The male norm continues to go unquestioned by many today, with some researchers continuing to insist, in the face of all the evidence, that biological sex doesn’t matter. One public-health researcher revealed that she had received the following feedback on two different grant applications: ‘I wish you’d stop with all this sex stuff and get back to science’, and ‘I’ve been in this field for 20 years and this [biological difference] doesn’t matter’.41 It isn’t just anonymous notes, either. A 2014 op-ed published in the journal Scientific American complained that including both sexes in experiments was a waste of resources;42 in 2015 an op-ed in the official scientific journal of the US National Academy of Sciences insisted that ‘focusing on preclinical sex differences will not address women’s and men’s health disparities’.43
Alongside insisting that sex differences don’t matter, some researchers advocate against the inclusion of women in research on the basis that while biological sex may matter, the lack of comparable data arising from the historical data gap makes including women inadvisable (talk about adding insult to injury).44 Female bodies (both the human and animal variety) are, it is argued, too complex, too variable,45 too costly to be tested on. Integrating sex and gender into research is seen as ‘burdensome’.46 It is seen as possible for there to be ‘too much gender’,47 and for its exclusion to be acceptable on the basis of ‘simplification’48 – in which case it’s worth noting that recent studies on mice have actually shown greater variability in males on a number of markers.49 So who’s too complicated now?
Beyond the argument that women’s bodies, with their fluctuating, ‘atypical’ hormones, are simply inconvenient research vessels, researchers also defend their failure to include women in trials by claiming that women are harder to recruit. And it is certainly true that, due to women’s care-giving responsibilities they have less leisure time and may find it harder to make, for example, clinic appointments during the school run. However, this is an argument for adapting trial schedules to women, rather than simply excluding them, and in any case, it is possible to find women if you really want to. While reviews of FDA-mandated medical product trials found that women made up only 18% of participants in trials for endovascular occlusion devices (used if your foetal blood vessel hasn’t closed of its own accord)50 and 32% of participants in studies on coronary stents (which, incidentally, are another device where women have worse outcomes than men),51 women represented 90% and 92% of participants in facial wrinkle correction trials and dental device trials, respectively.
A more novel approach to addressing the problem of female under-representation in medical research is simply to claim that there is no problem, and women are represented just fine, thank you very much. In February 2018 a paper was published in the British Journal of Pharmacology entitled ‘Gender differences in clinical registration trials: is there a real problem?’52 Following ‘cross sectional, structured research into publicly available registration dossiers of Food and Drug Administration (FDA)-approved drugs that are prescribed frequently’, the all-male-authored paper concluded that, no, the problem was not ‘real’.
Leaving aside any philosophical debate over what an unreal problem might be, the authors’ conclusions are baffling. For a start, data was available for only 28% of the drug trials, so we have no way of knowing how representative the sample is. In the data researchers were able to access, the number of female participants in over a quarter of trials did not match the proportion of women in the US affected by the disease the drug was supposed to treat. Furthermore, the study did not address trials for generic drugs, which represent 80% of prescriptions in the United States.53 The FDA describes a generic drug as ‘a medication created to be the same as an already marketed brand-name drug’ and they are sold after the patent for the original branded drug runs out. Drugs trials for generic drugs are much less rigorous than original trials, having only to demonstrate equal bioavailability, and they are conducted ‘almost exclusively’ in young adult males.54 This matters because even with the same active ingredient, different inactive ingredients and different fabrication technology can affect a drug’s potency.55 And sure enough, in 2002 the FDA’s Center for Drug Evaluation and Research showed ‘statistically significant differences between men and women in bioequivalence for most generic drugs compared with reference drugs’.56
Despite all this, the authors claimed that there was no evidence of any systematic under-representation of women in clinical trials because in phase two and three trials women were included at 48% and 49%, respectively. But the study authors themselves report that in phase one trials women represented only 22% of participants. And, contrary to what their conclusion might imply, the under-representation of women in phase one trials does matter. According to the FDA, the second most common adverse drug reaction in women is that the drug simply doesn’t work, even though it clearly works in men. So with that substantial sex difference in mind: how many drugs that would work for women are we ruling out at phase one trials just because they don’t work in men?
Digging deeper into the numbers, another issue the authors completely failed to address is whether or not the drugs were tested in women at different stages in their menstrual cycles. The likelihood is that they weren’t, because most drugs aren’t. When women are included in trials at all, they tend to be tested in the early follicular phase of their menstrual cycle, when hormone levels are at their lowest – i.e. when they are superficially most like men. The idea is to ‘minimise the possible impacts oestradiol and progesterone may have on the study outcomes’.57 But real life isn’t a study and in real life those pesky hormones will be
