University of Cambridge - NIHR Cambridge Biomedical Research Centre

Deaf opera singer welcomes new Cambridge-led cochlear implant trial

cjb250 — Wed, 06 May 2026 07:34:21 +0000

The UK trial will provide bilateral cochlear implants (cochlear implants on both sides) to some profoundly deaf adults. The results will be used to review NHS guidance for the provision of implants to adults.

Each year over 1,000 adults in the UK receive cochlear implants to restore their hearing. Under NHS guidance, adults currently only receive a single (unilateral) implant, yet evidence suggests having two could offer significant improvements in prospects and quality of life and may now be cost effective.

Janine said: “With bilateral implants, I no longer consider myself to be deaf. They have been utterly life changing and, for me, have broken a generational curse. I am excited that this trial will offer the same opportunity to others.”

Funded by the National Institute for Health and Care Research (NIHR), the trial is being co-led from Addenbrooke’s Hospital and the University of Cambridge. It will run in 14 hospitals and include over 250 adult participants, who will either receive one (unilateral) or two (bilateral) implants. Participants will be monitored for 12 months after surgery to assess the effects of the implants on wellbeing, ability to hear speech in noise, and quality of life. The study will also evaluate the economic benefits and cost of bilateral implants for the NHS.

Called LUCIA, the trial will be co-led by Dr Matthew Smith, an ear, nose and throat (ENT) surgeon at Addenbrooke’s Hospital, and Professor Debi Vickers, a speech and hearing scientist in the Department of Clinical Neurosciences, University of Cambridge, who leads the SOUND Lab.

Professor Debi Vickers, who also co-leads the Devices and Advanced Therapies theme at the NIHR Cambridge Biomedical Research Centre, said: “Children routinely receive bilateral cochlear implants. These can provide 3-dimensional hearing, enabling them to hear more naturally than unilateral, with improved access to sound and better engagement with society.

“Adults tell us, and I agree, that they should be given the same hearing opportunities as children. In turn these will result in reduced social isolation, enriched communication, improved mental health, and better overall quality of life.”

The trial, which is expected to begin recruiting patients in the autumn, has been designed in collaboration with Janine and other patients. By involving individuals with lived experience of cochlear implantation, the researchers aim to measure changes that patients consider to be most important.

The primary trial outcome will reflect participants’ own perceptions of their quality of hearing. The study will also measure common challenges faced by patients, such as listening effort and fatigue, a choice directly based on discussions with patient groups.

Dr Smith, who is also an academic surgeon at the University of Cambridge, said: “We know from giving bilateral implants to children that it can have a transformative effect on their quality of life and interactions with other people. Through this study, we can offer the same opportunity to adults who have become deaf, and understand the potential added value of bilateral cochlear implants, not just in terms of hearing, but also how they enrich quality of life.”

Janine was diagnosed as a teenager with a genetic condition that caused hearing loss and eventually led to her needing hearing aids. For over 30 years she hid her deteriorating hearing and became a well-known mezzo-soprano, performing in operas, operettas and musicals, including at the Royal Opera House in London.

It was only in 2019, after she had retired due to profound hearing loss, that she had cochlear implant surgery, and received bilateral implants partly through personal funding. She said: “Having two implants is lightyears away from just one. Sound quality is so much better, sounds are fuller, clearer, louder and more natural. It’s much easier to tell where sounds are coming from, especially in busy spaces.

“If you’re out in public, it can be hard to follow who is speaking, making joining in with conversations almost impossible. As a result, you have debilitating concentration fatigue at the end of every day.”

Just like at the cinema, multi-directional surround sound is a key part of creating an engaging immersive experience. By comparison, living with one implant can be like listening to life through a single, poor-quality speaker.

She explains: “Struggling to hear can be extremely isolating and many people experience anxiety or depression as a result. The implants are life changing. They reconnect you to the world and most importantly people. Communication is surely the longing of every human heart.

“I also feel safer and more secure having the two implants. I am more aware of and connected to what’s happening in the world around me. And, if anything goes wrong with one of the implants, I’m not suddenly plunged into a world of total silence.”

While hearing aids help people with mild to moderate hearing loss by making sounds louder, they often provide very little benefit for people with severe or profound hearing loss. Cochlear implants bypass the outer, middle and inner ear and send electrical impulses directly to the hearing nerve which carries signals to the brain.

Participants in the trial will need to have become deaf later in life and cannot already have an implant.

People with cochlear implants will also be involved in delivering the trial. They will be specially trained to participate in interviewing trial participants that will be used to measure the impacts of the trial.

Professor Anthony Gordon, Programme Director for the NIHR Health Technology Assessment Programme, which funded the trial, said: "We fund innovative trials like the LUCIA study which explore how advances in technology can help make a positive difference to the day-to-day lives of those affected. This study offers real hope to people with severe hearing loss and the chance of a significant improvement in their quality of life."

Adapted from a press release from Cambridge University Hospitals NHS Foundation Trust

Janine Roebuck, a formerly deaf opera singer who regained her hearing thanks to cochlear implants, has described as ‘life changing’ an upcoming Cambridge-led trial in hearing loss.

We know from giving bilateral implants to children that it can have a transformative effect on their quality of life and interactions with other people. Through this study, we can offer the same opportunity to adults

Matthew Smith

Janine Roebuck

Janine Roebuck as Flora in La Traviata by Verdi at New Sadler's Wells Opera

The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Scientists confirm precursor to commonest form of oesophageal cancer – offering opportunities to catch the disease early

cjb250 — Thu, 16 Apr 2026 09:00:43 +0000

The findings, published today in Nature Medicine, could help improve screening for and early detection of oesophageal cancer, the sixth most deadly cancer, helping improve outcomes for the disease.

Cancer of the oesophagus, including its most common form oesophageal adenocarcinoma (OAC), is on the rise in western countries. It is difficult to treat because it is often caught at an advanced stage, when treatment options are limited.

Scientists and doctors have known for some time that the development of oesophageal cancer is linked with Barrett’s oesophagus, which shows up in endoscopy as a pink patch in the surface of the oesophagus. Barrett’s oesophagus affects around one out of every 100 to 200 people in the United Kingdom.

Between three and 13 people out of 100 with Barrett’s oesophagus will go on to develop oesophageal adenocarcinoma in their lifetime. However, around half of OAC patients have no detectable Barrett’s oesophagus when their cancer is found, raising doubts about whether it is always the precursor.

Professor Rebecca Fitzgerald from the Li Ka Shing Early Cancer Institute at the University of Cambridge said: “Cancer generally takes many years to evolve, giving us a window of opportunity to catch it before if develops into a life-threatening condition. Screening and preventative strategies can have a massive impact on the number of people who die from cancer, but if the link between precancers and cancer is unproven or unclear, screening programmes risk doing more harm than good.”

To answer the question of whether Barrett’s oesophagus is a pre-requisite for OAC, researchers from Professor Fitzgerald and colleagues analysed epidemiological and clinical data from 3,100 OAC patients undergoing surgery to remove their tumour or diseased tissue. Patients were recruited from 25 centres across the UK.

The team also analysed whole genome sequencing data from 710 patients, which allows them to look at all of an individual’s DNA, and whole exome sequencing from multiple samples taken from 87 patients, allowing them to understand how their tumours evolved and how different parts of the same cancer may differ genetically.

The researchers hypothesised that if OAC can arise through different routes – not always involving Barrett’s oesophagus – then genomic data and associated risk factors would differ between these two groups. Conversely, extensive overlap would strongly suggest that Barrett’s oesophagus plays a central role in OAC progression.

Just over a third of participants (35%) had a diagnosis of Barrett’s oesophagus. However, the DNA, mutations, genomic patterns, and cellular ‘identity’ inside the cancers were essentially indistinguishable, regardless of whether doctors could identify Barrett’s oesophagus during endoscopy or in pathology samples.

The only major difference between cancers with or without visible Barrett’s oesophagus was the tumour stage – those patients without signs of Barrett’s oesophagus tended to have more advanced cancers. However, the team found biomarkers for Barrett’s oesophagus, such as the proteins TFF3 and REG4 present in the oesophagus cells at all disease stages including before the cancer has developed. This suggests that the growing tumour can destroy the original Barrett’s tissue, but importantly that proteins such as TFF3 and REG4 could be used to find individuals at future risk of oesophageal cancer.

Dr Shahriar Zamani, joint first author from the Li Ka Shing Early Cancer Institute at Cambridge and now based at the National Institutes of Health in Bethesda, US, said: “We found no evidence for an alternative pathway to oesophageal adenocarcinoma other than Barrett’s oesophagus. Because it seems to be the universal precursor, detecting Barrett’s oesophagus earlier could offer a clearer route to preventing oesophageal cancer.”

Dr Lianlian Wu, joint first author, also from the Li Ka Shing Early Cancer Institute, said: “What we need now are more sensitive, minimally invasive tests that identify people at risk based on molecular markers rather than relying solely on visible changes found during endoscopy.”

The research was supported by Cancer Research UK and the Medical Research Council, with additional support by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Dr Dani Skirrow, Research Information Manager at Cancer Research UK, said: "Detecting the earliest signs that cancer might develop gives us the opportunity to intervene and potentially prevent the disease.

“This research helps to clarify how the most common type of oesophageal cancer begins and, crucially, shows that the earliest signs are detectable even when doctors can’t see them.

“This opens the door to future tests that look for molecular clues of hidden pre-cancerous changes, helping people understand their risk of oesophageal cancer and get the necessary support to help keep the disease at bay."

Professor Fitzgerald is the Research Lead for Cambridge Cancer Research Hospital, a new hospital that will transform how we diagnose and treat cancer. She has led the development of a capsule sponge test to diagnose Barrett’s oesophagus, which can be easily administered at a GP surgery, speeding up diagnosis.

The University of Cambridge and Addenbrooke's Charitable Trust (ACT) are fundraising for Cambridge Cancer Research Hospital, where detecting cancer at its earliest stages will be a key goal. Set to be built on the Cambridge Biomedical Campus, the hospital will bring together clinical excellence from Addenbrooke’s Hospital and world-leading researchers at the University of Cambridge. The research that takes place there promises to change the lives of cancer patients across the UK and beyond. Find out more here.

Reference

Zamani, SA et al. Integrated epidemiological and molecular data yields insights into the relationship between precancer and cancer states of oesophageal adenocarcinoma. Nat Med; 16 Apr 2026; DOI: 10.1038/s41591-026-04331-8

Scientists have found the strongest evidence to date that a condition known as Barrett’s oesophagus is the starting point for all cases of oesophageal adenocarcinoma – the most common type of oesophageal cancer in the developed world – even when telltale signs of this pre-cancerous stage are no longer visible.

If the link between precancers and cancer is unproven or unclear, screening programmes risk doing more harm than good

Rebecca Fitzgerald

Stillvision

Rebecca Fitzgerald demonstrates the capsule sponge

Yes

Licence type:

Attribution

Study highlights stroke risk linked to recreational drugs, including among young users

cjb250 — Mon, 09 Mar 2026 00:01:00 +0000

Stroke is a major global health challenge – the third leading cause of death and disability combined. But it also a condition that, for the most part, results from modifiable risk factors, such as poor diet, lack of exercise and other lifestyle factors.

In 2024, 8.8% of adults aged 16 to 59 years in England and Wales – around 2.9 million individuals - reported having used a legal or illegal recreational drug in the past year. Recent data from the USA reports that over half of all those aged over 12 have used drugs such as cocaine, cannabis and opiates at least once.

There is increasing evidence that these drugs may increase the risk of stroke, but the evidence is often of differing quality and is observational only, meaning it is impossible to say whether the use of these drugs itself increases the risk of stroke, or whether this is purely a correlation.

To investigate this further, a team from the Department of Clinical Neurosciences at the University of Cambridge first carried out a meta-analysis of studies encompassing more than 100 million people. A meta-analysis is a method for pooling and analysing cohort data from all of the published evidence. This approach allows researchers to bring together studies which, on their own may not provide sufficient evidence and sometimes disagree with each other, to provide more robust conclusions.

In findings published in the International Journal of Stroke, the team found that the use of cocaine and amphetamines was associated with around double the risk of stroke (cocaine increased the risk by 96%, amphetamines by 122%), while cannabis use increased the risk by around 37%. The team found no statistically significant link between opioid use and stroke risk.

When the researchers restricted their analysis to individuals under 55 years, they found that amphetamine use almost tripled the risk of stroke (an increase of 174%); cannabis use increase stroke risk but by a smaller amount (14%), while cocaine use increased the risk by 97%.

To analyse these links further, the researchers used a statistical technique known as Mendelian randomisation, which looks at naturally occurring genetic variants related to risk factors and stroke and uses these to evaluate whether there is evidence to support a causal association with a particular risk factor.

This analysis showed that cocaine use disorders were particularly associated with brain haemorrhage and cardioembolic stroke (where a blood clot forms in the heart and travels to the brain, blocking blood flow and leading to damage of brain tissue). Cannabis use disorders were associated with stroke overall, particularly large artery stroke. This genetic evidence suggests a causal link, rather than just correlation.

Problematic alcohol use was linked to an increased risk of cardioembolic stroke and large artery stroke, while alcohol addiction increased the risk of stroke overall.

The researchers were unable to use Mendelian randomisation to look at associations with amphetamine as there are currently no large genetic datasets available with information on their usage.

The researchers suggest that possible reasons why these drugs are linked to an increased risk of stroke include sudden spikes in blood pressure, blood vessel spasm and constriction, heart rhythm problems, increased blood clotting (especially cannabis), and inflammation or vasculitis (especially amphetamines). These are all well-established pathways known to cause both ischaemic strokes, which result from blood clots, and haemorrhagic strokes.

Dr Megan Ritson from the Stroke Research Group at the University of Cambridge said: “This is the most comprehensive analysis ever conducted on recreational drug use and stroke risk and provides compelling evidence that drugs like cocaine, amphetamines, and cannabis are causal risk factors for stroke. These findings give us stronger evidence to guide future research and public health strategies.”

Dr Eric Harshfield, Alzheimer's Society Research Fellow at the Department of Clinical Neurosciences, said: “Our analysis suggests that it is these drugs themselves that increase the risk of stroke, not just other lifestyle factors among users. Taken together, our findings emphasise the importance of public health measures to reduce substance abuse as a way of helping also reduce stroke risk.”

The research was funded by the British Heart Foundation, with additional support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference

Ritson, M, et al. Does Illicit Drug Use Increase Stroke Risk? A Systematic review, Meta-Analyses and Mendelian Randomization analysis. International Journal of Stroke; 9 March 2026; DOI: 10.1177/17474930261418926

The recreational drugs cannabis, cocaine and amphetamines significantly increase the risk of stroke – including among younger users – Cambridge researchers have concluded after analysing data from more than 100 million people.

Our analysis suggests that it is these drugs themselves that increase the risk of stroke, not just other lifestyle factors among users

Eric Harshfield

Kindel Media (Pexels)

Close-up of a person holding a roll-up

Yes

Licence type:

Public Domain

High levels of testosterone in the blood raise risk of coronary artery disease in men

cjb250 — Mon, 02 Feb 2026 09:53:51 +0000

The findings could have implications for the use of testosterone supplements, which while they have approved medical applications, are increasing in popularity, particularly among younger men who see testosterone as a way to fight ageing, enhancing performance or building strength.

Testosterone supplementation is an approved treatment for hypogonadism, a condition in which the body doesn't make enough of the hormone, and which typically manifests with fatigue and sexual dysfunction. Evidence from randomised controlled trials has shown beneficial effects of testosterone supplementation on sexual function, lean mass and muscle strength. Low circulating testosterone – that is, testosterone in the blood – is also a risk factor for poor metabolic health.

Recent years have seen testosterone supplements being promoted increasingly on social media and by influencers, often aimed towards younger men to boost their testosterone levels for perceived benefits like muscle growth, strength, energy, and confidence.

However, questions remain about the long-term health impacts of testosterone levels.

Observational studies have linked low measured testosterone levels with an increased risk of coronary artery disease in men, but randomized controlled trials – the ‘gold standard’ for testing the effectiveness of treatments – have been inconclusive and often contradictory.

To address the question of the impact of testosterone supplements on coronary artery disease, a team led by scientists at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge turned to a technique known as Mendelian randomisation. Mendelian randomisation involves using genetic variants as a way of exploring causal links between exposures (often to environmental factors) and disease.

In this case, using data from more than 400,000 adults recruited to UK Biobank and over 1 million individuals recruited to CARDIoGRAMplusC4D, the researchers looked for genetic variants that lead to higher levels of testosterone in the blood and examined whether carriers of these variants were at a greater or lesser risk of coronary artery disease.

The results are published in the Journal of Clinical Endocrinology and Metabolism.

The team found that for men, having genetically higher testosterone was linked to a 17% higher risk of coronary artery disease. Previous studies have suggested that an individual’s risk of coronary artery disease is 7.3% over their lifetime – testosterone supplementation would raise this to 8.5%. The increased risk seemed to be in part due to the fact that testosterone raises blood pressure.

The researchers argue that the reason this appears to contradict observational studies is most likely explained by other, confounding health factors such as diabetes and obesity. People with these conditions tend to have lower testosterone levels and greater risk of coronary artery disease.

The researchers found no clear link between testosterone and risk of coronary artery disease in women.

Emily Morbey, a PhD student at the MRC Epidemiology Unit and King’s College, University of Cambridge, said: “More and more men are taking testosterone supplements, in part because of greater awareness of hypogonadism in men, but also because of increased marketing and social media trends, particularly targeted at younger men.

“Our work indicates that high levels of testosterone in the blood increase the risk of coronary artery disease, which in turn can put people at risk of heart attack and heart failure. When there is a medical need to boost testosterone, the benefits are likely to outweigh the risks, but this might not necessarily be the case when taken to boost performance.”

Senior author Professor Ken Ong, also from the MRC Epidemiology Unit, said: “The US Food and Drug Administration has already issued guidance on the potential cardiovascular risk associated with testosterone supplementation. In the UK, there is no national guidance on the potential cardiovascular risk of high levels of testosterone. Our results suggest there’s a need for more consistent warnings.”

The research was funded by the Medical Research Council, with additional support from the National Institutes for Health and Care Research Cambridge Biomedical Research Centre.

Reference

Morbey, EJ et al. Higher circulating testosterone linked to higher CAD risk in men: Mendelian randomisation and survival analyses. JCEM; 24 Oct 2025; DOI: 10.1210/clinem/dgaf582

High levels of testosterone in the blood have been linked to a greater risk of coronary artery disease in men, according to a new study from researchers at the University of Cambridge.

When there is a medical need to boost testosterone, the benefits are likely to outweigh the risks, but this might not necessarily be the case when taken to boost performance

Emily Morbey

Peter Dazeley (Getty Images)

Dumbbell weights in gym with pills

Yes

Menopause linked to loss of grey matter in the brain, poorer mental health and sleep disturbance

cjb250 — Tue, 27 Jan 2026 00:01:50 +0000

The study, published today in Psychological Medicine, found that hormone replacement therapy (HRT) does not appear to mitigate these effects, though it can slow the decline in reaction times.

Menopause is a key period in a woman’s life when her periods stop, due to lower hormone levels. It typically affects women between the ages of 45 and 55, during which time they may experience hot flushes, low mood and sleep problems. Menopause has previously been linked to cognitive decline, such as memory, attention and language deficits.

To counter the effects of menopause – particularly depressive symptoms and sleep problems – many women are prescribed HRT. In England, in 2023, 15% of women were prescribed the treatment. However, there is limited understanding of the effects of menopause and subsequent HRT use on the brain, cognition and mental health.

To address this question, researchers at the University of Cambridge analysed data from UK Biobank of almost 125,000 women, who were classified into three categories: pre-menopause, post-menopause who have never used HRT, or post-menopause who have used HRT.

As well as answering questionnaires that included questions related to their experience of menopause, self-reported mental health, sleep patterns and overall health, some participants took part in tests of cognition, including tests of memory and reaction times. Around 11,000 participants also underwent magnetic resonance imaging (MRI) scans, allowing the researchers to look at the structure of their brains.

The average age of onset of menopause among the participants was around 49.5 years, while the average age that women prescribed HRT began their treatment was around 49 years.

Post-menopausal women were more likely than those pre-menopause to have sought help from their GP or a psychiatrist for anxiety, nerves or depression, and to score more highly on questionnaires for symptoms of depression. Similarly, they were more likely to have been prescribed antidepressants.

Although women in the HRT group had greater anxiety and depression compared with the non-HRT group, further analysis showed that these differences in symptoms were already present before menopause. It is possible, say the researchers, that in some cases, a woman’s GP may have prescribed HRT in anticipation of menopause worsening her symptoms.

Women post-menopause were more likely to report insomnia, get less sleep, and feel tired. Those on HRT reported feeling the most tired of all three groups, even though there was no difference in sleep duration between these women and those women post-menopause not on the medication.

Dr Christelle Langley from the Department of Psychiatry said: “Most women will go through menopause, and it can be a life-changing event, whether they take HRT or not. A healthy lifestyle – exercising, keeping active and eating a healthy diet, for example – is particularly important during this period to help mitigate some of its effects.

“We all need to be more sensitive to not only the physical, but also the mental health of women during menopause, however, and recognise when they are struggling. There should be no embarrassment in letting others know what you’re going through and asking for help.”

Menopause also appeared to have an impact on cognition. Post-menopausal women who were not on HRT had slower reaction times than those yet to start menopause or who were on HRT. However, there were no significant differences between the three groups when it came to memory tasks.

Dr Katharina Zühlsdorff from the Department of Psychology at the University of Cambridge, said: “As we age, our reaction times tend to get slower – it’s just a part of the natural ageing process and it happens to both women and men. You can imagine being asked a question at a quiz – while you might still arrive at the correct answer as your younger self, younger people would no doubt get there much faster. Menopause seems to accelerate this process, but HRT appears to put the brakes on, slowing the ageing process slightly.”

In both groups of women post-menopause, the researchers found significant reductions in volume of grey matter – brain tissue that contains nerve cell bodies and helps process information, control movement and manage memory and emotions.

In particular, these differences occurred in the hippocampus (responsible for forming and storing memories); entorhinal cortex (the ‘gateway’ for passing information between the hippocampus and the rest of the brain); and the anterior cingulate cortex (part of the brain that helps you manage emotions, make decisions, and focus your attention).

Professor Barbara Sahakian, the study’s senior author from the Department of Psychiatry, added: “The brain regions where we saw these differences are ones that tend to be affected by Alzheimer’s disease. Menopause could make these women vulnerable further down the line. While not the whole story, it may help explain why we see almost twice as many cases of dementia in women than in men.”

The research was funded by the Wellcome Trust, with additional support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Reference

Zühlsdorff, K et al. Emotional and cognitive effects of menopause and hormone replacement therapy. Psychological Medicine; 27 Jan 2025; DOI: 10.1017/S0033291725102845

Menopause is linked to reductions in grey matter volume in key brain regions as well as increased levels of anxiety and depression and difficulties with sleep, according to new research from the University of Cambridge.

Most women will go through menopause, and it can be a life-changing event, whether they take HRT or not

Christelle Langley

Kate Wieser (Getty Images)

Sick woman lying in bed at home

Yes

Hot flush treatment has anti-breast cancer activity, study finds

cjb250 — Mon, 05 Jan 2026 10:00:14 +0000

A low dose of megestrol acetate (a synthetic version of progesterone) has already been proven as a treatment to help patients manage hot flushes associated with anti-oestrogen breast cancer therapies, and so could help them continue taking their treatment. The PIONEER trial has now shown that the addition of low dose megestrol to such treatment may also have a direct anti-cancer effect.

Around three-quarters of all breast cancers are ER-positive. This means the tumours are abundant in a molecule known as an oestrogen receptor, ‘feeding’ on the oestrogen circulating in the body. These women are usually offered anti-oestrogens, medication that reduces level of oestrogen and hence deprives the cancer of oestrogen and inhibits its growth. However, reducing oestrogen levels can bring on menopause-like symptoms, including hot flushes, joint and muscle pain, and potential bone loss.

In the PIONEER trial, post-menopausal women with ER-positive cancers were treated with an anti-oestrogen with or without the progesterone mimic, megestrol. After two weeks of treatment, those that received the combination saw a greater decrease in tumour growth rates compared to those treated with an anti-oestrogen only.

Although further work is required in larger patient cohorts and over a longer period of time to confirm the findings, researchers at the University of Cambridge say the trial suggests that megestrol could help improve the lives of thousands of women for whom anti-oestrogen medication causes uncomfortable side-effects and can lead to some women stopping taking the medication.

PIONEER was led by Dr Richard Baird from the Department of Oncology at the University of Cambridge and Honorary Consultant Medical Oncologist at Cambridge University Hospitals NHS Foundation Trust (CUH). He said: “On the whole, anti-oestrogens are very good treatments compared to some chemotherapies. They're gentler and are well tolerated, so patients often take them for many years. But some patients experience side effects that affect their quality of life. If you’re taking something long term, even seemingly relatively minor side effects can have a big impact.”

Some ER-positive breast cancer patients also have high levels of another molecule, known as progesterone receptor (PR). This group of patients also respond better to the anti-oestrogen hormone therapy.

To explain why, Professor Jason Carroll and colleagues at the Cancer Research UK Cambridge Institute used cell cultures and mouse models to show that the hormone progesterone stops ER-positive cancer cells from dividing by indirectly blocking ER. This results in slower growth of the tumour. When mice treated with anti-oestrogen hormone therapy were also given progesterone, the tumours grew even more slowly.

Professor Carroll, who co-leads the Precision Breast Cancer Institute and is a Fellow of Clare College, Cambridge, said: “These were very promising lab-based results, but we needed to show that this was also the case in patients. There’s been concern that taking hormone replacement therapy – which primarily consists of oestrogen and synthetic versions of progesterone (called progestins) – might encourage tumour growth. Although we no longer think this is the case, there’s still been residual concern around the use of progesterone and progestins in breast cancer.”

To see whether targeting the progesterone receptor in combination with an anti-oestrogen could slow tumour growth in patients, Dr Baird and Professor Carroll designed the PIONEER trial, which tested adding megestrol, a progestin, to the standard anti-oestrogen treatment letrozole.

A total of 198 patients were recruited at ten UK hospitals, including Addenbrooke’s Hospital in Cambridge, and randomised into one of three groups: one group received only letrozole; one group received letrozole alongside 40mg of megestrol daily; and the third group received letrozole plus a much higher daily dose of megestrol, 160mg. In this ‘window of opportunity’ trial, treatment was given for two weeks prior to surgery to remove the tumour. The percentage of actively growing tumour cells was assessed at the start of the trial and then again before surgery.

In findings published today in Nature Cancer, the team showed that adding megestrol boosted the ability of letrozole to block tumour growth, with comparable effects at both the 40mg and 160mg doses.

Joint first author Dr Rebecca Burrell from the Cancer Research UK Cambridge Institute and CUH said: “In the two-week window that we looked at, adding a progestin made the anti-oestrogen treatment more effective at slowing tumour growth. What was particularly pleasing to see was that even the lower dose had the desired effect.

“Although the higher dose of progesterone is licenced as an anti-cancer treatment, over the long term it can have side effects including weight gain and high blood pressure. But just a quarter of the dose was as effective, and this would come with fewer side effects. We know from previous trials that a low dose of progesterone is effective at treating hot flushes for patients on anti-oestrogen therapy. This could reduce the likelihood of patients stopping their medication, and so help improve breast cancer outcomes. Megestrol – the drug we used – is off-patent, making it a cost-effective option.”

Because women in the trial were only given megestrol for a short period of time, follow-up studies will be needed to confirm whether the drug would have the same beneficial effects with reduced side-effects over a longer period of time.

The research was funded by Anticancer Fund, with additional support from Cancer Research UK, Addenbrooke’s Charitable Trust and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Personalised and precise cancer treatments underpin the focus of care at the future Cambridge Cancer Research Hospital. The specialist facility planned for the Cambridge Biomedical Campus will bring together world-leading researchers from the University of Cambridge and its Cancer Research UK Cambridge Centre and clinical excellence from Addenbrooke’s Hospital under one roof in a brand-new NHS hospital.

Reference

Burrell, RA & Kumar, S, et al. Evaluating progesterone receptor agonist megestrol plus letrozole for women with early-stage estrogen-receptor-positive breast cancer: the window-of-opportunity, randomized, phase 2b, PIONEER trial. Nature Cancer; 5 Jan 2026: DOI: 10.1038/s43018-025-01087-x

A drug mimicking the hormone progesterone has anti-cancer activity when used together with conventional anti-oestrogen treatment for women with breast cancer, a new Cambridge-led trial has found.

In the two-week window that we looked at, adding a progestin made the anti-oestrogen treatment more effective at slowing tumour growth. What was particularly pleasing to see was that even the lower dose had the desired effect

Rebecca Burrell

Highwaystarz-Photography (Getty Images)

Menopausal woman experiencing a hot flush (stock image)

Yes

Neighbourhood deprivation linked to brain vessel damage and higher dementia risk

cjb250 — Wed, 05 Nov 2025 12:00:16 +0000

In research published today, they show how it is associated with damage to brain vessels – which can affect cognition – and with poorer management of lifestyle factors known to increase the chances of developing dementia.

Dementia disproportionately affects people who live in socioeconomically disadvantaged neighbourhoods. Individuals living in such areas show greater cognitive decline throughout their lives and higher dementia risk, regardless of their own socioeconomic status. Recent studies have also found that neighbourhood deprivation is linked to differences in brain structure and greater signs of damage to brain tissue.

To explore this link further, researchers examined data from 585 healthy adults aged 40–59 living in the UK and Ireland who had been recruited to the PREVENT-Dementia programme. Details of the study are published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

Among the data collected and examined were: neighbourhood deprivation according to postcodes; cognitive performance assessed through a series of tests; modifiable lifestyle risk factors; and MRI brain scans to look for signs of damage to the brain’s small blood vessels, which are crucial for delivering oxygen and nutrients to brain tissue.

The team found a strong link between living in a deprived neighbourhood and poorer management of lifestyle factors known to increase the chances of developing dementia. In particular, people living in areas of high unemployment, low income and/or poor education and training opportunities were more likely to experience poor sleep, obesity and high blood pressure, and do less physical activity.

However, people living in deprived neighbourhoods tended to consume less alcohol than those in less disadvantaged neighbourhoods. Alcohol consumption is another known risk factor for dementia.

The researchers also found a significant link between cognition and neighbourhood deprivation – particularly poorer housing and environment and higher levels of crime. This had the greatest impact on an individual’s ability to process information quickly, their spatial awareness and attention.

One possible explanation for this comes from the team’s finding that living in a deprived neighbourhood was associated with damage to the brain’s small blood vessels, which in turn affects thinking skills. Modifiable lifestyle habits are known to contribute to this damage, suggesting that the effect of deprivation on brain function – and hence performance in cognitive tests – may be down to lifestyle and vascular health.

First author Dr Audrey Low, from the Department of Psychiatry at the University of Cambridge and Mayo Clinic, Minnesota, said: “Where someone lives can affect their brain health as early as midlife. It doesn’t do this directly, but by making it more difficult for them to engage in positive lifestyle behaviours.

“This means that people living in these areas may face more challenges in getting quality sleep and exercise, and in managing blood pressure and obesity. This can then have a knock-on effect on the health of blood vessels in the brain, leading to poorer cognition.

“These lifestyle factors are no doubt influenced by both individual circumstances and the external environment in which they live. But importantly, the links we found were independent of educational attainment. So, even a person who has gone on to further or higher education and has a reasonably paid job may be better or worse at managing their lifestyle depending on where they live, perhaps due to better access to affordable healthy food options and safer recreational spaces.”

The researchers say their findings highlight the fact that dementia risk is influenced by environmental factors rather than just individual behaviours, and so reducing dementia risk will mean addressing the wider social determinants of brain health.

Senior author Professor John O’Brien, also from the Department of Psychiatry at Cambridge, said: “Where you live clearly plays an important role in your brain health and risk of dementia, putting people living in deprived neighbourhoods at a serious disadvantage. This risk is preventable, but our works shows it’s not enough to assume it’s down to the individual. If we’re serious about reducing health inequalities, it will require support from local and national policymakers.”

The study highlights how different areas face their own challenges and hence will need different approaches, say the researchers. In wealthier areas, strategies could focus on reducing alcohol consumption, for example. Lower-income neighbourhoods, on the other hand, may benefit from targeted campaigns promoting healthy lifestyles for dementia prevention. This will require policymakers and community leaders to tackle systemic barriers that are impeding individuals’ abilities to adopt healthy lifestyle changes. This could include improving access to affordable healthcare and healthy food options, reducing crime, and providing safe recreational areas for exercise.

While these findings hold true for the UK and Ireland, the researchers say that more research is needed into whether they apply in other cultures. There is some previous evidence that the opposite is true in certain Asian cultures, for example.

The research was supported by the Alzheimer’s Society, Alzheimer’s Association, Race Against Dementia, Wellcome Trust, Alzheimer’s Research UK and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference

Low, A et al. Neighbourhood deprivation and midlife cognition: evidence of a modifiable vascular pathway involving health behaviours and SVD. Alz & Dem; 5 Nov 2025; DOI: 10.1002/alz.70756

Cambridge researchers have discovered why living in a disadvantaged neighbourhood may be linked to an increase in an individual’s risk of dementia.

Where you live clearly plays an important role in your brain health and risk of dementia, putting people living in deprived neighbourhoods at a serious disadvantage

John O'Brien

Michael Greenwood (Getty Images)

London housing estate

Yes

Dementia linked to problems with brain’s waste clearance system

cjb250 — Thu, 23 Oct 2025 11:00:01 +0000

A study led by researchers at the University of Cambridge found that impaired movement of cerebrospinal fluid (CSF) – the clear liquid that cushions and cleans the brain – predicted risk of dementia later in life among 40,000 adults recruited to UK Biobank. Their findings are published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association and are being presented at the World Stroke Congress 2025 in Barcelona.

In the healthy brain, the so-called glymphatic system serves to clear out toxins and waste materials, keeping the brain healthy. Only discovered as recently as 2012, this system functions by flushing CSF through the brain along tiny channels around blood vessels known as perivascular spaces. It collects waste then drains out of the brain, helping keep it clean and healthy.

The glymphatic system is thought to be important in protecting against many of the common forms of dementia, which are often characterised by the build-up of toxic substances in the brain – for example, Alzheimer's disease sees amyloid ‘plaques’ and tau ‘tangles accumulate in brain tissue.

One of the most common forms of dementia is vascular dementia, caused by reduced blood flow to the brain. The most common cause of this type of dementia is cerebral small vessel disease, which affects the small blood vessels in the brain. But the impact of cerebral small vessel disease is even greater because it also interacts with other dementias making them worse; for example, a study of nuns in the US found that among those nuns whose brains showed signs of Alzheimer's disease post mortem, only around a half exhibited symptoms of dementia – but this increased to around nine in 10 if they also had cerebral small vessel disease.

Professor Hugh Markus and colleagues at the University of Cambridge wanted to see whether cerebral small vessel disease and other cardiovascular risk factors damage the glymphatic system – and whether this in turn increases the risk of dementia.

Until recently, it has only been possible to study glymphatic function in mice, but recent advances in MRI scanning have made it possible to study it indirectly in humans. Even so, it was only possible to do this practically in relatively small numbers, but Yutong Chen, while a medical student at the University of Cambridge, developed machine learning algorithms capable of assessing glymphatic functions from MRI scans at scale.

The team applied the algorithm to MRI scans taken from around 40,000 adults in UK Biobank. They found three biomarkers – biological signatures – associated with impaired glymphatic function assessed at baseline, predicted the risk of dementia occurring over the subsequent decade. One of these was DTI-ALPS, a measure of the diffusion of water molecules along the perivascular spaces. Another was the size of the choroid plexus, where the CSF is produced. The third measure reflected the flow velocity of CSF into the brain.

Yutong Chen, from the Department of Clinical Neurosciences at Cambridge, said: “Although we have to be cautious about indirect markers, our work provides good evidence in a very large cohort that disruption of the glymphatic system plays a role in dementia. This is exciting because it allows to ask: how can we improve this?”

Further analysis showed that several cardiovascular risk factors impaired glymphatic function – and hence increased dementia risk, and that this was partly via causing cerebral small vessel disease, which is visible in the MRI scans.

First author Hui Hong, now a radiologist at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China, said: “We already have evidence that small vessel disease in the brain accelerates diseases like Alzheimer's, and now we have a likely explanation why. Disruption to the glymphatic system is likely to impair our ability to clear the brain of the amyloid and tau that causes Alzheimer's disease.”

The research suggests possible approaches for reducing dementia risk. One is to look at strategies for improving glymphatic function. Sleep plays an important role in glymphatic function, and so disrupted sleep patterns are likely to impair its ability to clear toxins. Alternatively, there may be existing medicines that could be repurposed, or new ones that could be developed, to improve glymphatic function.

Another possible approach is to treat vascular risk factors such as high blood pressure. This is supported by recent studies: the SPRINT MIND trial, for example, showed that intensive blood pressure control (maintaining a systolic blood pressure of less than 120 mm Hg) led to a 20% reduction in cognitive decline or dementia compared to participants in the standard treatment group.

Professor Markus, who leads the Stroke Research Group at the University of Cambridge and is a Fellow of Clare Hall, Cambridge, said: “We already know the importance of cardiovascular risk factors when it comes to dementia, and our findings further emphasise this link.

“At least a quarter of all dementia risk is accounted for by common risk factors like blood pressure and smoking. If these impair glymphatic function, then we can intervene. Treating high blood pressure or encouraging people to stop smoking would be an achievable way to helping the glymphatic system work better.”

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “This study offers us a fascinating glimpse into how problems with the brain's waste clearance system could be quietly increasing the chances of developing dementia later in life. By improving our understanding of the glymphatic system, this study opens exciting new avenues for research to treat and prevent dementia. It also emphasises the importance of managing known cardiovascular risk factors, such as high blood pressure, for reducing dementia risk.”

The research was funded by the British Heart Foundation, with additional support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference

Hong, H et al. MRI markers of cerebrospinal fluid dynamics predict dementia and mediate the impact of cardiovascular risk. Alz & Dem; 23 Oct 2025; DOI: 10.1002/alz.70699

Problems with the brain’s waste clearance system could underlie many cases of dementia and help explain why poor sleep patterns and cardiovascular risk factors such as high blood pressure increase the risk of dementia.

Treating high blood pressure or encouraging people to stop smoking would be an achievable way to helping the glymphatic system work better

Hugh Markus

Maskot (Getty Images)

Caretaker and senior woman using digital tablet at nursing home - stock photo

Yes