Modern Medicine Forgot to Confirm It Works for Women, Too

Bohannon is a researcher and theorist in narrative cognition.

Elizabeth Shaw has a problem. The director Ridley Scott has impregnated her with a large, vicious alien squid. Aboard the spaceship Prometheus, she has to find a way to abort her uninvited guest without bleeding to death. Shambling to a futuristic surgery pod, she asks the computer for a C-section. “Error,” it says, “this medpod is calibrated for male patients only.”

“Shit,” said a woman behind me, “who does that?”

What follows is a gruesome scene involving lasers, staples, and writhing tentacles. As I sat in a darkened theater in New York in 2012 watching this prequel to Alien, I couldn’t help but think, Yes, who does that? Who sends a multitrillion-dollar expedition into space and forgets to make sure the equipment works on women?

Actually, modern medicine often does precisely that. One-size-fits-all doses of antidepressants are given to men and women, despite evidence that they may affect the sexes differently. Prescriptions for pain medications, too, are considered sex neutral, despite consistent proof that some may be less effective for women. Women are more likely to die of heart attacks, even though they’re less likely to have them — symptoms differ between the sexes, so women and their doctors alike fail to catch them in time. Anesthetics in surgery, treatments for Alzheimer’s, even public education curricula suffer from the ill-conceived notion that women’s bodies are just bodies in general — soft and fleshy, and missing a couple of significant nether bits, but otherwise, just the same as men’s.

And of course, nearly all of the studies that produced these findings include only cisgender subjects — in the world of scientific research, there’s been very little attention to what happens in the bodies of people assigned one or another sex at birth who then go on to identify differently. In part, that’s because there’s a massive difference between biological sex — something wound deep into the warp and weft of our physical development, from in-cell organelles all the way up to whole-body features, and built over billions of years of evolutionary history — and humanity’s gender identity, which is a fluid thing and brain based and at most a few hundred thousand years old.

But it’s not just that. The fact of the matter is that until very recently the study of the biologically female body has lagged far behind the study of the male body. It’s not simply that physicians and scientists don’t bother to seek out sex-specific data; it’s that until all too recently the data didn’t exist. From 1996 to 2006, more than 79% of the animal studies published in the scientific journal Pain included only male subjects. Before the 1990s, the stats were more disproportionate. And this is hardly unusual — dozens of prominent scientific journals report the same. The reason for this blind spot concerning female bodies, whether we’re talking about basic biology or the nuances of medicine, isn’t just sexism. It’s an intellectual problem that became a societal problem: for a long time, we’ve been thinking about what sexed bodies are, and how we should go about studying them, in entirely the wrong way.

In the biological sciences, there’s still such a thing as the “male norm” or male bias. The male body, from mouse to human, is what gets studied in the lab. Unless we’re specifically researching ovaries, uteri, estrogens, or breasts, the girls aren’t there. Think about the last time you heard about a scientific study — some article about a new window into obesity, or pain tolerance, or memory, or aging. More than likely that study didn’t include any female subjects. That’s as true for mice as it is for dogs, pigs, monkeys, and, all too often, humans. By the time a clinical trial for a new medication starts testing on human subjects, it might not have been tested on female animals at all. So, when we think about Elizabeth Shaw screaming her sci-fi head off at the misogynistic medpod, we shouldn’t just feel terror and pity and disbelief. We should feel recognition.

Why is this still happening? Aren’t the sciences supposed to be objective? Gender neutral? Bound by the empirical method?

Many researchers default to male subjects for practical reasons: it’s difficult to control for the effects of female fertility cycles, particularly in mammals. A complex soup of hormones floods their bodies at regular intervals, whereas males’ sex hormones seem more stable. A good scientific experiment aims to be simple, designed with as few confounding factors as possible. As a postdoc in a Nobel laureate’s lab once told me, using males “just makes it easier to do clean science.” The variables, in other words, are easier to control, thereby making the data more interpretable with less work, and the results more meaningful. This is especially true for the complex systems involved in behavioral research, but can even be a problem with basic things like metabolism. Taking the time to control for the female reproductive cycle is considered difficult and expensive; the ovary itself is thought of as a “confounding factor.” So, unless a scientist is specifically asking a question about females, the female sex is left out of the equation. The experiments run faster, the papers come out sooner, and the researcher is more likely to get grant funding and tenure.

But making such decisions to “simplify” is also prompted by (and perpetuates) a much older understanding of what sexed bodies are. It’s not that topflight scientists still think female bodies were made when God pulled a rib from Adam’s side, but the assumption that being sexed is simply a matter of sex organs — that somehow being female is just a minor tweak on a Platonic form — is a bit like that old Bible story. And that story is a lie. As we’ve increasingly learned, female bodies aren’t just male bodies with “extra stuff” (fat, breasts, uteri). Nor are testicles and ovaries hot swappable. Being sexed permeates every major feature of our mammalian bodies and the lives we live inside them, for mouse and human alike. When scientists study only the male norm, we’re getting less than half of a complicated picture; all too often, we don’t know what we’re missing by ignoring sex differences, because we’re not asking the question.

After being struck by the stubborn reality of the male norm, I did what researchers like to do: I dug into the databases to see how big a problem it was. And, well, it’s huge. It’s so huge that many papers don’t even mention that they used only male subjects. I often had to email the authors directly and ask.

Okay, maybe it’s just mice, I thought. Maybe this is only a problem with animal studies.

Sadly, that’s not the case. Thanks to regulations established in the 1970s, clinical trials in the U.S., for one, were actually strongly advised not to use female subjects who could be of “childbearing potential.” The use of pregnant subjects was all but verboten. While on the face of it, that may seem perfectly sensible — no one wants to mess with our kids — it also means we’ve been continuing to steer the ship in a fog. The NIH managed to update some of these regulations in 1994, but loopholes are regularly exploited: as of 2000, one in five NIH clinical drug trials still wasn’t using any female subjects, and of the studies that did, nearly two-thirds didn’t bother analyzing their data for sex differences. Even if everyone actually followed the new rules, given that it usually takes more than 10 years for drugs to move from clinical trial to market, 2004 was the first year any new drug approved for sale would have been tested on significant numbers of women. Drugs that were released before the new regulations took effect are in no way obliged to go back and redo their clinical trials. In 2014, Janine A. Clayton, MD, and Francis S. Collins, MD, PHD, of the NIH announced new policies to ensure preclinical research funded by the NIH considered females and males. While the NIH remains one of the world’s largest single funders of biomedical research, private funding has continued to outspend the NIH in recent years. What’s more, the funding of basic biological science continues to decline on all fronts, which is precisely where the models and theoretical frameworks are made that biomed advances later rely on; of the money that is still around for such research, not all of it is tied to the NIH, and the loss of an NIH grant only has a marginal effect on scientists’ productivity (it seems they simply look elsewhere). But perhaps most pressingly, any scientist will readily inform you that a scientific career is primarily built on publications (indeed, the likelihood of funding itself is tied to the number of first-author papers an applicant has produced). Many journals simply do not have a gatekeeping function to ensure the research they publish properly includes sex as a biological variable. Some, like Endocrinology, are actively working to change that. More need to. Ideally, all of them. But let’s start with more.

And so, the majority of subjects in clinical trials continue to be men, just as the vast majority of animal studies use male subjects. Like any paradigm shift, changing that will be a long road, with many stops and starts and unexpected detours. But let’s keep our foot on the pedal — lives depend on it.

Cat Bohannon, PhD, is a researcher, author, and expert in the evolution of narrative and cognition. This piece is an adapted excerpt from Eve by Bohannon. Copyright 2023 by Cat Bohannon. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.

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