Taking hormone replacement therapy (HRT) for as little as a year can raise the risk of dementia and Alzheimer’s, a study suggests.
Those who used HRT were almost a quarter more likely to develop the disease later in life, according to research involving more than 60,000 Danish women.
The chances increased the longer women were taking the medication, used to treat menopause symptoms including hot flushes, night sweats, mood swings and reduced sex drive.
But experts stressed the findings were observational, meaning other factors could also be behind these women’s higher risks.
The subject is controversial with the scientific community divided over whether HRT can heighten a person’s chances of dementia or actually improve their brain health.
Those who used HRT were almost a quarter more likely to develop the disease later in life, according to research involving more than 60,000 Danish women
Reasons for the apparent contradictory findings may come down to the age when HRT is given, differences in how HRT is used, and different types of HRT used by someone.
To try and fill these knowledge gaps, researchers in Denmark looked at use of combined oestrogen and progestin (synthetic progestogen) therapy and the development of dementia according to type of hormone treatment, duration of use, and age of the user.
They identified 5,589 cases of dementia, at an average age of 70, alongside a further 55,890 women of the same age, who were dementia-free between 2000 and 2018 for comparison.
Some 1,782 (32 per cent) of those who were diagnosed with dementia, had oestrogen-progestin therapy, from around the age of 53 for 3.8 years.
This compared to 16,154 (29 per cent) in the control group, who typically took HRT for 3.6 years.
Once other factors such as education, income, high blood pressure, diabetes, and thyroid disease were taken into account, women who took HRT had a 24 per cent increased rate of developing dementia and Alzheimer’s disease.
This stood true even in women who received treatment at the age of 55 years or younger, according to the findings published in the BMJ.
The risk increased the longer someone took the HRT – starting at 21 per cent after 12 months to 74 per cent at 12 years or more.
Both daily HRT and another form taken 10-14 days a month, were found to have similar results, although the study could not distinguish between tablets and other ways to take hormone therapy, such as patches.
But both progestin-only therapy and vaginal oestrogen had no higher links to dementia, they found.
The University of Copenhagen and Danish Dementia Research Centre researchers could not isolate vascular dementia from other types of dementia, which could provide further insight.
They acknowledged women using HRT may already have a predisposition to both menopausal vasomotor symptoms – such as hot flushes and night sweats – and dementia.
As such, they conclude: ‘Further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women in need of these treatments.’
Experts from Harvard and the Mayo Clinic in the US said while there were strengths to the study – including its large size, good data and varied treatments – observational research like this cannot replace clinical trials.
In a linked editorial, they write ‘confounding factors could be producing a spurious signal for higher dementia risk in younger women using hormone therapy for either a short or long duration.’
‘These findings cannot inform shared decision making about use of hormone therapy for menopausal symptoms.
Dr Susan Kohlhaas, of Alzheimer’s Research UK, said understanding whether HRT plays a role in dementia risk has been a priority for the research community but findings so far have been ‘inconclusive and contradictory’.
She said: ‘This large, nationwide Danish study has found an association between both short- and long-term use of HRT and an increased risk of dementia.
‘Unfortunately, it doesn’t provide a conclusive answer on whether HRT contributes to dementia risk, because the study did not consider some of the other factors known to be involved, such as social isolation, smoking or dietary factors like alcohol.
‘Women need to understand the implications of deciding to take HRT in terms of benefits and risks and, at the moment, as far as dementia is concerned, we’ll need to wait for more research to give clearer answers.
‘In the meantime, people should speak to a qualified healthcare professional if they would like to know more about the known benefits and risks of taking HRT to manage symptoms of the menopause.’
In the accompanying editorial, the US researchers said women with brain fog, hot flashes and sleep disturbances would be likely seek hormone therapy more often than those who do not experience these symptoms.
During the early years of this study, hormone treatment was also seen as a strategy for slowing cognitive decline and was even prescribed for that purpose.
These women prescribed HRT would potentially remain in the health system longer and therefore be diagnosed with dementia earlier than women who were not treated and did not seek medical attention, they said.
Doctors were keen to stress that HRT is an effective and safe treatment for most women with menopause symptoms, adding that any associated risk is ‘small’.
Dr Anita McGrogan, of the University of Bath, noted the study was conducted in Denmark where prescribing practices could be different, adding that more information is needed before generalising these findings to other populations.
She said other risk factors for dementia – such as smoking, physical activity, levels of obesity – have not been addressed.
She said: ‘The prescribing and availability of HRT in Denmark may be different to other countries such as the UK where we know that prescribing and access to HRT differs and may be related to ability to seek this out and pay for the treatment.
‘In the paper, those taking HRT for a long time may have different reasons for this than those taking HRT for a short time (and a different risk of dementia); similarly those with more health conditions may have greater access to healthcare providers and could result in dementia symptoms being more likely to be identified and investigated.’
Dr Sarah-Naomi James, of the Lifelong Health and Ageing at University College London, said the study has both ‘strengths’ and ‘fundamental limitations’ for such a complex issue.
She said: ‘Changes in sleep or mood are very common symptoms of menopause and reasons to seek out HRT; meanwhile we are starting to understand that sleep and mood may play an important role in in the expression and progression of dementia.
‘The best way to understand whether HRT medication itself causes dementia comes from clinical trials, and to date, there is not enough evidence to support a direct link from the medication itself, and this new study alone should not change practice.’
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