Default-male medicine

Since 1989, cardiovascular disease has been the leading cause of death in US women and, following a heart attack, women are more likely to die than men. This disparity in deaths has been the case since 1984, and young women appear to be particularly at risk: in 2016 the British Medical Journal reported that young women were almost twice as likely as men to die in hospital.

Perhaps the greatest contributor to the numbers of women dying following a heart attack, however, is that their heart attacks are simply being missed by their doctors. Research from the UK has found that women are 50 per cent more likely to be misdiagnosed following a heart attack (rising to almost 60 per cent for some types of heart attack). This is partly because women often don’t have the “Hollywood heart attack”, as it’s known in medical circles (chest and left-arm pains). Women (particularly young women) may in fact present without any chest pain at all, but rather with stomach pain, breathlessness, nausea and fatigue.

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In 2016, the American Heart Association also raised concerns about a number of risk-prediction models “commonly used” in patients with acute coronary syndrome, because they were developed in patient populations that were at least two-thirds male. The performance of these risk-prediction models in women “is not well established”.

These symptoms are often referred to as “atypical”, a designation to which the British Medical Journal took exception in a 2016 article, saying that the term “may lead to the under appreciation of risk associated with this presentation”. And under appreciation of the risk may in turn explain why a 2005 US study found that “only one in five physicians across multiple specialties was aware that more women than men die from cardiovascular disease each year, and most of these physicians did not rate themselves as effective in treating sex-tailored cardiovascular disease”.

Robert Blemmel Schniebbelie

Atypical or not, for certain types of heart attacks, women (and, again, especially young women) who present without chest pain are at particular risk of death. This makes it extremely concerning that current NHS England guidelines specify “acute cardiac sounding chest pain” as part of the criteria for a patient being referred for primary percutaneous coronary interventions (PPCI) at one of the country’s specialist 24-hour heart-attack centres.

PPCI is an emergency treatment that restores blood flow during a heart attack, and which, according to one doctor I spoke to, has “massively improved survival and outcome”. But this treatment is only carried out at the 24-hour heart-attack centres and, perhaps as a result, 75 per cent of those who receive this treatment are men.

Common preventative methods may also not work as well in women. Acetylsalicylic acid (aspirin) has been found to be effective in preventing a first heart attack in men, but a 2005 paper found that it had a “nonsignificant” effect in women aged between 45 and 65.

A more recent study from 2011 found that not only was aspirin ineffective for women, it was potentially harmful “in the majority of patients”. Similarly, a 2015 study found that taking a low dose of aspirin every other day “is ineffective or harmful in the majority of women in primary prevention” of cancer or heart disease.

Indeed, women’s heart attacks may not only present differently, but may in fact be mechanically different, so the technology we’ve developed to search for problems may not be suitable for female hearts. For example, a heart attack is traditionally diagnosed with an angiogram, which will show where there are obstructed arteries. But women often don’t have obstructed arteries, meaning that the scan won’t show up any abnormalities, and women who turn up at hospital with angina (chest pain) may simply be discharged with a diagnosis of “non-specific chest pain” and told they have no significant disease.

Assuming a woman gets lucky and has her heart disease diagnosed, she must then navigate the obstacle course of male-biased treatment: sex differences have not generally been integrated either into “received medical wisdom” or even clinical guidelines. For example, say a man and a woman are both diagnosed with a swollen aorta (the aorta is the main blood vessel that runs from the heart down through the chest and stomach). They are both suffering from an equal level of swelling – but their risk is not the same: the woman has a higher risk of rupture, which carries with it a 65 per cent chance of death. And yet, in Dutch clinical guidelines, the thresholds for surgery don’t differ for each sex.

The “default male” problem in medicine goes even further than just heart attacks, however. It is endemic within medicine.

It begins with how doctors are trained. Historically, it’s been assumed that there wasn’t anything fundamentally different between male and female bodies other than size and reproductive function. And so, for years, medical education has been focused on a male “norm”, with everything that falls outside that designated “atypical” or even “abnormal”. References to the “typical 70kg man” abound, as if he covers both sexes (as one doctor pointed out to me, he doesn’t even represent men very well).

When women are mentioned, they are presented as if they are a variation on standard humanity. Students learn about physiology, and female physiology. Anatomy, and female anatomy. “The male body”, concluded the social psychologist Carol Tavris in her 1992 book The Mismeasure of Woman, “is anatomy itself.”

Wikipedia

This male-default bias goes back at least to the ancient Greeks, who kicked off the trend of seeing the female body as a “mutilated male” body (thanks, Aristotle). The female was the male “turned outside in”. Ovaries were female testicles (they were not given their own name until the 17th century) and the uterus was the female scrotum. The reason they were inside the body rather than dropped out (as in typical humans) is because of a female deficiency in “vital heat”. The male body was an ideal women failed to live up to.

Of course, modern doctors no longer refer to women as mutilated males, but the representation of the male body as the human body persists. A 2008 analysis of a range of textbooks recommended by 20 of the “most prestigious universities in Europe, the United States and Canada” revealed that across 16,329 images, male bodies were used three times as often as female bodies to illustrate “neutral body parts”.

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The gender data gaps found in medical textbooks are also present in your typical medical-school curriculum. A 2005 Dutch study found that sex and gender-related issues were “not systematically addressed in curriculum development”. A 2006 review of Curr-MIT, the US online database for med-school courses, found that only nine out of the 95 schools that entered data into the system offered a course that could be described as a “women’s health course”. Only two of these courses (obstetrics and gynaecology, taught in the second or third academic years) were mandatory. Even conditions that are known to cause the greatest morbidity and mortality in women failed to incorporate sex-specific information. Ten years later, another review found that the integration of sex and gender-based medicine in US med schools remained “minimal” and “haphazard”, with gaps particularly identified in the approach to the treatment of disease and use of drugs.

Deasy et al.

These gaps matter because, contrary to what we’ve assumed for millennia, sex differences can be substantial. Researchers have found sex differences in every tissue and organ system in the human body, as well as in the “prevalence, course and severity” of the majority of common human diseases. There are sex differences in the fundamental mechanical workings of the heart. There are sex differences in lung capacity, even when these values are normalised to height (perhaps related is the fact that, among men and women who smoke the same number of cigarettes, women are 20 to 70 per cent more likely to develop lung cancer).

Deasy et al.

Sex differences appear even in our cells: in blood-serum biomarkers for autism; in proteins; in immune cells used to convey pain signals; in how cells die following a stroke. A recent study also found a significant sex difference in the “expression of a gene found to be important for drug metabolism”. Sex differences in the presentation and outcome of Parkinson’s disease, stroke and brain ischemia (insufficient blood flow to the brain) have also been tracked all the way to our cells, and there is growing evidence of a sex difference in the ageing of the blood vessels, “with inevitable implications for health problems, examination and treatment”.

There is also just less interest in medical problems that afflict women compared with problems for men. Premenstrual syndrome (PMS) is a collection of symptoms that can include, among other things, mood swings, anxiety, breast tenderness, bloating, acne, headaches, stomach pain and sleep problems. PMS affects 90 per cent of women, but is chronically understudied: one research round-up found five times as many studies on erectile dysfunction than on PMS.

And yet, while a range of medication exists to treat erectile dysfunction, there is very little available for women, to the extent that over 40 per cent of women who have PMS don’t respond to treatments currently available. Sufferers are still sometimes treated with hysterectomies; in extreme cases, women have tried to kill themselves. But researchers are still being turned down for research grants on the basis that “PMS does not actually exist”.

Period pain – dysmenorrhea – similarly affects up to 90 per cent of women, and, according to the American Academy of Family Physicians, it affects the daily life of around one in five women. The level of pain women experience on a monthly basis has been described as “almost as bad as a heart attack”. But despite how common it is, and how bad the pain can be, there is precious little that doctors can or will do for you.

A rare 2007 grant application for research into primary dysmenorrhea described its causes as “poorly understood” and treatment options as “limited”. The vailable prescription medications have serious possible side effects and are by no means universally effective.

When I went to my (male) doctor about period pain that wakes me up at night and leaves me in a moaning foetal position in the daytime, he more or less laughed me out of the room. I haven’t bothered trying again. So imagine my joy when I read about a 2013 study that seemed to have found a cure. The “primary outcome” of a double-blind, randomised, controlled trial of sildenafil citrate, was – ladies, you may want to sit down for this – “total pain relief over four consecutive hours”, with “no observed adverse effects”. Imagine.

Created in 1989, sildenafil citrate is the medical name for Viagra. In the early 1990s, the drug was being tested as a heart-disease medication. It turned out not to be great at that, but one thing participants did report was an increase in erections (yes, all the trial participants were men). Total erectile dysfunction affects between 5 and 15 per cent of men depending on age, with about 40 per cent experiencing it to some degree – and so, naturally, the researchers were keen to explore this alternative use for their drug. By 1996, sildenafil citrate had been patented in the US and by March 1998 it was approved by the FDA. A happy ending for men, then.

But what if the trial had included women? The outcome of the 2013 study is indicative. The trial had to be stopped because the funding ran out, meaning the researchers did not meet their sample size and therefore could not confirm the primary hypothesis. They called for “larger studies of longer duration, likely multi-centre” to confirm their findings.

These studies have not happened. Dr Richard Legro, who led the study, told me he applied twice to the NIH (National Institutes of Health) for funding “to do a longer and larger study, and also to compare sildenafil to the standard of care, a non-steroidal anti-inflammatory agent”. He was rejected both times.

In each case, the grant “was deemed to be in the lower half of grants submitted”. It wasn’t even reviewed. Legro tells me that the comments he received “indicated that the reviewers did not see dysmenorrhea as a priority public health issue”. They also didn’t “fully understand clinical trial design of dysmenorrhea trials”. When I ask him if he thinks he will ever get funding, he says: “No. Men don’t care or understand dysmenorrhea. Give me an all-female review panel!”

There are a range of areas where a presumption of a male default is an annoyance. Shivering in offices set to a male temperature norm, for example, or struggling to reach a top shelf set at a male height norm. But medicine is one – only one – of the areas where differences can kill.

There are still vast medical gender data gaps to be filled in, but the past 20 years have demonstrably proven that women are not just smaller men: male and female bodies differ down to a cellular level. So why aren’t we teaching this, researching this and addressing this? In the meantime, indifference is killing women.

This is an edited extract from Invisible Women: Exposing Data Bias in a World Designed for Men by Caroline Criado Perez, published by Chatto & Windus on 7 March at £16.99. Copyright © Caroline Criado Perez 2019.