Closing the sex and gender gap in medical research
By Dr Alison Simmons, our Director of Research, for International Women's Day 2023.
If you were having a heart attack and went to the doctor, you would expect your symptoms to be swiftly recognised, and the cause of them to be treated effectively.
However, if you’re female (in either sex or gender), you are 50 per cent more likely to be misdiagnosed, and therefore more likely to suffer serious outcomes from a heart attack - just because you are female (1, 2).
Gender inequalities between men and women exist in the world of work, homelife, and culture, but when they occur in medical research, the consequences can be life-threatening.
The processes underpinning disease, disease symptoms, and the way drugs work in the body (such as aspirin) all differ between men and women because of what we call the ‘gender data gap’. This refers to the fact that across society, the vast majority of data is based on the male body, and male experiences – and this puts women at risk.
The world of medical research is driven by rigorous processes, and it can be hard to believe that a simple fact such as sex or gender can be overlooked. However, the data gap begins at the earliest stages of medical research – when scientists study cells growing in a laboratory – and persists right up to clinical trials, which are testing treatments in patients.
In the lab
In the laboratory, scientists grow a number of what we call cell lines – cells which grow and divide indefinitely, making it easy to test how they respond to different drugs, or treatments. But these cells have a biological sex, as they have either an XX or XY chromosome – and male cells respond differently to female cells, for example in the way they metabolise drugs, or how an immune cell reacts to an invading virus.
A recent study has shown that less than half of scientific studies report the sex of their cells, and where they do, they are more likely to use cells which are male (3). The results are then often applied equally to female cells, even though they may respond completely differently.
The next stage of scientific research is testing laboratory findings in animal models. However, most studies are done on groups of animals which are all male. Female animals have often been excluded from studies because of the misconception that female hormones would skew and complicate the reading of the results. This has widespread implications, including developing drugs which have different effects, or increased side effects, in women.
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Similarly, in the past, clinical trials in medical research have taken place with study groups which are mainly male. There is a historical reason behind this – in 1977, in response to the sad story of thalidomide use in pregnancy, the US Food and Drug Administration advised that women of childbearing potential should be excluded from drug trials. Although reversed in the 1990s, this meant women were excluded from these trials for decades. As a result, it was assumed that the occurrence and outcomes of disease as it happens to a man can apply equally to a woman.
Finally, when it comes to analysing data, even when both sexes are used in experiments or trials, studies rarely break down the results by sex or gender. This means that even when all the underlying work is there, the end result doesn’t give us any more information on health impacts for women.
The accumulation of all these factors has created an ever-widening gap in our knowledge of how disease processes occur and can be treated in women. For example, the insomnia drug Ambien (Zolpidem) is broken down much more slowly in women than men, meaning it is much more potent – but it had been through predominately male animal studies and male clinical trials before this was realised (4).
The first step is to recognise that, by closing this gap, we can fund higher quality science which can make a genuinely life-changing difference for women, as well as men. Dr Alison Simmons
What can research funders do?
Medical research funders can play a critical role in addressing these issues. Thankfully, in recent years scientists, funders and patients have recognised, and begun to tackle this problem. For example, the largest funder in Europe, the European Commission through its Horizon funding programme now requires all proposals to include intersectional sex and gender analysis, unless the exclusion is justified. And the largest funder in the US, the National Institutes of Health, in 2019 implemented its Advancing Science for the Health of Women programme to ensure sex and gender is integrated into biomedical research.
Here at the Medical Research Foundation, we are making changes to address this inequality. We have recently become members of EDIS – the Equality, Diversity and Inclusion in Science and Health coalition – to learn and develop best practice in the area. Since early 2022, we have asked all grant applicants to tell us how the sex/gender dimension of their research has been accounted for in their experimental design - and if not, why not. We have also guided our peer reviewers and Expert Review Panel members to specifically address this issue in the applications they assess.
Clearly, there is still a long way to go in narrowing the huge gender data gap which exists in medical research. The first step is to recognise that, by closing this gap, we can fund higher quality science which can make a genuinely life-changing difference for women, as well as men.
1 - https://doi.org/10.1152/physre... Mechanistic Pathways of Sex Differences in Cardiovascular Disease
2 – BHF – Misdiagnosis of heart attacks in women
3 - https://doi.org/10.1152/ajpcel... Sex omission and male bias are still widespread in cell experiments
4- DOI: 10.1126/science.aaw757 Are hormones a “female problem” for animal research?
5 - https://www.ncbi.nlm.nih.gov/p... The Integration of Sex and Gender Considerations Into Biomedical Research: Lessons From International Funding Agencies