Inferior: How Science Got Women Wrong – and the New Research That’s Rewriting The Story. Angela Saini
says Kathryn Sandberg. ‘If you look across all the different types of infections, women have a more robust immune response.’ It isn’t that women don’t get sick. They do. They just don’t die from these sicknesses as easily or as quickly as men do.
One explanation for this gap is that higher levels of oestrogen and progesterone in women might be protecting them in some way. These hormones don’t just make the immune system stronger, but also more flexible, according to Sabine Oertelt-Prigione, a researcher at the Institute of Gender in Medicine at the Charité University Hospital in Berlin. ‘This is related to the fact that women can bear children,’ she explains. A pregnancy is the same as foreign tissue growing inside a woman’s body that, if her immune system was in the wrong gear, would be rejected. ‘You need an immune system that’s able to switch from pro-inflammatory reactions to anti-inflammatory reactions in order to avoid having an abortion pretty much every time you get pregnant. The immune system needs to have mechanisms that can, on one side, trigger all these cells to come together in one spot and attack whatever agent is making you sick. But then you also need to be able to stop this response when the agent is not there any more, in order to prevent tissues and organs from being harmed.’
The hormonal changes that affect a woman’s immune system during pregnancy also take place on a smaller scale during her menstrual cycle, and for the same reasons. ‘Women have more plastic immune systems. They adapt in different ways,’ says Oertelt-Prigione. Many types of cell in the body are involved in immunity, but the kind that come into closest contact with viruses and bacteria are known as T cells. They inject substances into bacteria to kill them, or secrete other substances that call more cells to action, some of which ‘eat up’ infected cells and bacteria, like Pac-Man in the video game, she explains. Researchers know that a certain type of T cell that’s crucial to managing the body’s response to infections becomes more active in the second half of a woman’s menstrual cycle, when she’s able to get pregnant.
The discovery that sex hormones and immunity might be linked is fairly recent. In men, scientists have explored connections between testosterone and lower immunity, although the evidence is relatively thin. In 2014, for example, Stanford University researchers found that males with the highest levels of testosterone had the lowest antibody response to a flu vaccine, which meant they were the least likely to be protected by the jab. As yet, though, it’s an unsubstantiated link. In women, the connection is far clearer. So much so that patients themselves have noticed these fluctuations. For years, doctors assumed that a woman’s immunity didn’t change during her menstrual cycle. If she did report a difference in pain levels, doctors might dismiss it as premenstrual syndrome, or some vague psychological complaint. It was only when these links were increasingly backed up by hard research that scientific interest was sparked, and more research began to flourish.
This problem runs all the way through research into women’s health. If a phenomenon affects women, and only women, it’s all too often misunderstood. And this is compounded by the fact that even though they’re better at surviving, women aren’t healthier than men. In fact, quite the opposite.
‘If you could add up all the pain in the world, all the physical pain, I suspect that women have way, way more of it. This is one of the penalties of being a better survivor. You survive, but maybe not quite as intact as you were before,’ says Steven Austad. Statistically, this could explain why women seem proportionally sicker than men. ‘Part of the reason that there are more women than men around in ill health is to do with the fact that women have survived events that would kill men, and so the equivalent men are no longer with us.’
Another reason is that women’s immune systems are so powerful that they can sometimes backfire. ‘You start regarding yourself as foreign, and your immune system starts attacking its own cells,’ explains Kathryn Sandberg. Diseases caused in this way are known as autoimmune disorders. The most common include rheumatoid arthritis, lupus and multiple sclerosis. ‘It’s kind of a double-edged sword with the immune system. In some ways it’s better to have a female immune system if you’re fighting off infection of any kind, but on the other hand, we are more susceptible to autoimmune diseases, which are very problematic.’
This isn’t to say that autoimmune disease is always hardest on women. When men get multiple sclerosis, they tend to get it worse. Women also survive with it longer than men do. Even so, of the roughly 8 per cent of Americans who suffer from auto-immune diseases, estimates suggest that at least three-quarters are women.
‘In autoimmune diseases, they almost all tend to get worse right before the menstrual cycle in women who are premenopausal,’ says Sabine Oertelt-Prigione. In the same way that varying hormone levels may boost a woman’s immunity at different times of the month, there are theories that they might also affect her experience of illness. There are reports, for instance, that women with asthma are at highest risk of an attack just before or at the start of their period. As oestrogen and progesterone levels drop in the years following the start of the menopause, a woman’s immunity advantage starts to drop away as well.
When it comes to viral infections, too, a woman’s strong immune response may be a problem as well as a benefit. Research on influenza by Sabra Klein, an immunologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, has shown that while women are generally hit by fewer viruses during an infection, they tend to suffer more severe flu symptoms than men do. She reasons that this may be because women’s immune systems mount sturdier counter-attacks against viruses, but then suffer when the effects of these counter-attacks impact their own bodies.
Women also tend to get more painful joint and muscle diseases, observes Steven Austad. Part of this is down to autoimmune diseases that affect the joints, such as arthritis. The physical toll of childbearing and the hormonal changes of menopause may also leave women with physical problems and disabilities, especially in later life. Bone density is known to fall short-term after pregnancy, and after the menopause. Weight gain is now also recognised as a symptom of menopause.
But the overall picture of pain and ill-health is complicated. ‘Cross-culturally, women just report more physical limitations and more disabilities. It’s really widespread,’ says Austad. When it comes to biological clues about the underlying reasons for this sex difference in disease or survival, however, he adds, ‘I don’t feel very confident of any explanation.’
It’s difficult to tear apart biology from other effects. Society and the environment can sometimes impact illness more than a person’s underlying biology. ‘Women are less likely to go to the hospital when they’re feeling chest pain than men,’ says Kathryn Sandberg, who has looked at gender differences in heart disease in particular. There are countless other ways in which men’s and women’s health habits differ throughout the world. Sabine Oertelt-Prigione points out that where families eat collectively and food is scarce, women are sometimes the last to eat and are the most likely to go without food, which can raise their risk of malnutrition. This in turn can affect their susceptibility to disease.
Not only a woman’s own behaviour, but that of others around her, can affect her health. From the second a girl is born, she’s placed in a different box from a boy. She may be handled differently, fed differently and treated differently. And this marks the beginning of a lifetime of differences in the way doctors and medical researchers approach her as well. Only very recently, for instance, have doctors begun to acknowledge the severity of some women’s experience of period pain. In 2016, professor of reproductive health at University College London, John Guillebaud, told a reporter that period pain can be ‘almost as bad as having a heart attack’, and admitted that it hasn’t been given the attention it deserves, partly because men don’t suffer from it. In 2015, a team of British researchers studying cancer diagnosis in the UK found that it took longer for women to be diagnosed after going to a doctor in six of the cancers that affect both men and women, including bladder and lung. For gastric cancer, a woman waited on average a full two weeks longer for a diagnosis.
If there are underlying biological sex differences in health, and the differences aren’t largely down to society and culture, then scientists need to go deeper inside the body to find them.
‘Females get sicker but males die quicker,’ says Arthur Arnold, a