Pod Insights Short Wave Is there still a gender gap in medical research? About this episode When you go to the doctor’s office, your doctor has to figure out which treatment is best for you. Physicians rely on medical research and clinical trials to make sure those treatments are safe and effective. But that research has not always been inclusive, which impacts patient care. Women and people of color were only required to be included in medical trials funded by the NIH starting in 1993. Now, studies are more inclusive – but how we study sex and gender in research is still controversial. In this episode, we unpack how medicine sorts the sexes – and why it’s not as simple as it seems.
If you liked this episode, check out our previous one unpacking biological sex https://lnk.to/yirSfo.
Interested in more science behind medicine? Email us your questions at [email protected] mailto:[email protected] .
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Transcript Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
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0:18 Emily Kwong? You're listening to Short Wave from NPR.
0:23 Emily Kwong? Hey, Shortwavers. Emily Kwong here with Short Wave's intern, Arun Nair.
0:27 Speaker 02 Hi, Emily.
0:28 Emily Kwong? Hi. And Angela Zhang, who has joined our team through the Stanford Health Equity Media Fellowship and is an actual doctor.
0:35 Speaker 03 Hey, Emily. It's so good to be here.
0:37 Emily Kwong? Good to have you. Now, Arun, I hear you have a medical fact you wanted to share with us.
0:41 Speaker 02 So, Emily, did you know that it wasn't mandatory to include women in medical trials funded by the National Institutes of Health until 1993?
0:51 Emily Kwong? Wait, medical trials, like drug trials?
0:53 Speaker 03 Yeah, partially. And these trials are really important. The N H is the largest single-public funder of biomedical research in the world. Like, I'm a doctor, right? So I'm constantly looking at results of research on different drugs or treatments. And this helps me decide if a test or medicine I'm using is safe or effective for my patients.
1:12 Emily Kwong? And you're saying it wasn't mandatory for women to be included in those until the 1990s?
1:17 Speaker 03 Yeah, we probably need some backstory here. So there was this global scandal, starting in the late 1950s, where tens of thousands of pregnant women, mainly in Europe, took this sedative called bilitamide for morning sickness.
1:29 Speaker 02 People who took the drug while pregnant ended up having babies whose limbs were poorly developed or even absent. This happened to over 12,000 kids. And it led to the Food and Drug Administration creating a policy excluding, quote, "women of childbearing potential in early drug trials." That was in 1977.
1:48 Emily Kwong? Oh, so they just excluded most women?
1:50 Speaker 02 Yeah, exactly. But that's not the only reason that women have been historically excluded from biomedical research.
1:56 Speaker 04 Women have been seen as either too kind of variable, hormonally, like noisy and therefore bad sources of data. And/or we have just taken a male body as a standard and used that to produce knowledge for everyone.
2:10 Speaker 03 So that's Marina DeMarco. She's a philosopher of science at Washington University in St. Louis. And she told us that over time, scientists and activists realized that there was this huge gap in data for research on women.
2:22 Emily Kwong? Yeah.
2:23 Speaker 03 They started pushing for more inclusive policies, and there were even protests about this in the 1980s and 90s.
2:29 Speaker 02 And Congress listened. They passed a law in 1993 requiring researchers to include women and people of color in federally-funded medical trials.
2:37 Emily Kwong? Wow, nice.
2:38 Speaker 03 Now, women are in a lot more studies. And we study differences between the sexes by enrolling men and women, and then we compare data from each group. But many people say the way we include women in medical research can still get pretty messy.
2:54 Emily Kwong? To end the show, how we sort the sexes in medicine and why there's a lot of problems with that. You're listening to Short Wave, the science podcast from NPR.
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4:04 Emily Kwong? Okay, Aru and Angela. Today, we're talking about sex differences as it relates to the world of medicine, medical care, medical research. And I remember from a previous episode that our colleague Hannah Chin reported, learning that sex is hard to define. It can be defined, in fact, by a lot of things, like anatomy, or hormones, or chromosomes.
4:22 Speaker 03 So many things. And Marina says that confusion can carry over into how sex is defined when you're a patient in a doctor's office.
4:28 Speaker 04 I've never been to a doctor's appointment where someone checked how many X chromosomes I had, or what kinds of gametes I make. As far as I know, like, no one's ever even measured my estrogen or testosterone levels. And yet, my clinical treatment is supposed to be based on sex categories.
4:46 Speaker 02 And before we go further, we just want to say that we're using women and men in super-binary ways, because many studies and experts still use these terms, even though we know that gender and even sex are not binary.
4:57 Emily Kwong? That makes sense, yeah. So, how do researchers or doctors account for this complexity in sex?
5:03 Speaker 03 Well, we kind of don't.
5:05 Speaker 02 Well.
5:06 Speaker 03 Metaphorically speaking, our medical system tends to sort people into two buckets: a blue bucket, or a pink bucket. And it's really easy to do that. But a lot of researchers say that that might cause some problems.
5:16 Speaker 02 The first one is that we might be missing similarities between the pink and the blue buckets. In many cases, there's a lot of overlap, like with height, for example.
5:24 Speaker 06 You can look around, and you can see, yes, on average, men are taller than women.
5:29 Speaker 02 This is Donna Maney. She's a neuroscientist at Emory University.
5:33 Speaker 06 But also, as everyone knows, if I say to you, "Oh, this person is 5'9", what's their sex? I mean, you might be able to guess, but you're not always going to get that right.
5:46 Emily Kwong? Right. I mean, I'm 5'8", and there are plenty of men who are my exact height.
5:49 Speaker 02 Totally. So Donna says ignoring the overlaps between sexes could have real consequences, like in women who experience heart attacks.
5:57 Emily Kwong? How so?
5:58 Speaker 03 Okay, so the most common symptom of a heart attack, regardless of your sex or gender, is chest pain. But the American Heart Association says that women may experience a wider, less-recognized range of symptoms, like fatigue or indigestion.
6:12 Speaker 07 Is that because we have different ways of having a heart attack pathophysiologically? Or is it because women present their symptoms in a different gendered way?
6:24 Speaker 03 Alison McGregor is a doctor at the Medical University of South Carolina. She spent years looking into women's health and medicine and how it might be different than men's, including whether those differences are why women with heart attacks are treated later than men and die at a higher rate. And at the same time...
6:42 Speaker 07 There's definitely crossover between men and women of who has those symptoms. If we could just make it so that way, these are all symptoms that people could present in and then have those be flagged, that's ideal.
6:55 Speaker 02 Donna pointed out the same thing. Like, this has real-life stakes.
6:59 Speaker 06 You can imagine that a man might be having a heart attack and he might be having nausea and jaw pain, but he's been told that those are women's symptoms of heart attack. And so that's very dangerous for him because that will delay his treatment.
7:12 Emily Kwong? This is dangerous for everyone because of the oversimplification of the two bucket system, blue and pink. It misses overlaps.
7:21 Speaker 03 Mm-hmm. Yeah, it totally can. And this leads to our second problem, because when you store people into two big buckets, you're just going to get averages. And so Marina says that when we do this, we can miss the diversity within those categories. So I'll give you an example. The three of us identify as women, but we might actually be really genetically different. So I could be more similar to a male coworker than I am to the two of you.
7:47 Speaker 04 We make a recommendation for all of the pink, and it only actually works for, like, a subset of them. As my collaborator, Madeline Pape, has put it, like, we're really just moving from a one-size-fits-all approach to a two-size-fits-most approach.
8:05 Emily Kwong? I think about this all the time. Like, when I go to the gym, there are so many different types of bodies. Even if people are the same sex, they can look vastly, vastly different. So averages can only take us so far because at the end of the day, doctors are treating individuals.
8:20 Speaker 02 Exactly. Marina also brought this up to us.
8:22 Speaker 04 If you have variation in that population, or if the population you studied is different from the person that you're prescribing a medication to... There has to be some kind of like leap or inferential move there, right? You're taking a risk.
8:36 Speaker 02 And on top of that, there's the issue that some people don't fit into either of those buckets, like intersex people and trans people who have started gender-affirming hormone treatment.
8:45 Speaker 04 We reinforce the idea that people come in those two types when in fact, we have significant evidence that they don't.
8:52 Speaker 03 And Emily, you're not going to believe this. There is another problem with the two-bucket system.
8:59 Emily Kwong? Of course there is. Tell me.
9:01 Speaker 03 Yeah, it only lets you ask questions about two buckets. And if you find a difference, then you might think it's about the buckets. But there are lots of other reasons we might see differences between the buckets or between the sexes. And we talked about this with another expert, Sarah Richardson. She says those reasons don't exclusively have to do with your sex, like your weight, your age, your hormones, even if you're taking other medication.
9:26 Speaker 02 Women are not only prescribed drugs at a higher rate, but more drugs at the same time.
9:31 Speaker 03 Sarah is the director of the Gender Assi Lab at Harvard, where she works with Marina.
9:35 Speaker 02 So we would expect that drug usage is also higher.
9:39 Speaker 03 Partially, this is because women tend to go to the doctor more often than men do. Like, they just interact with hospitals and healthcare way more often.
9:47 Emily Kwong? Right, like in drug research, we may see differences in outcomes that we think have to do with sex, but actually it could come from a multitude of different factors.
9:56 Speaker 02 Yeah, and one of the most controversial ways that this can play out is through sex-based drug dosing. Like, the idea that women should be taking a different amount of medication than men. And that's exactly what happened with the drug Zolpidem, which is also known as Ambien.
10:11 Speaker 06 You fall asleep fast, stay asleep longer, and generally wake without feeling groggy the next morning. Ambien works like a dream.
10:19 Emily Kwong? Yes, Ambien, the pill that is designed to help people fall asleep.
10:23 Speaker 02 Right, so there's research showing that, on average, Ambien stays longer in women's systems than in men's. Which means that a woman might be more sleepy the morning after taking it and could be at risk for driving accidents.
10:36 Speaker 03 So in 2013, the FDA actually lowered Ambien's recommended starting dose for women, which was a huge deal.
10:43 Emily Kwong? Wow.
10:43 Speaker 03 Yeah, it's the first and only drug where there is a dose based on your sex. And many people saw this as a huge win for women's health.
10:52 Speaker 02 But some researchers pointed out a few concerns with the FDA making this change. One was that, like we talked about earlier, there was still a lot of overlap with how quickly men and women process the drug.
11:04 Speaker 06 That does not mean that all women are going to respond the same way to a drug and all men are going to respond another way to the drug. And yet, that's kind of how a statistically significant difference is interpreted.
11:14 Speaker 03 It was also not entirely clear who was causing the sex difference. Some people say that more research is needed and even say the lower starting dose could lead to women being under-treated.
11:25 Emily Kwong? That's wild. Given these examples, ambience and heart attack symptoms, it makes me think about how sex is such a problematic variable when it comes to research, right? Because sex difference is so nuanced. So, hot take, should we just not look at sex in medical research at all and maybe just put everyone together in one big group?
11:44 Speaker 02 Well, not exactly. From talking to all these experts, it's really just about being super specific about what you mean when you study sex. Like, if you're studying cervical cancer, your definition of sex will probably focus on anatomy.
11:57 Speaker 03 And being more clear will also help us get at what the real problem is. Marina says sometimes the focus on biology actually obscures the fact or distracts from the fact that women aren't always treated the same as men at the doctor's office.
12:09 Speaker 04 If you focus on biology as an explanation for differences in outcomes across members of social groups, it naturalizes inequality by putting biology first and assuming that whatever is different about men and women, it's about their bodies instead of about how society treats us.
12:27 Speaker 03 And it could be both. So lots of studies show that women's pain is taken less seriously. This really matters with the heart attack issue. Studies as recently as this year show that women who come to the hospital with chest pain get seen by a doctor later than men do for the same symptoms.
12:41 Emily Kwong? So, I want to make sure I have this all right. You're saying it is still important to include both men and women in medical studies?
12:48 Speaker 02 Yeah, to make sure that you're studying a diverse set of people that represents society.
12:52 Emily Kwong? Yes, but we need to be more specific about it and more inclusive. And if we find a difference, we should think about whether that is because society treats different sexes differently.
13:02 Speaker 02 Yeah, pretty much. And some experts have said there's still work to be done. We've been focusing on NIH-funded studies, but there's still a lot of research that's funded privately. That's why some people suggest that the policy requiring that women be involved in medical research should be extended to agencies like the FDA that review these studies and not just limited to the organizations that fund them.
13:24 Emily Kwong? OK, and Angela, Dr. Zhang, what kind of medical world do you want to live in that would get around this problem?
13:32 Speaker 03 Yeah, so I think we dream of this world of precision medicine, where everyone gets exactly the care that's right for them, right? And know exactly what makes up your body and your genes and your hormones. But we're not there yet. And in the meantime, we need to focus on what we know and can do right now. So I can't change your genes yet. I don't have these tests yet. But I can help you get to your appointments, and I can try to make sure that you feel listened to and taken care of.
13:56 Emily Kwong? Angela Aru, thank you so much for bringing us this story.
14:01 Speaker 02 Thanks, Emily.
14:01 Speaker 03 Thanks, Emily. It's great to be here.
14:03 Emily Kwong? If you liked this episode of Short Wave, please share it with a friend because we know, based on multiple studies, that word of mouth is one of the top ways to grow a podcast. Please and thank you. This episode was produced by Hannah Chin. It was edited by our showrunner, Rebecca Ramirez. Tyler Jones checked the facts. Kwesi Lee was the audio engineer. I'm Emily Kwong. Thank you for listening to Short Wave, the science podcast from NPR.
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