Exposing the bias; the role gender plays in cancer

For too long our health community has not acted sufficiently on the disproportionate impact of cancer on the lives and livelihoods of women, and the impacts this creates for societies. The International Agency for Research on Cancer note for example that worldwide two thirds of cancer deaths under 50 happen to women (i). In this blog I will look at some of the shocking biases faced by women when it comes to cancer.

Of interest in terms of gender you may also want to see a previous blog on the Yes to Life website where we looked at how men don’t do Complementary Medicine(ii) particularly when it’s looking at the mind-body stuff.

What got me writing this blog was a book by Caroline Criado Perez, ‘Invisible Women, Exposing data bias in a world designed for men’ (2019)(iii). Before reading this book I was aware of some of the bias but the story it tells is truly totally shocking. The book shows us how, in a world largely built for and by men, we are systematically ignoring half the population. Perez exposes what she describes as the “gender data gap – a gap in our knowledge that is at the root of perpetual, systemic discrimination against women, and that has created a pervasive but invisible bias with a profound effect on women’s lives”.

There is so much in this book that I can only point to a few of the facts that highlight some of the problems we face relating to cancer. I’ll start with work-related cancers then look at drugs and how because they have never been tested on women they can have very different outcomes to those planned by medical teams.

 
Work-related cancers

In terms of the workplace 8,000 people die every year from work-related cancers. We have seen, for example, the numbers of breast cancers rise in the last 50 years but it has not been researched what is behind this rise. In contrast dust disease amongst miners has been well research. Rory O’Neill, professor of occupational and environmental policy research at Stirling University commented in Perez’ book; “You can’t say the same for exposures, physical or chemical, in ‘womens’ work.”

The data studies that do exist rely on data from studies done on men, mostly 70kg Caucasian and aged 25 to 30 – and the research is done as if this data also applies to women. Perez writes: “This is ’Reference Man’ and his superpower is being able to represent humanity as a whole. Of course, he does not.”

In fact women tend to be smaller and have thinner skin which can lower the levels that make exposure to toxins more safe. A higher percentage of body fat can also impact as that is where chemicals can accumulate. This means that exposure to radiation and many commonly used chemicals could quite likely be outside a safe range. Add to this that the chemicals are usually tested in isolation and on the basis that there is only one exposure. This is just not how any of us are likely to come into contact with chemicals in the home or at work.

A shocking example is the nail salons where many of the chemicals that have been linked to cancer, miscarriages and lung diseases are not only absorbed through womens’ thinner skin but also their fumes are breathed in. Recent studies show air quality in salons exceeds occupational exposure limits that are based on ‘Reference Man’. Many  of the chemicals are endocrine disrupting chemicals which can have significant impacts with even small doses – and been shown to be linked to Hodgkin’s disease, multiple myeloma and breast and ovarian cancers.

Other examples of women using many chemicals are home and hotel cleaners. There is also no account that many might be exposed to some chemicals at work and different ones at home or in a second job. Even those products deemed safe may well be problematic when exposed with other chemicals at the same time.

Every now and then there are headlines about commonly used products which suggests they are not tested often enough. “Always” menstrual pads were found in 2014 to include a number of chemicals including styrene, chloroform and acetone – all either carcinogenic or reproductive and developmental toxins.

In a previous blog I’ve noted other examples like in 2016 Johnson and Johnson’s baby powder and other talc products for feminine hygiene were determined by a Missouri state court to cause ovarian cancer (iv). Last year 75 hand sanitiser brands were recalled in the States as they contained toxic ingredients. We've also just seen last December dozens of Pantene and Herbal Essences dry shampoo sprays recalled for a cancer-causing chemical (v).


Shift-related cancers

In the UK the Health and Safety Executive note that around 2,000 women develop shift-related breast cancer every year. Shift work includes early, late and night shifts at work. Yet this is not listed on the state prescribed disease list and not one of the women is compensated by industrial disease pay outs. Asbestos related ovarian cancer, the most common gynaecological cancer in UK women, is also missing, despite having Industrial Injuries Advisory Council’s top cancer risk ranking. It is also absent from HSE’s occupational cancer body count (vi).

Drugs don’t work?

Perez covers many other aspects of bias but one of the chapters I found particularly concerning relating to cancer was the one entitled ‘The Drugs Don’t Work’. It starts by looking at how doctors are trained. The assumption has been that there is no difference between male and female bodies other than reproductive function and size. She suggests this bias goes back to the Greeks and Aristotle arguing women’s bodies were ‘mutilated male’ bodies(vii).

Today doctors don’t argue that (!), but the male body persists. For example;

-      a 2008 study of textbooks found male bodies were three times more often used to illustrate ‘neutral body parts’,
-      women being excluded from medical trials (viii),
-      a study of courses found huge under-representation of women in medical school curriculums.
-      researchers have argued against the use of women in studies as they can complicate the picture with for example greater fluctuating ‘atypical’ hormones! (ix)

Perez notes that “researchers have found sex differences in every tissue and organ system in the human body, as well as in the prevalence’, course and severity’ of the majority of common human diseases.” This includes differences in lung capacity, fundamental workings of the heart and a host of differences in diseases.

At a most basic level, as mentioned above, women tend to have a higher body fat percentage than men, which, along with the fact that blood flow to fat tissue is greater in women (for men it’s greater to skeletal muscle) can affect how they metabolise certain drugs.” Other sex differences include kidney enzymes, bile acid composition, intestinal enzyme activity and more.

One example quoted is that women develop higher antibody responses to vaccines. A 2014 paper proposed there should be different versions of the influenza vaccines for men and women (x). Other examples include differences in outcomes of diseases like strokes, depression, Parkinsons’ and brain ischaemia, plus cell differences in responses to stress. Yet despite this evidence progress and change seems incredibly slow.

In 1960 my Mum was prescribed the thalidomide drug for morning sickness when she was pregnant with me. Drug manufacturers already knew as early as 1959 that it affected foetal development. It was only taken off the market in 1962 with over 10,000 children having thalidomide-related disabilities. Our family GP when the case came to light commented that he couldn’t understand why I was not amongst those who were disabled as my Mum had had such a high dose. Of interest is that this case led to the FDA in 1977 excluding women of childbearing potential from drug trials; again the acceptance of the male norm went unquestioned.

Women are clearly not just smaller men, but it seems this is still not being taught – or properly considered when prescribing medication.


Chemotherapy drugs

In 2018 a paper (xi), not mentioned by Perez that I came across, entitled ‘Sex Differences in Cancer’ highlighted a host of differences between men and women, genetic, molecular and hormonal plus differences in the efficacy and toxicity of chemotherapy. Again the vast majority of research has only been done on men, yet the research has shown some  clear differences. In particular the paper notes the following chemo drugs have different impacts: 5-fluorouracil, Paclitaxel, Doxorubicin, Cisplatin, Bevacizumab and Rituximab.

The paper concluded: “Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women…. Further studies are needed to provide greater insight into sex differences in cancer and improve treatment outcomes with anticancer agents.”

 
Heart disease

Another example of differences is in the death rates from heart disease - they are way higher in women than men. Again this is likely to be that conventional medicine doesn’t always recognize the core biological, psychosocial, hormonal, and metabolic differences between women and men. On top of that, current cardiometabolic diagnostic criteria are based on clinical trials done in men, which means many of the factors that are specific to women get overlooked. One factor is likely to be that women are more susceptible to the damaging effects of insulin resistance than men, yet it seems not enough is being done to tackle this issue.


Highest standards not being used

This bias towards women is clearly hugely problematic but we must also remember that many treatments are not fully tested even on the so-called ‘Reference Man’. In August 2022 a Cochrane Review (recognized worldwide as the highest standard in evidence-based healthcare) found that only one in 20 medical treatments have robust evidence to support their use. Additionally the risks and harms of these treatments are rarely measured (xii).

It is hard to draw conclusions other than most of these treatments are more about benefiting Big Pharma rather than the health of those being prescribed such treatments?


Diet and exercise differences

In 2011 the World Cancer Research Fund found that half of studies looking at diet and cancer that included both men and women did not separate the data by gender. This clearly makes it hard to establish dietary guidelines for both sexes (xiii). Women who face more muscle mass loss should probably eat more protein but these studies can’t tell us if this is right.

Similarly research into exercise is largely male-based. Studies show that resistance training, for example, is good for reducing heart disease but papers warn against this if you have high blood pressure as it can increase artery stiffness (xiv). However a 2008 paper found the advice is not gender-neutral (xv). Resistance training lowers blood pressure to a greater extent in women and they don’t suffer from the same increases in artery stiffness. This is possibly good news as blood-pressure drugs developed using male subjects don’t work with women as effectively but the resistance training might just do the trick?

Evidence is also mounting for how men and women experience pain differently. Womens’ pain sensitivity changes through her menstrual cycle. Even basic drugs like Paracetamol and morphine work differently. It also seems that women have to experience pain longer before having treatment.

Perez has many other such examples. She writes: “None of this should surprise us, because despite obvious sex differences, the vast majority of drugs, including anaesthetics and chemotherapeutics, continue with gender-neutral dosages, which puts women at risk of overdose.


Time for change

Perez argues that part of the answer lies in closing the female representation gap. When women are involved in decision-making and research then women are considered.

Awareness is growing that we face a huge problem.

Last year The Lancet Commission on women and cancer was established to explore the relationship between gender, power and cancer (xvi). In particular they are looking at three main areas:

-      Women as cancer patients; for example the disparities in access to diagnosis and care often affect women more than men. I have written to them to see if they will cover some of those disparities highlighted by Perez (no reply yet).
-      Women in cancer caregiving roles; women are more often caregivers and this impacts on earnings and more.
-      Women as health care providers; for example women are underrepresented in the workforce especially in the higher tiers of cancer care and face salary disparities in comparison to men.

The Commission’s work is due to be published next year. It cannot come soon enough.

Also last year there was a part acknowledgement of the problem and the government called for evidence (xvii) to help inform the development of the government’s Women’s Health Strategy. The forward to the call notes: “This ‘male by default’ problem of the past must be put right. Despite living longer than men, women spend a greater proportion of their lives in ill health and disability, and there are growing geographic inequalities in women’s life expectancy. This makes levelling up women’s health an imperative for us all.”

This week the results of the call for evidence, which saw over 100,000 submissions, are published (xviii). Some of the challenges include that doctors’ routinely dismiss women’s debilitating health problems as “benign” which research suggests have contributed to gynaecology waiting lists rising by 60% to more than half a million patients.

Some of the actions promised by the Government seem limited when compared to the size of the challenges I’ve touched on in this blog - like mandatory training for doctors to better treat female medical conditions, more mobile breast screening and updated guidance around endometriosis. However this is a start and will hopefully lead to further improvements.

Personalised care

To wrap up this blog that is already too long I wanted to mention one of the other books I’ve come across; ‘Am I Normal? The 200-Year Search for Normal People (and Why They Don’t Exist)’. This book is just out by Sarah Chaney and she questions the standards that have emerged from sexist and racist scientific endeavours. She goes onto challenge why we ever thought ‘normal’ might be a desirable thing to be. Indeed she argues normal does not, in fact, exist.

So while we do need to close the female representation gap it seems more than clear that what we need overall is a more personalised approach to our health. We are all not the same and using ‘Reference Man’ or any other idea of ‘normal’ is fraught with problems.

6/9/22 update; See also Tedx talk on pain: https://www.ted.com/talks/sheetal_decaria_the_bias_behind_your_undiagnosed_chronic_pain


Notes:

(i)            https://www.rti.org/insights/feminist-approach-womens-cancer

(ii)           https://yestolife.org.uk/where-are-the-men/

(iii)         https://carolinecriadoperez.com/book/invisible-women/

(iv)         https://yestolife.org.uk/a-look-at-environmental-toxins/

https://nutritionfacts.org/video/friday-favorites-talcum-powder-and-fibroids

(v)          https://edition.cnn.com/2021/12/20/business/procter-and-gamble-dry-shampoo-recall/index.html

(vi)         https://www.hazards.org/compensation/meantest.htm

(vii)       https://medium.com/lessons-from-history/misogynist-aristotle-viewed-women-as-mutilated-deformed-men-a2715d7e20e4

(viii)     https://www.theguardian.com/lifeandstyle/2015/apr/30/fda-clinical-trials-gender-gap-epa-nih-institute-of-medicine-cardiovascular-disease

(ix)         https://pubmed.ncbi.nlm.nih.gov/17197669/

(x)          https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157517/

(xi)         https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029678/

(xii)       https://www.sciencedirect.com/science/article/abs/pii/S0895435622001007 It is also worth noting that Systematic Reviews do not seem to address sex/gender differences as the data is more often not available. See 2014 paper: https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/2046-4053-3-33

(xiii)     http://genderedinnovations.stanford.edu/case-studies/colon.html#tabs-2

(xiv)     https://physoc.onlinelibrary.wiley.com/doi/pdfdirect/10.1113/EP085369

(xv)       https://pubmed.ncbi.nlm.nih.gov/18573479/

(xvi)     https://womenandcancercommission.org

(xvii)   https://www.gov.uk/government/consultations/womens-health-strategy-call-for-evidence/womens-health-strategy-call-for-evidence

(xviii)  https://www.gov.uk/government/publications/womens-health-strategy-for-england and https://www.theguardian.com/society/2022/jun/02/dismissal-of-womens-health-problems-as-benign-leading-to-soaring-nhs-lists