation to date of the link between cognitive health and menopause hormone therapy (MHT), also known as hormone replacement therapy (HRT), which seeks to replenish ovarian hormones after the cessation of menstruation.
The study, which covers the health data of more than a million women, was commissioned by the World Health Organization (WHO), which currently provides no specific guidance on dementia and MHT, despite recent controversy.
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"This review will help to inform the upcoming WHO guidelines on reducing the risk of cognitive decline and dementia, which are expected to be released in 2026," says senior author Aimee Spector, a clinical psychologist from University College London (UCL).
Experts generally agree that when prescribed properly, hormone replacement therapy is safe and very effective at treating symptoms of menopause, such as hot flashes, night sweats, poor sleep, low libido, and osteoporosis.
The quality of life benefits for the average healthy person generally outweigh the potential risks of MHT, which can include a very small increased risk of blood clots and a slightly increased chance of breast cancer for those with specific risk factors. But these risk increases still depend on the timing, hormone mix and even delivery method of the therapy.
While some studies suggest that menopause is linked to dementia, and that hormone changes in life are associated with changes in the brain, it is not yet clear if MHT helps or hinders cognition as a person ages.
"Menopause hormone therapy is widely used to manage menopausal symptoms, yet its impact on memory, cognition, and dementia risk remains one of the most debated issues in women's health," says lead author and aging cognition researcher Melissa Melville from UCL.
"Conflicting research and concerns about potential harms have fueled public and clinical debate, leaving women and clinicians unsure whether menopause hormone therapy might raise or reduce their risk of dementia."
Ultimately, the current analysis was unable to find any strong evidence that MHT impacts the risk of dementia, either for better or worse.
Most studies were observational only, which means they can't prove cause or effect. Their results show inconsistent and slight associations with dementia, some positive and some negative, but all with very low certainty.
Across these studies, MHT formulations, doses, and prescription timing varied considerably, making comparisons difficult. Women who start MHT formulations after the age of 60, for instance, may face more risks, and the medication may not be as advisable.
Only one randomized controlled trial found that estrogen-only MHT products may increase the risk of dementia in women over the age of 65. But the certainty of those results, the authors of the review say, is "low due to serious imprecision."
"The absolute risk difference was 6.27 additional cases per 1000 women, indicating little to no difference in dementia risk when initiated after age 65 years," add Melville and colleagues.
The findings support a 2024 Lancet Commission on dementia, which also found insufficient evidence to suggest MHT increases or decreases the risk of dementia.
The results also align with a November announcement by the US Food and Drug Administration (FDA) detailing plans to remove the 'black box' warnings on MHT products, which had previously cautioned about an increased risk of dementia.
In this same announcement, the FDA cited one study that suggested HRT products might actually reduce the risk of Alzheimer's. But this new review suggests that claim is not supported by robust evidence.
Nevertheless, the European Society of Human Reproduction and Embryology 2024 guidelines also recommend MHT for the prevention of dementia if someone has experienced premature ovarian insufficiency.
"Overall, available evidence to date does not support MHT solely for risk reduction of dementia nor does MHT increase dementia risk," conclude Melville and colleagues.
"There is a need for further high-quality research to clarify the role of MHT in relation to dementia."
The review research team specifically calls for further data on those who enter menopause prematurely, either because of a hysterectomy, where the uterus is surgically removed, or an oophorectomy, where one or both of the ovaries are removed.
Recently, some studies have shown that having an oophorectomy under the age of 50 can come with a serious risk to the brain. A hysterectomy, meanwhile, is tied to a higher risk of stroke. There is insufficient data to compare these subgroups as it stands.
Menopause research is seriously underfunded worldwide.
After some initial studies linked MHT to adverse health outcomes, prescriptions around the globe dropped sharply, despite the serious limitations of these findings and the many caveats that later emerged.
It will take time and research to build trust in this life-changing therapy once again.
The study was published in the journal Healthy Longevity.