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A new American study confirms it: hormone therapy is safer when started just after menopause. Taking it after several years could also increase the risk of developing Alzheimer’s disease.
Representing two-thirds of people with Alzheimer’s disease, women are more at risk of developing this cognitive degeneration than men. But a new study, led by researchers at Mass General Brigham, now sheds light on an existing relationship between the risk of Alzheimer’s disease, the age of menopause and the use of hormone therapy. The results, published in JAMA Neurologyindicate that early menopause may be a risk factor for Alzheimer’s disease, but that women who were prescribed hormone therapy early in menopause did not show an increased risk.
Hormone therapy, long suspected of accelerating dementia
A little backtracking is necessary to understand the content of the information. Premature menopause, which occurs spontaneously before age 40 or due to surgery before age 45, has been associated with an increased risk of dementia. Hormone therapy improves many serious menopause-related symptoms and has been speculated that it also prevents cognitive impairment.
However, two decades ago, the Women’s Health Initiative’s landmark study found that use of this hormone therapy was associated with nearly twice the incidence of dementia compared to placebo in women aged 65. and older, possibly due to the initiation of hormone therapy several years after the onset of menopause.
“Hormone therapy is the most reliable way to improve severe menopausal symptoms, but over the past few decades there has been a lack of clarity about how hormone therapy affects the brain”confirmed Rachel Buckley the new study recipe author.
Delayed initiation of hormone therapy increases tau protein levels
Buckley and his team used what’s called positron emission tomography (PET or PET) neuroimaging, a medical imaging test using scintigraphy, to study how the presence of two proteins implicated in the disease dementia Alzheimer’s disease, β-amyloid and tau protein, was linked to age, menopause and the use of hormone therapy.
The researchers used data from the Wisconsin Registry for the Prevention of Alzheimer’s Disease (WRAP), one of the few longitudinal studies of Alzheimer’s disease dementia that includes detailed information on menopause and use of hormone therapy as well as PET neuroimaging.
They analyzed imaging data from 292 adults without cognitive impairment to determine levels of amyloid and tau in seven brain regions. The Tau protein, which is known to be present in greater amounts in women than in men in these brain regions, was the focus of the investigation, as its presence may provide insight into gender-specific aspects of dementia of Alzheimer’s disease and the resulting risks.
- As expected, women had higher tau protein levels than men of the same age, especially in cases where they also had elevated β-amyloid. But the researchers also discovered other elements;
- The association between abnormal β-amyloid levels and tau protein was much stronger in women who had early menopause, even after adjusting for known causes of premature menopause, such as smoking and oophorectomy, and even genetic risk factors for dementia;
- Tau protein levels were elevated especially in the entorhinal and lower temporal regions, which are located close to the memory center of the brain and are known to be involved in the progression of dementia.
Since many women who experience premature menopause use hormone therapy, the researchers also examined whether its use was associated with β-amyloid and tau protein. They observed that the late initiation of hormone therapy – five or more years after menopause – was at the root of this relationship.
Research continues on specific female factors
Main conclusion of this study: the highest levels of Tau, a protein implicated in Alzheimer’s disease, are only observed in users of hormone therapy who reported a long delay between the age at the onset of menopause and the start of hormone therapy. Observational results that support clinical guidelines that hormone therapy should be given near the onset of menopause, but not several years later.
“When it comes to hormone therapy, timing is everything,” said co-author JoAnn Manson, “Our previous results suggested that starting hormone therapy at the onset of menopause, rather than late initiation, provides better outcomes for heart disease, cognitive function and all-cause mortality – and this study suggests that the same goes for tau deposition.”
In the future, the researchers plan to continue studying sex-specific risk factors in Alzheimer’s disease by analyzing biological signatures, including sex hormones, in blood plasma and on the X chromosome. They are also continuing their efforts to understand the unique role that tau plays in women compared to men, its impact on the brain, and why early menopause and late initiation of hormone therapy may be associated with increased tau, even in women without cognitive disorders.