They were no longer little men… the need for female standards in medical research and innovation.

In all fields of research, young men have been considered as the default human for a long time; with the majority of medical tests being conducted on male subjects, personal protective equipment (PPE) being designed for male users, even crash test dummies being modelled on a 77 kg, 175 cm man.

And, this was the norm for a long time; the norm being an average Cis male.

For a multitude of socio-economic reasons, women have long been left out of the testing pool in many fields of biomedical and technological innovations and, as a result when it came to retrofitting medical science for women, they have long been considered as “little men”, and, while in a number of aspects this is true…. two arms, legs, lungs etc… this is a gross simplification, and increasingly more data is now showing the extent of just how unsatisfactory (and perhaps grossly negligent) this assumption has been for the health and wellbeing of all of those who are not male.

The problem with equating women as just being “little men” is that it does not take into account the multitude of physiological and morphological differences between CIS males and females, a massive data gap that has been up to now, carelessly plugged with an easy fix answer.

Within the medical sciences, this means that the way that female bodies work remains a far greater mystery in comparison to how men’s work, and, as a consequence, just how they interact with a plethora of approved medicines remains mostly unknown. The fact that drug doses are often just scaled down accordingly to better fit the generally smaller build of women bodies does not take into account the potential interactions between different levels of hormone or any other physiological differences. The data are just not there, and even when non-human test subjects are used, male cell cultures (1) and male animals (2) are far more abundantly used than the female counterparts. Female test subjects are, in the main being considered as “too complex, too variable, too costly to be tested on” (13).

However, it turns out the assumption that female bodies are just “atypical” males is far more deep-seated than just the lack of female representation in medical research trials. From the birth of medical science in ancient Greece, differences in women’s bodies were considered as deviations from male anatomy. Even today, medical training uses the male body as the “universal model” for a human being, with a 2008 study showing that within the recommended reading and medical textbooks used by students attending the top 20 most prestigious universities across the EU, Canada, and the United States, these manuals were three times more likely to use male anatomy diagrams (3), and gender specific information on aliments such as coronary heart disease, depressive disorders, alcohol abuse, and pharmacology are often lacking or omitted (4).

When men are seen as the default, it labels much of the female lived experience as “atypical”.

The actualisation of this knowledge gap in medical professionals can be seen in the number of misdiagnoses of serious ailments in female patients. If a medical textbook uses male symptoms as key identifiers for conditions; when a female patient visits a doctor with a list of “atypical” symptoms, doctors are far more likely to misdiagnose women (5), woman are often diagnosed later than male patients (6), or women can even be summarily dismissed by the doctors treating them (7).

It is perhaps not that surprising then that recent scientific publications have started to shine a light on the impact that this data deficit is having on 49.58% of the world’s population. Female patients are twice as likely to suffer adverse side effects when taking medication (8), women are 32% more likely to die after operations when these surgeries are performed by male doctors (9), and medical innovations are designed with male patients in mind, such as the development of early artificial hearts which were too big for 80% of female patients who were in need of a replacement heart (10).

As a result of this data gap, women and non-cis men have truly been dealt a bad hand throughout medical science history through to the present day, resulting in a lack of understanding of just how the female body works, and through this deficiency of research, development and medical innovation for non-male patients, the number of lives that have been negatively affected by this lack of information is incalculable.

But, it is not just female patients that are at risk though, those administering treatments are also being affected. 70% of the worlds health and social care workers are women (11), however the PPE they are provided with has often been designed for male workers, and during the COVID-19 pandemic, less than 1 in 5 female front-line health workers felt that the PPE provided to them was fit for purpose. Results taken from a global survey people from the Women in Global Health network, (892 respondents from more than 50 countries), showed that clothing was either too big or restrictive for female workers, placing the people who were helping ensure our own safety and wellbeing at a greater risk (12).

So how do we move forward? Unfortunately, a lot of the harm has already been done, the research has been carried out and the textbooks have been written, female patients have suffered, and a whole generation of medical staff and researchers have been trained with men in mind.

However, it is never too late to make amends; measures can be put into place to help alleviate some of these problems. In the UK under the new Women’s Health strategy, after 2024 all new doctors will have to participate in a mandatory training on women’s health to help them better treat female patients, and changing policy over the inclusion of women in clinical trials, greater transparency in medical research about the demographics of the test subjects used in medical trials (14) will help female patients and health professionals in the future.

It will take a long time for researchers to close this data gap, if it is possible at all. But when planning future medical trials or designing PPE; medical researchers should take into account the following quote from Prof Jeffrey Mogil, from McGill University:

“Failing to include both sexes ‘right at the way beginning’ of the research is not only scientifically idiotic and a waste of money, but it is also an ethical issue as well.”

Chris Styles, Project Officer, EUSEA

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References:

1. Taylor KE, Vallejo-Giraldo C, Schaible NS, Zakeri R, Miller VM. Reporting of sex as a variable in cardiovascular studies using cultured cells. Biol Sex Differ. 2011 Nov 7;2:11. doi: 10.1186/2042–6410–2–11. PMID: 22060014; PMCID: PMC3224776.
2. https://cos.northeastern.edu/news/most-biomedical-research-is-done-on-male-animals-thats-a-public-health-problem/
3. https://www.sciencedaily.com/releases/2008/10/081015132108.htm
4. Dijkstra, A.F., Verdonk, P. and Lagro‐Janssen, A.L., 2008. Gender bias in medical textbooks: examples from coronary heart disease, depression, alcohol abuse and pharmacology. Medical Education, 42(10), pp.1021–1028.
5. Wu, J., Gale, C.P., Hall, M., Dondo, T.B., Metcalfe, E., Oliver, G., Batin, P.D., Hemingway, H., Timmis, A. and West, R.M., 2018. Editor’s Choice-Impact of initial hospital diagnosis on mortality for acute myocardial infarction: A national cohort study. European Heart Journal: Acute Cardiovascular Care, 7(2), pp.139–148.
6. Westergaard, D., Moseley, P., Sørup, F.K.H., Baldi, P. and Brunak, S., 2019. Population-wide analysis of differences in disease progression patterns in men and women. Nature communications, 10(1), pp.1–14.
7. Chen EH, Shofer FS, Dean AJ, Hollander JE, Baxt WG, Robey JL, Sease KL, Mills AM. Gender disparity in analgesic treatment of emergency department patients with acute abdominal pain. Acad Emerg Med. 2008 May;15(5):414–8. doi: 10.1111/j.1553–2712.2008.00100.x. PMID: 18439195
8. Zucker, I., Prendergast, B.J. Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ 11, 32 (2020). https://doi.org/10.1186/s13293-020-00308-5
9. Wallis CJD, Jerath A, Coburn N, et al. Association of Surgeon-Patient Sex Concordance With Postoperative Outcomes. JAMA Surg. 2022;157(2):146–156. doi:10.1001/jamasurg.2021.6339
10. https://www.livescience.com/52093-artificial-hearts-too-large-for-many-to-receive.html
11. https://www.who.int/activities/value-gender-and-equity-in-the-global-health-workforce
12. https://www.scidev.net/global/news/medical-ppe-unfit-for-women-on-covid-19-frontlines/
13. Perez, C. C. (2020). Chapter 10: The Dugs Don’t Work. In Invisible Women : Exposing Data Bias in a World Designed for Men (pp. 195–216). London: Vintage.
14. Bennett, J.C., 1993. Inclusion of women in clinical trials — policies for population subgroups. New England Journal of Medicine, 329(4), pp.288–292.