Early menopause may be a risk factor for Alzheimer’s disease, but women who begin hormone therapy (HT) at the start of menopause do not have an increased risk of the condition, new research has suggested.
Women are more likely than men to develop Alzheimer’s and they make up two-thirds of the population living with it.
A new small study sheds light on the relationship between the risk of Alzheimer’s and age of menopause and use of HT, also known as hormone replacement therapy (HRT).
The findings indicate a later start to hormone therapy may increase the risk of Alzheimer’s disease.
These observational findings support clinical guidelines that state hormone therapy should be administered close to menopause onset, but not several years after— Gillian Coughlan, Massachusetts General Hospital
Researchers say the findings support guidelines that suggest hormone therapy should begin close to the start of menopause, and not several years later.
Corresponding author Rachel Buckley, of the Department of Neurology at Massachusetts General Hospital (MGH), US, said: “HT is the most reliable way to ameliorate severe menopause symptoms, but over the last few decades there has been a lack of clarity on how HT affects the brain.
“We found that the highest levels of tau, a protein involved in Alzheimer’s disease, were only observed in hormone therapy users who reported a long delay between age at menopause onset and their initiation of hormone therapy.
“The idea that tau deposition may underlie the association between late hormone therapy intervention and Alzheimer’s disease dementia was a huge finding, something that hadn’t been seen before.”
Previous studies have linked premature menopause, defined as menopause that occurs spontaneously before the age of 40 or due to surgical intervention before the age of 45, with increased risk of Alzheimer’s disease dementia.
Hormone therapy is used to improve severe symptoms related to menopause and past research has also suggested it could prevent cognitive impairment.
Two decades ago, the women’s health initiative (WHI) study found HT use was associated with a nearly two-fold higher incidence of dementia compared to a placebo among women aged 65 years and older, possibly due to the initiation of HT many years after menopause onset.
For the new study, researchers used brain imaging to study how the presence of two proteins involved in Alzheimer’s dementia, beta-amyloid and tau, related to age at menopause and HT use.
The researchers looked at scans from 292 cognitively unimpaired adults to determine levels of amyloid and tau in seven regions of the brain.
According to the findings, women had greater levels of tau compared to men of the same age, especially in cases where they also had elevated beta-amyloid.
However, the researchers also found the association between abnormal levels of the proteins was much stronger in women who had earlier menopause onset.
Tau levels were high in the regions of the brain close to the memory-centre of the brain and areas that are known to be involved in the progression of Alzheimer’s dementia.
Given that many women who undergo premature menopause use HT, researchers examined whether it was linked with the two proteins.
While the study confirmed this association, researchers found that starting the therapy late – five years or more after menopause – drove this relationship.
Many women in the late-HT-initiation group started therapy close to a decade after menopause.
First author Gillian Coughlan, of the MGH Department of Neurology, said: “Up to 10% of women experience premature or early menopause, and our findings suggest that earlier age at menopause may be a risk factor for Alzheimer’s disease dementia.
“Hormone therapy can have negative effects on cognition, but only if initiated several years after age at menopause.
“These observational findings support clinical guidelines that state hormone therapy should be administered close to menopause onset, but not several years after.”
The findings are published in Jama Neurology.
Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said: “While we understand that news like this can seem concerning, this study doesn’t show that hormone therapy causes Alzheimer’s.
“The researchers didn’t look at whether the participants went on to develop symptoms of dementia and we can’t be sure of cause and effect in this kind of research.”
She added: “Hormone therapy provides important benefits to many women, helping to combat the symptoms that menopause can bring.
“Women who take, or are thinking of taking, hormone therapy should not be put off by these results and anyone concerned about the effects of this treatment should speak to their doctor.”
In January, a study by UEA researchers suggested that HRT may help prevent Alzheimer’s in women at risk of developing the condition.
According to the findings, the use of HRT, which helps control symptoms of the menopause, is associated with better memory, cognitive function and larger brain volumes in later life in women carrying a gene called APOE4.
About a quarter of women in the UK are thought to carry the APOE4 gene and Alzheimer’s is more common in women than men.
The researchers found that HRT was most effective when given during perimenopause – where symptoms build up months or years before periods actually stop – and could lead to brains that appear several years younger.
