Do hormone treatments against the menopause increase the risk of dementia?

A big new one examination in Denmark suggested that hormone therapy – which women use to manage menopausal symptoms – was associated with an increased risk of developing Alzheimer’s disease and other forms of dementia. The study found that the increased risk was even present in women who started treatment at age 55 or younger and short-term users.

The authors of the study cautioned that it was unable to distinguish between the effects of the hormones and the menopausal symptoms that drove women to seek treatment, which are themselves associated with an increased risk of dementia. And in the same journal where the Danish study was published, researchers from the Mayo Clinic and Harvard Medical School published an editorial officetitled “A Causal Link Remains Unlikely,” and notes that the study did not provide evidence that hormone therapy causes Alzheimer’s or other dementias.

Using Denmark’s national register, 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 over 55,800 women who had not been diagnosed with the conditions. The study found that women who used hormones had a 24 percent higher rate of dementia (including Alzheimer’s) than women who did not use hormones.

The results resonate previous studies who have identified some associations between taking hormones for menopausal symptoms and dementia, some of which had limitations similar to the current study. IN 2003The Women’s Health Initiative in the US found that women aged 65 and over on hormone therapy had a greater risk of developing dementia than those on placebo.

“As with any other pharmaceutical treatment, hormone therapy also has side effects,” says Dr. Nelsan Pourhadi, researcher at the Danish Dementia Research Center at Rigshospitalet and lead author of the recent study. “These should be weighed against the benefits.”

Dr. Pourhadi noted that this study and others like it should not alarm women so much that they abandon their hormone treatments. Last week, the North American Menopause Society sent a notice to its members, which are board-certified practitioners, that the study “should not change practice,” said Dr. Stephanie Faubion, Medical Director of NAMS and a Director of NAMS. Mayo Clinic Center for Women’s Health.

The survey, she added, is a source of uncertainty and fear but does not provide much useful information.

Confounding factors

The biggest limitation of the study is that it was observational, said Dr. Faubion, and was therefore unable to establish causation.

Some experts suggest that the true link may be between the symptoms of menopause and dementia. “If you have symptoms of menopause — hot flashes, insomnia, depression, brain fog — you’re more likely to ask for hormones,” said Dr. Lisa Mosconi, director of the Alzheimer’s Prevention Program at Weill Cornell Medicine. Studies have shown that these symptoms have a correlation with the development of Alzheimer’s and other dementias.

For example, hot flashes have been linked to the amount of white matter hyperintensities, which are small lesions in the part of the brain that contains the fibers that connect the neuron cells, said Dr. Mosconi. A study published last year showed that higher frequencies of hot flushes were associated with an increase in the amount of white matter hyperintensities. The lesions “are considered a risk factor for dementia,” said Dr. Mosconi. (It is not clear whether hot flashes cause brain damage, or whether hot flashes and white matter damage share an underlying cause.)

Insomnia in midlife – which may be driven by night sweats – is considered a risk factor to develop neurodegenerative diseases later in life. “Certain proteins, which are the precursors of Alzheimer’s disease, build up during the day in the brain. And when we sleep, there is actually a mechanical wave, like a wave in the ocean, that pushes them out of the brain,” said Dr. Pauline Maki , director of the Women’s Mental Health Research Program at the University of Illinois Chicago. “We know that many women go with their hot flushes untreated for years and have disrupted sleep night after night after night—so that’s an important consideration as well.” Studies have yet to Insomnia specifically caused by night sweats has not been shown to be a risk factor for dementia, but it is an ongoing area of ​​research, Dr. Maki said.

Midlife depression—another common symptom of menopause—is also considered a risk factor to develop dementia later in life.

The Danish study does not clarify whether these underlying problems drove women to seek out hormone treatments in the first place, nor did it consider genetic predisposition to developing Alzheimer’s, which Dr. Pourhadi acknowledged, could be viable explanations for the results.

Conflicting evidence

Just as there are previous studies that show a link between hormone therapy and neurodegenerative diseases, there are a number of studies that show the opposite: that hormone therapy is associated with a reduced risk of developing dementia and Alzheimer’s, said Dr. Mosconi. An observational study, released in 2021looked at nearly 380,000 women’s medical records and found that long-term use of hormone therapy had an apparent “protective effect” against neurodegenerative diseases in general.

And, added Dr. Mosconi, three separate surveys that randomly gave women hormone therapy or a placebo—which is considered the gold standard for determining the effects of drugs—found that hormone use found no negative effects on cognition. These studies, including one published in 2013, looked again at Data from the Women’s Health Initiative in the United States, concluded that starting hormone therapy at age 55 or younger was a significant factor in mitigating adverse effects on cognition.

The experts also noted that the Danish study only looked at the effects of a particular formulation of hormones – estrogen with synthetic progestins – whereas other formulations, such as bio-identical progesterone or, for women who have had a hysterectomy, estrogen alone, may have very different results, said Dr. Faubion. “We’re lumping hormone therapy into a single group, and we really shouldn’t,” she said. “These are all very different chemical compounds and they don’t affect the body in the same way, so we should stop referring to them as a single entity.”