Invisible Women: Exposing Data Bias in a World Designed for Men

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 4 consecutive hours’, with ‘no observed adverse effects’.⁹⁶ 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.⁹⁷ 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 5-15% of men depending on age,⁹⁸ with about 40% of men 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.⁹⁹ A happy ending for men, then.

But what if the trial had included women? The outcome of the 2013 study is suggestive. 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-center’ to confirm their findings.

These studies have not happened. Dr Richard Legro, who led the study, told me he applied twice to the NIH 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!’

The failure of pharmaceutical companies to step in here and capitalise on what is surely a gold-plated commercial opportunity may seem baffling, but it’s quite possibly just another data-gap problem. In an email, Legro told me that, for cost reasons, the pharma industry ‘doesn’t usually fund investigator-initiated projects’, particularly of drugs that are available generically. And this may be where the data gap comes in: there simply isn’t much research done on dysmenorrhea,¹⁰⁰ which makes it difficult for pharma companies to know exactly how much money could be made on such a drug – and therefore makes it harder for them to decide to fund trials. Especially if the people making the decisions happen not to be women. Legro also suggested that pharma companies may not want to risk doing tests in women in case of negative findings that would endanger the use of sildenafil in men. In short, it seems that pharma companies may in fact not see this as a gold-plated commercial opportunity. And so women carry on being incapacitated by pain on a monthly basis.

Male-dominated funding panels may also explain why we have so few drugs available for uterine failure. Every day 830 women around the world die due to complications during pregnancy and childbirth¹⁰¹ (in some African countries more women die annually from childbirth than at the height of the Ebola epidemic¹⁰²). Over half of these deaths are explained as being a result of problems with contractions, often because the contractions are too weak for the woman to give birth. The only medical treatment available for women whose contractions aren’t strong enough is the hormone oxytocin, which works about 50% of the time. Those women go on to give birth vaginally. Women who don’t respond to oxytocin are given an emergency caesarean. In the UK weak contractions are the reason given for a majority of the 100,000 emergency caesareans carried out each year.

We currently have no way of knowing which women will respond to oxytocin, which clearly isn’t ideal: all women, including those for whom it will result in a pointless and harrowing delay, have to go through the process. This happened to a friend of mine in 2017. After being in hospital in excruciating pain for two days (on her own for much of it as her partner had been sent home), she was only 4 cm dilated. Eventually she was taken off for a C-section, and she and the baby were fine. But the experience left her traumatised. She had flashbacks for the first few weeks after she gave birth. When she talks about the internal exams and procedures, she describes it as a violent assault. It was, she says, brutal. But what if it didn’t have to be this way? What if they’d known from the beginning that she was going to need a caesarean?

In 2016 Susan Wray, a professor of cellular and molecular physiology at the University of Liverpool, gave a lecture to the Physiological Society.¹⁰³ Wray is also the director of the Centre of Better Births in Liverpool Women’s Hospital and she explained that recent research revealed that women with contractions that were too weak to give birth had more acid in their myometrial blood (the blood in the part of the uterus that causes contractions). The higher the levels of acid were, the higher the likelihood a woman would end up needing a caesarean, because oxytocin isn’t, it turns out, that effective on women with an acidic blood pH.

But Wray didn’t simply want to be able to predict the need for a caesarean. She wanted to be able to avoid it. Together with her fellow researcher Eva Wiberg-Itzel, Wray conducted a randomised control trial on women with weak contractions. Half of them were given the usual oxytocin; half were given bicarbonate of soda, and then given the usual oxytocin an hour later. The change was dramatic: 67% of women given just oxytocin went on to give birth vaginally, but this rose to 84% if they were