When it comes to our health, it seems there is still a gender gap in what we know and how we treat men and women.
Research suggests that women are missing out on potentially life-saving treatments and tests because doctors and researchers have failed to take fundamental biological differences between the sexes into account.
Certain behavioural or social factors mean that women are less likely to be diagnosed with particular conditions, or get treatment, too.
For example, a study concluded women in the early stages of Alzheimer’s are going undiagnosed because they tend to have superior verbal memories — the type that helps them remember words from stories or lists, for example.
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In the study by the University of Illinois, presented to the Alzheimer’s Association International Conference earlier this year, women managed to sustain their performance in memory tests even when scans showed Alzheimer’s was beginning to damage key parts of the brain.
The scientists concluded that ‘while the female advantage may be functionally beneficial, it could mask the early stages of Alzheimer’s, resulting in a more severe burden of disease at the time of diagnosis, with more rapid deterioration thereafter’.
Also, for years, heart attacks have been thought of as a ‘man’s disease’, mainly because men have traditionally tended to be more likely to smoke, have unhealthy lifestyles or succumb to stress.
The symptoms of a heart attack in women are also often thought of as less typical, so tend to be missed. As a result, cases in women are also missed. Women are more likely to die following an attack, partly due to misdiagnosis.
WOMEN’S BREASTS CAN AFFECT HEART SCANS
‘Women with heart attacks are more likely to be taken to hospital and discharged with an irrelevant diagnosis such as panic attacks or indigestion,’ says Georgios Kararigas, a professor of translational gender research at Charité University Hospital in Berlin, Germany.
‘This means they are not properly treated, which is detrimental to their health and can lead to unnecessary deaths,’ he adds.
A further complicating factor is that ‘typical’ symptoms of a heart attack — such as chest pain, rapid heartbeat and shortness of breath — are more common in men.
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Women, instead, are more likely to experience fatigue, anxiety, light-headedness and sleep disturbances over a period of several days or weeks, rather than a sudden pain. These problems can be easily mistaken for other, less serious conditions.
Even if a heart attack is suspected, getting a diagnosis in women is tricky because breast tissue creates confusing shadows on the scan commonly used to detect coronary heart disease, known as Spect (single-photon emission computerised tomography).
‘Male and female hearts share the same physiology and function, but the response to disease differs significantly,’ says Professor Kararigas. That’s partly because hormones play a role.
Most women have a regular hormonal cycle after puberty, driven by the sex hormone oestrogen. This hormone has a protective effect against heart disease, though it’s not clear why.
However, once oestrogen levels drop after the menopause, this protection is lost and the risk of developing heart problems rises dramatically.
Heart disease even looks different in men and women. Men tend to have larger fatty blockages in their arteries which trigger an attack. These can be treated with a small tube, called a stent, to open up arteries and restore blood flow.
By contrast, women’s arteries tend to get ‘furred up’ with a layer of fatty material over a larger area. Stents or similar surgical approaches don’t work, and treatment tends to focus on lifestyle changes and drugs such as blood-thinning aspirin or beta blockers to reduce strain on the heart.
These gender differences extend into doctors’ perceptions of illnesses affecting men and women. Alarmingly, a study of A&E admissions in Florida, published in the Proceedings of the National Academy of Sciences earlier this year, showed that women are more likely to die if they are treated by male rather than female doctors.
This is likely due to stereotyped views about how a ‘typical’ (male) heart attack patient should be treated.
RESEARCH STUDIES LEAVE OUT WOMEN
One of the main reasons for the lack of knowledge about the impact of female hormones and biology on a whole range of conditions is a historical focus on using males for research.
‘In laboratory studies, we have to use animal models to look at what’s going on — for example, in the brain — so to use as few animals as possible most studies only include males,’ says Professor Spires-Jones.
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‘Males have less variation in behaviour and don’t have hormonal cycles, so are easier to study — but we’re missing out on information about how females behave, and they are potentially very different.’
This lack of female-specific data extends across all aspects of health research, from dementia and cardiovascular disease to asthma and autoimmune conditions.
For example, one review found that more than a fifth of studies didn’t state the sex of the animals, while 80 per cent of those that did used males.
A major study published in 2017 by researchers at the Wellcome Sanger Institute studied data of more than 200 characteristics including bone mass, metabolism and behaviour, finding that differences between the sexes could affect results in more than half of experiments.
One of the study’s authors, Professor Judith Mank of University College London, said the results show how often differences occur in characteristics that would otherwise be assumed to be the same in both sexes.
‘The fact that a mouse’s sex influenced genes indicates that males and females differ right down to the underlying genetics behind many traits. Only studying males paints half the picture,’ she said.
WOMEN’S DRUGS ARE TESTED ON MEN
As well as missing out on developments in laboratory research, women have long been ignored in clinical trials of new therapies.
In 1977, the U.S. Food and Drug Administration (FDA) banned women of ‘childbearing potential’ from most trials, even if they weren’t pregnant or planning to conceive. This was overturned in 1994, but disproportionately few women take part in trials today.
In fact, anti-anxiety drug Valium — known as ‘mother’s little helper’ — was originally never tested on women.
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Disturbingly, a 2016 study by Brazilian researchers, published in the Journal of Depression and Anxiety, showed that the menstrual cycle could have a major impact on Valium’s effectiveness depending on the time of the month, even rendering it useless.
A recent study to test the interactions between alcohol and Addyi, a drug designed to boost female libido, enrolled 23 men and two women.
This failure to study the effectiveness and side-effects in women has potentially serious safety consequences.
Between 1997 and 2001, eight out of ten previously approved prescription drugs pulled from the shelves by the FDA due to ‘unacceptable health risks’ were found to be more harmful to women than men, even though half of them were more likely to be given to women.
‘We know women are more likely to suffer drug reactions, and the menstrual cycle affects how well a treatment works,’ says Caroline Criado-Perez, author of the upcoming book Invisible Women, investigating gaps in research data relating to women.
‘This has been used as an excuse to ignore females, but the reality is that women have these hormones and the drugs will interact with them.’
Additionally, she says, many trial drugs don’t work when they’re tested on males. But this means treatments that might only work in females are shelved, so women may miss out on potential therapies.
‘People say women are too complex for medical research but we have to do more to study sex differences in males and females,’ adds Professor Kararigas.
‘We need to understand the differences in the underlying mechanisms of disease and identify novel drug targets for more appropriate treatment for both men and women, taking us towards the true realisation of personalised medicine.
‘If we don’t study both males and females, how can we find therapies that would be good for each of them?’ he says.
Caroline Criado-Perez would like to see legislation forcing researchers to include data from males and females from the earliest stages of laboratory research, and to properly separate trial data by sex as a condition of bringing a new treatment to market.
Professor Spires-Jones agrees: ‘We need to make sure we’re helping 100 per cent of the population, not half.’
FEMALE PAIN IS OFTEN DISMISSED
Variations in the way men and women are treated can be found in almost all areas of medicine, suggesting that there are more complex social factors at play than mere differences in physiology.
For example, women’s pain is less likely to be taken seriously than men’s, and women are more likely to receive sedatives rather than effective pain medication.
Chronic, debilitating conditions such as endometriosis are frequently dismissed as ‘period problems’ — leading the health watchdog NICE to issue guidelines telling GPs to listen a lot more carefully to their female patients.
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The symptoms of aggressive ovarian cancer are also often put down to ‘bloating’. And psychiatrists have only recently begun to acknowledge that autism may be far more widespread in girls and women than previously believed, because the condition can present differently between the sexes.
Dementia is another area where women are being sidelined.
Women have a higher risk of developing dementia during their lifetime than men, and around two-thirds of the people living with dementia in the UK are female.
But while some of this difference is due to the fact that women tend to live longer than men, there’s still a lot we don’t know about how sex affects dementia risk, according to Professor Tara Spires-Jones, an expert in Alzheimer’s disease at the University of Edinburgh.
‘Male and female brains are different, though that’s not to say one is better or worse,’ she says.
‘Both have around 100 billion nerve cells wired up with more than 100 trillion connections.
These are particularly impacted by hormones such as oestrogen, which changes during the menstrual cycle and in the menopause.
‘There’s so much we don’t know — the brain is incredibly complicated and complex, so when you add in hormones and sex differences, it becomes even more difficult.’
Given that Alzheimer’s disease is more common in women than men, it seems likely that there are fundamental biological differences at play.
This suggests that sex-specific tests or treatments might be beneficial.
But, as Professor Spires-Jones points out, ‘we simply don’t know, because there is a lack of research in this area’.