Year: 2025

Categories : OphthalmologyTags :

Retinal Repair Work is Done by Microglia, not Neutrophils

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Findings have implications for understanding what goes wrong in retinal diseases

Photoreceptor cells in the retina. Credit: Scientific Animations

In a new study from the Flaum Eye Institute and Del Monte Institute for Neuroscience at the University of Rochester, researchers have discovered that the retina responds to damage differently than many other tissues in the body. When photoreceptor cells in the retina are damaged, microglia, or the brain’s immune cells, respond, and the neutrophils are not recruited to help despite passing through nearby blood vessels.

“This finding has high implications for what happens for millions of Americans who suffer vision loss through loss of photoreceptors,” said Jesse Schallek, PhD, associate professor of Ophthalmology and senior author of the study published in eLife. “This association between two key immune cell populations is essential knowledge as we build new therapies that must understand the nuance of immune cell interactions.”

Using adaptive optics imaging, a camera technology developed by the University of Rochester that allows the imaging of single neurons and immune cells inside the living eye, researchers studied the retinas of mice with photoreceptor damage. They found that while both neutrophil and microglia cells are present in the retina, only microglia cells respond to photoreceptor injury, and they do not call upon neutrophils to help repair the photoreceptor damage. Researchers believe this suggests a type of cloaking occurs during retinal injury to protect the retina from a rush of immune cells that could do more harm than good.

“What is remarkable here is that the passing neutrophils are so close to the reactive microglia, and yet they do not signal to them to assist in damage recovery,” said Schallek.

“This is notably different than what is seen in other areas of the body where neutrophils are the first to respond to local damage and mount an early and robust response.”

Source: University of Rochester Medical Center

Categories : Genetics Respiratory DiseasesTags :

Scientists Reconstruct the Genome of the 1918 Influenza Virus

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Genetic analysis of the early pandemic virus shows key adaptations to humans.

Creative artwork featuring colourised 3D prints of influenza virus (surface glycoprotein hemagglutinin is blue and neuraminidase is orange; the viral membrane is a darker orange). Note: Not to scale. Credit: NIAID

Researchers from the universities of Basel and Zurich have used a historical specimen from UZH’s Medical Collection to decode the genome of the virus responsible for the 1918-1920 influenza pandemic in Switzerland. The genetic material of the virus reveals that it had already developed key adaptations to humans at the outset of what became the deadliest influenza pandemic in history.

New viral epidemics pose a major challenge to public health and society. Understanding how viruses evolve and learning from past pandemics are crucial for developing targeted countermeasures. The so-called Spanish flu of 1918-1920 was one of the most devastating pandemics in history, claiming some 20 to 100 million lives worldwide. And yet, until now, little has been known about how that influenza virus mutated and adapted over the course of the pandemic.

More than 100-year-old flu virus sequenced

An international research team led by Verena Schünemann, a paleogeneticist and professor of archaeological science at the University of Basel (formerly at the University of Zurich) has now reconstructed the first Swiss genome of the influenza virus responsible for the pandemic of 1918-1920. For their study, the researchers used a more than 100-year-old virus taken from a formalin-fixed wet specimen sample in the Medical Collection of the Institute of Evolutionary Medicine at UZH. The virus came from an 18-year-old patient from Zurich who had died during the first wave of the pandemic in Switzerland and underwent autopsy in July 1918.

Three key adaptations in Swiss virus genome

“This is the first time we’ve had access to an influenza genome from the 1918-1920 pandemic in Switzerland. It opens up new insights into the dynamics of how the virus adapted in Europe at the start of the pandemic,” says last author Verena Schünemann. By comparing the Swiss genome with the few influenza virus genomes previously published from Germany and North America, the researchers were able to show that the Swiss strain already carried three key adaptations to humans that would persist in the virus population until the end of the pandemic.

Two of these mutations made the virus more resistant to an antiviral component in the human immune system – an important barrier against the transmissions of avian-like flu viruses from animals to humans. The third mutation concerned a protein in the virus’s membrane that improved its ability to bind to receptors in human cells, making the virus more resilient and more infectious.

New genome-sequencing method

Unlike adenoviruses, which cause common colds and are made up of stable DNA, influenza viruses carry their genetic information in the form of RNA, which degrades much faster. “Ancient RNA is only preserved over long periods under very specific conditions. That’s why we developed a new method to improve our ability to recover ancient RNA fragments from such specimens,” says Christian Urban, the study’s first author from UZH. This new method can now be used to reconstruct further genomes of ancient RNA viruses and enables researchers to verify the authenticity of the recovered RNA fragments.

Invaluable archives

For their study, the researchers worked hand in hand with UZH’s Medical Collection and the Berlin Museum of Medical History of the Charité University Hospital. “Medical collections are an invaluable archive for reconstructing ancient RNA virus genomes. However, the potential of these specimens remains underused,” says Frank Rühli, co-author of the study and head of the Institute of Evolutionary Medicine at UZH.

The researchers believe the results of their study will prove particularly important when it comes to tackling future pandemics. “A better understanding of the dynamics of how viruses adapt to humans during a pandemic over a long period of time enables us to develop models for future pandemics,” Verena Schünemann says. “Thanks to our interdisciplinary approach that combines historico-epidemiological and genetic transmission patterns, we can establish an evidence-based foundation for calculations,” adds Kaspar Staub, co-author from UZH. This will require further reconstructions of virus genomes as well as in-depth analyses that include longer intervals.

Source: University of Zurich

Categories : NeurologyTags :

Why Do We Need Sleep? Oxford Researchers Find the Answer May Lie in Mitochondria

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New study uncovers how a metabolic “overload” in specialised brain cells triggers the need to sleep.

Photo by Cottonbro on Pexels

Sleep may not just be rest for the mind – it may be essential maintenance for the body’s power supply. A new study by University of Oxford researchers, published in Nature, reveals that the pressure to sleep arises from a build-up of electrical stress in the tiny energy generators inside brain cells.

The discovery offers a physical explanation for the biological drive to sleep and could reshape how scientists think about sleep, ageing, and neurological disease.

Led by Professor Gero Miesenböck from the Department of Physiology, Anatomy and Genetics (DPAG), and Dr Raffaele Sarnataro at Oxford’s Centre for Neural Circuits and Behaviour, the team found that sleep is triggered by the brain’s response to a subtle form of energy imbalance. The key lies in mitochondria – microscopic structures inside cells that use oxygen to convert food into energy.

When the mitochondria of certain sleep-regulating brain cells (studied in fruit flies) become overcharged, they start to leak electrons, producing potentially damaging byproducts known as reactive oxygen species. This leak appears to act as a warning signal that pushes the brain into sleep, restoring equilibrium before damage spreads more widely.

‘You don’t want your mitochondria to leak too many electrons,’ said Dr Sarnataro. ‘When they do, they generate reactive molecules that damage cells.’

The researchers found that specialised neurons act like circuit breakers – measuring this mitochondrial electron leak and triggering sleep when a threshold is crossed. By manipulating the energy handling in these cells – either increasing or decreasing electron flow – the scientists could directly control how much the flies slept.

Even replacing electrons with energy from light (using proteins borrowed from microorganisms) had the same effect: more energy, more leak, more sleep.

Professor Miesenböck said: ‘We set out to understand what sleep is for, and why we feel the need to sleep at all. Despite decades of research, no one had identified a clear physical trigger. Our findings show that the answer may lie in the very process that fuels our bodies: aerobic metabolism. In certain sleep-regulating neurons, we discovered that mitochondria – the cell’s energy producers – leak electrons when there is an oversupply. When the leak becomes too large, these cells act like circuit breakers, tripping the system into sleep to prevent overload.’

The findings help explain well-known links between metabolism, sleep, and lifespan. Smaller animals, which consume more oxygen per gram of body weight, tend to sleep more and live shorter lives. Humans with mitochondrial diseases often experience debilitating fatigue even without exertion, now potentially explained by the same mechanism.

‘This research answers one of biology’s big mysteries,’ said Dr Sarnataro.

‘Why do we need sleep? The answer appears to be written into the very way our cells convert oxygen into energy.’

The paper, ‘Mitochondrial origins of the pressure to sleep‘, is published in Nature.

Source: University of Oxford

Categories : Cardiovascular Disease Metabolic DisordersTags :

Study Finds Higher Cardiovascular Risk for One Particular Sulfonylurea

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Photo by Stephen Foster on Unsplash

New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the US within this category, but not available in South Africa – was linked to higher incidence of heart failure, related hospitalisation and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published in JAMA Network Open.

“Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest,” said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors.”

Turchin and co-authors emulated a target trial by analysing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48 165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those covered by two different national health insurance plans.

The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide) or DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.

“Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits,” said Turchin. 

Source: Mass General Brigham

Categories : Cancer GeneticsTags :

Women of African Ancestry May Be Biologically Predisposed to Early-onset or Aggressive Breast Cancers

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Photo by National Cancer Institute

While the incidence of breast cancer is highest for white women, Black women are more likely to have early-onset or more aggressive subtypes of breast cancer, such as triple-negative breast cancer. Among women under 50, the disparity is even greater: young Black women have double the mortality rate of young white women.

Now, research from the University of Notre Dame is shedding light on biological factors that may play a role in this disparity. The study published in iScience found that a population of cells in breast tissues, dubbed PZP cells, send cues that prompt behavioural changes that could promote breast cancer growth.

Funded by the National Cancer Institute at the National Institutes of Health, the study set out to explore what biological differences in breast tissue could be related to early onset or aggressive breast cancers. Most breast cancers are carcinomas, or a type of cancer that develops from epithelial cells. In healthy tissue, epithelial cells form linings in the body and typically have strong adhesive properties and do not move.

The researchers focused on PZP cells as previous studies had shown that these cells are naturally and significantly higher in healthy breast tissues of women of African ancestry than in healthy breast tissues of women of European ancestry. While PZP cell levels are known to be elevated in breast cancer patients in general, their higher numbers in healthy, African ancestry tissues could hold clues to why early-onset or aggressive breast cancers are more likely to occur in Black women.

“The disparity in breast cancer mortality rates, particularly among women of African descent, is multifaceted. While socioeconomic factors and delayed diagnosis may be contributing factors, substantial emerging evidence suggests that biological and genetic differences between racial groups can also play a role,” said Crislyn D’Souza-Schorey, the Morris Pollard Professor of Biological Sciences at Notre Dame and corresponding author of the study.

The study showed how PZP cells produce factors that activate epithelial cells to become invasive, where they detach from their primary site and invade the surrounding tissue.

For example, a particular biological signaling protein known as AKT is often overactive in breast cancers. This study showed that PZP cells can activate the AKT protein in breast epithelial cells, which in part allows them to invade the surrounding environment. PZP cells also secrete and deposit certain proteins outside the cell that guide the movement of breast epithelial cells as they invade.

Overall, the results of the study emphasize multiple mechanisms by which PZP cells may influence the early stages of breast cancer progression and their potential contribution to disease burden.

The researchers also looked at how a targeted breast cancer drug, capivasertib, which inhibits the AKT protein, impacted PZP cells and found it markedly reduced the effects of the PZP cells on breast epithelial cells.

“It’s important to understand the biological and genetic differences within normal tissue as well as tumours among racial groups, as these variations could potentially influence treatment options and survival rates. And consequently, in planning biomarker studies, cancer screenings or clinical trials, inclusivity is important,” said D’Souza-Schorey, also an affiliate of Notre Dame’s Berthiaume Institute for Precision Health and Harper Cancer Research Institute.

Source: University of Notre Dame

Categories : GeneticsTags :

US Self-reported Race and Ethnicity Are Poor Proxies of Genetic Ancestry

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Photo by ROCKETMANN TEAM

Genetic ancestry is much more complicated than how people report their race and ethnicity. New research, using data from the National Institutes of Health’s (NIH) All of Us Research Program, finds that people who identify as being from the same race or ethnic group can have a wide range of genetic differences. The findings are reported in the American Journal of Human Genetics, a Cell Press journal.

As doctors and researchers learn more about how genetic variants influence the incidence and course of human diseases, the study of genetic ancestry has become increasingly important. This research is driving the field of precision medicine, which aims to develop individualised healthcare.

People whose ancestors came from the same part of the world are likely to have inherited the same genetic variants, but self-identified race and ethnicity don’t tell the whole story about a person’s ancestors. NIH’s All of Us Research Program was created in part to address this puzzle and to learn more about how genetic ancestry influences human health.

In the current study, the investigators looked at the DNA of more than 230 000 people who have volunteered to share their health information for All of Us. They compared it to other large DNA projects from around the world using a technique called principal component analysis (PCA) to visualize population structure and help identify genetic similarity between individuals and groups of people. This analysis showed that people in the US have very mixed ancestry, and their DNA doesn’t always match the race or ethnicity they write on forms. Instead of falling into clear groups based on race or ethnicity, people’s genetic backgrounds show gradients of variation across different US regions and states.

This is especially significant for people who identify as being of Hispanic or Latino origin. These people have a wide-ranging blend of ancestries from European, Native American, and African groups. Importantly, genetic ancestry among these people varies across the US in part because of historic migration patterns. For example, Hispanics/Latinos in the Northeast are more likely to have Caribbean (and thus African) ancestry, and those in the Southwest are more likely to have Mexican and Central American (and thus Native American) ancestry.

One specific discovery was that ancestry was significantly associated with body mass index (BMI) and height, even after adjusting for socio-economic differences. For example, West and Central African ancestries were associated with higher BMI, whereas East Africa ancestry was associated with lower BMI. There were similar findings showing that people with ancestral origins from different parts of Europe have different body measurements including height, with northern European ancestry associated with greater height and southern European ancestry associated with shorter height. This suggests that subcontinental differences in ancestry can have opposite effects on biological traits and diseases.

This finding suggests that the subcontinental differences in ancestry between individuals can have opposite effects on biological traits, diseases, and health outcomes, emphasizing the importance of not classifying individuals into broad ancestry groups such as African, European, or Asian. Doing this will help to make this research more accurate and will help to improve the field of precision medicine.

Source: EurekAlert!

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

How Obesity also Affects the Next Generation

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Study reveals why children of obese mothers are more likely to develop metabolic disorders

Metabolites – from the mother permanently reprogram Kupffer cells. This changes their function, causes liver cells (hepatocytes) to accumulate fat and ultimately leads to a fatty liver. The graphic was created with BioRender.com (http://BioRender.com). © Image: AG Mass/University of Bonn

Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn published in the journal Nature offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans.

The team focused on the so-called Kupffer cells. These are macrophages that help protect the body as part of the innate immune system. During embryonic development, they migrate into the liver, where they take up permanent residence. There, they fight off pathogens and break down ageing or damaged cells.

“But these Kupffer cells also act as conductors,” explains Prof Dr Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

Changing the tune: From Beethoven to Vivaldi

It appears, however, that it is this conducting function that is changed by obesity. This is what mouse experiments carried out by Mass in cooperation with other research groups at the University of Bonn suggest. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”

The cause of this disorder seems to be a kind of “reprogramming” of the Kupffer cells in the offspring. As a result, they send out molecular signals that instruct the liver cells to take up more fat. Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi.

This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”

No fatty liver without the molecular switch

When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.

If new treatment approaches emerge from this, it would be good news. The altered behaviour of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause increasing numbers of hepatocytes to die and be replaced with scar tissue, resulting in fibrosis. At the same time, the risk that hepatocytes degenerate and become cancerous increases.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”

Source: University of Bonn

Categories : Diet and Nutrition PaediatricsTags :

Consuming Certain Sweeteners May Increase Risk of Early Puberty

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Photo by Amit Lahav on Unsplash

Consuming certain sweeteners commonly found in foods and beverages may increase the risk of early puberty in children, particularly among those who are genetically predisposed, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif. 

The researchers found that consuming aspartame, sucralose, glycyrrhizin and added sugars was significantly associated with a higher risk of early puberty, especially in children with certain genetic traits. The more of these sweeteners the teens consumed, the higher their risk of central precocious puberty.

“This study is one of the first to connect modern dietary habits – specifically sweetener intake – with both genetic factors and early puberty development in a large, real-world cohort,” said Yang-Ching Chen, MD, PhD, of Taipei Municipal Wan Fang Hospital and Taipei Medical University in Taipei, Taiwan. “It also highlights gender differences in how sweeteners affect boys and girls, adding an important layer to our understanding of individualised health risks.” 

A type of early puberty known as central precocious puberty is increasingly common. It can lead to emotional distress, shorter adult height, and increased risk of future metabolic and reproductive disorders.

Chen’s previous research found that certain sweeteners can directly influence hormones and gut bacteria linked to early puberty. For example, one artificial sweetener, acesulfame potassium or AceK, was shown to trigger the release of puberty-related hormones by activating “sweet taste” pathways in brain cells and increasing stress-related molecules. Another sweetener, glycyrrhizin (found in liquorice) was found to change the balance of gut bacteria and reduce the activity of genes involved in triggering puberty. 

“This suggests that what children eat and drink, especially products with sweeteners, may have a surprising and powerful impact on their development,” Chen said.

The new findings come from the Taiwan Pubertal Longitudinal Study (TPLS), begun in 2018. The study included data from 1407 teens. Central precocious puberty was diagnosed in 481 teens. The researchers assessed teens’ sweetener intake through validated questionnaires and testing of urine samples. Genetic predisposition was quantified using polygenic risk scores derived from 19 genes related to central precocious puberty. Early puberty was diagnosed based on medical exams, hormone levels and scans. 

Sucralose consumption was linked to a higher risk of central precocious puberty in boys and consumption of glycyrrhizin, sucralose and added sugars was associated with a higher risk of central precocious puberty in girls.

“The findings are directly relevant to families, paediatricians and public health authorities,” Chen said. “They suggest that screening for genetic risk and moderating sweetener intake could help prevent early puberty and its long-term health consequences. This could lead to new dietary guidelines or risk assessment tools for children, supporting healthier development.”

Source: The Endocrine Society

Categories : Immunology PaediatricsTags :

Prenatal Exposure to PFAS ‘Forever Chemicals’ Shapes Baby Immunity

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PFAS lurks in numerous consumer products – from nonstick cookware and food packaging to stain-resistant fabrics and personal care items. Photo by Cooker King on Unsplash

New research reveals that tiny amounts of per- and polyfluoroalkyl substances (PFAS; widely known as “forever chemicals”) cross the placenta and breast milk to alter infants’ developing immune systems, potentially leaving lasting imprints on their ability to fight disease.

University of Rochester Medical Center (URMC) researchers tracked 200 local healthy mother–baby pairs, measuring common PFAS compounds in maternal blood during pregnancy and then profiling infants’ key T‑cell populations at birth, six months, and one year. By age 12 months, babies whose mothers had higher prenatal PFAS exposure exhibited significantly fewer T follicular helper (Tfh) cells – vital coaches that help B cells produce strong, long‑lasting antibodies – and disproportionately more Th2, Th1, and regulatory T cells (Tregs), each linked to allergies, autoimmunity, or immune suppression when out of balance.

“This is the first study to identify changes in specific immune cells that are in the process of developing at the time of PFAS exposure,” said Kristin Scheible, MD, an associate professor of Pediatrics and Microbiology & Immunology at URMC and lead author of the study, which appears in the journal Environmental Health Perspectives. “Identification of these particular cells and pathways opens up the potential for early monitoring or mitigation strategies for the effects of PFAS exposure, in order to prevent lifelong diseases.”

Implications for vaccines, allergies, and autoimmunity

Tfh cell depletion helps explain previous findings that higher PFAS levels in children correlate with weaker vaccine responses to tetanus, measles, and other routine immunisations. Conversely, the uptick in Th2 and Treg cells can predispose to allergic inflammation or dampened defences, while excess Th1 activity raises concerns about future autoimmune conditions such as juvenile arthritis or type 1 diabetes.

“The cells impacted by PFAS exposure play important roles in fighting infections and establishing long-term memory to vaccines,” said Darline Castro Meléndez, PhD, a researcher in Scheible’s lab and first author of the study. “An imbalance at a time when the immune system is learning how and when to respond can lead to a higher risk of recurrent infections with more severe symptoms that could carry on through their lifetime.”

Minimising PFAS exposure

Although Rochester’s drinking water meets current safety standards, PFAS lurks in numerous consumer products – from nonstick cookware and food packaging to stain-resistant fabrics and personal care items. The study’s mothers had relatively low PFAS blood levels compared to other regions, yet the immune shifts were pronounced even in this small sample.

While not all environmental exposures can be avoided, families can reduce PFAS contact during critical windows of foetal and infant immune development. “Use water filters, minimise cooking in damaged nonstick pans, switch to alternatives like stainless steel or cast iron, and store food in glass or ceramic containers,” said Scheible. “Small steps can help lower the cumulative burden of exposure.”

The team plans a longer follow-up to determine whether these early T‑cell imbalances persist into toddlerhood and whether they translate into more infections, allergies, or autoimmune diseases. Measuring PFAS in infants directly and unravelling the molecular underpinnings of these immune disruptions are key objectives for future research.

Source: University of Rochester

Categories : Obstetrics & Gynaecology Skeletal SystemTags :

Stopping HRT Leads to a Period of Higher Fracture Risk for Most Women

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Photo by Mehmet Turgut Kirkgoz on Unsplash

A new study has found that the bone fracture protection women get from menopausal hormone therapy (MHT, also known as HRT) disappears within a year of stopping treatment.

In the new study, published in Lancet Healthy Longevity, experts from the School of Medicine at the University of Nottingham, also found that in most cases, stopping treatment is then followed by some years of elevated fracture risk compared to women who have never used MHT. Fracture risks then falls to be similar to, and then lower than women who have never used MHT.

The study was funded by the National Institute for Health and Care Research (NIHR) SPCR.

During menopause, all women experience a drop in hormone levels, particularly of oestrogen. This can cause a range of distressing mental and physical side effects, requiring use of MHT. However, oestrogen deficiency in women also leads to increased age-related bone weakening. Previous studies have confirmed a protective role of the oestrogen component in MHT treatments, and MHT is known to decrease fracture risk when it is being used.

However, MHT is also associated with increased risk of breast cancer and blood clots, so long-term MHT use is not recommended. For women using MHT to counteract increasing bone fragility, it is, therefore, important to know the strength and persistence of any protective effect after stopping treatment. Detailed information on this aspect from past studies has been unclear – covering only the first couple of years, and also being somewhat conflicting.

In this new study, experts used data for 6 000 000 women from around 2000 GP surgeries in the UK, which allowed them to follow-up of fracture risk levels for up to 25 years. The researchers identified all women with records of first fracture (cases) and matched each to a number of women of the same age and from the same practice, but without record of fracture (controls). They then compared the MHT use in cases before their fracture with the MHT use among their matched controls.

The findings of our study confirmed that women on MHT show a progressively reducing fracture risk compared with women not using MHT. More importantly, we also observed a clear pattern of risk change after therapy was discontinued. For most women, the bone protective effect of MHT use disappears completely within about one year of treatment being stopped, then their fracture risk rises compared to never users, peaking after about three years, before declining to become again equivalent to never users – about 10 years after discontinuation – and then again continuing to decline relative to never users. So, even after stopping MHT, women should benefit from notably reduced fracture risk in their later decades.”

Dr Yana Vinogradova, from the Centre for Academic Primary Care in the School of Medicine, and lead author of the study

This observed risk pattern was the same for all menopausal hormonal treatments, but the level of excess risk depended on the treatment type and the length of past MHT use.

“Our comparative illustration of observed patterns of fracture risk for short and long use can help doctors and patients when discussing MHT treatment options, and to consider how fracture risk may change after stopping MHT use. Anticipating periods of increased risk might prompt doctors to check patients’ bone health at discontinuation, particularly for patients most at risk with other fracture risk factors such as smoking or inactivity.

“These novel findings may also usefully stimulate further clinical and biological research into these treatments,” adds Dr Vinogradova.

Source: University of Nottingham