Inferior: How Science Got Women Wrong – and the New Research That’s Rewriting The Story. Angela Saini
But does it have to be one or the other? Is the only alternative to women being thought of as ‘little men’ to have them treated as an entirely different kind of patient? As more detailed research is done, it’s becoming clear that seeing some variation between women and men when it comes to health and survival doesn’t mean we should ditch the notion that our bodies are in fact similar in most ways.
This is a cautionary tale of two drugs.
The first is digoxin, which has long been used to treat heart failure. In 2002 researchers at the Yale University School of Medicine decided to take a look at the data around the drug, analysing its effects by sex. Between 1991 and 1996, other researchers had carried out randomised trials on heart patients using digoxin. They found that it didn’t affect how long a patient lived, but it did on average reduce their risk of hospitalisation. The Yale researchers noted that the drug was tested on around four times as many men as women, and that they didn’t respond identically. A slightly higher proportion of women taking digoxin died earlier than those taking a placebo. For men, the gaps between those taking the drug and the placebo group were much smaller. The sex difference, the Yale team concluded, ‘would have been subsumed by the effect of digoxin therapy among men’.
But science never stands still. The Yale result later turned out not to be what it seemed. More recent studies, including one with a much larger sample group published in the British Medical Journal in 2012, have suggested that in fact there isn’t a substantially increased risk of death for women from digoxin use at all.
The second example is the insomnia drug zolpidem, commonly sold in the United States under the brand name Ambien. Sleeplessness is big business for pharmaceutical companies. Around sixty million sleeping pills were prescribed in the US in 2011, up from forty-seven million just five years earlier, according to data collected by the healthcare intelligence company IMS Health. And Ambien is among the most popular. Its side effects, however, include severe allergic reactions, memory loss and the possibility of it becoming habit-forming. The effects of zolpidem can also lead to drowsiness the following day, which can make it dangerous to drive. Long after the drug was approved for market, research emerged that women given the same dose as men were more likely to suffer this morning drowsiness. Eight hours after taking zolpidem, 15 per cent of women but only 3 per cent of men had enough of the drug in their system to increase their risk of a traffic accident.
At the start of 2013 the US Food and Drug Administration took the landmark decision to lower the recommended starting dose of Ambien, halving it for women. ‘Zolpidem is kind of like a signal case,’ says Arthur Arnold.
Again though, just as with digoxin, the finding needed to be unpicked a little further. In 2014, additional research exploring the effects of zolpidem, carried out by scientists at Tufts University School of Medicine in Boston, suggested that its lingering effect in women may be mostly down to the fact that they have a lower average body weight than men, which means the drug clears from their systems more slowly.
Digoxin and zolpidem highlight the pitfalls of including sex as a variable in medical research. Besides a lower average body weight and height, women also have a higher percentage of body fat than men on average. And they generally take longer to pass food through their bowels. Both are things that might affect how drugs behave in their bodies. But they are also factors on which men and women overlap. There are many women who are heavier than the average man, for instance. It’s not always the case that the sexes belong in two separate categories.
What also counts is the experience of being a woman, socially, culturally and environmentally. ‘Both sex and gender are important factors for health,’ says Janine Clayton. Ideally, then, people should be treated according to the spectrum of factors that set them apart. Not just sex, but social difference, culture, income, age and other considerations. As Sarah Richardson has written, ‘a female rat – not to mention a cell line – is not an embodied woman living in a richly textured social world’.
The problem is that ‘medicine is very binary. Either you get the drug or you don’t. Either you do this or you do that,’ says Sabine Oertelt-Prigione. ‘So the only step, I believe, is to incorporate the notion that there is actually not one neutral body, but at least two. I believe it’s just another way of looking at things. In medicine, just having a way to change paradigms and look at things differently can open up whole arrays of possibilities. It could be looking at sex differences, but there are many other things that could help to make healthcare more inclusive in the end.’
‘What are we trying to do? We’re trying to improve human health, right?’ says Kathryn Sandberg. ‘So if we see a disease is more prevalent or more aggressive in men than women, or vice versa, we can learn a lot about that disease by studying why one sex is more susceptible while the other is more resilient. And this information can lead to new treatments that benefit all of us.’ Understanding why women tend to live longer could help men live longer. Including pregnant women in research may open up the cabinet of drugs that doctors can’t currently prescribe because their effects on foetuses are uncertain. Medical dosages might be affected by a better understanding of how a woman’s body responds across her menstrual cycle.
At the moment at least, the verdict of politicians and scientists seems to be that including sex as a variable when carrying out medical research can improve overall health. In 1993 the US Congress introduced the National Institutes of Health Revitalization Act, which includes a general requirement for all NIH-funded clinical studies to include women as test subjects, unless they have a good reason not to. By 2014, according to a report in Nature by Janine Clayton, just over half of clinical-research participants funded by the NIH were women.
Since the start of 2016 the law in the USA has been broadened to include females in vertebrate animal and tissue experiments. The European Union now also requires the researchers it funds to consider gender as part of their work.
For women’s health campaigners and researchers like Janine Clayton and Sabine Oertelt-Prigione, this is a victory. To have females equally represented in research is something they’ve spent decades fighting for. Male bias, where it exists, is being swept away. Women are being taken into account. Maybe we will finally understand just what it is that makes women on average better survivors, and why men seem to report less sickness.
But as science enters this new era, scientists need to be careful. Research into sex differences has an ugly and dangerous history. As the examples of digoxin and zolpidem prove, it’s still prone to errors and over-speculation. While it can improve understanding, it also has the potential to damage the way we see women, and to drive the sexes further apart. The work being done into genetic sex differences by people like Arthur Arnold doesn’t just impact medicine, but also how we see ourselves.
Once we start to assume that women have fundamentally different bodies from men, this quickly raises the question of how far the gaps stretch. Do sex chromosomes affect not just our health, but all aspects of our bodies and minds, for example? If every cell is affected by sex, does that include brain cells? Do oestrogen and progesterone not just prepare a women for pregnancy and boost her immunity, but also creep into her skull, affecting how she thinks and behaves? And does this mean that gender stereotypes, such as baby girls preferring dolls and the colour pink, are in fact rooted in biology?
Before we know it we land on one of the most controversial questions in science: are we born not just physically different, but thinking differently too?
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Girls and boys, in short, would play harmlessly together, if the distinction of sex was not inculcated long before nature makes any difference.
Mary Wollstonecraft, A Vindication of the Rights of Woman (1792)
‘We live in jeans, don’t we? They go with everything!’ coos the mother. Her six-month-old daughter is wearing the tiniest pair of jeans I’ve ever seen, and she herself is dressed head to foot