Does HRT prevent dementia? Or cause it? Experts give the answer

Does HRT prevent dementia? Or cause it? Women’s health experts PROF ANNICE MUKHERJEE and PROF JOYCE HARPER have studied ALL the research to cut through the hype and give the definitive answer

It’s hard to know what to believe when it comes to HRT and dementia. Does the treatment have the unexpected benefit of protecting the brain in older age? Or could it have the opposite effect?

One study, which made headlines last month, suggested HRT – taken by millions of women in mid-life to fight the symptoms of menopause – could increase the risk of dementia by a quarter.

The news provoked understandable panic and prompted fierce debate.

Menopause campaigners and some private doctors rushed to play down the findings, pointing out that it involved women who took old-style HRT pills.

They also highlighted other studies that suggested newer forms of HRT – taken in gel, patch or spray form – can significantly reduce the risk of dementia.

Some have gone as far as to say that the menopause should be classed as a neurological disorder – like Parkinson’s – which can be treated by replacing the sex hormones which deplete as we age.

So are they right?

It’s hard to know what to believe when it comes to HRT and dementia. Does the treatment have the unexpected benefit of protecting the brain in older age? Or could it have the opposite effect? (stock photo)

Professor Annice Mukherjee

A Manchester-based hormone doctor with more than 30 years of experience, she is an expert on diabetes, metabolic and reproductive health. She authored the bestselling Complete Guide To The Menopause.

Professor Joyce Harper

A reproductive health expert at University College London, she is the author of more than 200 scientific publications and three fertility books, and also hosts the health podcast Why Didn’t Anyone Tell Me This?

As two scientists – one medic and one researcher – who have dedicated our careers to women’s health, we trawled through the most significant research on the subject to get to the bottom of the matter – and our conclusions may surprise you.

It’s important to urge you not to panic about the most recent report linking hormone therapy to an increased risk of dementia. There is absolutely no reason to stop taking HRT if it is helping you with your menopause symptoms.

While a number of studies now appear to suggest a very slightly raised risk of dementia among women who take some forms of HRT, no study has ever proven that one thing causes the other.

Most of this research is what we call observational, which means researchers look at thousands of medical records to see who took HRT, including which type, and then work out whether they developed dementia. The latest study was no different. Carried out by scientists in Denmark, it looked at the records of 61,000 women across an 18-year period. It found those who had taken HRT – specifically tablets containing a combination of female sex hormones oestrogen and progesterone – were 24 per cent more likely to develop either dementia or Alzheimer’s disease than those of a similar age who had not.

The risk increased the longer women took the medication – but that risk perhaps isn’t as scary as you might think.

The lead researcher, Dr Nelsan Pourhardi, told Radio 4’s Woman’s Hour that it was at least ‘possible’ that women who require HRT and experience the most debilitating menopause symptoms – such as hot flushes and insomnia – are also predisposed to dementia.

He added that there was also an average of 18 years between women getting their first HRT prescription and being diagnosed with dementia, regardless of whether they took HRT for a year or more than 12 years. As a consequence, there was no ‘immediate effect’ from the hormones.

Importantly, the women who developed dementia were more likely to have other risk factors which could also have influenced the results. They had higher blood pressure and type 2 diabetes, and were more likely to come from poorer socioeconomic backgrounds than those who didn’t develop dementia.

Even the authors of the research said that their results did not prove HRT caused dementia.

Other studies that have uncovered a possible link found the risk may specifically relate to certain types of HRT and dementia, but even these are conflicting. One large UK study, published in the British Medical Journal in 2021, involving over 600,000 participants – again, based on medical records – initially found a slightly increased risk of dementia among women who took HRT.

Once the researchers took other risk factors into account, such as body weight, alcohol consumption and smoking habits, the association disappeared.

However, it did find an apparent increased risk of Alzheimer’s disease – the most common form of dementia – but only in women who took combined oestrogen and progesterone for between five and nine years.

It concluded that this risk increased by about 1.2 per cent for every year of HRT use. But this is still small, and equivalent to an extra four cases of the disease in every 10,000 women taking the medication for this length of time.

Another good study from Finland found a similarly increased risk of Alzheimer’s disease from taking combined HRT. But, contrary to the UK study, it discovered the same risk with oestrogen-only HRT, too.

But we can’t rely on this as proof that HRT is the cause of the problem, because other studies suggest the opposite is true.

A US research paper published in 2021, which is frequently quoted by HRT advocates, showed a dramatic 58 per cent reduction in dementia among women who take the most modern and frequently prescribed form of HRT known as ‘body identical’ HR.

This is a type of the treatment which has a chemical composition that is very similar to the body’s own hormones.

Led by researchers from the University of Arizona, it was even referenced in Davina McCall’s 2021 documentary Sex, Mind And The Menopause.

At first glance it appears to be great news, implying that risks of dementia were associated with older versions of the medication. But this is also just an observational study.

Ironically, it’s also worth pointing out that some campaigners dismissed the Danish study, which found a link between HRT and dementia, on the basis that it was observational, but have embraced the findings of this one despite its methods being so similar.

And as experts have pointed out, the women in this study were already significantly healthier than most.

The participants were wealthy enough to get their medication via America’s private healthcare system. Studies show that those with higher incomes – who are therefore able to afford insurance – have a lower than average risk of some of the world’s biggest killers, including dementia.

The women in this study also had good heart health.

As Prof Susan Davis, one of the world’s leading HRT experts from Monash University in Melbourne, explains: ‘At the time, HRT wasn’t being prescribed in the US for women at risk of cardiovascular disease because it was believed that it could increase the risk of heart attacks and stroke.’

It’s well established that a healthier heart means a lower risk of developing dementia. So it is logical that the women in this study deemed healthy enough to get HRT would be less likely to get dementia than other women .

Of course, this doesn’t mean there is no protective benefit. There are early signs it might benefit some people who are already at increased genetic risk of Alzheimer’s. Several studies suggest that HRT, particularly oestrogen-only, may protect against the changes in the brain that lead to the disease in women who carry the ‘Alzheimer’s gene’ known as APOE4.

This increases the risk of developing the condition and causes symptoms to appear at a younger age.

One US study investigated the effects of either oral or transdermal (cream or gel-based) oestrogen on the brain. Over seven years, it found women with the APOE4 gene who used it maintained their brain volume and had fewer of the plaques which are a tell-tale sign of Alzheimer’s.

But this is far from conclusive: not all people who have these plaques develop Alzheimer’s, and none of those in the study had dementia by the time the findings were published.

Similar signs have been picked up by researchers from the University of East Anglia. They found women with the APOE4 gene were best protected if they started taking HRT during perimenopause – the period leading up to the menopause.

The researchers said more work needed to be done before conclusions could be drawn.

They also added that the potential protective effect would only materialise in a small number of women – and advised against all women taking HRT in a bid to avoid dementia.

And it’s worth knowing that some pro-HRT studies are backed by a significant number of pharmaceutical companies, which means they should be treated with some scepticism.

It’s a conflict of interests and such studies only tend to publish positive results.

The conflicting evidence makes it easy to cherry-pick studies to back up any particular claim – for instance, that HRT will dementia-proof you in old age.

This is what some pro-HRT campaigners have been doing for several years. The truth is ultimately far more boring: we just don’t have any proof either way.

One reason why the research may be conflicting is because the risk may differ depending on when a woman takes HRT.

Studies have shown that women who take HRT earlier, for instance in the perimenopausal period, are less likely to develop dementia than women who didn’t. However, taking it later on in life could increase the risk (stock photo)

As we get older, oestrogen can negatively affect the blood vessels that supply the heart, which raises the risk of dementia (stock photo)

Studies have shown that women who take HRT earlier, for instance in the perimenopausal period, are less likely to develop dementia than women who didn’t.

However, taking it later on in life could increase the risk.

As we get older, oestrogen can negatively affect the blood vessels that supply the heart, which raises the risk of dementia. Perhaps it is for this reason that some people will be at greater risk of dementia from HRT, and others will not.

But experts are still yet to find solid proof for this theory.

Looking at the evidence as a whole, there is nothing either way that can tell you for certain whether HRT increases or decreases the risk of dementia.

In our view, anyone who tells you different is being misleading.

A recent review of all of the studies simply acknowledged that existing findings on the topic were ‘contradicting’, likely because studies use a mixture of women with different risk factors for the disease.

The evidence on HRT protecting bone strength is much stronger than that for dementia, but we still don’t give it to every woman to prevent osteoporosis because of the delicate balance of risks and benefits.

In other words, in some women, the benefit is not worth the risks.

To prevent one fracture, you might have to treat 35,000 women, but maybe 100 of them will get breast cancer, 50 might have a heart attack and some might develop dementia.

Attempting to rebrand menopause as a neurological disorder does no one any good, either. That is not based on facts or science, and it will only scare those who, for various medical reasons, may be unable to take HRT. It could also encourage some women to start taking medication for the wrong reasons.

But we do have many other, evidence-based ways to reduce your risk from dementia.

For a start, maintain a healthy weight, follow a balanced Mediterranean-style diet, get enough exercise, quit smoking and don’t drink too much. Reduce your blood pressure and cholesterol and watch your blood sugar so you don’t end up with type 2 diabetes. And if you’re taking HRT and it’s working to ease your menopause symptoms, there’s no reason to stop taking it.

However, if you’re hoping it’ll help you prevent dementia, the jury is still out.

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