In this latter failure, they are not alone. Several reviews of papers published in major journals over the past ten years have all identified a routine failure to either present results by sex, or to explain why the influence of sex has been ignored.77 A 2001 US Government Accounting Office (GAO) audit of FDA records found that about a third of documents didn’t sex-disaggregate their outcomes and 40% didn’t even specify the sex of the participants. The auditors concluded that the FDA had ‘not effectively overseen the presentation and analysis of data related to sex differences in drug development’,78 a finding that was confirmed in a 2007 analysis of new drug applications submitted to the FDA which found a failure to establish standards for data analysis of applications.79 In 2015 the GAO criticised the US National Institutes of Health (NIH) for failing to routinely track whether researchers had actually evaluated any differences between the sexes.80 Things are often even worse in non-government-funded trials – which represent the majority of studies. A 2014 investigation into sex analysis in cardiovascular trials found that thirty-one of sixty-one NIH-sponsored trials analysed outcomes by sex compared with only 125 of 567 non-NIH-sponsored clinical trials.81
The lack of sex-disaggregated data affects our ability to give women sound medical advice. In 2011 the World Cancer Research Fund complained that only 50% of studies into the impact of diet on cancer that included both men and women disaggregated their data by sex, making it hard to establish dietary guidelines for cancer prevention that are valid for both sexes.82 Women, for example, should probably eat more protein than men as they age (because of muscle mass loss), but ‘the optimal dose per meal to support muscle protein synthesis in older women has not been determined’.83
The failure to sex-disaggregate when you’ve actually gone to the effort of including both sexes is baffling, not to mention, as Londa Schiebinger at Stanford University puts it, ‘money wasted [and] research that is lost to future meta-analysis’.84 And when female representation in trials is so low, the ability to conduct meta-analysis can mean the difference between life and death.
In 2014 a review of the FDA database of a cardiac resynchronisation therapy device (CRT-D – essentially a more complicated kind of pacemaker) trials found that women made up about 20% of participants.85 The number of women included in each individual study was so low that separating out the data for men and women didn’t reveal anything statistically significant. But when the review authors combined all the trial results and sex-disaggregated that data, they found something alarming.
A CRT-D is used to correct a delay in your heart’s electrical signals. They are implanted for established heart failure and the D stands for defibrillator. This defibrillator (a larger version of which most of us will have seen in one hospital drama or other) performs something like a hard reset on the heart, shocking it out of its irregular rhythm so that it can restart in its correct rhythm. A doctor I spoke to described CRT-Ds as ‘symptom control’. They aren’t a cure, but they prevent many early deaths, and if your heart takes 150 milliseconds or longer to complete a full electrical wave, you should have one implanted. If your heart completes a full circuit in under that time, you wouldn’t benefit from one.
Unless, the meta-analysis found, you happened to be female. While the 150 milliseconds threshold worked for men, it was twenty milliseconds too high for women. This may not sound like much, but the meta-analysis found that women with an electrical wave of between 130-49 milliseconds had a 76% reduction in heart failure or death and a 76% reduction in death alone from having the advanced pacemaker implanted. But these women would not be given the device under the guidelines. And so because the trials treated male bodies as the default, and women as a side-show, they had condemned hundreds of women to avoidable heart failure and death.
The CRT-D is far from the only piece of medical tech that doesn’t work for women – which is unsurprising given a 2014 analysis which found that only 14% of post-approval medical-device studies included sex as a key outcome measure and only 4% included a subgroup analysis for female participants.86 A 2010 paper found that ‘the female gender is associated with an increased risk of acute complications during primary pacemaker implantation, being independent from age or type of device implanted’.87 In 2013, a supposedly revolutionary artificial heart was developed that was too big for women.88 Its designers are working on a smaller version, which is great, but it’s striking that, like other artificial hearts,89 the female version comes years after the default male one.
Even something as basic as advice on how to exercise to keep disease at bay is based on male-biased research. If you run a general search for whether resistance training is good for reducing heart disease, you’ll come across a series of papers warning against resistance training if you have high blood pressure.90 This is in large part because of the concerns that it doesn’t have as beneficial an effect on lowering blood pressure as aerobic exercise, and also because it causes an increase in artery stiffness.
Which is all true. In men. Who, as ever, form the majority of research participants. The research that has been done on women suggests that this advice is not gender-neutral. A 2008 paper, for example, found that not only does resistance training lower blood pressure to a greater extent in women, women don’t suffer from the same increase in artery stiffness.91 And this matters, because as women get older, their blood pressure gets higher compared to men of the same age, and elevated blood pressure is more directly linked to cardiovascular mortality in women than in men. In fact, the risk of death from coronary artery disease for women is twice that for men for every 20 mm Hg increase in blood pressure above normal levels. It also matters because commonly used antihypertensive drugs have been shown to be less beneficial in lowering blood pressure in women than in men.92
So to sum up: for women, the blood-pressure drugs (developed using male subjects) don’t work as effectively, but resistance training just might do the trick. Except we haven’t known that because all the studies have been done on men. And this is before we account for the benefits to women in doing resistance training to counteract osteopenia and osteoporosis, both of which they are at high risk for post-menopause.
Other male-biased advice includes the recommendation for diabetics to do high-intensity interval training; it doesn’t really help female diabetics93 (we don’t really know why, but this is possibly because women burn fat more than carbs during exercise94). We know very little about how women respond to concussions,95 ‘even though women suffer from concussions at higher rates than men and take longer to recover in comparable sports’.96 Isometric exercises fatigue women less (which is relevant for post-injury rehabilitation) because men and women have different ratios of types of muscle fibre, but we have ‘a limited understanding of the differences’ because there are ‘an inadequate number of published studies’.97
When even something as simple as ice-pack application is sex-sensitive, it’s clear that women should be included in sports-medicine research at the same rates as men.98 But they aren’t.99 And researchers continue to research men and act as if their findings apply to women. In 2017, a Loughborough University study100 was hailed around the UK news media as proving that a hot bath has anti-inflammatory and blood-sugar response benefits similar to exercise.101 Published in the journal Temperature with the sub heading ‘A possible treatment for metabolic diseases?’ the study included no women at all.