Sex matters in medicine
Obscuring biological differences is dangerous
This week Scientific American published an article entitled “Here’s why human sex is not binary.” The author, Princeton University anthropologist Agustin Fuentes, argued that, “dishonest ascriptions of biology are being deployed to restrict women’s bodily autonomy, target LGBTQIA+ individuals broadly, and, most recently, attack the rights of transexual and transgender people.” Fuentes is not alone in promoting the idea that binary sex is “a false representation of biology.” In recent years, medical ethicists have plunged into the debate arguing that binary sex, “can actually hinder diagnoses, care, and treatments”.
As a medical ethicist who pays attention to reality and science, I take issue with these claims as reckless and irresponsible. In fact, embracing the view sex is on a continuum risks real calamities in healthcare. Worse still, in a festival of cognitive dissonance, far from protecting patients, the denial of biology harms the very patient populations that Fuentes and others purport to care about.
The vast majority of us are born biologically male or female. Certainly, there are exceptions. Some people are born intersex. Hermaphrodites possess one testis and one ovary; male pseudohermaphrodites possess testes and some aspects of female genitalia but no ovaries; and female pseudohermaphrodites have ovaries and some aspects of male genitalia but no testes. These individuals comprise around 0.018 percent of the population; even within these groups there is broad variety. But the fact that very rare human variations exist does not refute the reality of a binary sex norm. Moreover, most trans people are not intersex: they have either biological male or female anatomy.
Fuentes and others see themselves as endorsing cutting edge ideas. In medicine, if there is any continuum to be identified it is an historical one. Just like Fuentes, for most of medicine’s long history, clinical researchers, and consequently, physicians have also failed to master the obvious: male and female bodies differ. Biological sex and hormones, even at a cellular level, can affect symptoms, immunity, responses to infections, disease progression, and even how we respond to treatments. As Dr Alyson McGregor, co-founder of the Sex and Gender Women’s Health Collaborative asserts, “women are not just men with boobs and tubes.” Owing to biological sex differences, people also experience different environmental and social stressors in their lifetime, as well as distinctive vulnerabilities to disease.
Even today, however, in standard medical textbooks, half the world’s population is grossly underrepresented — a point elegantly drawn out in Caroline Criado Perez’s tour-de-force Invisible Women: Exposing data bias in a world designed for men. In 2008, for example, a Dutch study found that images of biological male bodies were used three times as often in medical textbooks as females to illustrate “neutral” images of human anatomy. In 2019, a study conducted at the prestigious Yale School of Medicine found only 8 percent of all first and second-year teaching included in-depth discussion about the role of biological sex on medical diagnoses, prognoses, and drug and treatment effects. Only in July 2022, following a report by the UK government, was it announced that doctors in England would receive mandatory training to better treat healthcare sex differences.
Gaps in learning directly lead to systemic sex-based blind-spots
Gaps in learning directly lead to systemic sex-based blind-spots. Endometriosis, for example, is a debilitating illness in which tissue normally found in the uterus affects other organs, chronic pain, heavy periods, and other symptoms, and can lead to infertility. It’s believed to affect 10 percent of reproductive age girls and women. In 2020, a US study estimated patients wait an average of 8.6 years to receive a diagnosis with around three quarters receiving earlier diagnoses that were wrong.
More generally, from auto-immune illnesses to depression, and from thyroid conditions to osteoporosis, the prevalence and risks of illness differ for women and men. Even common ailments differ according to biological sex. Pain is the most widely presented symptom in healthcare. Women endure higher incidences of acute pain that last longer. Yet, likely reflecting structural omissions and biases in medical education, women’s pain is underestimated. Doctors — including female medics — tend to believe women are “more likely to exaggerate” pain which is also more likely to be discredited as “emotional.”
When it comes to coronary heart failure, men are more likely to experience crushing chest pains, but women are more likely to experience what are, by the biological male default, “atypical” symptoms. Onset of heart disease is also 7 to 10 years later among women than men. Again, because male bodies are assumed to be the anatomical norm, women are vulnerable to diagnostic and treatment delays.
Sex differences are consequential when it comes to treatments too. Yet most drug trials enrolled men, or used male animals, extrapolating findings to female bodies. Biological sex differences also influence how quickly medications are metabolized and excreted from our bodies.
In 1993, the Revitalization Act in the US, attempted to address these baked in biases by requiring the representative inclusion of women into federally funded clinical trials. However, there is little evidence that these obligations are being met or successfully regulated by national research funding bodies. A review of nearly 800 clinical trials, published in top medical journals in the year 2015, determined that in 72 percent of studies researchers did not include sex in their analyses nor provide an explanation as to why it might be irrelevant. Published in 2018, the report, entitled “The More Things Change, The More They Stay The Same” found 15 percent of taxpayer-funded NIH clinical trials enrolled fewer than 30 percent of female participants.
Under-recruitment of women in clinical trials means, treated as biologically male, women experience an almost twofold risk of adverse physiological drug reactions compared with men. The practice of enrolling exclusively male recruits in clinical trials, and a mentality of “one size fits all” can lead to patient safety oversights. For example, Zolpidem — a sedative sold under the brand name “Ambien” in the US — was first approved by the US Food and Drug Administration (FDA) in 1992 but in 2013, it was discovered women experienced 25-30 percent higher levels of the drug in their system the morning after taking it.
Women bear the brunt of medicine’s long legacy of one-sided curricula. But trans people are also at considerable risk if doctors and patients choose to deny biological sex differences. Plucking one recent example from the UK context, a trans man told the BBC he was overlooked for his cervical smear tests because his biological sex was not recorded in his medical charts. Similarly, trans women are at risk of prostate cancer if doctors are not aware that the person in front of them has male genitalia.
To avoid perpetuating and compounding medicine’s original sin of sex-based inequalities, and to prevent new sources of disparities for trans patients, we must robustly defend the facts. They aren’t complicated. Biological sex differences matter in medicine.
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