When Cheryl Carcel was in medical school, little attention was paid to the role that sex and gender can play in the detection and treatment of many major diseases.
“We weren’t taught that men and women might present differently or have different outcomes.”
Associate Professor Cheryl Carcel is a neurologist and head of the Brain Health Program at The George Institute for Global Health. (Supplied: The George Institute of Global Health)
But Dr Carcel, a neurologist and head of the Brain Health Program at the George Institute for Global Health, said in her own field — and many other areas of medicine — such differences were stark.
Last year, she co-authored a study investigating the medical care that people with stroke receive before arriving at hospital in NSW, and found women were less likely to have their stroke recognised compared to men.
“[Women] were thought to be having a migraine, high blood pressure, or some type of headache or nausea,” she said.
“And we think one of the reasons is because some of the symptoms of women are not recognised as being stroke.”
Stroke isn’t unique in this regard: women are less likely to be diagnosed and appropriately treated if they suffer a serious heart attack, less likely to have chronic pain acknowledged and treated, and more likely to be misdiagnosed or discharged during a serious medical event.
Bronwyn Graham, director of the Centre for Sex and Gender Equity in Health and Medicine at the George Institute, said part of the reason was because women had been under-represented in medical research for decades.
“Our models of how diseases emerge in humans, the ways they look and the ways they can be treated, are based on the male body, and those findings don’t always translate,” said Professor Graham.
“The consequence is that we see poorer health outcomes and treatments that are not evidence-based for certain sex and gender groups.”
Major funding body calls for attention on sex and gender
In early August, the National Health and Medical Research Council (NHMRC) released a statement encouraging sex, gender, variations of sex characteristics and sexual orientation to be routinely considered in health and medical research.
The NHMRC is the largest public funder of health and medical research in Australia and distributes hundreds of millions of dollars in research grants every year, including through the Medical Research Future Fund (MRFF).
“What it means in practice is that researchers should consider these variables at all stages of the research process,” said Professor Graham, who is also a professor of psychology at the University of New South Wales.
“So that’s from the very start (what questions should we be asking?) through to the conduct of the study (do we have equal representation of sexes and genders?) to how data are analysed and reported … and then how things get translated into healthcare practices.”
Gender bias in medicine means conditions that primarily affect women and other under-represented groups have been understudied and are therefore less understood. (Getty Images: dragana991)
A growing body of evidence suggests there are clinically significant sex and gender differences across a broad range of diseases, from susceptibility and screening to risk factors, treatment and prognosis.
The aim of the statement, according to the NHMRC, is to improve health outcomes and ensure medical research produces evidence that is relevant to all people.
It encourages researchers to increase the representation and involvement of historically under-represented groups, including women, trans and non-binary people, people with variations of sex characteristics (intersex) and diverse sexual orientations.
A recent study showed while women were over-represented in research perceived to ‘female-patient’ dominated, they were they were significantly under-represented in other areas, such as cardiology.
Meanwhile, intersex and non-binary people were found to be severely under-represented across all areas of medical research.
“Women are often the people who are missing out here — women, intersex, trans and non-binary folk,” Professor Graham said.
“We see in practice, for example, that women are 50 per cent more likely to have adverse reactions to drugs and vaccines than men; that pain medications don’t work as effectively in women as they do in men; and that women are more likely to develop chronic pain conditions and addictions to pain medication.”
Professor Bronwyn Graham is director of the Centre for Sex and Gender Equity in Health and Medicine at the George Institute for Global Health. (Supplied: The George Institute of Global Health)
In Australia, research shows women disproportionately experience delayed diagnosis, overprescribing, and a failure to have their symptoms properly investigated.
Professor Graham said that failing to consider biological and physical characteristics in research, as well as gender roles and behaviours, also meant that men miss out.
“If we’re looking at things in a sex- and gender-blind fashion, we’re also not thinking about what are the unique things about men that we need to pay attention to that might actually impact the prognosis of an illness … and also response to treatment.”
Australia lags behind on sex and gender equity
Last year, a study co-authored by Dr Carcel found just 30 per cent of health and medical research publications in Australia analysed their findings by sex and/or gender.
“The NHMRC statement is groundbreaking for Australia,” she said.
“It’s not meant to increase the pool of researchers who focus on these variables, but is for all researchers applying for NHMRC and MRFF grants.”
Historically, the tendency to conduct scientific research on men and generalise the findings, including to women, has been driven largely by concerns over potential harm to the female reproductive system.
Martha Hickey, a professor of obstetrics and gynaecology at the University of Melbourne, said the exclusion of women was also a product of the misguided belief that female hormonal fluctuations may affect the reliability of study results.
“There were a number of false assumptions made at different levels,” said Professor Hickey, an NHMRC Leadership Fellow.
“I think all of us have been surprised by how far down this goes. It wasn’t just about [research on] people, it was also animals, and even cell-based research.”
Professor Hickey, who contributed to the development of the new NHMRC statement, said when it came to recognising sex and gender differences, Australia lagged behind Europe and North America.
“The Americans have been doing this for more than 20 years, by which I mean stating that there needs to be equal numbers of males and females and other important variable groups taken into consideration,” she said.
“I think we’ve all learnt that research is better if it’s inclusive, and it’s more likely to be taken up.”
Research grants should reflect new recommendations, experts say
While Professor Graham described the statement as “an incredibly positive step”, she expressed concern that the new recommendations were not yet “written into policy”.
“There is nowhere in the grant application process where researchers are required to indicate how they have taken sex, gender, variations of sex characteristics and sexual orientation into account.”
Traditionally, researchers have worked with male lab animals and primarily used men in clinical trials. (Getty Images: SolStock)
In some circumstances, having equal gender representation or analysing data by sex may not be necessary, but she said researchers should still have clear reasoning as to why.
“They should still need to justify the sample: how is it actually representative? Is the research being conducted in the population that stands to benefit from this research?”
Dr Carcel agreed, and said the statement should be followed up with an implementation and evaluation plan requiring sex and gender to be addressed in grant applications where appropriate.
A spokesperson for the NHMRC said researchers and their institutions were being “encouraged to reflect on the statement and start doing what they can now”, but no formal requirement was in place.
“The next phase of work will include consideration of how to incorporate the statement in granting processes,” the spokesperson said.
Improving knowledge and healthcare requires sector-wide change
In addition to funding bodies, Dr Carcel stressed that universities, medical research institutes, and health and medical journals had a significant role to play in improving sex and gender equity.
“[Journal editors] act as gatekeepers of bad science, and bad science is what we get if we don’t include sex and gender into our research.”
Professor Graham agreed: “The places in which we practise research have a huge amount of control over our code of conduct. If [universities and medical research institutes] implement their own policies, that is a further support to ensure things like the NHMRC statement can gain momentum.”
In 2023, the NHMRC introduced measures to ensure an equal number of men and women were awarded senior investigator grants, which Professor Hickey said would also help to “change the nature of research”.
She added that there had been a major “feminisation” of the medical workforce and that awareness of sex and gender differences was “much more apparent” than in the past, but that improvements in knowledge wouldn’t solve the problem alone.
“The bias isn’t only around clinicians not understanding how women may present, it also appears to be how doctors and other health personnel respond to them,” she said.
In a recent survey of almost 3,000 Australian women, two in three reported health care-related bias and discrimination, with many women feeling dismissed and disbelieved.
“We’ve got a lot to learn,” Professor Hickey said.