Tag: sex differences

Uncovering Sex-specific Immune Differences in Glioblastoma

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

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

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.

Chimeric RNA Unique to Women Is an Important Controller of Health

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

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

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

Testosterone Increases Severity of Staph Skin Infections

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

How Oestrogen in the Brain Impacts Stress and Trauma Response

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

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

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 Geneticsproposes 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

Why is Migraine More Common in Women than Men?

Photo by Andrea Piacquadio

Lakshini Gunasekera, Monash University; Caroline Gurvich, Monash University; Eveline Mu, Monash University, and Jayashri Kulkarni, Monash University

We’ve known for a long time that women are more likely than men to have migraine attacks.

As children, girls and boys experience migraine equally. But after puberty, women are two to three times more likely to experience this potentially debilitating condition.

Recently, an Australian study showed it may be even more common than we previously thought – as many as one in three women live with migraine.

For comparison, migraine affects roughly one in 15 men in Australia.

So, what’s behind the difference? Here’s what we know.

More than a headache

Migraine is not just a bad headache – it is a complex disorder that causes the brain to process sensory information abnormally.

This means “migraine brains” can have difficulty processing information from any of the five senses:

  • sight (leading to problems with light sensitivity and glare)
  • sound (leading to noise sensitivity)
  • smell (certain smells can trigger headaches)
  • touch (leading to face or scalp tenderness)
  • taste (causing distorted taste, nausea and vomiting).

Migraine attacks typically last anywhere from four hours to three days – but can be longer.

In addition to the symptoms above, attacks can include throbbing head pain, dizziness, fatigue and difficulty concentrating. It is these extra symptoms that help diagnose migraine – not the location of head pain or pain severity.

Why are attacks more frequent in women?

Puberty is when the difference between men and women emerges. This is when our bodies massively increase the production of sex hormones.

People are often surprised to learn that both men and women produce oestrogen, progesterone and testosterone. Testosterone levels are higher in men, whereas women have higher levels of oestrogen and progesterone.

However, it is not just the type of hormone that makes a difference, but the way they fluctuate over time.

For many women, there are certain “milestone moments” when their migraine tends to worsen due to hormonal fluctuations – puberty, menstruation, pregnancy and perimenopause (the lead-up to your final period).

For example, some women notice migraine flare-ups every month, linked to phases in their monthly menstrual cycle when oestrogen levels drop.

They might even be able to predict when their period will start, as migraine attacks typically start a few days before the bleeding.

How hormones affect the brain

Women with migraine can be more sensitive to hormonal changes. This is particularly the case for sudden decreases in oestrogen. But even more subtle changes to hormone levels can cause migraine attacks.

These hormonal changes can activate brain processes that trigger migraine, such as cortical spreading depression. This is a very slow wave of electrical activity that spreads in the brain, causing some areas to function more slowly than others after it passes.

Decrease in oestrogen can also affect how we receive and process information through the trigeminal nerve. This plays a key role in the onset and maintenance of migraine pain.

Diagram showing the trigeminal nerve in the head.
Oestrogen can affect how we process information through the trigeminal nerve. ttsz/Getty

All kinds of fluctuations can be a trigger

Pregnancy can often destabilise migraine again and make attacks more likely, even when someone has previously enjoyed a period of good migraine control.

Migraine symptoms often become uncontrolled in the first trimester in particular, due to rapid hormonal changes needed to sustain a pregnancy. This usually settles in the second and third trimesters, when hormonal changes stabilise.

However, giving birth is yet another change.

Towards the end of pregnancy, oestrogen levels can be 30 times higher than pre-pregnancy levels, and progesterone can be 20 times higher. When these hormones plummet back to normal after giving birth, migraine attacks can often sharply worsen again.

Perimenopause can also involve random surges of oestrogen from the dwindling supplies of eggs within the ovaries – which previously produced these hormones cyclically and in abundance. This irregular hormone production can cause random spikes in migraine attacks. It can be extra challenging when combined with other symptoms of menopause such as hot flushes or mood changes.

Hormonal contraceptives and menopause hormone therapy can also affect migraine control. Sometimes, supplementing hormones at a regular, steady daily dose can help manage the hormone-sensitive headaches and other symptoms. However, for others, adding extra hormones can cause head pain to flare up.

Does migraine run in the family?

Genes also play a role. It’s not a coincidence that migraine is passed down in families through the maternal side.

This is because mothers pass on mitochondria to children (while fathers do not). Mitochondria are parts inside the cell that control energy.

People with migraine have fewer functional enzymes within their mitochondria, meaning their brains are in an energy-deficient state. This worsens with migraine attacks as there is even more stress to the system.

This is also why extra stress (such as sleep deprivation, missed meals, or emotional stress) can trigger a migraine and worsen pain.

There is also a strong link between migraine in women and anxiety and depression – conditions women are more likely to develop in response to stressful life events.

Knowing your own patterns

If you suspect hormones may be affecting your migraine attacks, it is helpful to keep a diary of symptoms, including headaches. Mark each day per month where you get migraine symptoms, as well as your period, to find patterns.

Identifying patterns in pain flares helps doctors guide you to a personalised medication plan, which may include hormone therapies or non-hormonal therapies.

Lakshini Gunasekera, PhD Candidate in Neurology, Monash University; Caroline Gurvich, Associate Professor and Clinical Neuropsychologist, Monash University; Eveline Mu, Research Fellow in Women’s Mental Health, Monash University, and Jayashri Kulkarni, Professor of Psychiatry, Monash University

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

Gap in Onset of Cardiovascular Disease Still Persists Between Sexes

Credit: American Heart Association

Historical data indicate that men develop coronary heart disease (CHD) 10 years before women. A recent study in the Journal of the American Heart Association indicates that this sex gap still remains.

Investigators analysed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, in which US adults aged 18–30 years enrolled in 1985–1986 and were followed through August 2020.

Among 5112 participants (54.5% female, 51.6% Black) with an average age of 24.8 years at enrolment and a median follow-up of 34.1 years, men had a significantly higher cumulative incidence of cardiovascular disease. They had higher cumulative incidence rates of the cardiovascular disease subtypes of CHD and heart failure compared with women, but no difference in stroke.

Men reached a 5% incidence of cardiovascular disease 7.0 years earlier than women (50.5 versus 57.5 years). CHD was the most frequent cardiovascular disease subtype, and men reached a 2% incidence 10.1 years earlier than women. There were no significant differences in the age at which men and women reached a 2% incidence for stroke (57.5 versus 56.9 years) or a 1% incidence for heart failure (48.7 versus 51.7 years)

Differences emerged in the fourth decade of life and were not explained after accounting for differences in cardiovascular health.

“Sex differences in cardiovascular disease risk are apparent by age 35, highlighting the importance of initiating risk assessment and prevention strategies in young adulthood,” said corresponding author Alexa Freedman, PhD, of the Northwestern University Feinberg School of Medicine.

Source: Wiley

Rates of Autism in Girls and Boys May Be More Equal than Previously Thought

Study raises questions around why female individuals are diagnosed later than males

Photo by Ben Wicks on Unsplash

Autism has long been viewed as a condition that predominantly affects male individuals, but a study from Sweden published by The BMJ shows that autism may actually occur at comparable rates among male and female individuals.

The results show a clear female catch-up effect during adolescence, which the researchers say highlights the need to investigate why female individuals receive diagnoses later than male individuals.

The prevalence of autism spectrum disorder (ASD) has increased over the past three decades, with a high male-to-female diagnosis ratio of around 4:1.

The increase in prevalence is thought to be linked to factors including wider diagnostic criteria and societal changes (eg, parental age), whilst the high male to female ratio has been attributed to better social and communication skills among girls, making autism more difficult to spot. However so far no large study has examined these trends over the life course.

To address this, researchers used national registers to analyse diagnosis rates of autism for 2.7 million individuals born in Sweden between 1985 and 2022 who were tracked from birth to a maximum of 37 years of age.

During this follow-up period of more than 35 years, autism was diagnosed in 78,522 (2.8%) of individuals at an average age of 14.3 years.

Diagnosis rates increased with each five year age interval throughout childhood, peaking at 645.5 per 100,000 person years for male individuals at age 10-14 years and 602.6 for female individuals at age 15-19 years.

However, while male individuals were more likely to have a diagnosis of autism in childhood, female individuals caught up during adolescence, giving a male to female ratio approaching 1:1 by age 20 years.

This is an observational study and the authors acknowledge that they did not consider other conditions associated with autism, such as ADHD and intellectual disability. Nor were they able to control for shared genetic and environmental conditions like parental mental health.

However, they say the study size and duration enabled them to link data for a whole population and disentangle the effects of three different time scales: age, calendar period and birth cohort.

As such, they write: “These findings indicate that the male to female ratio for autism has decreased over time and with increasing age at diagnosis. This male to female ratio may therefore be substantially lower than previously thought, to the extent that, in Sweden, it may no longer be distinguishable by adulthood.”

“These observations highlight the need to investigate why female individuals receive diagnoses later than male individuals,” they conclude.

These findings align with recent research and seem to support the argument that current practices may be failing to recognise autism in many women until later in life, if at all, says Anne Cary, patient and patient advocate, in a linked editorial.

She notes that studies like this are essential to changing the assumption that autism is more prevalent in male individuals than in female individuals, but points out that as autistic female individuals await proper diagnosis, “they are likely to be (mis)diagnosed with psychiatric conditions, especially mood and personality disorders, and they are forced to self-advocate to be seen and treated appropriately: as autistic patients, just as autistic as their male counterparts.”

Source: BMJ Group