Study linking HRT with dementia risk ‘unhelpful’

Women’s health researchers and clinicians have said a new study linking the use of menopausal hormone treatment (MHT) with an increased risk of developing dementia and Alzheimer’s disease needs to be interpreted cautiously. 
 
The research, led by Dr Nelsan Pourhadi from the Danish Dementia Research Centre, used a nationwide dataset to track more than 55,000 Danish women aged 50–60 over an 18-year period.
 
It found that those who used combined MHT – often referred to as hormone replacement therapy (HRT) – were significantly more likely to be diagnosed with dementia and Alzheimer’s disease.
 
‘Menopausal hormone therapy was positively associated with development of all cause dementia and Alzheimer’s disease, even in women who received treatment at the age of 55 years or younger,’ the authors wrote.
 
‘The increased rate of dementia was similar between continuous and cyclic treatment.’
 
However, Professor Susan Davis, Director of the Monash University Women’s Health Research Program, told newsGP the observational nature of the study means it cannot prove causation, while she also pointed out that much of the findings are not relevant to therapies currently used in Australia.
 
For these reasons, she said the information presented in the study is ‘unhelpful’ in practical terms and should not be used by GPs to counsel women on MHT risks.
 
‘Almost all of the women were on oral estradiol with norethisterone [Kliovance, Kliogest or Trisequens] as this is what was used as HRT in Denmark at that time. These preparations are almost never used in Australia,’ Professor Davis said.
 
‘As [with] all observational studies, despite statistical adjustments for variables such as weight or education etcetera, women who choose to take MHT are different from women who do not.
 
‘The main difference is symptoms. So, while multiple adjustments have been made in the analysis for dementia risk factors such as living alone and education, no consideration was given to the reasons why women take MHT.’
 
She believes that, rather than the therapy itself, menopausal symptoms that lead women to seek hormonal treatment may in part explain why users are at increased risk of cognitive decline.
 
‘Women who take MHT usually do so for vasomotor symptoms [such as] hot flushes and sweats, sleep disturbance and/or mood symptoms,’ Professor Davis said.
 
‘Hot flushes are associated with reduced blood vessel function and brain-specific blood flow, and poor sleep and low mood are both established risk factors for dementia.
 
‘So, the real elephant in the room for this analysis is: is the observed risk of dementia in MHT users due to the use of oral synthetic MHT or due to the reasons why women ever took MHT?
 
‘This has been overlooked.’
 
Professor Martha Hickey, Head of Menopause Services at the University of Melbourne and the Royal Women’s Hospital, also voiced concern over the results and suggests GPs review recent guidelines to help determine MHT indications and risks.
 
‘This is an observational study so cannot prove that MHT causes dementia,’ she said. ‘However, the findings are concerning and reinforce recent guidance from the United States Preventive Task Force [2022] that HRT should not be used for the prevention of chronic conditions, including dementia.’
 
Previous research looking at the use of MHT and the risk of developing dementia has presented conflicting results, with other studies reporting either no change in risk or decreased risk of cognitive decline.
 
Dr Stephanie Daly, coordinator of the RACGP Specific Interests dementia subgroup, says gender bias within the research landscape has contributed to a lack of understanding regarding hormones and cognitive function.
 
She encourages GPs to utilise dementia risk assessment tools such as CogDRisk to help concerned patients identify risk reduction strategies that may offset any potential risk posed by MHT.
 
‘Whilst this study looks at women on HRT, it is still failing to understand the root cause of women’s increased risk,’ she told newsGP.
 
‘We know that women in midlife also experience significant stress and poor-quality health as a result of menopausal symptoms, which may lead to poorer health choices such as increased alcohol or poor diet or lack of exercise. All of these increase your risk of Alzheimer’s disease and dementia.
 
‘The bottom line is more research is needed. HRT alone is unlikely to be the single factor and women need to feel able to treat menopausal symptoms if they are impacting on their daily life.’
 
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