In women, a low resting heart rate is associated with a slightly raised incidence of criminal offending as well as of unintentional injuries, in a large all-female study published March 27 in the open-access journal PLOS ONE by Sofi Oskarsson of School of Behavioural, Social and Legal Sciences, Örebro University, Sweden, and colleagues. This is the first time such an association has been shown in women, although it is well established in studies of men.
Intervention efforts for crime tend to focus on structural and social factors as well as personality traits and behaviors. Less is known about biological factors, although there is an established association between the autonomic nervous system – a network of nerves that regulates unconscious body processes like breathing and heartbeat – and criminal offending in men. Sofi Oskarsson and colleagues from Örebro University, Sweden, wanted to see if the same is observed in women.
Using population registers, the team identified 12 500 Swedish women who volunteered for military service at around 18 years old, where physical assessments recorded resting heart rate and blood pressure. They also tracked records for violent and nonviolent criminal offences and unintentional injuries for up to 40 years.
Female conscripts with the lowest resting heart rates (under 69bpm) had 35% higher risk for any criminal conviction compared to those with rates above 83bpm. However, no significant associations were found for violent crime. Lower resting heart rate was associated with an increased risk of unintentional injuries, which in past research has been interpreted as potentially reflecting fearlessness and stimulation seeking tendencies. The team found a significant association between blood pressure and violent crime, but no significant association was found for non-violent crime.
The authors state that low autonomic nervous system arousal might drive stimulation-seeking tendencies, but that their findings should be interpreted with caution. They saw lower rates of criminal offending compared to women who had not done military service, and a higher rate of unintentional injuries, so further work is needed to establish whether the same is seen in wider cohorts. If replicated by further research, this finding could have the potential to serve as a predictor of criminal offending, in women as well as men.
The authors add: “Our research reveals a compelling link between lower resting heart rate and an elevated risk of criminality and unintentional injuries among female conscripts. This association, previously underscored primarily in men, paves way for innovative strategies predicting crime risk among women.”
Women experiencing fear tended to prioritise smaller short-term gain compared to men
Photo by Monstera on Pexels
Fear may affect women’s decisions in choosing immediate rewards versus larger delayed ones, while men’s decisions appear unaffected by emotion, according to a study published March 20, 2024 in the open-access journal PLOS ONE by Eleonora Fiorenzato, Patrizia Bisiacchi, and Giorgia Cona from the University of Padua, Italy.
Decision making is complex and still not fully understood, especially when weighing short- versus long-term benefits or costs. The known phenomenon “delay discounting” describes the common tendency to prefer an immediate reward rather than a later one, even if the later reward is significantly greater. In this study, Fiorenzato and colleagues examined how emotions like fear and joy, along with gender, affect decision making, especially when weighing immediate versus later rewards.
The authors recruited 308 participants (63% women, 37% men) via a social media survey. Survey participants were shown a brief standardised and validated movie clip intended to induce an emotional state – for the fear group, this was a scary movie, like The Sixth Sense or Silence of the Lambs; for the joy group, this was a positive documentary clip with subjects like forests or waterfalls; the neutral affect group watched a documentary clip on urban environments. Then, the subjects were asked hypothetical reward questions such as: “Would you rather have €20 000 today or €40 000 after 3 years?”
Women in the fear group were significantly more likely to use “delay discounting” when choosing financial rewards (selecting the immediate, smaller amount) compared to men in the fear group or women in the joy or neutral movie groups. There were no significant gender differences for decisions made across the joy or neutral movie groups, and men’s decision-making on monetary rewards appeared to be unaffected by their emotional state. The findings suggest that fear specifically might provoke different types of time-bound decision making for women versus men – the authors speculate these may be due to either differences in evolutionary strategies around safety versus risk, or different emotion-regulation approaches in stressful situations.
The authors note that the sample size and range of emotions studied here is relatively small compared to the real world. However, the suggestion that emotions (particularly negative ones such as fear) and gender do interact with regard to intertemporal choices warrants further investigation.
The authors add: “Women are more prone to choose immediate rewards when in a fearful emotional state than when in joyful one. Our research underscores the importance of gender as an influential factor in the interaction between emotions and decision-making processes.”
Investing in women’s health is not only a moral imperative; it makes economic sense. International Women’s Day (8 March 2024) should serve as a rallying cry that it is time to turn talk into action – and a lasting commitment to regenerating women’s health.
“Shaping the private and public health agenda through increased advocacy and awareness, with governments and medical professionals putting women’s health on – and higher up – the agenda and targeting sources of stigma and bias – this is what we need to do right now,” says Jo Pohl, Associate Director at global management consultancy Kearney.
Pohl was speaking (this week) on the eve of International Women’s Day, and following an event organised by Kearney to commemorate the day. Guests listened to the story of ‘Tina B’, the longest-surviving heart and bilateral lung transplant recipient in Africa (during a gathering at Kearney’s Johannesburg offices on Wednesday 6 March 2024).
The event explored Tina’s resilience, the challenges she faced, the odds she beat, and just how different her journey could have been with the advent of Artificial Intelligence (AI) in donor healthcare decision-making.
She shared her opinion on the use of AI in selecting organ donors. Tina told guests at the event that she believes if AI had to decide whether she should receive her surgery or not, it would have decided against her based on inherent biases or rather what the AI was asked to solve for.
According to her, AI would have assessed the state of her lungs and heart and potentially rejected her as a candidate for organ donation. Since she needed three organs, AI would have viewed her as one, high risk candidate versus the potential to save three “better” candidates.
The human element – from intuition to hope and optimism – is key. She told guests that her doctors echoed the same in terms of leveraging experience, expertise, and an understanding of a patient’s mindset.
“I am not an expert in AI, but I am an expert in being a patient,” she said. “AI could help inform options but needs to be questioned, and experienced doctors need to be able to apply their human intuition in any results.”
Typically, there are over 4000 people on the organ transplant waiting list at any given time, with only 0.2% of the population opting-in for organ donation. These kinds of numbers lead to questions such as “how is one candidate chosen over another and why”, questions that become even more important as we increasingly incorporate AI in healthcare decisions.
“Just think of the implications for healthcare professionals, researchers, and policymakers to develop and implement AI in healthcare ethically, equitably, and inclusively, if we consider transplant patients,” says Pohl.
“AI in healthcare should be used to benefit all members of society, regardless of gender, race, or socio-economic status. How can we co-create a world where everyone is seen, heard and the human considered in healthcare decision-making,” says Theo Sibiya, Kearney’s Africa MD.
“There needs to be a deliberate focus on keeping women front of mind and lending our expertise to continue breaking down barriers such as the gender health gap by redesigning healthcare that can put women first,” he adds.
Tina B has now become an advocate for organ donation and aims to help others going through the waiting process. She told guests of her experience of having to wait three years on the organ donor waiting list.
“You start to lose hope. You get excited to get on the list, but time drags on, and your body starts to fail you…it is a very dark place. I was tired of fighting to breathe, to stay awake; I remember saying to my God if you don’t give me a transplant, then take me home.”
AI has the potential to revolutionise the healthcare industry. With the ability to analyse large amounts of data quickly, AI can help healthcare professionals make more informed decisions, improving patient outcomes. It is an “and” versus “or” proposition.
“We need to be mindful, however, of inherent gender biases, overcome programming that favours males, and address flaws in the interpretation of data that exclude human perspectives. Doing so can make AI in healthcare more representative and inclusive,” says Sibiya.
Pohl explains that a women-informed lens is essential to ensuring equity and inclusivity in AI development and application.
“Regenerate is Kearney’s answer to “what’s next” in a post-resilience world and a timely approach to how businesses can and should be ready for the future. Tina B is a living example of regeneration, her story amplifies our Kearney commitment to a global campaign to “be the difference” for women’s health which we launched in Davos earlier this year,” says Sibiya.
“This amplifies our vision, rooted in a regenerative mindset that recognises the interconnectedness of our actions and their impact on the world around us, including how we make and execute healthcare and people decisions.”
As part of this vision, an open letter was released by Kearney and FemTechnology during the World Economic Forum Annual Meeting on behalf of the Redesigning Healthcare with Women in Mind signatories.
The letter is addressed to all those within the healthcare ecosystem whose innovations have impact and decisions have power: from pharma, biotech, and medtech firms to investors, tech companies, and consumer health players serving women and girls.
The signatories call for a commitment to challenge institutional gender inequalities and shape the future of public and private healthcare for those it has failed for far too long.
A new study from the Smidt Heart Institute at Cedars-Sinai shows there is a gender gap between women and men when it comes to exercise. The findings, published in the Journal of the American College of Cardiology (JACC), show that women can exercise less often than men, yet receive greater cardiovascular gains.
“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” said Martha Gulati, MD, director of Preventive Cardiology in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, the Anita Dann Friedman Chair in Women’s Cardiovascular Medicine and Research and co-lead author of the study.
“The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivising notion that we hope women will take to heart.”
Investigators analysed data from 412 413 US adults utilising the National Health Interview Survey database. Participants between the time frame of 1997 to 2019 – 55% of whom were female – provided survey data on leisure-time physical activity.
Investigators examined gender-specific outcomes in relation to frequency, duration, intensity and type of physical activity.
“For all adults engaging in any regular physical activity, compared to being inactive, mortality risk was expectedly lower,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute, and senior author of the study.
“Intriguingly, though, mortality risk was reduced by 24% in women and 15% in men.”
The research team then studied moderate to vigorous aerobic physical activity, such as brisk walking or cycling, and found that men reached their maximal survival benefit from doing this level of exercise for about five hours per week, whereas women achieved the same degree of survival benefit from exercising just under about 2 ½ hours per week.
Similarly, when it came to muscle-strengthening activity, such as weightlifting or core body exercises, men reached their peak benefit from doing three sessions per week and women gained the same amount of benefit from about one session per week.
Cheng said that women had even greater gains if they engaged in more than 2 ½ hours per week of moderate to vigorous aerobic activity, or in two or more sessions per week of muscle-strengthening activities.
The investigators note their findings help to translate a longstanding recognition of sex-specific physiology seen in the exercise lab to a now-expanded view of sex differences in exercise-related clinical outcomes.
With all types of exercise and variables accounted for, Gulati says there’s power in recommendations based on the study’s findings.
“Men get a maximal survival benefit when performing 300 minutes of moderate to vigorous activity per week, whereas women get the same benefit from 140 minutes per week,” Gulati said.
“Nonetheless, women continue to get further benefit for up to 300 minutes a week.”
Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology, says concrete, novel studies like this don’t happen often.
“I am hopeful that this pioneering research will motivate women who are not currently engaged in regular physical activity to understand that they are in a position to gain tremendous benefit for each increment of regular exercise they are able to invest in their longer-term health,” said Albert, professor of Cardiology.
Women have long been known to outlive men. But new research published in JAMA Internal Medicine shows that, at least in the United States, the gap has been widening for more than a decade. Among the factors driving the trend are the COVID pandemic and the opioid overdose epidemic.
The study, led by UC San Francisco and Harvard T.H. Chan School of Public Health, found the difference between how long American men and women live increased to 5.8 years in 2021, the largest since 1996. This is an increase from 4.8 years in 2010, when the gap was at its smallest in recent history.
The pandemic, which took a disproportionate toll on men, was the biggest contributor to the widening gap from 2019–2021, followed by unintentional injuries and poisonings (mostly drug overdoses), accidents and suicide.
“There’s been a lot of research into the decline in life expectancy in recent years, but no one has systematically analysed why the gap between men and women has been widening since 2010,” said the paper’s first author, Brandon Yan, MD, MPH, a UCSF internal medicine resident physician and research collaborator at Harvard Chan School.
Life expectancy in the US dropped in 2021 to 76.1 years, falling from 78.8 years in 2019 and 77 years in 2020.
The shortening lifespan of Americans has been attributed in part to so-called “deaths of despair.” The term refers to the increase in deaths from such causes as suicide, drug use disorders and alcoholic liver disease, which are often connected with economic hardship, depression and stress.
“While rates of death from drug overdose and homicide have climbed for both men and women, it is clear that men constitute an increasingly disproportionate share of these deaths,” Yan said.
Interventions to reverse a deadly trend
Using data from the National Center for Health Statistics, Yan and fellow researchers from around the country identified the causes of death that were lowering life expectancy the most. Then they estimated the effects on men and women to see how much different causes were contributing to the gap.
Prior to the COVID pandemic, the largest contributors were unintentional injuries, diabetes, suicide, homicide and heart disease.
But during the pandemic, men were more likely to die of the virus. That was likely due to a number of reasons, including differences in health behaviours, as well as social factors, such as the risk of exposure at work, reluctance to seek medical care, incarceration and housing instability. Chronic metabolic disorders, mental illness and gun violence also contributed.
Yan said the results raise questions about whether more specialised care for men, such as in mental health, should be developed to address the growing disparity in life expectancy.
“We have brought insights to a worrisome trend,” Yan said. “Future research ought to help focus public health interventions towards helping reverse this decline in life expectancy.”
Yan and co-authors, including senior author Howard Koh, MD, MPH, professor of the practice of public health leadership at Harvard Chan School, also noted that further analysis is needed to see if these trends change after 2021.
“We need to track these trends closely as the pandemic recedes,” Koh said. “And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched.”
To mark Men’s Health Awareness Month, International SOS, the world’s leading health and security risk services company, emphasises the importance of creating supportive workplace environment that foster men’s health and mental wellbeing.
Men’s health remains a significant concern and poorer health profiles for men than for women have been reported, with discrepancies found in metrics including life expectancy, mortality rates, disability-adjusted life years, and non-sex-specific disease death rates.1 The World Health Organization (WHO) reports that non-communicable diseases (NCDs), are claiming around 74% of all lives lost each year2, and in 2018, NCDs and injuries accounted for 86% of all male fatalities.3
The WHO data shows that men across all socioeconomic groups demonstrate unhealthier smoking practices, unhealthier dietary patterns, higher alcohol consumption levels and higher rates of injuries than women.3 In fact, among the global population that used tobacco in 2020, a significantly higher percentage were men (36.7%), compared to women (7.8%).4 These statistics highlight the need to focus on improving men’s health and organisations can play a vital role in enhancing men’s health within their workplaces.
Men are significantly less likely than women to seek preventive care services, which can often lead to undiagnosed conditions.1 Men are also found to be less likely to have received mental health treatment than women. The stigma attached to illness and men perceiving illness as a weakness are often found to be the reasons why men are not as vocal about their health and mental wellbeing concerns.5
Dr Anthony Renshaw, Regional Medical Director at International SOS, said “Men’s Health Awareness Month provides a crucial opportunity for organisations to re-evaluate their approach to supporting the health and wellbeing of male employees. In addition to physical health, we must also prioritise mental health, as it has a direct impact on overall productivity and workplace satisfaction. Employers can play a pivotal role in fostering open discussions, reducing stigma, and promoting a supportive environment for men to seek the help they may need.”
International SOS offers guidelines for organisations to provide workplace support specific for men’s health and wellbeing with the ‘H-O-P-E’ approach:
Hold workplace men’s forum that can act as a safe space. Having a supportive work environment where everyone, particularly men, know that they are allowed the time to address any health concerns is extremely enabling.
Offer male-specific confidential support from mental health professionals.
Provide your team leads with appropriate training to enable them to spot early signs of poor physical and mental health and know where they can signpost their employees to.
Encourage employees to have regular health check-ups, particularly screening for early detection and treatment of NCDs, as well as a mental health assessment if needed.
Injuries of the knee’s anterior cruciate ligament (ACL) are typically thought to be caused by acute traumatic events, such as sudden twists. Published in the Journal of Orthopaedic Research, new work analysing an animal model of ACLs suggests that such injuries can also occur as a result of chronic overuse, specifically due to a reduced ability to repair microtraumas associated with overuse. Importantly, the team said, females also are less able to heal from these microtraumas than males, which may explain why females are two to eight times more likely to tear their ACL ligaments than males.
“ACL tears are one of the most common injuries, affecting more than 200 000 people in the US each year, and women are known to be particularly susceptible,” said principal investigator Spencer Szczesny, associate professor of biomedical engineering and of orthopaedics and rehabilitation at Penn State. “While recent research suggests that chronic overuse can lead to ACL injuries, until now, no one had investigated the differential biological response of female and male ACLs to applied force.”
In the Penn State-led study, researchers placed ACLs from deceased male and female rabbits in a custom-made bioreactor that simulated the conditions of a living animal but allowed direct observation and measurement of the tissue. Next, they applied repetitive forces to the ACLs that mimicked those that would naturally occur during activities such as standing, walking and trotting and measured the expression of genes related to healing.
In male samples, the team found that low and moderate applied forces, such as those that would occur during standing or walking, resulted in increased expression of anabolic genes, which are related to building molecules needed for healing. By contrast, larger applied forces, such as those that would occur with repetitive trotting, decreased expression of these anabolic genes. For female samples, however, the amount of force applied did not influence the level of anabolic gene expression.
“It didn’t matter whether there was low, medium or high activity for females,” said Lauren Paschall, graduate student in biomedical engineering at Penn State and first author on the paper. “Female ACLs exposed to chronic use just didn’t heal as well as male ACLs, which may explain why women are predisposed to injuries. This supports the hypothesis that noncontact ACL injuries are attributed to microtraumas associated with chronic overuse that predispose the ACL to injury.”
According to the researchers, one explanation for the sex differences the team observed could be due to the higher amounts of oestrogen in females.
“Some studies have found that the overall effect of oestrogen on ACL injury is negative,” Paschall said. “Specifically, studies have shown that human women are more likely to tear their ACLs during the preovulatory phase, when oestrogen levels are high, than during the postovulatory phase, when oestrogen levels are low.”
She said the team plans to further investigate the role of oestrogen on ACL injury.
Szczesny noted that although the team’s study was not in humans, the findings may suggest that providing additional recovery time for women following injuries could be advantageous.
“Ultimately, this work could also help to identify targets for therapeutics to prevent ACL injuries in women,” he said.
Getting enough sleep is becoming more of a challenge in today’s busy society. New research from investigators in the Channing Division of Network Medicine of Brigham and Women’s Hospital, highlights why getting a good night’s sleep is critical to staying healthy. Their research unveils that women who struggled with getting enough sleep were at greater risk of developing hypertension, or high blood pressure. Results are published in the journal Hypertension.
“These findings suggest that individuals who struggle with symptoms of insomnia may be at risk of hypertension and could benefit from preemptive screening,” explained Shahab Haghayegh, PhD, a research fellow at the Brigham and Harvard Medical School. “Hypertension is associated with many other physical and mental health complications. The sooner we can identify individuals with high blood pressure and treat them for it, the better we can mitigate future health issues.”
Haghayegh and colleagues followed 66 122 participants between 25 and 42 years of age in the Nurses’ Health Study II (NHS2) cohort, all without hypertension at the study’s onset, over sixteen years (from 2001 until 2017). Investigators collected information on participants’ age, race, body mass index (BMI), diet, lifestyle, physical activity, history of sleep apnoea, and family history of hypertension and assessed the incidence of hypertension among the group every two years. They first began measuring sleep duration in 2001, then did so again in 2009, recording the average number of hours slept over a 24-hour period. They also tracked sleeping difficulties, such as having trouble falling or staying asleep or waking up early in the morning, collecting responses at several time points throughout the study.
Data analyses revealed that women with sleeping difficulties had higher BMIs, lower physical activity, and poorer diets, on average. Researcher also found that those who struggled with sleep were more likely to smoke and drink alcohol and have previously gone through menopause.
Among the 25 987 cases of hypertension documented over the follow-up, women who slept less than seven to eight hours a night had a significantly higher risk of developing hypertension, according to the data collected. Similarly, women who had trouble falling asleep and staying asleep were also more likely to develop hypertension. Waking up early in the morning was not associated with this increased risk. Notably, these associations, remained significant after controlling for participant shift work schedules (night versus day shifts) and chronotype (morningness versus eveningness).
While the exact nature of the relationship between sleep and risk of hypertension is unknown, Haghayegh said that sleep difficulties can lead to a chain of events that can increase sodium retention, arterial stiffness, and cardiac output, potentially leading to hypertension. Disruptions to the sleep/wake cycle can also influence blood vessel constriction/relaxation activity and the function of cells that regulate the vascular tone.
One limitation is that the study only looked at the association between sleep and hypertension in women, so researchers hope to expand their work to include men and non-binary participants. A second is that researchers could only collect data on sleep quality at select time points throughout the study. Some of the study’s strengths include the larger number of participants and length of follow-up duration.
Haghayegh emphasises that these findings do not indicate causality. He wants to understand why this association exists and how treating one condition may also treat the other. In future clinical studies, he aims to investigate if sleep medications could have a beneficial effect on blood pressure.
“I hope these findings further underscore the crucial role of quality sleep in our overall well-being. The American Academy of Sleep Medicine recommends sleeping seven or more hours a night, and if you cannot fall or stay asleep, it might be worth exploring why that is,” said Haghayegh. “This study highlights yet another reason why getting a good night’s sleep is so important.”
New research published in the journal Diabetes Therapy suggests that the diagnosis threshold for type 2 diabetes (T2D) should be lowered in women aged under 50 years, since natural blood loss through menstruation could be affecting their blood sugar management.
Analysis of the national diabetes audit results has shown that women of younger age with type 2 diabetes mellitus (T2D) seem to have a higher mortality rate than men. The underlying mechanisms remain unclear. However, it is known that women are on average diagnosed with T2D at a later age than men. In this new study, the authors investigated whether a contributing factor to this late diagnosis may be a sex difference in the levels of glycated haemoglobin (HbA1c) due to haemoglobin replacement linked to menstrual blood loss.
This mechanism behind this could be shorter erythrocyte (red blood cell) survival which results in shorter exposure of haemoglobin to glucose compared with individuals who do not menstruate. Given that the diagnosis of T2D is also based on HbA1c, the use of the same reference range irrespective of age and sex, when a slightly lower point for T2D for premenopausal women may be appropriate, could potentially lead to under diagnosis of T2D in women and missed opportunities for intervention.
The study, by Dr Adrian Heald, Salford Royal Hospital, UK, and colleagues, examined HbA1c testing across seven UK laboratory sites (representing 5% of UK population). They conducted an exploratory analysis in two cohorts: cohort 1 was from one laboratory tested between 2012 and 2019 (146 907 participants). They assessed the sex and age differences of HbA1c in individuals who underwent single testing only, that had not been diagnosed with diabetes and had an HbA1c result of equal to or less than 48mmol/mol (the cutoff for diagnosing diabetes). The process was replicated in cohort 2 results from six laboratories with individuals tested between 2019 and 2021 (total people included 938 678). The possible national impact was estimated by extrapolating findings based on the Office of National Statistics (ONS) England population data and National Diabetes Audit published T2D prevalence and related excess mortality.
At age 50 years, average HbA1c levels in women lag by approximately five years compared to men. The data also show women aged under 50 years old had an HbA1c distribution that was lower than that of men by an average of 1.6mmol/mol (4.7% of the overall mean) while the difference in the distribution of HbA1c for individuals aged 50 years and over was less pronounced. Further analysis showed that, at HbA1c of 48mmol/mol, 50% fewer women could be diagnosed with T2D than men under the age of 50, whilst only 20% fewer women could be diagnosed with T2D than men over or equal to the age of 50. These findings were consistent with those in cohort 2.
Based on these observations, the authors estimated the effects of lowering the threshold for diagnosis of diabetes from HbA1c (48mmol/mol) by 4.2% to 46mmol/mol for women under the age of 50. This analysis showed that an additional 35 345 currently undiagnosed women in England would be reclassified as being diagnosed with T2D (17% more than the current 208 000 recorded women with T2D aged under 50 years). Lifestyle changes and treatment for diabetes would then be initiated for these women enabling improvement in health outcomes over both the short and longer term.
The authors also highlight that sex and gender difference in adverse cardiovascular risk factors are known to be present prior to the development of T2D. Once diagnosed, the prevalence of atherosclerotic cardiovascular disease is twice as high in patients with diabetes mellitus compared to those without diabetes mellitus. For women, diabetes mellitus is a stronger risk factor for cardiovascular disease than for men: women with diabetes aged 35–59 years have the highest relative cardiovascular death risk across all age and sex groups.
Furthermore, there is disparity in cardiovascular risk factor management between men and women, including in high-risk groups such as women with T2D. Women are less likely than men to receive treatment and cardiovascular risk reduction interventions that are recommended by international guidelines on diabetes. In addition, concordance with medication or prescription treating cardiovascular risk factors is lower in women than men with T2D, with less use of statins, aspirin and beta blockers. The authors say taken together, these factors mean “timely diagnosis of type 2 diabetes and initiation of preventative treatment has the potential to improve cardiovascular risk profile over lifetime and facilitate longer life quality and expectancy in women. Our findings provide evidence that the HbA1c threshold for this group should be re-evaluated.”
Improved modelling of male and female livers can help lead to safer drugs
Photo by Danilo Alvesd on Unsplash
Researchers report in PLOS Computational Biology that they developed a powerful new tool to understand how medications affect men and women differently, and that will help lead to safer, more effective drugs in the future.
Women are known to suffer a disproportionate number of liver problems from medications but also usually underrepresented in drug testing. To address this, University of Virginia scientists have developed sophisticated computer simulations of male and female livers and used them to reveal sex-specific differences in how the tissues are affected by drugs.
The new model has already provided unprecedented insights into the biological processes that take place in the liver, the organ responsible for detoxifying the body, in both men and women. But the model also represents a powerful new tool for drug development, helping ensure that new medications will not cause harmful side effects.
“There are incredibly complex networks of genes and proteins that control how cells respond to drugs,” said UVA researcher Jason Papin, PhD, one of the model’s creators. “We knew that a computer model would be required to try to answer these important clinical questions, and we’re hopeful these models will continue to provide insights that can improve healthcare.”
Harmful side effects
Papin, of UVA’s Department of Biomedical Engineering, developed the model in collaboration with Connor Moore, a PhD student, and Christopher Holstege, MD, a UVA emergency medicine physician and director of UVA Health’s Blue Ridge Poison Center. “It is exceedingly important that both men and women receive the appropriate dose of recommended medications,” Holstege noted. “Drug therapy is complex and toxicity can occur with subtle changes in dose for specific individuals.”
Before developing their model, the researchers first looked at the federal Food and Drug Administration’s Adverse Event Reporting System to evaluate the frequency of reported liver problems in men and women. The scientists found that women consistently reported liver-related adverse events more often than did men.
The researchers then sought to explain why this might be the case. To do that, they developed computer models of the male and female livers that integrated vast amounts of data on gene activity and metabolic processes within cells. These cutting-edge liver simulations provided important insights into how drugs (xenobiotics) affect the tissue differently in men and women and allowed the researchers to understand why.
They found that xenobiotic metabolism was more active in untreated males, while pentose and glucoronate interconversions were female-biased, suggesting a difference in pretreatment gene expression, which may result in different initial responses of phase I and phase II metabolism to hepatotoxic drugs. They also observed sex-bias in bile acid biosynthesis, which in combination with xenobiotic metabolism, this result may suggest differences in bacterial deconjugation driven by sex differences in the gut microbiome. Differences were also found in several essential metabolic pathways, such as glycolysis/gluconeogenesis, nucleotide metabolism, and lipid metabolism with supporting evidence in human or rat hepatocytes.
“We were surprised how many differences we found, especially in very diverse biochemical pathways,” said Moore, a biomedical engineering student in Papin’s lab. “We hope our results emphasise how important it is for future scientists to consider how both men and women are affected by their research.”
The work has already identified a key series of cellular processes that explain sex differences in liver damage, and the scientists are calling for more investigation of it to better understand “hepatotoxicity” — liver toxicity. Ultimately, they hope their model will prove widely useful in developing safer drugs.
“We’re hopeful these approaches will be help address many other questions where men and women have differences in drug responses or disease processes,” Papin said. “Our ability to build predictive computer models of complex systems in biology, like those in this study, is truly opening all kinds of new avenues for tackling some of the most challenging biomedical problems.”
