A large study in Denmark suggests that hormone therapy – used by women to manage menopausal symptoms – is associated with an increased risk of developing Alzheimer’s disease and other types of dementia. The work points out that the greater chances are present even in women who started the treatment at age 55 or before and in short-term users.
The authors caution that the study failed to distinguish between the effects of hormones and the very menopausal symptoms that led women to seek treatment, which they themselves linked to a higher risk of dementia. In the same scientific journal where the Danish study came out, researchers from the Mayo Clinic and Harvard Medical School published an editorial titled “A causal link remains unlikely” in which they highlighted that the study did not provide evidence that hormone therapy causes Alzheimer’s or other types of dementia.
Using Denmark’s national registry, the study examined the medical records of more than 5,500 women diagnosed with dementia and Alzheimer’s between 2000 and 2018 and compared them with more than 55,800 women who did not receive these diagnoses. The conclusion was that women who used hormones had a 24% higher rate of dementia (including Alzheimer’s) than women who did not.
The findings echo previous studies that identified some associations between the use of hormones to combat menopausal symptoms and dementia, some of which had limitations similar to the current study.
In 2003, the Women’s Health Initiative in the US concluded that women aged 65 and older who were taking hormone replacement therapy were at greater risk of developing dementia than those taking a placebo.
“As is the case with any pharmaceutical treatment, hormone therapy also has side effects,” says Nelsan Pourhadi, a researcher at the Danish Center for Research on Dementia, Rigshospitalet University Hospital in Copenhagen, and lead author of the recent study. “They must be weighed against the benefits.”
Pourhadi points out that this research and others like it should not worry women to the point of giving up hormone replacement therapy. The North American Menopause Society recently sent a notice to its members who are board-certified physicians saying the study should not change their practice, said Stephanie Faubion, the society’s chief medical officer and director of the Mayo Clinic’s Women’s Health Center.
She adds that work is a source of uncertainty and fear, in addition to not bringing useful information.
Factors that cause uncertainty
The biggest limitation of the study is that it was observational, says Faubion. Therefore, he could not establish a causal link. Some experts suggest that the real connection may be between menopausal symptoms and dementia.
“If you have menopausal symptoms — hot flashes, insomnia, depression, mental confusion — you’re more likely to seek hormone treatment,” says Lisa Mosconi, director of the Alzheimer’s Prevention Program at Weill Cornell Medicine. Studies have already shown that these symptoms have a link with the development of Alzheimer’s and other dementias.
For example, hot flashes have been associated with the amount of white matter hyperintensities, which are small lesions in the part of the brain that contains the fibers that connect neurons, points out Mosconi. A paper published last year showed that higher rates of hot flashes are associated with an increase in the number of white matter hyperintensities.
According to Mosconi, these injuries are considered a risk factor for dementia. (It’s not clear whether hot flashes can harm the brain or whether hot flashes and white matter damage share an underlying cause.)
Midlife insomnia, which can be brought on by night sweats, is considered a risk factor for developing neurodegenerative diseases later in life. “Certain proteins that are precursors of Alzheimer’s disease accumulate in the brain throughout the day,” says Pauline Maki, director of the Women’s Mental Health Research Program at the University of Illinois Chicago.
“When we sleep, there’s a mechanical wave, like an ocean wave, that pushes them out of the brain. We know that many women suffer untreated hot flashes for years and years and sleep poorly night after night. So that’s also a consideration. important.”
Work has not yet shown that insomnia caused specifically by night sweats is a risk factor for dementia, but this is an area that is being studied, says Maki.
Midlife depression, another common symptom of menopause, is also considered a risk factor for developing dementia later in life.
The Danish study does not clarify whether it was precisely these underlying problems that led women to seek hormone treatment, nor did it take into account the genetic predisposition to the development of Alzheimer’s, both of which Pourhadi acknowledges may explain its results.
Translated by Clara Allain