HRT and dementia risk: what a new UK study means for women in midlife

Could HRT reduce dementia risk? What a new UK study really found.

At 50, I’m interested in what is happening inside my body than on the outside. Perimenopause has a way of making you notice things you once took for granted, from sleep to memory and mood. So when I saw a new study on HRT and dementia risk, I wanted to look beyond the headline and see what it actually found.

I’ve never been particularly interested in chasing eternal youth. What does interest me is staying strong, healthy and reasonably sharp as I get older.

That makes women’s health particularly interesting to me now. We spend so much of our lives talking about periods, pregnancy, fertility and then, suddenly, menopause. But what happens to our health in the decades that follow?

This particular study caught my attention because it looked at whether women who had used hormone replacement therapy (HRT) were less likely to develop dementia. The headline sounds encouraging. But, as I’ve learned from reading rather too many health stories over the years, the headline isn’t always the whole story.

What does a large UK study actually tell us about HRT, dementia risk and women in midlife?

Researchers from the University of East Anglia and the University of Exeter looked at health data from 183,450 postmenopausal women in the UK Biobank.

The women were followed for an average of 13.3 years. During that time, almost 4,000 cases of dementia were recorded.

The researchers found that HRT use was associated with:

• around a 10% lower observed risk of dementia overall
• around a 16% lower observed risk of Alzheimer’s disease
• larger reductions in some groups of women

The strongest association was seen among women who had experienced a surgical menopause, such as women who had their ovaries removed. In that group, HRT use was associated with around a 26% lower risk of dementia.

The researchers also found that women who had experienced naturally lower lifetime exposure to oestrogen appeared to have a greater reduction in dementia risk. And then there was genetics. The association was stronger among women carrying APOE4, a genetic variant associated with a higher risk of Alzheimer’s disease. That’s interesting, but there is a rather important word doing a lot of work here.

No, and I think this is where we need to slow down before the headline gets ahead of the evidence. This was an observational study. Researchers looked at what happened to a large group of women and examined the relationship between HRT use and dementia. They found a link. They did not prove that HRT caused the lower dementia risk.

Researchers have found an interesting link between HRT use and lower dementia risk, and that link appears to vary between different groups of women.

It’s less exciting than the headline. It’s also much more honest.

This is the part that interests me because menopause is often reduced to a list of symptoms from hot flushes to night sweats, but hormones affect much more than our reproductive system. Oestrogen receptors are found throughout the body, including in the brain.

During perimenopause and menopause, changing hormone levels can coincide with changes in things such as sleep, mood, concentration and memory.

• brain fog
• difficulty concentrating
• changes in memory
• poor sleep
• mood changes

I’ve certainly had days when my brain seems to be running on a slightly different operating system.

Forgetting why you’ve walked into the kitchen is irritating. It is not, on its own, evidence that you’re developing dementia. But when dementia has touched your own family, it is perhaps understandable that the thought can linger. It certainly did for me.

Another finding that caught my eye was the apparent importance of when women started HRT. Women who began HRT between the ages of 46 and 56 showed the greatest reduction in dementia risk in this study.

Again, that is an association, not evidence that starting HRT within that age range will prevent dementia.

This fits with what researchers call the “critical window” hypothesis. The idea is that there may be a period around menopause when hormone therapy affects the brain differently from when it is started much later. But this study doesn’t prove that theory. It simply adds another piece of evidence to a much bigger scientific conversation.

The findings around surgical menopause were particularly interesting. When the ovaries are removed, the fall in ovarian hormones can happen much more abruptly than during a natural menopause. In this study, women who had experienced surgical menopause and used HRT had around a 26% lower risk of dementia than those who had not used HRT.

A woman who reaches menopause naturally at 51 is having a different experience from a woman whose ovaries are removed at 42. It makes sense that researchers would want to understand those differences.

The genetic part of the research is fascinating, although it is also an area where I’d be especially cautious about drawing conclusions. APOE4 is a genetic variant associated with an increased risk of Alzheimer’s disease. The study found that the association between HRT use and lower dementia risk was stronger among women carrying APOE4. That raises an interesting question.

Could our understanding of menopause eventually become more individualised? Perhaps the future will involve considering things such as age, menopause type, genetics and individual health alongside symptoms when women and healthcare professionals discuss treatment. But that’s a possibility for future research. It isn’t a recommendation to take HRT because you’ve read about APOE4 on the internet.

This is actually the bit I care about most. For years, menopause has often been discussed as something women need to get through. Manage the hot flushes. Sleep when you can. Try not to snap at everyone. Eat less. Exercise more. Keep calm and carry on.

I’m increasingly uncomfortable with that version of the story. Women’s health doesn’t happen in separate little boxes. Hormones, sleep, muscle, bones, cardiovascular health, mood and cognition are all part of the same body. And midlife is a point when many of us start thinking beyond the next five minutes. I’d rather feel strong, think clearly, sleep reasonably well and remain capable of hauling my own suitcase through an airport. That feels like a much better ambition.

This study does not mean that every woman should take HRT to prevent dementia.

It doesn’t prove that HRT prevents dementia. It doesn’t establish HRT as a treatment for dementia. And it doesn’t mean that every woman will experience the same benefits.

Whether to use HRT is an individual healthcare decision. If you’re considering it, the conversation needs to include your symptoms, age, menopause history, medical history, individual risk factors and the type and timing of treatment. The potential benefits and risks are personal too.

So if this research makes you wonder whether HRT might be right for you, that’s a good reason to talk to your GP or a qualified menopause healthcare professional.

It isn’t a reason to change your treatment because of a headline.

That’s perhaps the least satisfying part of science. We don’t get to know everything immediately.

This research raises intriguing questions about how HRT, timing, menopause type, lifetime oestrogen exposure and genetics might interact in brain health. But we still don’t know whether HRT itself is responsible for the lower dementia risk observed, which women might benefit most, or whether different forms of HRT have different effects.

For now, it is another piece of the puzzle.

I think that’s what stays with me after reading this study. When you’re somewhere in the middle of perimenopause, it’s very easy to focus on getting through the day. Getting some sleep, remembering what you’re supposed to be doing and working out whether you’re hungry, tired, hormonal or all three.

Trying to recognise the woman in the mirror once again matters, but so does thinking about the women we’re going to be in 10, 20 or 30 years.

What protects our brains? What keeps our bones strong? What protects our hearts? What helps us maintain muscle and independence? And how do we make those decisions based on good evidence rather than fear, fashion or whichever alarming social media post happens to find us at 10.30pm? That’s the version of midlife I’m interested in.

The menopause transition isn’t simply an annoying interruption between one stage of life and another. It is a major biological transition. And if research continues to suggest that it may have implications for long-term brain health, women deserve a much bigger and better conversation about it.

The study

The research, “Hormone replacement therapy and dementia risk among postmenopausal women: identifying responsive subgroups in the UK Biobank,” was led by researchers at the University of East Anglia and the University of Exeter and published in Alzheimer’s & Dementia.

The study analysed data from 183,450 postmenopausal women in the UK Biobank, with participants followed for an average of 13.3 years.

This article discusses publicly available research and reflects my personal interest in women’s health and midlife wellbeing. It is not medical advice. Speak to your GP or a qualified healthcare professional about your own health and treatment.

Are we finally starting to think about menopause as a long-term women’s health issue, rather than something women simply have to get through?