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.
