Menopause, hormones and the brain: how hormone therapy could help protect against Alzheimer’s
As dementia and other neurodegenerative diseases become more common worldwide, researchers are searching urgently for ways to protect the brain as we age. One area attracting growing attention is hormones, particularly the role of hormone therapy during and after menopause.
This interest is partly driven by the fact that women develop Alzheimer’s disease more often than men, especially after midlife, suggesting that hormonal changes around menopause may influence long-term brain health.
Our research has focused on tibolone, a synthetic form of hormone therapy prescribed to relieve menopausal symptoms such as hot flashes and poor sleep. While it is commonly prescribed to ease menopausal symptoms, our findings suggest tibolone may also offer important protection for the brain.
In laboratory studies, tibolone helped brain cells survive under stressful conditions. These included reduced glucose use (glucose is the brain’s main fuel) and the build-up of saturated fats such as palmitic acid, which is often higher in people with obesity. Both reduced glucose use and excess saturated fat are known risk factors for cognitive decline and neurological diseases.
Tibolone appears to protect brain cells in several ways. It activates protective proteins, reduces inflammation and limits damage from free radicals. Free radicals are unstable molecules produced during normal energy production or when the body is exposed to pollution or cigarette smoke. They behave like tiny sparks inside cells, damaging structures unless neutralised.
Why women are at higher risk
Alzheimer’s disease affects women far more than men, by roughly three to one. Even after accounting for women’s longer life expectancy, their risk remains around 12% higher.
This gap likely reflects a combination of genetic, hormonal and social factors. Certain genes, including the APOE ε4 variant, a version of a gene linked to how the brain processes fats and clears harmful proteins, are associated with a higher risk of Alzheimer’s. Other genes on the second X chromosome may also contribute. Differences in reproductive history, number of pregnancies and access to education and healthcare also play a role, because these factors influence lifelong brain health, cardiovascular risk and how early cognitive problems are detected and treated.
However, hormonal changes around menopause appear to be especially important. When menstruation ends, levels of estradiol (the main form of oestrogen) fall sharply, while follicle-stimulating hormone rises. Both changes are linked to cognitive decline and Alzheimer’s disease.
Many women experience the everyday effects of these shifts: forgetfulness, difficulty concentrating, slower thinking, low mood, poor sleep and reduced motivation. Estradiol normally helps brain cells use energy efficiently. When levels drop, the brain uses glucose less effectively, producing a metabolic pattern similar to that seen in early Alzheimer’s.
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Estradiol also helps regulate fat distribution and cholesterol. When it declines, women often gain visceral fat around the abdomen. This type of fat releases inflammatory chemicals that can damage blood vessels and the brain. The loss of estradiol’s natural anti-inflammatory effects further increases the risk of metabolic syndrome (a cluster of conditions including high blood pressure and insulin resistance), cognitive decline and dementia.
Can hormone therapy help?
These findings have led researchers to ask whether hormone therapy might offset some of this risk.
Hormone therapy usually combines oestrogen and progesterone and is widely prescribed to relieve hot flashes, insomnia and mood changes. It can also improve mood and reduce depression, which indirectly supports cognitive health.
Until the early 2000s, millions of women used hormone therapy and reported benefits. Then, in 2002, the Women’s Health Initiative (WHI) trial reported a higher risk of breast cancer and cardiovascular events in women taking combined hormones. Headlines warning that hormone therapy “increases cancer risk” led many women to stop treatment or avoid it altogether.
Read more: Busting brain myths: The evolving story of menopause hormone therapy and cognitive health
The WHI memory studies also found that starting hormone therapy at age 65 or older did not protect cognition and was linked to a higher risk of dementia. Later analyses revealed an important nuance: timing matters.
Lower lifetime exposure to oestrogen is linked to faster cognitive decline and greater build-up of Alzheimer’s-related changes in the brain. Women who enter menopause early (before about age 45 to 50) face higher risks of Alzheimer’s and more pronounced memory loss. Surgical menopause, caused by removal of both ovaries, leads to a sudden drop in oestrogen and can trigger noticeable problems with memory and attention, particularly in younger women.
Growing awareness of the link between menopause and brain health is beginning to shape public policy.
In a landmark move, Ireland introduced a programme in June 2025 providing hormone therapy free of charge. Removing cost barriers allows women to start treatment earlier and continue it consistently, conditions that may maximise its benefits.
Elsewhere in Europe, access varies. In England, women who do not qualify for free NHS prescriptions can purchase an annual hormone therapy prepayment certificate for £19.80. Prescriptions are free in Scotland, Wales and Northern Ireland, while France and Spain partially reimburse costs through national insurance.
Read more: Menopause: our study revealed how it affects the brain, cognition and mental health
Given tibolone’s protective profile, reducing financial barriers could improve access and support larger clinical trials to test its effects on brain health.
Hormone therapy is not a guaranteed way to prevent dementia. The strongest protection still comes from a broad approach: managing menopausal symptoms effectively, possibly with hormone therapy, while also controlling blood pressure, cholesterol and diabetes, staying physically active, sleeping well and avoiding smoking.
Women face a higher lifetime risk of Alzheimer’s because of intertwined genetic, hormonal and social factors. Hormone therapy, particularly when started around menopause, may help protect cognitive function as well as relieve symptoms. Alongside a healthy lifestyle, it offers one promising tool for supporting brain health and narrowing the gender gap in dementia risk.
George Barreto receives funding from Research Ireland.
Miguel G. Borda does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.