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expert reaction to study looking at long-term hormone therapy in postmenopausal women and Alzheimer’s disease risk

Research published in the BMJ shows that long term use of systemic hormone therapy might be accompanied with an overall increased risk of Alzheimer’s disease.

Prof Tara Spires-Jones, UK Dementia Research Institute Programme Lead and Deputy Director of the Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study by Dr Mikkola and colleagues in Finland found an association between use of hormone therapy in women and an increase in risk of developing Alzheimer’s disease.  Researchers looked at data from around 85,000 women who developed Alzheimer’s between 1999 and 2013 and compared then to the same number of women who did not develop Alzheimer’s.

“This study is important because it adds to what we know about the role of hormones in developing Alzheimer’s disease, however, this study has several limitations.  Observational studies like this cannot determine whether the association with increase dementia risk was due to hormone therapy or other possibly related factors.  In this study, scientists did not have information about potentially important factors like hysterectomy or well-established risk factors for Alzheimer’s like diabetes, cardiovascular factors, and inheritance of genes that increase risk of Alzheimer’s.

“When other scientists have conducted randomized control trials to directly test whether hormone therapy increases risk, there have been conflicting results with some studies indicating no effect of hormone therapy on cognitive function and one study indicating that in women over 65, hormone therapy increased risk of dementia.  So, while this is an interesting study of a large number of women, it does not conclusively prove a link between hormone therapy and Alzheimer’s disease.  We need more experiments to find out whether hormone therapy affects disease risk and importantly at what age any effects are most pronounced.”

Dr David Reynolds, Chief Scientific Officer from Alzheimer’s Research UK said:

“Previous research into hormone therapy and Alzheimer’s risk is mixed and inconclusive.

“Studies that look for patterns in medical records can be extremely useful for identifying factors linked with Alzheimer’s risk, but they can’t tell us the root cause of that link.

“While this large study suggests that women who received some forms of hormone therapy were slightly more likely to be diagnosed with Alzheimer’s, it doesn’t show that hormone therapy is responsible for this increased risk.

“Hormone therapy provides important benefits to many women, helping to combat the symptoms that menopause can bring.  Women who require hormone therapy should not be put off by these results, and anyone concerned about the effects of this treatment should speak to their doctor.”

Dr Channa Jayasena, Clinical Senior Lecturer and Consultant in Reproductive Endocrinology and Andrology, said:

“Oestrogen has powerful effects on the brain.  But I am surprised by the results of this study, since other studies have found that HRT actually improves cognitive function.  HRT plays a vital role to treat menopausal women with debilitating hot flushes or other severe symptoms.  The results of this study should not change the way HRT is prescribed or viewed.  Even if HRT increased the future risk of Alzheimer’s, several years of treatment would be needed, and the effect is marginal.  The study uses a national database containing information on everyone in Finland.  This approach has been used successfully for other diseases, but cannot tell you why two things such as HRT and Alzheimer’s may be linked to each other.”

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“What is fascinating is how this study focuses on women – a hot topic in dementia research with twice as many women living with the condition.  There are still many unanswered questions before we can fully understand risk particularly for women.  But with one person developing symptoms of dementia every three minutes in the UK, this is an area our researchers are working hard on.

“This large and well-controlled study adds to a conflicting pool of evidence around the effect of hormone therapy on risk of developing dementia.  In this case, some women on hormone therapy had a slight increased risk of Alzheimer’s, but this increase was so small it shouldn’t cause alarm or deter women from the their prescribed treatment – particularly those taking it over a short period of time.”

‘Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study’ by Hanna Savolainen-Peltonen et al. was published in the BMJ at 23:30 UK time on Wednesday 6 March 2019.

Declared interests

Prof Tara Spires-Jones: “I have no conflicts of interest with the current study.  For completeness my full list of funding follows: I receive research funding is from the EU, UK Dementia Research Institute, Alzheimer’s Research UK, Alzheimer’s Society, MND Scotland, the Wellcome Trust, and three collaborating pharmaceutical companies.  I am also on the Scientific Advisory board of the company Cognition Therapeutics.”

Dr David Reynolds: “No interests to declare.”

Dr Channa Jayasena: “CJ holds a patent with Imperial Innovations and has received grant funding from the Medical Research Council (UK) for the treatment of menopausal hot flushes using neurokinin 3 receptor antagonists.”

None others received.

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