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Hormone therapy is commonly prescribed to alleviate menopausal symptoms such as hot flashes and night sweats. However, there has long been debate among scientists about whether it influences the risk of developing dementia. Recent research adds a new perspective by suggesting that a biomarker associated with Alzheimer’s disease might help identify women more susceptible to dementia when using certain hormone therapies.
The study analyzed blood samples from 2,766 women who participated in a clinical trial between 1996 and 1999. Researchers tracked these women until 2021 to determine if initial levels of plasma p-tau217, a biomarker linked to Alzheimer’s, were connected to the development of dementia, and whether this relationship varied based on hormone therapy use.
Plasma p-tau217 is a biological indicator of Alzheimer’s; elevated levels in the blood are associated with brain changes characteristic of the disease. The women in the study received either a placebo or two types of hormone therapy: one combining estrogen and progesterone, often prescribed for women with intact wombs, and another with estrogen alone, typically given after hysterectomy.
Women with higher biomarker levels faced a significantly increased risk of dementia. Specifically, those with elevated p-tau217 levels at the start had roughly three times the risk. The risk was even higher among women on combined hormone therapy—about four times greater—compared to those taking a placebo or estrogen-only therapy. This heightened risk was most pronounced in women over 70, white women, and carriers of the APOE4 gene variant, which increases Alzheimer’s risk.
Scientists believe the differences between hormone therapies may relate to how hormones interact with the brain’s biology. Estrogen is thought to protect brain cells and influence the processing of amyloid and tau proteins, both of which accumulate in Alzheimer’s. Progesterone’s role in modifying these effects is not yet fully understood.
Prior studies from the Women’s Health Initiative, a large set of clinical trials, initially linked hormone therapy after age 65 with a doubled risk of dementia and observed that its risks outweighed potential benefits. These findings led many women to discontinue hormone therapy. More recent research shows that starting hormone treatment closer to menopause—around age 50—may not impact cognitive function significantly over a span of several years and may be relatively safe.
However, initiating hormone therapy later in life appears to have different effects. Women who started treatment after age 65 generally experienced cognitive decline, with MRI scans indicating shrinkage in brain areas like the hippocampus, which is often affected in Alzheimer’s disease. This suggests that hormone therapy later in life could exacerbate existing brain vulnerabilities.
The new findings reinforce previous evidence indicating that combining estrogen with progestin later in life may increase Alzheimer’s risk, unlike estrogen alone. Additionally, severe menopausal symptoms such as hot flashes and night sweats—especially when they occur late in life—are linked to higher dementia risk and often lead to hormone therapy use, which complicates the picture.
These insights imply that hormone therapy itself doesn’t directly cause dementia. Instead, biological risk markers and individual factors—such as age at treatment onset and genetic predispositions—may determine vulnerability. Starting combined hormone therapy late in life, particularly after age 65, could raise the likelihood of cognitive decline for some women. Conversely, short-term use around menopause—less than five years—has not been associated with increased dementia risk.
Most women are prescribed hormone therapy for a limited time to manage menopausal symptoms, which generally doesn’t elevate their risk of dementia when initiated around age 50. For those concerned about brain health, exploring additional studies on topics like vitamin B9 deficiency’s link to dementia or how cranberries might support memory could prove beneficial. Recent research also highlights that certain heartburn medications may raise dementia risk, while following diets like the MIND diet could help protect cognitive function.
— Eef Hogervorst, The Conversation
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