Tag: sex differences

Categories : Metabolic DisordersTags : Leave a comment

Women with Type 2 Diabetes More Likely to Develop Mental Health Conditions

On By ModernMedia

Men, on the other hand, experience more cardiovascular and renal disease post-diagnosis

Photo by isens usa on Unsplash

In the years following type 2 diabetes diagnosis, women are more likely to develop mental health conditions, while men are more likely to develop cardiovascular and renal complications, according to a study published August 25th in the open access journal PLOS Medicine by Fabiola Eto from Queen Mary University of London, UK, and colleagues.

Type 2 diabetes, a metabolic disorder defined by high blood sugar, results from resistance to or insufficient production of insulin. Globally, type 2 diabetes affects about 536.6 million people between 20 and 79 years old, or 10.5% of the population; by 2045, this number is expected to rise to 700 million. Cardiovascular disease, end-stage renal disease, and mental health disorders like depression and anxiety are all associated with type 2 diabetes. Women and men are known to experience these conditions differently, but research has not yet described the disease trajectories according to sex and age in people with type 2 diabetes.

Eto and colleagues examined anonymized health records from 28,720 men and women in the UK who developed type 2 diabetes between 2010 and 2020. Men constituted 62% of the cohort with a median age of 54 at type 2 diabetes onset; women were on average older at diagnosis.

In the years following diagnosis, 39% of the participants experienced at least one significant health event. The events’ trajectory and timing differed by sex. For example: women were more likely to develop mental health conditions post-diagnosis (8.1% compared to 5.3%) and to experience trajectories culminating in death, while men showed higher proportions of cardiovascular disease (8.4% compared to 5.3%), end-stage renal disease, and hypertension (21.1% compared to 20.2%). The researchers noted that on average, women used more health services and long-term prescriptions than men, which may contribute to the increased diagnoses.

There were several similarities between the sexes as well. Both women and men who had a combination of type 2 diabetes and a mental health condition experienced premature mortality compared to other trajectories. Across all age groups and sexes, hypertension was the most frequent event following type 2 diabetes.

Current UK medical guidelines lack sex-specific prevention strategies and management for type 2 diabetes and comorbidities, especially mental health conditions. This study highlights the need for healthcare interventions differentiated by characteristics like sex and age.

The authors add, “One of the clearest signals in our data was the sex difference. Younger women with type 2 diabetes were showing mental health complications earlier and more often than we expected, which suggests routine psychological screening should be incorporated into standard diabetes care. For men, the pattern looked different: cardiovascular and kidney risks tended to emerge earlier, pointing to a need for earlier monitoring and stronger strategies to support men’s engagement with their treatment over time.”

Provided by PLOS

Categories : Gender NeurologyTags : Leave a comment

Neuroscience Reports of Sex-dependent Effects Often Lack Evidence

On By ModernMedia
Photo by Daniil Onischenko on Unsplash

Studies in the behavioural and brain sciences reporting a major sex-dependent effect – that a drug, treatment or other intervention is more effective in one sex than another – are supported by appropriate evidence less than 25% of the time, an analysis finds.

The Proceedings of the National Academy of Sciences (PNAS) published the analysis of 200 recent articles with a claim of a sex- or gender-dependent effect in the title. The articles included studies on human and non-human subjects and spanned six brain-related research areas: behavioural sciences, clinical neurology, neurosciences, psychiatry, psychology and substance abuse.

“We found that studies in psychology had the highest rate of appropriate evidence – 39% of the published papers included statistical evidence to support the claim of a sex difference,” says Donna Maney, corresponding author of the study and professor of psychology at Emory University. “Research in neuroscience had the lowest rate of appropriate evidence, at just 18%.”

The low rate of appropriate evidence in neuroscience is particularly troubling, Maney says. She notes that claims of sex-dependent effects are more numerous in neuroscience, where such reports are currently being published at triple the rate seen in any other field.

“The high number of reports seen in neuroscience may be due to bias – neuroscientists looking harder for sex differences than other scientists,” Maney says. “But most current evidence shows that the brain is one of the least sexually differentiated organs in the body.”

Maney’s team was particularly alarmed by the number of calls for changes in clinical approaches that were based on faulty analyses. Many of the 200 articles they reviewed, for example, called for sex-specific approaches to suicide prevention, stress-related psychiatric disorders, substance-use disorder and psychopathy – all without providing statistical comparisons of effects across sex.

First author of the PNAS paper is Madeline Olivier, who did the work as an Emory student and has since graduated with a BS in psychology. 
 

Summary of findings

  • In 24% of the 200 papers, the effect compared statistically across sex and the results supported the claim of a sex-dependent effect.
  • In 9%, the researchers tested for a sex difference, but the results were missing.
  • In 9.5%, the sex difference in the effect was reported as not statistically significant, which was incompatible with the claim in the title.
  • In 57.5%, the sexes were not statistically compared — the researchers did not test the claim in the title at all.


A logical error 

Maney is a neuroscientist who studies hormonal and genetic influences on behaviour. For more than a decade, she has also focused on investigating how sex differences are tested for and reported in biomedical research. 

One issue she emphasises is that, instead of comparing the sexes directly with each other, researchers often test for the effect in each sex separately. Although it might make sense on the surface, the practice reduces the number of subjects to the point where a real effect can be missed. If the effect is detected in one sex but missed in the other, researchers are vulnerable to a logical error: that the effect differs between the sexes, when they have not been directly compared. 

To show that the sexes differ, females and males must be directly compared with each other in a statistical test. Most of the articles analysed by Maney and colleagues for the current PNAS paper did not do that. Instead, the researchers relied on the individual, within-sex tests – an invalid way of comparing the sexes that produces the illusion of a difference up to 50% of the time. “It’s no better than flipping a coin,” Maney says.

It’s also easy to miss true sex differences with a subgroup approach. For example, men and women could respond differently to a treatment but when the sample is divided in half and tested separately, the effect could be missed in both.

Maney cites the classic example of a large clinical trial showing that aspirin significantly reduced mortality from heart attacks. To illustrate the problem with the subgroup error, cardiologist Peter Sleight reanalysed the data by dividing participants into subgroups according to their astrological signs. Once the trial was split into 12 zodiac groups, the benefit of aspirin was no longer statistically detectable among the Libras and Geminis.

Sleight’s “findings” demonstrated how dividing a large group into subgroups can make a real effect disappear in some of the groups, even when the treatment is clearly beneficial. 

“This problem is not new,” says Maney. “I made the error myself until I learned about it. “Many researchers don’t receive training in how to test whether an effect differs between two groups.”
 

A simple solution

To provide evidence that an effect differs by sex, the effect must be statistically compared between males and females, Maney emphasises. Only that approach can show sufficient evidence for a sex difference.

She designed an open-source tool, housed on the web at sexdifference.org, to help guide researchers to verify sex-specific effects.

Maney’s interests extend beyond statistical sex comparisons.

“Ultimately,” she says, “I would like to see researchers not treat sex as the most important variable in a biomedical study. Variation in participants’ weights, ages or habits, for example, likely explains variation in the effect of a treatment better than which sex category they are in.”

Original written by Carol Clark

Source: Emory University

Categories : UncategorizedTags :

Coffee’s Biological Benefits Linked to Metabolic Health and Sex Hormones

On By ModernMedia
Photo by Porapak Apichodilok on Pexels

Coffee is one of the world’s most widely consumed beverages, and previous research has linked its consumption to a lower risk of conditions such as type 2 diabetes and cardiovascular disease. However, the biological mechanisms behind these benefits remain unclear. A new Finnish study links habitual coffee consumption to healthier body composition and metabolic markers, while revealing distinct associations with sex hormones in men and women.

The study, conducted at the University of Oulu, analysed data from 2264 participants aged 46 in the Northern Finland Birth Cohort 1966. Researchers examined how habitual coffee consumption was associated with circulating metabolites, cardiometabolic risk markers and sex hormones.

Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.

In both men and women, higher coffee consumption was correlated with lower circulating levels of branched-chain amino acids, biomarkers that have previously been linked to insulin resistance and an increased risk of type 2 diabetes when chronically elevated.

The strongest sex-specific associations were observed in men. Higher coffee consumption was linked to a more favourable glucose–insulin profile, higher concentrations of total and bioavailable testosterone, and increased levels of sex hormone-binding globulin (SHBG). At the same time, free testosterone and the free androgen index were modestly lower. In women, hormonal associations were more limited and were primarily characterised by higher SHBG and lower measures of free androgens.

“Coffee is consumed by millions of people every day, yet we still know surprisingly little about how it relates to our metabolism and hormones. What stood out in our findings was a distinct hormonal signature that didn’t disappear even after we took into account BMI and lifestyle factors, with several of these associations differing between men and women,” says Luca Verroest, lead author of the study and Doctoral Researcher at the University of Oulu.

The results suggest that hormonal pathways may partly explain the relationship between coffee consumption and metabolic health. However, as this was an observational study, the findings demonstrate associations rather than cause-and-effect relationships.

The study is particularly relevant in Finland, one of the world’s highest coffee-consuming countries, where annual consumption averages around 11.8 kilograms per person.

The researchers say the findings provide a foundation for future studies aimed at determining whether coffee itself drives these biological changes and identifying the compounds responsible. These questions are currently being investigated in animal models, with the long-term goal of progressing to human intervention studies. Further research will be needed before the findings could inform dietary recommendations.

The study, Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland Birth Cohort 1966 study, has been published in the European Journal of Nutrition on 16 July 2026.

Source: University of Oulu

Categories : CancerTags :

Uncovering Sex-specific Immune Differences in Glioblastoma

On By ModernMedia
Photo by Anna Shvets

Men and women experience many diseases very differently. Certain diseases present more commonly in one sex than in another. Some conditions like heart attacks may cause different symptoms in men and women. Some treatments work better or not at all for one sex over the other.

Cancer is no exception. There are major differences in male and female immune systems, a system critical for cancer’s growth and for successfully becoming cancer-free. For example, some immunotherapies work better in men than in women and vice versa.

Glioblastoma, the most common and fatal form of brain cancer, is more common and more deadly in men than in women. The reasons behind this difference and how the cancer’s biology differs between men and women remain largely unclear.

Now, a study has identified a cellular mechanism that differs between male and female laboratory models with glioblastoma. The study was published in the journal Nature Cancer and led by Defne Bayik, PhD, assistant professor of molecular and cellular pharmacology at the University of Miami Miller School of Medicine, and Asmita Pathak, PhD, a former postdoctoral fellow in the Bayik Lab.

“We have a growing appreciation that cancer doesn’t act the same way in men and women. There are differences in incidence rates. There are differences in treatment responses. There are differences in outcomes,” Dr Bayik said. “But we don’t really have a good, fundamental understanding of the mechanisms underlying these observational studies.”

Delving Into Immune Differences

To uncover that mechanism for glioblastoma, Dr Bayik and her colleagues focused on a certain class of immune cells in the brain known as myeloid-derived suppressor cells, or MDSCs. As their name suggests, these cells suppress other cells’ immune activity, especially that of T cells. In healthy contexts, their activity is important for regulating the immune system and keeping inflammation under control. But in the context of cancer, these cells are often recruited by tumours to suppress surrounding T cells and other immune cells, protecting cancerous cells from the rest of the immune system and allowing them to grow unchecked.

In previous work, Dr Bayik found sex-specific differences in the immune landscape of glioblastoma, with higher levels of monocytic myeloid-derived suppressor cells associated with disease in male laboratory models. Granulocytic MDSCs play a more prominent role in females. In studies of human glioblastoma tumours, she observed a similar pattern. Men tend to have more monocytic MDSCs within their tumours, Granulocytic MDSCs, or proteins associated with these cells, correlate with worse outcomes for women but not for men.

Women still constitute 40% of glioblastoma patients. By identifying these differences, we can better tailor treatments for both men and women.

Dr Defne Bayik

In the new study, Dr Bayik and her colleagues wanted to understand what drives this difference. How do granulocytic MDSCs act to promote cancer growth in female but not male laboratory models? In Dr Bayik’s previous study, she’d found several drug candidates that are predicted to act on granulocytic MDSCs. A few of these candidate drugs target proteins related to GABA, a brain signaling molecule also known as a neurotransmitter.

By exposing different populations of MDSCs to GABA in the lab, the scientists found that the neurotransmitter specifically affects cellular metabolism only in female granulocytic MDSCs. The process is unaffected in male MDSCs. They also found that this reprogramming of the cells’ metabolism by GABA made the granulocytic MDSCs more immunosuppressive. Finally, they found that blocking the GABA receptor in female laboratory models with glioblastoma improved their outcome. This had no effect on male laboratory models with the cancer.

Potential for treatment personalised by sex

Dr Bayik and her colleagues found that many of their lab findings held up in human samples donated by patients with glioblastoma. Tumour biopsies from women had higher levels of GABA and the GABA receptor in granulocytic MDSCs than did those from men. They also found that GABA reprograms granulocytic MDSC metabolism in women as it does in lab models.

These findings point to the potential for a sex-specific treatment for glioblastoma, Dr. Bayik said. She’s currently working to understand the basis for the difference in cellular metabolism in these immune cells between male and female laboratory models. Further uncovering the mechanism of this sex difference will help her and other scientists find new potential drug targets for the disease. MDSCs are involved in many other types of cance. Drugs that target these cells could have broader applications than just glioblastoma.

“Glioblastoma may be more common in men, but women still constitute 40% of patients,” said Dr Bayik. “By identifying these differences, we can better tailor treatments for both men and women.”

By Rachel Tompa, PhD

Source: University of Miami

Categories : Mental HealthTags :

Women Report Poor Sleep Despite a Good Night’s Rest – While Men Overestimate Their Own Sleep Quality

On By ModernMedia
Men reported sleeping better than they objectively did, while the opposite was true for women. Photo by Ketut Subiyanto on Pexels

Torbjörn Åkerstedt, Karolinska Institutet

Disturbed sleep is a common problem — and one that has many serious consequences beyond feeling tired the next day. Research has linked insomnia and poor sleep to early mortality and diseases including diabetes and cardiovascular disease.

Women often report experiencing disturbed sleep more frequently than men. They also constitute the majority of patients in sleep clinics. Yet strangely, some studies show worse objective sleep quality in men – a bit of a paradox.

To understand what might explain the paradox, my colleagues and I conducted a study that directly compared sleep quality ratings and objective sleep measures between men and women.

We found that women complained more of sleep problems – but slept objectively much better than men. We think this paradox can probably be explained by men overestimating their sleep quality as they’re less able to perceive how often they wake up at night.

A total of 238 randomly selected women participated in the study, plus 238 men who were matched on age and BMI with the women to ensure similar participants were compared against each other.

Sleep was recorded in each participant’s home using a recorder that measured brain waves (electroencephalography – EEG), muscle tension (electromyography – EMG) and eye movements (electrooculography – EOG). These devices tracked what stage of sleep a participant was in and for how long, how much time they spent awake and how quickly they fell asleep.

A researcher visited the participant’s home in the evening, mounted the recording equipment and left. The participant went to bed and awoke at their usual time.

In the morning, the participant rated the degree of difficulty they had falling asleep, if their sleep was restless, if they woke up early, how often they thought they’d woken up, how long it took them to fall asleep, how long they slept and their overall sleep quality.

The sleep recording was scored by a sleep technician based on visual inspection of the EEG, EOG and EMG recordings. The data was then analysed to understand the objective quality of each participant’s sleep and its relation to gender and age.

Analyses were also adjusted for factors such as gender, age and alcohol consumption and smoking, which may affect sleep.

Sleep quality

The results show that women subjectively reported significantly lower sleep quality than men. Yet women actually had considerably fewer nighttime awakenings, less stage one (superficial) sleep and higher sleep efficiency (they spent more time asleep while in bed). Women also experienced more stage three (deep) sleep and slept longer (400 minutes versus 382 minutes for men).

When women did wake up at night, they spent more time awake on average. Photo by Cottonbro on Pexels

The results suggest that women objectively had a good nights’ sleep, compared to men. The only variable that suggests worse sleep in women was that when they did wake up at night, they spent more time awake than men did – around nine minutes each time for women versus just under seven minutes for men.

It only takes around five minutes of being awake at night for a person to remember it the next morning. This may explain why women were better able to remember if they’d woken up the night before and estimate how many times they had. Men, on the other hand, grossly underestimated their number of awakenings (by 72% compared to women’s 37%).

For other quantitative measures, like time to fall asleep, sleep duration and time awake, men and women were equally good at estimating their objective values. And they were relatively correct.

We took this further and found that men who only woke up for a short period of time during the night (around eight minutes or so each time they woke up) often didn’t remember they had.

When this group of men was removed, no gender difference in subjective sleep quality remained. This suggests that men with short nighttime awakenings report better sleep quality than would be expected from their objective sleep measures as they didn’t remember they’d woken up.

It’s also noteworthy that men’s objective sleep deteriorated faster with age than women. This was particularly obvious for stage three sleep. While women aged over 65 got around 80 minutes of stage three sleep each night, men had only 53 minutes. Among those between 30 and 50 years of age, the amount was similar for men and women (around 70 minutes).

Sleep and wellbeing

A key reason women may complain of having a worse nights’ sleep than they objectively had may therefore be the amount of time they spent awake when they woke up, making it easier for them to notice. Likewise, men may overestimate their sleep quality because they’ve spent less time awake when they’ve woken up, so they don’t remember it happening.

Both findings would work towards reducing subjective sleep quality in women and increasing it in men. We assume then, that the experience of awakenings has an important influence on subjective sleep quality.

As our study was only conducted over one night, it will be important for future research to investigate whether these findings remain when participants are studied over longer periods of time.

Future studies may also want to explore the reasons for poor sleep in men – especially since common sources of disturbed sleep, such as alcohol, smoking and BMI, were all adjusted for in our analysis. Researchers may also want to investigate why men’s sleep becomes objectively worse as they get older.

Our research illustrates how sleep quality doesn’t just involve the physiological aspects of sleep. It also includes our own subjective experiences, which can impact our wellbeing and how rested we feel.

It also suggests that because many men overestimate their sleep quality, they may also overlook any sleep problems they’re experiencing. This could mean that some men aren’t getting help for conditions that could be affecting their health and wellbeing.

Torbjörn Åkerstedt, Senior Professor of Psychology, Department of Clinical Neuroscience, Karolinska Institutet

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : ImmunologyTags :

Chimeric RNA Unique to Women Is an Important Controller of Health

On By ModernMedia

Strange “chimeric” RNA once thought to be the product of cancer is actually an important controller of women’s health, including influencing their susceptibility to infectious disease and autoimmune disorders, new University of Virginia School of Medicine research suggests.

UVA’s Hui Li, PhD, and colleagues have identified a chimeric RNA called UBA1-CDK16 that is found only in women. This RNA plays important roles in their blood cell development and in determining the severity of diseases such as COVID-19, the scientists found. The findings, published in Science Advances, could open the door to blood tests to help diagnose diseases or identify women at greatest risk for bad outcomes.

“Chimeric RNAs are RNA molecules composed of parts from different genes,” said Li, of UVA’s Department of Pathology and the UVA Comprehensive Cancer Center. “They were once believed to be cancer-specific. However, our research shows that they can also be part of normal physiology and play important roles in human health.”

Powerful Chimeras

RNA provides instructions for our cells, telling them what to do based on the genetic material, called DNA, that we inherit from our parents. Chimeric RNAs were long thought to be mistakes, as they are made up of instructions mashed together from different genes. This is why they were believed to be a byproduct of cancer; cancer itself is the result of cellular copying mistakes.

Li’s discovery, however, suggests that UBA1-CDK16  plays important roles in maintaining women’s health and in controlling their immune systems. This chimeric RNA is found only in women because women have two X chromosomes, while men have an X and Y. Normally, one of the two X chromosomes found in women’s cells are inactive. But Li found that the inactive X chromosome produces this peculiar chimeric RNA that he could identify in women’s blood.

Based on his findings, Li believes UBA1-CDK16 plays an important role in regulating blood cell formation. But his work also suggests the chimera may play an important role in the immune system’s response to infection. He found that the chimeric RNA was lost in 50% women who developed severe COVID-19 infections, while it was present in women who were asymptomatic. Further, the decrease in chimeric RNA correlated with the increasing severity of the infection.

Li suspects that the chimeric RNA may play an important role in governing the development of immune cells called neutrophils that act as the body’s first responders to infection. (Neutrophil count has already been identified as a way to predict how patients will fare against COVID-19.) 

“As humans share similar number of genes with fruit flies and worms, gene number does not explain why we are much more sophisticated than these lower organisms” Li said. “We believe chimeric RNAs are another means to expand the functional genome, without an actual increase in gene number.”

Li’s findings suggest that the chimeric RNA also may serve as a natural brake to protect women from excessive autoimmune activity. Women are far more likely to suffer autoimmune disorders than men, and Li is urging additional research to better understand the role chimeric RNA could be playing – and how it could be targeted to improve patient outcomes.

“This finding highlights there is another layer of control for gene expression,” Li said. “These chimeric RNAs may represent a hidden repertoire for biomarkers and therapy targets as well.”

Source: University of Virginia

Categories : CancerTags :

Age, Sex, and Cancer Type Influence Risk of Subsequent Cancers Among Survivors

On By ModernMedia

Findings may have implications for long-term cancer survivorship surveillance

Researchers assess the risk of developing a subsequent primary cancer based on demographic factors and cancer characteristics. Tara Winstead, Pexels (CC0, https://creativecommons.org/publicdomain/zero/1.0/)

Risk of developing a subsequent primary cancer varied significantly by age at initial diagnosis, sex, and type of first cancer, according to a study by Oxana Palesh and Susan Hong and colleagues at Virginia Commonwealth University, U.S., published April 28th in the open-access journal PLOS Medicine.

Advances in cancer detection and treatment have led to a growing population of cancer survivors. In the U.S., the number of cancer survivors is expected to grow by 22% over the next decade – from 18 million in 2025 to more than 22 million by 2035. Survivors remain at higher risk for developing new primary cancers distinct from their original diagnosis. This risk may be influenced by factors such as older age, exposure to radiation and/or chemotherapy and ongoing lifestyle factors like smoking, obesity and poor diet. Understanding who is at greater risk and how this risk changes over time can help to inform prevention and monitoring strategies.

Using retrospective data from more than 3 million cancer survivors in the U.S., researchers examined how demographic factors and cancer characteristics correlate with subsequent cancer risk. Several factors were associated with developing a subsequent cancer, including older age at initial diagnosis and male sex. In addition, survivors of lung, bladder, and skin melanoma were at higher risk of developing new cancer.

These findings reinforce the importance of long‑term survivorship care and risk‑based monitoring. By identifying survivor groups at heightened risk, studies like this can help to inform tailored prevention strategies, surveillance guidelines, and survivorship care planning as the cancer survivor population continues to grow.

First author Hui Cheng adds, “By examining nearly five decades of national data, we found population-level shifts in subsequent primary cancer risk, with several survivor groups experiencing rising risks. These findings can help design more tailored surveillance and prevention strategies.”

Provided by PLOS

Categories : DermatologyTags :

Testosterone Increases Severity of Staph Skin Infections

On By ModernMedia

Study led by UTSW researchers defines how skin hormones influence bacteria and results in potential treatment for Staph infections

This laboratory image shows Staphylococcus aureus bacteria streaked in the shape of a sex steroid, like testosterone. The left shape is of wild-type S. aureus, with the lighter halo around the shape indicating haemolysis, or the breakdown of red blood cells, releasing their haemoglobin into the surrounding fluid. The right shape is a quorum-sensing mutant strain of S. aureus, which cannot damage blood cells.

Men are more susceptible than women to skin infections caused by Staphylococcus aureus bacteria, but the biological basis for this disparity has remained unclear. A new study led by UT Southwestern Medical Center researchers is the first to reveal that testosterone as a key driver of infection. The sex steroid activates a bacterial communication pathway known as quorum sensing, increasing skin cell death and promoting the destruction of red blood cells and white blood cells called neutrophils. 

Published in Nature Microbiology, the study also reported that a mirror-image form of testosterone, known as an enantiomer (ent-T), blocks quorum sensing and prevents S. aureus from damaging tissue in mouse models.

Senior author Tamia Harris-Tryon, MD, PhD, Associate Professor of Dermatology and Immunology at UT Southwestern, and first author Maria S. John, PhD, a UTSW postdoctoral researcher, have a patent pending for an ent-T-based therapeutic along with collaborators at the University of Colorado.

“This research has important implications for treating Staph skin infections and conditions complicated by Staphylococcus, such as atopic dermatitis, pemphigus, abscesses, and wound infections, including the deadliest skin infections caused by methicillin-resistant Staphylococcus aureus [MRSA],” Dr Harris-Tryon said. “It also explains why men are more susceptible to Staph infections.” 

S. aureus is the leading cause of skin infections. When it enters the bloodstream, it can cause septicaemia, a life-threatening infection that may lead to organ failure.

During infection, the bacteria use quorum sensing to detect neighbouring cells of the same species. As bacterial density rises, they produce short signalling molecules called auto-inducing peptides (AIP), which activate virulence programs and trigger toxin release, resulting in host-cell damage. 

The research team found that male skin cells consistently secrete higher levels of testosterone than female skin cells. They also found the same is true for male mice, which were significantly more susceptible to S. aureus colonisation and skin damage than female mice when exposed to a strain of MRSA. However, mice engineered to secrete less testosterone displayed greater resistance to the bacteria, while applying testosterone to the skin of female mice increased MRSA’s severity. 

In laboratory experiments, testosterone activated quorum sensing even in the absence of AIPs. Other sex steroids, including progesterone and oestrogen, had no measurable effect on quorum sensing. 

While using ent-T as an experimental control, the researchers unexpectedly identified its therapeutic potential. In lab tests, ent-T inhibited quorum sensing and reduced the bacteria’s virulence. The molecule also inhibited quorum sensing on male and female mice when applied to their skin. 

Dr Harris-Tryon won an Innovation Award from the UTSW Office for Technology Development in 2024 to fund development of an ent-T-based transdermal therapeutic for Staph.

“Our exciting finding suggests we can inhibit S. aureus virulence rather than killing the bacteria directly, an approach that prevents infection, preserves beneficial skin microbes, and reduces the selective pressure that drives antibiotic resistance while offering a potential new strategy to treat infections, including MRSA,” Dr. John said.

This work builds on Dr Harris-Tryon’s studies in 2023 and 2025 with Jeffrey McDonald, PhD, Professor in the Center for Human Nutrition and of Molecular Genetics at UTSW, which demonstrated sex-specific differences in skin hormone production. The team also has previously uncovered how the immune system stimulates testosterone production in skin cells. Dr Harris-Tryon said the current research builds on UT Southwestern’s longstanding leadership in steroid and skin hormone biology, a field in which the institution has been a global leader for decades.

Source: UT Southwestern

Categories : Mental Health NeurologyTags :

How Oestrogen in the Brain Impacts Stress and Trauma Response

On By ModernMedia

New research reveals how oestrogen levels in the brain influence vulnerability to stress-related memory problems, helping explain sex differences in PTSD risk.

Photo by Sherise Van Dyk on Unsplash

For some people, a single traumatic event like a shooting, a natural disaster or a violent assault, can leave an imprint that lingers long after the immediate danger has passed. Memories of that event may return with unusual intensity, shaping mood, behaviour, and mental health in ways that are difficult to predict. Others exposed to similar trauma recover without developing lasting memory problems or trauma-related symptoms.

Why those outcomes diverge is a central question in stress and trauma research. Clinicians have long observed that severe acute stress can permanently alter memory for some people but not others, and that women face roughly twice the lifetime risk of posttraumatic stress disorder (PTSD). Recent research from the University of Pennsylvania in collaboration with the University of California-Irvine suggests that part of the answer may lie in the brain’s biological state at the precise moment trauma occurs.

Elizabeth Heller, PhD, an associate professor of Pharmacology in the Perelman School of Medicine at the University of Pennsylvania, and her team in the Heller Lab, have now shed light on how the brain’s biological state at the time of stress, particularly its oestrogen levels, can shape vulnerability long after the acute stress has lifted. Heller helped uncover that oestrogen levels in the brain may play a surprising role in this vulnerability, and for both sexes. The study, published in Neuron, also provides new insight into why women are more likely than men to develop post-traumatic stress disorder (PTSD) and to face higher dementia risk later in life.

Unpacking oestrogen’s role in memory vulnerability

Oestrogen is widely known to support learning and memory. This study found that high levels of oestrogen in the hippocampus, a brain region critical for memory, help the brain’s cells change and adjust more easily. However, in the context of severe acute stress, this flexibility can increase vulnerability to stress-related memory problems.

Heller and the Penn team mapped how high levels of oestrogen interact with chromatin structure (the storage packaging up DNA inside cells) in the hippocampus to make some brains more susceptible to PTSD‑like memory changes.

The findings help explain why traumatic events such as natural disasters, mass violence, and assaults can cause long-term memory problems, and why women are roughly twice as likely as men to develop PTSD.

“A lot of what determines vulnerability is the state your brain is already in,” Heller explained. “If a traumatic event hits during a period when oestrogen is already unusually high, the resulting plasticity can amplify the impact in lasting ways, promoting vulnerability to stress. Even with these findings in hand, the word oestrogen can mislead readers into assuming the biology applies only to women. That assumption shaped public understanding for decades, but it doesn’t hold up against what this research, and years of foundational neuroscience, actually shows.

As Heller notes, oestrogen is a critical brain hormone in both sexes. It is produced locally in regions like the hippocampus where it helps regulate learning, mood, and responses to stress. Recognising that universality is essential to understanding what this study truly reveals.

“The striking thing is that oestrogen levels are actually high in both males and in females in some parts of the hormonal cycle. Thus, the effects of high oestrogen levels happen in both males and females,” Heller said. “We tend to treat oestrogen as a women’s health hormone, but the brain makes its own oestrogen, and it plays powerful roles in stress, memory, mood, and emotion across sexes.”

By Eric Horvath

Source: Penn Medicine

Categories : NeurologyTags :

X-chromosomes: A New Lens on Autism’s Sex Bias

On By ModernMedia

Autism has a significant and enduring sex bias, with roughly four boys diagnosed for every girl. For many years, experts have believed this disparity arises primarily from diagnostic inequities because much of autism research – and the screening tools that grew out of it – has historically focused on boys, effectively setting a male standard for what autism “looks like.” As a result, girls and women are more likely to be overlooked, misdiagnosed, or diagnosed much later in life.

This disparity has also shaped the science around autism. When fewer females with the condition are identified, fewer are included in research studies, creating a feedback loop where scientific understanding of autism in females remains limited. Because of this underrepresentation of females, it has been difficult for scientists to disentangle how much of the sex bias in autism reflects social inequities versus underlying biological differences between the sexes. 

While the search for biological explanations has largely lagged behind, one leading theory, known as the “female protective effect,” proposes that females may be biologically buffered against developing autism in a way males aren’t. 

The idea can be traced back to studies showing that females diagnosed with autism tend to carry a higher number of genetic mutations or “hits” than males with the condition, meaning that they require a higher load of the same genetic mutations for autism to manifest. But, until now, there’s been little clarity on the exact biological mechanism behind this apparent resilience.

Now, a perspective from the lab of Whitehead Institute Member David Page, published March 30 in Nature Genetics, proposes a genetic explanation for the female protective effect and suggests that biological differences between males and females contribute to autism’s strong sex bias.

The work is one of many projects from the Page lab uncovering the biological underpinnings of sex bias in everything from heart health and autoimmune disease to certain cancers. 

“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page, who is also a professor of biology at Massachusetts Institute of Technology and an investigator at the Howard Hughes Medical Institute (HHMI).

The researchers propose that this protective effect extends beyond autism, and could help explain why 17 other congenital and developmental disorders predominately affect males. By characterizing the biological factors that make one sex more or less likely to develop certain health conditions, scientists see an opportunity to improve how these conditions are diagnosed and how people receive care.

“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page.

Page and Harvard-MIT MD-PhD student Maya Talukdar trace the female protective effect to the X chromosome. Talukdar is a graduate student in Page’s lab and the lead author of the perspective. 

Most females have two X chromosomes (XX) while most males have one X and one Y chromosome (XY). Sex chromosomes can dial up and down the expression of thousands of genes on the other 22 pairs of chromosomes in a cell, impacting cell function across the entire body. 

Historically, scientists believed that the second X chromosome in females is largely inactive. But, in recent years, research out of the Page lab has shown that the so-called “inactive X,” also called Xi, plays a crucial role in regulating gene expression on the active X chromosome, and the rest of the chromosomes.

In this perspective, the researchers point to a subset of genes that are expressed from both the active and inactive X chromosome — often known as genes that “escape” X chromosome inactivation. Many of these genes are dosage-sensitive regulators of key cellular processes. These processes influence thousands of other genes across the genome, including many linked to autism. 

Because females have an extra copy of these regulatory genes expressed from Xi, Page and Talukdar propose that they may be better able to buffer the effects of autism-associated mutations than males.

The female protective effect beyond autism

This mechanism, the researchers say, extends beyond autism to a range of congenital and developmental diseases with a male bias. 

“Many of the other congenital or developmental conditions we’re pointing to aren’t subject to diagnostic inequities in the way autism is,” says Talukdar. “This strengthens the idea that the female protective effect is emerging from genetic differences in males and females.”

One example is pyloric stenosis, which like autism, affects four boys for every girl. Infants with the condition experience severe vomiting due to thickening of the pyloric sphincter, the passage between the stomach and small intestine. As with autism, girls with pyloric stenosis appear to require more genetic “hits” in order to develop the condition.

The researchers’ new framework of looking at Xi to understand sex differences in disease could impact treatment and care not just for conditions that predominately affect males, but also for those that are more common in women, such as autoimmune diseases. 

“Our biology isn’t one-size-fits-all,” Talukdar says “Sex differences clearly play a huge role in health, and it’s so important that we understand them.”

By Shafaq Zia

Source: Whitehead Institute for Biomedical Research