Latest / The XX Lab / How Sex Hormones Shape the Male & Female Brain | Sarah E. Hill & David Puts | #18

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How Sex Hormones Shape the Male & Female Brain | Sarah E. Hill & David Puts | #18 · The XX Lab

• speaker-0: Today on the XX Lab, I'm joined by Dr. David Putz, one of the world's leading experts on hormones, sex differences, and human behavior. David is a professor of anthropology at Penn State University, whose research explores how hormones shape who we are, from before we're even born, through puberty, and across our adult lives. In this conversation, we take a deep dive into the fascinating world of hormones and behavior. We talk about how hormones help shape male and female development in the womb. The profound changes that occur during puberty, and the way hormones continue to influence our thoughts, feelings, motivations, and behaviors in real time throughout adulthood. David also helps us unpack one of the most debated topics in behavioral science, sex differences. We discuss what hormones actually do in the process of sex differentiation, why men and women tend to differ in predictable ways, and what modern science can and can't tell us about the origins of these differences. And because this is the XX Lab, we also spend time talking about how women's cycling hormones influence everything that women feel and do across the cycle. So we talk about whether women really experience shifts in mate preferences across the menstrual cycle, what the evidence says, and where the science has evolved. This is a wide-ranging, thought-provoking, and incredibly informative conversation that touches on some of the biggest questions in biology and psychology. How do hormones make us who we are? How much of our behavior is shaped by our biology, and what can understanding our hormones teach us about ourselves? I learned so much from this conversation, and I think you will too. This is the XX Lab. I'm Dr. Sarah Hill. Let's get started. Dr. David Putz, welcome to the XX Lab. I'm really excited to talk to you today about all things hormones, because especially people in my audience know about speaker-1: Thank you. Good to be here. speaker-0: you know, what hormones do sort of on a day-to-day basis with women. But I think that there is much less of an appreciation for just like the wide range of effects that hormones have. And before we get started, I'm just curious, like what actually got you interested in studying hormones? Cause you're actually in a department of anthropology, right? So you're an anthropologist, which I think people would also be really surprised to learn that This is something that anthropologists do, is study hormones. So yeah. So how how did you get into this? speaker-1: You know, when I was in college I was sort of interested in big questions about human nature and I really liked philosophy and I also took some anthropology classes and liked those a lot. I think I liked thinking about human evolution and sort of th you know, like why we have the psychological and behavioral traits especially that we do. And I felt like anthropology addressed those things empirically, like the philosop ⁓ it's Philosophers now do empirical research, but the at least the things that I was reading seemed like a lot of introspection, you know, that you're you're thinking about it, but then you need to test your ideas with data. And so anyway, so so that's what got me into anthropology. And then and I really was just interested in sort of understanding especially the evolution of human nature, human behavior, human psychology. And then I got to graduate school and my advisor was looking at sex differences, and you know. I don't think that either of us had any special interest in sex or sex differences beyond what like a normal person has, but it was ⁓ looking where the light is, you know, that there were you could make predictions about psychology and behavior by thinking about how evolution would have shaped males and females differently. And so there was a lot of good research happening in those areas, and I think that's what started me doing that. And I was mostly thinking about evolution and evolution of behaviors and psychology related to mating and mating competition and and sex differences and so on. And then that got more and more into thinking about, okay, those are evolutionary causes in the past, but how do these things actually develop? And so then thinking about how, you know, how does that work? What males and females have almost the same DNA. In some species there's no genetic difference between males and females and in humans and other mammals, there's a small genetic difference, but really it's almost entirely the same DNA. So The way that this happens is that sex hormones regulate patterns of gene expression. You have the same genes, but exposed to different gonadal steroid hormones, sex hormones, those genes are expressed differently. So anyway, just thinking about how this actually happens at a developmental level got me more and more into this sort of, you know, endocrinology and you know, how do hormones influence behavior, psychology of the brain. And so I started studying that as a graduate student, but my my graduate work was mostly evolutionary and I I finished that work and I had done a one year I was hired as a postdoc, but it didn't make sense that I I didn't have a doc yet, but I was a postdoc in a neuroscience lab at University of Pittsburgh where I did my graduate work. And but it wasn't doing sex difference stuff and and I thought, you know, I think this is what I'd like to do for a a postdoc is go to a lab that studies neuroscience, that studies the sexual differentiation of the nervous system, to learn more about this, to to sort of complement So that my research has these two areas, sort of the evolution of and how does that actually work in terms of hormones and gene expression and the brain and so on. And so I did a three year postdoc in a in a neuroscience lab at Michigan State and then ended up at my current position. So speaker-0: Interesting, because your path is actually similar to mine. I don't know if you know that my undergrad is in anthropology. I did anthropology and was also like in taking philosophy classes and trying to understand human nature. And I was actually in a class called human nature and they had us reading like Rousseau and then and Rousseau's this idea of the the noble savage, right? That without society that, you know we would be these peaceful, you know, everybody singing kumbaya around the campfire and that society corrupts us. And then we were reading Hobbes, right, which is the opposite of that, which is this idea that, you know, without society to tame human nature, that, you know, life would be nasty, brutish, and short. And I remember I was reading all this, I'm like, I didn't buy any of it. You know, I was like, I I don't think that people are all bad. And I don't believe that people are all good. I I felt like there's a lot of complexity that was missed. And then I took a class in ⁓ human sociobiology and evolutionary psychology. And that was what sort of connected all of the dots because I had taken a lot of classes in ⁓ physical anthropology, you know, which taught me all of the great cool things about ⁓ evolutionary theory. But then like taking that ⁓ sociobiology and evolutionary psychology class, put everything together, right? Where it was like, ⁓ yeah, we can actually use the same theory that we use to understand the shape of the hand. To understand the design of the mind. And so and humans are not all bad or not all good. Like we're really complex and we've inherited these predispositions that ultimately led our ancestors to be able to reproduce. And sometimes that leads to really beautiful behavior and sometimes it leads to terrible behavior. And so for me it was like this like aha kind of moment that I had learning about those things. speaker-1: That that's really interesting because then our our paths are more similar th than I knew because I had the same experience taking biological anthropology classes too, that like this stuff is cool, you know, the the the bones and the fossils and stuff, vr awesome. I'm very interested in it. But you know what the most special thing about us I think is our behavior and our social behavior, especially. And I wanted to know more about that and and I wasn't getting it in my biological anthropology classes and the cultural anthropology classes I took was like Yeah, but tell me about like evolution, you know. And so we had a senior class, ⁓ you know, that like a sort of capstone course that that all the senior anthropology undergraduate students had to take. And it was a theory course, and it was kind of the professor taught some, but then you had to go out and research a theoretical perspective. And I was talking to my professor about sort of how I thought about things, and he said, That sounds like sociobiology, which I had never heard of. And he said, You know, read E.O. Wilson and David Barish. And so I got these books out of the library and it was just you know, mind blowing because I I started reading these I have thought that sentence and those words before and I've never heard anybody say that before and it was so rewarding to, you know, even know that like people were thinking about these things ⁓ in the same way. And so anyway, that that's yeah. speaker-0: Yeah, no, I felt that I felt that way very much because like you, I was like seeing the the evolutionary stuff and I was like, ⁓ that makes perfect sense. Like I totally understand everything. And then I was interested in behavior. And yeah, it was like when I read ⁓ it was actually David Buss's the first edition of Evolutionary Psychology, I was like, ⁓ my gosh, this puts all the pieces together. It was like this, it was like the missing piece. I love it. It's so fun. In addition to understanding the why, which ⁓ for those of you listening who don't have any familiarity with ⁓ evolutionary approaches to behavior, it's just, you know, just this idea of like ⁓ we ask these why questions of ultimately we try to understand like why does a trait exist? And then we sort of unpack it using ⁓ evolutionary logic. And you are also interested in the how, right? So it sounds like that was what led you into endocrinology ultimately, like trying to understand. You know, what are the processes by which ⁓ men and women are different from one another? And ⁓ and it turns out that hormones ⁓ have a big role in this. And I like want to start but as we start our conversation about hormones, ⁓ just like letting people know like what like what is a hormone and like what do they actually do and like how they work. ⁓ just sort of an overall view because I I think that that there's a lot of confusion. And sort of bad PR that hormones that hormones have to overcome. speaker-1: Sure. Okay. So a hormone is a chemical messenger. And the cool thing about hormones, you have your body has all kinds of ways of signaling to other parts of the body, right? You've got a nervous system and you've got other but a hormone is released into the bloodstream. So it can it travels everywhere in the body and that makes it a broadcast signal. So hormones are great for coordinating many br body processes together because they travel everywhere. And then anywhere in the body, any kind of a tissue where those cells have a receptor, then they can receive that signal. And so your brain is lousy with hormone receptors, but you have them all over. Like if it's you know androgen receptors that are responsive to things like testosterone, well we have them in our skeletal muscle, and that's why taking anabolic steroids like testosterone makes muscle, you know, grow and get thicker and so on. And so anyway, that's what a hormone is and the way that it works is a little bit complicated, but basically the hormone binds to its receptor and if it's a esteroid hormone, like esterdiol, estrogens, progestogens, androgens, and so on, it binds to the receptor, and then that hormone receptor complex binds to DNA inside the nucleus of the cell, and that regulates gene expression. And so that's how it has its effect, is that it increases the expression of some genes or it decreases the expression of other genes. So it has a specific effect at a specific tissue by binding to With the with the receptor to DNA and affecting what that cell does in that tissue by the the genes that it expresses. speaker-0: So you're saying that when it binds to these receptors that and when it changes gene expression, that essentially has the effect of changing what the cell does, right? speaker-1: Yeah, that's it. I mean, 'cause w yeah, what what makes the cell what it is is really the the proteins that it's making, but that's determined by what genes are being expressed. speaker-0: Right. And so given that hormones, when they get into the bloodstream and they travel everywhere, that blood goes and anywhere that has a receptor for the hormone will go essentially get switched on. Is there such a thing as a locally acting hormone? A lot of times women. So so just to give you a little bit of context here, a lot of times women are told like there's this hormonal IUD that it's like an interuterine device that releases progestin down near the cervix area. And women are told that the the effects of this are are are local and given how hormones travel and influence the body, like is that fact or fiction? ⁓ speaker-1: I don't know much about that, but it seems like if it's getting into the bloodstream at all then it's gonna be transported around the body. speaker-0: Well, it's so funny because it's like when you even talk to doctors, 'cause they get this literature from the drug companies that imply now they never say it because if you actually said it, that would obviously be not true. And especially when you look at the hormonal IUD, like most women have their HPG access shut down. Like they don't ovulate when they're on it, at least for the first couple of years, which suggests, I mean, not only that of course the hormones are getting into the bloodstream, but that they're affect in sufficient levels to shut down, you know, the hormonal cascade that prompts ovulation. And but but yeah, it's ⁓ that's one of those one of those little hormonal urban legends that lives out in in the world is that is that you can have these like locally acting hormones and they don't really work that way. speaker-1: Maybe it's possible in s in some cases I'm I'm trying to think. You know, th there's one way that people do experiments with hormones where they have people say, inhale them and it gets onto your, you know, epithelium in your in your nose, or they put like like ox oxytocin studies or testosterone where you just rub it on your skin. But the the point isn't to affect gene expression in your skin, it's because it gets into your system, it affects everything because it travels in the blood. So yeah, I don't I don't know. Yeah, I I can't think of a case where that's true. speaker-0: Yeah, I know. ⁓ people are gonna say what they're gonna say. So you've heard it here, folks, for the eight hundredth time I always tell people this because women will tell me that that their doctors will tell them that, ⁓ well, this is just acting locally, and so these mental health side effects that you're having aren't real because this is a locally acting well locally acting hormone. It's like mm, I don't I don't think that they work. I don't think they work that way. With sex hormones, one of the things that folks think, like I think one of the misconceptions about sex hormones. Is that they only matter when it comes to reproduction and the functioning of the reproductive organs. And tell us a little bit what types of things do sex hormones do? What are the what are their different responsibilities in the body? speaker-1: Yeah. Well, I mean, should we start with, you know, fetal development, I guess, because they affect the development of the external genitalia early on. So, you know, once the once the gonads, the the testes or the ovaries have developed, which is early, you know, first trimester, they develop and then once they do, they can start producing gonadal steroids. So I'm sure your listeners know by now that both gonads produce all kinds of sex hormones. But testes produce a lot more androgens like testosterone and and ovaries produce a lot more estrogens like like estradiol and progesterone. But both pr produce both kinds. And so androgens, testosterone, and especially ⁓ a real potent androgen called dihydrotestosterone cause the external genitalia to develop into a penis and scrotum instead of ⁓ a clitoris and and labia. And then they also affect brain sexual differentiation and the evidence for that is more circumstantial in humans because we can't do experiments like we can in in laboratory animals, but almost certainly it affects brain development ⁓ early in in you know ingestation and and then there's another point right after birth, sometimes called mini puberty, in the first few months of life when ⁓ the gonads again produce high levels of sex hormones and we don't know quite what happens there. Probably has some effect on brain sexual differentiation. Also that testes doing this ⁓ cause the penis to get bigger a little bit ⁓ in infancy. And then the gonads are pretty quiescent until puberty, at which point they again cause the development of secondary sex traits. And then in adulthood, hormones affect our brains and our moods and psychology and so on. speaker-0: Sex hormones have these different effects throughout the lifespan, and they influence both development and then also behavior, right? In real time. And oftentimes in the literature, so for those of you who want to nerd out, we talk about this as the difference between organizational effects, right? Which is where the hormone is actually shaping the way that the brain behaves or shaping ⁓ tissues, like for example, shaping the reproductive organs, shaping ⁓ sex sexual dimorphism in the brain. And then ⁓ activational effects. And these are the day-to-day effects of hormone release. So like if you're ovulating right the effects of your hormones, that would be activational effects. And so I want to talk a little bit. I want to start from the beginning. And talk about organizational effects. And you had mentioned, because I this is something that I don't know all that much about. So I'm hoping to learn a few things. I know the things that I learned in my essentially my neuroendocronology class as a graduate student. And it's a little bit rusty, but my understanding of development. So let's let's start in the uterus, right? So we're gonna start with embryonic and fetal development. Is that, you know, essentially that the developmental, like sort of the default developmental pathway for a little tiny human is to be female, right? And that sex differentiation is primarily the result of the release of prenatal androgens. Is that correct? Prenatal testosterone? speaker-1: Yeah, that's almost the whole story. It's not all of it because estrogens also have an influence and it varies across mammals, the effect how estrogens can have an effect on brain development. But it is most of the sex differences are due to androgen exposure causing development to be diverted ⁓ onto a male specific pathway. speaker-0: I remember the stories about the chickens where they would like shoot the eggs with androgen or with testosterone, right? And so it was like developing chicks. And then they looked at the developmental effects once the chicks hatched from the eggs, looking at the behaviors of the the chicks. And and so some of these chicks were male and some of the chicks were female. And what they found is that for all of them, having exposure to this prenatal shot daily shot of testosterone. had the effect of leading the chicks to behave like males, right? They were more aggressive. They would do the male typical mating stance. Is am I remembering that research correctly? speaker-1: I can think of studies on zebra finches ⁓ that have manipulated hormones. I thought you were gonna talk about how we sort of first discovered the effects of hormones was like taking rooster testes and and I think im implanting them into a female chick or something and it actually had an effect on masculinizing the the female. Yeah, I don't know about the not to say that it doesn't exist, I just don't know it. The study that you're thinking of, but certainly, you know, in rodents too, they're born Say rats and mice, they're born at the equivalent of our beginning of our third trimester. They're very altricial, it's called like eyes are closed, no hair. They still have a lot of development to do. So you can actually manipulate gonadal sec you know steroids in the first say week to ten days and completely influence brain development in rodents. And so you can treat females with testosterone and then they a they end up you know, being aggressive and mounting their sexual behavior. You know, males mount and females are receptive to mounting. And you can totally manipulate those things in in rodents by treating females with testosterone or castrating males and treating them with estrogen in adulthood and things like that. So but the same thing would apply to birds. I just don't know the particular study that you're thinking of. speaker-0: So yeah, and and who knows whether or not this actually exists. This could be something that my professor just made up. speaker-1: It probably exists. It's just my ignorance. speaker-0: Yeah, no, or or he like misremembered the study. But yeah, no, it's like of course none of us is a perfect repository for every single study that's ever been done in our field. I've even had the experience and I'm sure you have too, where somebody's talking to you about a paper that you that you have published and you're like, Did I do that? Like, ⁓ that's an interesting that's an interesting set of results. Who did that paper? Like you published that ten years ago. ⁓ yeah. ⁓ yeah. speaker-1: That's happened. If you publish enough papers. I I can remember talking to a a senior colleague about one of his papers years ago and and it was like one of the coolest results that I I know. And he was like, ⁓ yeah, yeah, I forgot about that. And I kind of marveled at that. Like, wow, what how cool to be at a point in your career when you publish so much that you don't remember the these amazing reasons or you kind of forgot that you'd done that. speaker-0: That's so funny. So, what are some of the things that we can learn about from human studies? Now, obviously, we can't, you know, manipulate exposure to androgens in humans ethically, but there are a number of different types of biological conditions like androgen and sensitivity syndrome or congenital adrenal hydroplasia or hyperplasia. I always mess that one up, or some of these other types of conditions ⁓ that lead to different types of developmental outcomes. Can you tell us a little bit about these and about what they tell us about the role of hormones in development? speaker-1: Yeah, and maybe just starting briefly with non human animals because as I said, we can manipulate these things in in non humans and in every mammal where we've manipulated sex hormones, especially you know, most of them let's just type take testosterone. Every one of them, ⁓ you know, testosterone masculinizes the brain and behavior. And that's been, you know, thousands of species across dozens of mammals and other vertebrates as well, right? I mean and and just I don't know, just about every animal that is, you know. you can manipulate sex hormones that affect their behavior and affect their nervous system. So it'd be really, really weird if that were not also true in people. Like really? The one? You know, millions of animal species and we're the one that the that sex hormones don't ⁓ organize, you know, sex differences in the nervous system and behavior. speaker-0: But can can I just like a c really quick, I've gotta ask a question. So you say masculinized male behavior. Masculinize, yeah. Yeah, operationalize that for me. So like what does it mean to have masculinized male is it just more aggressive and more sexual? Is that like speaker-1: Yeah, that's a great question. When when neuroscientists and neuroendocrinologists use that term, they just mean in a male typical direction or if female typical would be feminized or demasculinized. You know, so estrogens can have demasculinizing effects or feminizing effects as well. So that's all it means. So in some species, females are, you know, more aggressive. And they are so I'm thinking of for vertebrates, you we have some water birds like jacanas phalar ropes, where Females are more competitive for mates. ⁓ males are the ones making the nest and taking care of the eggs. Females are bigger and more aggressive. ⁓ and so feminizing in in phalleropes would be to make them, you know, bigger, more aggressive, and more competitive for mates. So it just depends on the species. But ⁓ all all that means is yeah, that it make make it more male typical or more female typical would be feminized. speaker-0: Okay, so in a human, and if we were saying that XYZ and we'll talk about the sort of natural experiments that happen that allow us to look at this, but like what if we're saying that that this causes masculinization of behavior, like what would we be looking for? speaker-1: So if you're thinking about behavior, what are some of the biggest sex differences ⁓ in behavior or psychology? One of the top two would be sexual orientation. So, you know, males on average are attracted to females exclusively or almost exclusively in females. ⁓ of course we know there's overlap and, you know, qu wide variation within sexes, but but that's a big sex difference of about ⁓ I'm forgetting, is it about seven standard deviations? Very you know, the th there's like One to two percent of females are exclusively or almost exclusively attracted to other females and about two to three percent of males across studies. I mean, it's hard to measure these things ⁓ accurately because there can be reporting biases and things like that, but but th those are good estimates. And so, you know, ninety-some percent of people within any sex are over ninety-five percent are attracted to members of the opposite sex, either exclusively or almost exclusively. But ⁓ what are some other things You know, males tend to engage in more rough and tumble play. ⁓ this is typical of mammals, you know, that i same with rats and mice and chimps and gorillas and so on, that they young males like play fighting and they do that more. And that's not to say again there's even more overlap in that particular trait, but males do it more, you know, and you know, more physically aggressive throughout childhood and and adulthood. And what's another sex difference that you see? You know, maternal behaviors across mammals that, you know, so so parental behaviors tend to be highly sexually differentiated. And in humans, you know, young females like babies and dolls and playing with, you know, that more. And I'm not making a judgment or saying that this is how things should be. I'm just saying that if you measure behavior, observe behavior in kids that there's a sex difference there. speaker-0: There was actually this really wonderful study that was done. And it was done, I think it was in Sweden. It was done in one of the ⁓ Scandinavian countries. But they had this daycare where it was like a sex neutral daycare, and they had parents trying to raise their children in sex neutral ways. ⁓ so everybody was very committed to this idea. And so they would put the boys in rooms with, you know, Barbie dolls and that sort of thing, and girls in rooms with trucks and blocks. And what they found was that you still had sex typical forms of play. with these opposite gender toys. And so they and there's this ⁓ amazing video of boys shooting each other, you know, with Barbies. And and then yeah. And then a girl there was a video of this little girl rocking, yeah, rocking a fire truck and saying, yeah, saying, Don't worry, trucky, you know, it's gonna be okay. Yeah. And so yeah, a lot of these things, you know, that we tend to think of as being purely socialized. It's like we really do come into the world kind of speaker-1: Yeah, anticipated that. speaker-0: prepackaged with a certain set of interests and proclivities. And th they do tend to be sex differentiated. speaker-1: I can think of, you know, i especially if you have kids, ⁓ you know, you s you observe this and it's like ⁓ I can remember, you know, my oldest, ⁓ my daughter, when she was little, she'd make everything into families and babies. Like she would just be outside playing in a rock bed and she'd have like this is the mommy, the daddy, and the baby, or she did that with our our T V remotes. You know, she was like, There are three remotes and it's like, you know, but anyway, so okay, so you asked about non-human animals. You can do experiments where you manipulate sex hormones, all kinds of ways. You could treat animals with a drug that interferes with the the ability of the hormone to bind to its receptor or you can treat them with with the hormones themselves. You could castrate or rev remove ovaries and so on. All these things have been done over and over, always with the same result, which is that, you know, gonadal hormones influence the brain and the be and behavior. So almost certainly that would be true in people, but y you know, we're scientists, right? And we want evidence that it's, you know, and so You know, you can't do the same kind of experiments in humans, but you can look at what are sometimes called experiments of nature or natural experiments, just natural variation in people's hormone production or their sensitivity. And so there's one condition that you mentioned called there's androgen and sensitivity syndrome where the androgen receptors are less functional, and then there's complete androgen and sensitivity syndrome, C A I S, where the androgen ⁓ receptors are non-functional. And so people who have this condition, they're XY and so they're speaker-0: Right, which is which is male for those of you who like haven't had a biology. speaker-1: So yeah, well, females have two X chromosomes and males have an X and a Y. And on that Y chromosome, there's a gene that causes the gonads to develop into testes. And then testes, you know, once they develop, they start to secrete androgens like testosterone, which then organize the body and brain and behavior to go in a male typical direction. But people with this condition, complete androgen and sensitivity syndrome, are XY, they have a Typical Y chromosome that causes the development of testes. Those testes produce high levels of androgens, male typical or maybe even a little bit higher because there's no sort of negative feedback happening. And that androgen has no effect on the brain, the body, behavior, anything, because it can't, because the androgens are not functional. And so as a result, they develop in a female typical pattern. When they're born, they look like girls, they're raised as girls, they their testes are undescended, they're in their abdominal cavity. You wouldn't know. And it's detected when they don't go through puberty and then they have to do a bunch of tests and discover, okay, this girl ⁓ has complete antigen insensitivity syndrome. So you're not gonna have periods. We should remove the testes because they can become, you know, cancerous and you can get on and they they tend to have some sexual development because the testes are still producing. estrogens and there's no message, it's kind of a balance of estrogen to to androgen. And because there's no androgen message, they they'll still start to ⁓ develop a bit, but they usually get on ⁓ hormones to develop a you know female external appearance. But you know, in no point in their life do they say, ⁓ I'm actually a male or something like that. Like, I mean in in a way, chromosomally and gonadally, ⁓ sure, but they never they're raised as girls. They feel like girls. In fact, in some ways, you know Their evidence isn't great, but they may actually be a bit more feminine in their female typical and their psychology and behavior because there's zero androgen message. speaker-0: I think I'd heard from somebody who's a behavioral geneticist and he has studied a large populations of of these and large populations. It's a very small population of people who have this, but it was like he would look he looked at rel relatively large samples of these these women and and he said he was struck by how beautiful ⁓ so many of them were because they had no you know, expression of androgens. So their skin was like perfectly clear. No no body. Yeah, no body hair. I mean, and a couple of them were like supermodels in because and they were tall and, you know, kind of f flawless in a lot of ways because androgen d I mean, testosterone does a lot of really wonderful things, but it also has some some negative side effects, especially for speaker-1: Side effects of testosterone, which we could talk about for society. ⁓ no no offense. ⁓ you know, I like I like males, you know. ⁓ but anyway. So ⁓ but the issue with using women with CAIS as a sort of ⁓ natural experiment to understand, ⁓ okay, so they're they have no androgen signal and they're completely feminine in their psychology and behavior, therefore androgen masculinizes Behavior is not a really a good natural experiment because they also look like girls and as ra are raised as girls. And of course, there are plenty of social scientists, I would say, you know, yeah, of all kinds. I mean, especially I don't know. I'm not gonna qu sociologist, anthropologist, psychologist of all kinds who think that sex differences in behavior and psychology are almost entirely socialized, you know? You could say, and certainly social learning. We're very smart and we're very social and social learning plays a huge role in our behavior. And if you're somebody who thinks that that's all that matters, then you could say, well, that's not not evidence either way, because they're raised as girls and socialized as girls, so that's why they're feminine in their psychology and behavior. So you really need to really understand this in people. The best evidence are from studies where people are raised as their gonadal and chromosomal. sex and they look sex typical in their behavior, so they're socialized and raised that way, but they nevertheless had atypical sex hormone signaling during early development. So you may mention another case which is congenital adrenal hyperplasia. And so that's a pretty good also rare, like less than one in 20,000 or something like that. It's a condition where the adrenal glands, which are glands that sit on top of the kidneys, renal, you know, adrenal glands, They normally produce ⁓ cortisol, which is a stress hormone, but people with CAH lat an enzyme that converts a precursor into cortisol. And so that precursor actually gets shunted down the androgen pathway. So girls with this condition, then their adrenal glands during fetal development, and then later on, unless they get on hormone replacement therapy, which they do early on, but during fetal development at least, their adrenal glands are producing really high levels of androgens. And so then you can look at what is psychology and behavior like in a girl raised as a girl, but who was exposed to elevated androgens before she was born. What's the effect on psychology and behavior? And, you know, the evidence is pretty clear there that, you know, they're still more likely to be heterosexual, qu quite likely to be heterosexual, but, you know, attracted to I prefer androphilic. It helps you, you know, ⁓ especially when people's gender identity may be one way or the other. d specify, so attracted to males. But they're still maybe two or three times as likely to be attracted to females as a ⁓ an unaffected female. Engage in more physical aggression ⁓ during childhood. Their preferences for ⁓ playmates and play patterns and toys and so on is more male typical. And actually quite sort of intermediate between ⁓ an unaffected female relative and a and a male. So there's a good ⁓ sort of experiment of nature. And then I can talk to you about a s ⁓ a condition that we've been studying lately that I think is maybe the best natural experiment so far. ⁓ but I don't know if you have anything you want to speaker-0: Yeah. I well, so one thing that I just like popped into my head and I and I was trying to write it down and then I was too busy listening to the other things you were saying. So given the role that androgens play in attract like potentially like attraction to women, right? You know, there's this research out there on ⁓ hormonal birth control and and the preference for less masculinized male faces. I'm wondering whether the androgenic forms of hormonal birth control, because there's some that ⁓ in addition to Stimulating progesterone receptors also stimulate androgen receptors because most, I don't know if you know this, but most progestin is synthesized from testosterone. And some of it they do less of a good job of making it like because it lacks binding specificity for a lot of these, especially second generation progestins. They are pretty androgenic. And I was just wondering, I wonder whether that is actually what's happening. So that it's not so much about flatlining the estrogen. Right, but that whether adding something that is stimulating androgen receptors is making you kind of tilt a little bit toward a feminized male face. speaker-1: I don't know, that's a good question because I've studied the effects of ovarian steroids on preferences for masculine and feminine traits. And in fact, that my dissertation research was ⁓ you know, ⁓ partly on that, that, you know, I was maybe we can back things up a little bit. Why did I do this? Well, I was interested in studying mating competition and I thought, you know, really the voice hasn't been studied in that domain. And so I decided I'm gonna do that. And one of the things that I looked at was do based on the literature that was around at the time on face preferences, I thought, I wonder if voice preferences work the same way in women, that they prefer more masculine voice like in the way that it had been shown that women prefer more masculine faces at the fertile time in the cycle, that maybe they prefer more masculine voices. So I manipulated male voices and I had women come into the lab and I got where they were in the cycle, you know, ⁓ by using self-report. Data like how long is your average cycle, and when was the last day of, you know, first day of your last menstruation and so on to figure out, okay, these women are probably in the fertile time of the cycle, these ones are in the luteal phase, non-fertile, or early follicular, non-fertile. And I found, lo and behold, that women preferred more masculine voices only in the fertile time of the cycle. And I remember getting that result. And I did that in the basement in the laboratory, in the bioanthropology laboratory, in the basement of ⁓ my building and taking that and running up three flights of stairs to my advisor's office and showing this paper saying, here's my dissertation. I was so excited about it. But and then a couple of other labs found the same thing. But then a few years ago with I I did a better study. I I collected instead of between subjects, ⁓ so just all different women, just where do they happen to be in the cycle, a better design study is looking at the same women at different times in their cycle. And so I had two hundred and two women come in once during the Late follicular phase when they're f you know ⁓ estradiol is high, when they're when conception is possible. These are all ⁓ normally cycling women, not on hormonal birth control. And then another time in the midluteal phase when conception is not possible, and progesterone is high, and there's also a little spike in estrogen as well. And they were counterbalanced, so half came in first during the fertile phase, and half came in first during the the the non-fertile phase. And I also measured estradiol and progesterone from saliva. So a better design study. And do they prefer more masculine voices at the fertile time when estrogen is high and progesterone is low? No. I did not find that. And I also, you know, was talking to collaborators at University of Göttingen in Germany, who d also did a nice study. They measured women, fewer women, but still a good sample. I think it was maybe a hundred and something. 120, 140, something like that, but four times in the cycle, and also had hormones and also found no change. And so, you know, I don't know anymore because ⁓ I I saw it in my own data and I have ideas, and we've actually just finished a really nice study that I could talk about that will settle my mind one way or the other. But right now I don't know if women's preferences for masculine traits really change over the cycle because also other studies that have been better designed looked at women's face preferences and and also have not replicated those initial results, including by some of the same authors. speaker-0: the things ⁓ and and we're definitely gonna circle back to this because i and i want to march our way through development and puberty but before we do that i just want to say that like one thing that i've always worried about and i didn't start worrying about this until until we were doing this research in my lab about counterbalancing the order of cycle phase is that like Every ovulation is a every cycle is a little bit different. And I think that comparing the luteal phase, like if you do luteal phase first, I th then that means you're gonna be doing a different cycle for early follicular and mid-follicular phase. And that could be apples and oranges. I mean, just in terms of fertility. So we because we had some issues where and and we then ran some follow-up tests where we only looked at the subsample of women where we were actually measuring them within an individual menstrual cycle. And those results were more consistent with our hypotheses. And because, you know, you don't know whether the cycle before was an ovulatory and then this one's ovulatory, or whether this one was an or just even like bad ovul, because you, you know, you have like sort of varying degrees of ovulation, like where some of it's like like good, like like this was a really good cycle. And then some of it where it's like, you know, your body's just kind of like ⁓ You know, and ⁓ and and you don't release a lot of progesterone and it's just kind of a but then your next cycle could be really amazing. And so ⁓ we have switched to looking at things only within cycle because I think that just in terms of the f the ⁓ sort of ecological validity of it, that even though it's less, you know, desirable from a purely experimental standpoint of having counterbalancing, which I totally understand, we decided that the That what's lost in terms of ecological validity isn't worth that cost. speaker-1: No, that's a really good point because the differences across cycles. And so the study that we just completed and my brilliant graduate student, So Jung Beck, is the you know leader on this study, and she's gonna have some cool papers, including one on women's preferences for masculine voices, which th those data have not been analyzed yet, but she has some other really cool results. So one problem with doing everything within one cycle, starting at the beginning of the cycle and finishing at the end of the cycle, is that hormone levels and cycle phase are forever confounded with day of participation in the study. So that if there's some effect of just time, like I've done this several times now and it that's there's an effect of that, you can never pull those apart except w what what we did in this most recent study is we recruited women and had them come into the lab whenever, just as soon as they were available, random time in the cycle, and have them start doing the study. And so some of them would have almost a full cycle in the study before they start actually started the next one. And some of them would have a short time, the average was there in the middle of the cycle. And then we record we got the next cycle phase, a full cycle. And so that way, you know, the day of of when they started participation in the study is actually random with respect to cycle phase. But then we have the full next cycle, so we can see how that affects anyway. But point well taken. And so in this speaker-0: That's that's cool. speaker-1: The study that I did in my postdoc at Michigan State where I counterbalanced, good point. Those are different cycles. But we also looked at just for session to see if there's any effect, you know, between women. And then the German data, I am pretty sure those were like the same way that you did it, where it was within a full cycle, just, you know, one, two, three, four, every like every week across an entire cycle. But but yeah, more more needs to be done on this. And the reality is that like there are some aspects of women's psychology that I am very confident now do change. Like sexual desire, libido, you know, change is higher at during the fertile phase of the cycle, with, you know, estrogen seems to play a role in that. And it's not huge. I mean, the reality is that like there are lots of mammals where they have like esteros and y then like females are like totally uninterested in sex. They don't they're not receptive to males. They don't solicit copulations, you know, lots of social primates are that way. And they have like really pronounced genital swellings where like everybody knows when you're in the fertile time in your in your cycle. And rodents are are like that too, you know, that there they some are that there's a a pronounced estrus. And that's not the case in humans, you know, it's much more subtle changes where we need to do these really carefully designed studies with lots of participants and, you know, to find something. But but there are changes and so you know we'll find out. And I wouldn't be at all surprised if there are changes in mate preferences as well. I mean Just because it w what we are more confident changes over the cycle. Like if you're more sexually interested at the fertile time in the cycle, wouldn't you maybe be more interested in sexy males then or sexy partners of any ki you know, depending on your sexual orientation? It just kinda ⁓ makes logical sense that that might be true, you know. speaker-0: Yeah, yeah. No, we very much as I've studied especially things related to hormonal birth control and sexual desire and attraction and some of these other things. One of the things that I have sort of ⁓ it it's really shaped my thinking has been thinking about the changes in sexual desire that you get in naturally cycling women, where you get this like increase in ⁓ sexual desire and they feel sexier and then you know, and they're sort of more attuned to sexual related stimuli. And ⁓ and then you see that women who are using hormonal birth control that this gets flatlined a little bit, right? There were there's like they have relatively lower sexual desire, they're at a greater risk of ⁓ sexual dysfunction, et cetera. And, you know, there's always been that question of what happens, you know, does it influence who women choose as their partners, right? Do women choose, you know, a less masculinized male male face or voice or whatever it is. And ⁓ and ultimately, you know, what I think it is, and we have a study that we just ⁓ we're doing revisions on and we're about to resubmit it. But we looked at ⁓ data from natural cycles, which is a cycle tracking app. And all of the women who are on it are naturally cycling. But we took a subsample of these women and sent them a survey within the app asking them what type of birth control they were on when they met their current partner. And we about half of them chose their partners when they were using hormonal birth control, and the other half chose their partners when they were naturally cycling. And but they're all now currently naturally cycling, but they also All had experience using hormonal birth control. Right. And so we had women who had experience using hormonal birth control, experienced naturally cycling, currently naturally cycling. Half of them chose their partners on hormonal birth control, half off. And what we found was that the women who chose their partners when they were using hormonal birth control logged less sexual activity across the cycle and just reported less attraction to their partner in general than the women who chose their partners when they were cycling. And ultimately, here's what I think is going on is that I think that when you have libido kind of flatlined, you know, just kind of the volume turned down on your libido, that doesn't matter as much when you're choosing your partner. It's like anytime any of us chooses a partner, it's like we're always choosing based on a variety of qualities, including like how sexually attracted am I to this person, but also like how good of a partner is this person gonna be? You know, are they gonna be a good parent? Are they stable? Are they fun? Like, you know. And so all of us are always counterbalancing our multiple demands because we all have a laundry list of things that we're hoping to get in a partner. And ⁓ and I think that for women who are on the pill, it's just like the the sexual attraction piece of it just becomes a little bit less important because their libido is less important to them at that moment. And then, you know, this can ultimately lead to changes in ⁓ relationship patterns. But one thing I also like wanna point out for anyone listening who's like, Like alarm bells are ringing. These aren't huge differences, right? So when we're looking at the average number of like sexual encounters that people log, it's not like we're looking at the difference between, you know, people who are never having sex and people who are having tons of sex. It's like it's it's a small difference. It's just a reliable difference. And the differences in attraction are also that way. It's small, but we find it again and again. And so but I I but I think that's what it is. It's like just that nudging effect that hormones have. speaker-1: That's a nicely designed study, and I'm I'm glad that you did that because I I had, you know, I we've looked at some of those things before too, comparing women who are normally cycling to women taking the pill. And I've also looked at other research and I've always wondered how much of it is sort of affects her like self-selection. Like if you're looking between women, well, women who decide to take the pill or take some kind of hormonal contraception. are probably different in some ways. Like maybe they're engaging in more sexual activity and that's why they're taking it. Or, you know, whatever. And so d having a a study where it's the same women, you know, who have both taken and not taken, that sounds like a a cool study. So speaker-0: And just to really quickly, I I want to float back really quick to talking about sex differentiation in utero. And so in humans, essentially what we find, and you have a really cool group of folks that you've been looking at, you've published a couple of papers on these on these folks who have a particular, is it a genetic based difference? speaker-1: It's multifactorial. It's not simple like in congenital like in complete antigen and sensitivity syndrome, we know it's the antigen receptor gene. And CAH and congenital adrenal hyperplasia, it's one of a few genes that affect enzymes that are necessary. In the condition that I study, IHH, idiopathic hypogenadotropic hypogonadism, let's just say IHH. there are I think that so one of my early collaborators on this was a lab at speaker-0: Yeah, let's just do that. speaker-1: Mass General Hospital, Harvard Medical School, studying the genetics of the condition. And I think it was either 40% of the variation, they could maybe something like that, that they could explain with genetic variance. So there's a bunch of causes of the condition that aren't known, that that genes have not been identified. So it's not so simple. But the condition is one where ⁓ so we have, you know, the hypothalamus. You mentioned the HPA axis or the HBG, I think HBG axis is what you mentioned, the hypothalamic gonat ⁓ pituitary gonadal axis. So the hypothalamus part of the brain tells the pituitary, another part of the brain, to tell the gonads to produce hormones, you know, and if they're ⁓ ovaries and they produce specific levels of hormones, or if they're testes it produce another levels. And people with IHH have The cells in their hypothalamus that normally tell the pituitary to tell the gonads to produce sex hormones, they don't develop typically. And so they don't have the ability to tell the the gonads to produce sex hormones later in fetal development or mini puberty or puberty. So without getting on hormone replacement therapy, they would never go through puberty. And so we can study this condition. And, you know, I mentioned And s we say, ⁓ what's the effect of people so they do, like when they don't get go through puberty, then it's very rare. It's like less than one in various estimates, but less than one in a hundred and twenty thousand people. I mean, I think it's maybe one in one thirty or one forty. Super rare, right? They don't go through puberty and then there are a bunch of tests because there's all kinds of things that cause you not to go through puberty. And if they have this diagnosis, then they get on hormone replacement therapy to develop, you know, sexually it at puberty, you know, have typical ⁓ secondary sex traits at puberty. Their early development, their first trimester and sort of early development is actually pretty much sex typical. And the reason why is because human chorion corionic gonadotropin, HCG, the thing that you detect when you take a pregnancy test, that actually binds, I don't want to get too complicated here, but it binds the receptors in the gonads to cause them to produce sex hormones. in the first trimester. And that's when the external genitals develop. And so, yeah. And so they're born, you know, if they're male, they look like males. You know, they some cases a micropenis or undecended testes, but it's unambiguous. You don't think, ⁓ this is this a male, this is a female. It's, you know, male or they're look like a female. And they're so they're raised as boys or raised as girls. And nobody knows their condition. In fact, if you didn't test them it during mini puberty, the first few months of life, Then you actually can't test it until they don't go through puberty. And so almost always they don't know they have the condition, their physicians don't know, their parents don't know. So not they can't be treated differently like somebody with CAH, congenital adrenal hyperplasia that can actually they are treated differently because they're they have a condition and their doctor knows it and they have hormone replacement therapy and their parents know it and so on. So there could be some effect of differential treatment by society. You know, parents. Everybody, you know, whoever happens to know about their condition. But with IHH, they don't even know they have it. And so then we can say, well, what was their you know, after HCG levels go down, normally it's the hypothalamus that's telling, you know, that's running the show and telling the gonads to produce sex hormones, but it doesn't. So all the only gonadal sex hormone exposure that they have is that little bit w of HCG that's left at the end of gestation. And so males are producing really low levels of androgens, females really low levels of estrogens throughout gestation after the first trimester, no mini puberty, and then no puberty until they get on hormone replacement therapy, but raised as boys and girls, you know, according, you know, same as their gonads and same as their chromosomes. So then we can say, well, what's the effect of having if you're a male raised as a boy? exposed to really low levels of testosterone and other androgens early in development, or what's the effect of being a female and having been exposed to low estrogens. And for males, so far, I mean, we're not probably ever gonna have longitudinal data on somebody like this across childhood because you just have to have hund you know hundreds of thousands to have one or two participants who happen to have IHH. But we can do rec retrospective questionnaires and s ask about gendered or sexually differentiated behavioral patterns like you know gender conforming nonconforming behaviors they're sometimes called and what we found is that males with IHH reported, you know, more gender nonconformity in in childhood on a questionnaire that they had sort of less male typical, more female typical childhoods, not a huge difference, but a large by conventional statistical standards. And then for females, and this maybe is even more interesting, we found that women with IHH were less androphilic. They were less attracted to males. And that suggested estrogen might play a role in attraction to to males later on. speaker-0: Yeah, that's really to circle back really quick with the with the boys. And when you say that they're measuring male typical like behaviors, is this like rough and tumble play, like tendency toward aggression? ⁓ speaker-1: Remember how many questions in the questionnaire, but somewhere between 20 and 25, I think. That, you know, some things like, what did you fantasize about doing? What did you like? What kinds of toys? What kinds of activities? ⁓ when you when you were a kid, what kinds of things did you want to do when you grow up? Things like that. That, you know, we know show sex differences. And none of this, again, I mean, none of this is like judgmental about hit, you know, anybody should be like this or anybody trying to reinforce gender norms or anything, but it's just like We know that these things tend to be different across boys and girls and so we can measure them and then say how, you know, male typical or female typical are were you as a kid and your behavior and and preferences and things like that. speaker-0: Right. Yeah. And people who don't ⁓ like I I found that most people who don't appreciate the role that biology plays in sex differentiation doesn't have children. Or yeah, or like they don't have children. Like I've got, ⁓ I don't know, ⁓ 'cause do you have a do you have ⁓ sons and daughters? Yeah, yeah. I've got one of each and ⁓ and you know, and you can try to be as gender neutral as and and know when they come out in the world and you know, and they're making re T V remote control families. speaker-1: D girl, boy, girl. Yeah. speaker-0: When you've got when you've got girls and ⁓ and hitting each other with Barbie dolls when you've got boys oftentimes. Yeah. speaker-1: Absolutely. And and that's also true of, you know, parents with gender nonconforming kids too. That it's like it doesn't matter. You know, like if you have a boy who's very feminine and interested in Barbies and dolls and and pink and all that kind of stuff and and once girls as playmates, like they're gonna be who they are. And it really has y like our job is just to keep them safe and give them an education and you know and they're they're you know, you can't really do much about like personality or anything like that. speaker-0: Yeah, no, absolutely. And so what what you found in the girls is that that it seems like estrogen, because these girls, their ovaries are not producing estrogen at like a typically developing woman or girl is, and ⁓ and that they have a less androphilic, I love this. So less of a sort of a male tip like a preference for men, essentially as sex partners. And suggesting that estrogen ⁓ could develop in and this is developmentally, right? Like you're suggesting that this might be play a d a role developmentally in shaping women's preference for men. Yep. When I was ⁓ taking neurondocrinology ⁓ as a graduate student, ⁓ there was a lot of discussion about testosterone and all of its roles in development. And there was almost no discussion of estrogen outside of, you know, genital development. speaker-1: I could tell you why. In rodents, where we know most of what we know about the brain and behavior is like interestingly, rats. Mice are the animal model for the genetics of behavior in the brain. And it's just historically, and rats are the hor hormone example, you know. But in the rodents that we study in in lab rodents like mice and rats, it is all testosterone. And the reason why is this is really weird, but I think it's a fun story. The way that Testosterone masculinizes rat brains, is it goes into the brain, it cr crosses the blood-brain barrier, goes into the brain, it's converted into estrogen and to esterdiol, and it binds estrogen receptors and it masculinizes the brain. That's bizarre. It's actually estrogen masculinizing the brain in rats, but it does it because testosterone is converted into estrogen. And you might say, well, wait a minute. Then why are female rats' brains not super masculinized? Because they're producing way more estrogen than males. And the reason why is because the estrogen can't get into the brain. It's bound up in the blood with a protein called alpha phatoprotein. And when a when that binds to estrogen, it prevents it from crossing the blood-brain barrier and getting into the brain. So it's really interesting because people studying rodents often don't know that it's actually different in humans. And other, probably other anthropoid primates, at least rhesus monkeys, it seems to be different different. And people studying humans often think that we're the same as rodents, but the d it's true that andergens masculinize the brain and rodents and primates alike. But the way that it does it is different. And I can tell you some lines of evidence for that. speaker-0: So with humans the masculinization of the male brain is actually v via testosterone acting on testosterone receptor. speaker-1: Yeah, and one p one line of evidence for that is if you have non functional androgen receptors, then you're in general adrenal hyperplasia that we just mentioned, you're totally feminine in your psychology and behavior. It's also there are a few cases, I think I found like eight in the literature of males that we know had a non functional estrogen receptor. And the reports were that they were typical in their gender behaviors. So it doesn't seem like estrogen receptor is critical in humans like it is in rodents, where that would be totally different. If you if a know, you didn't have a functional estrogen receptor, you couldn't masculinize the brain. That protein that I mentioned, alpha feta protein, binds estrogens very strongly in rodents, but it actually doesn't in humans. It seems like it actually binds androgens more. So it would prevent females lower androgen levels for for androgen from getting into the brain and masculinizing their brain. But estrogen probably does get into the brain and s in humans and in other during development in a way that it can't in rodents. And so it could do something. We decided to look, you know, like so estrogen probably can get into the brain in humans during development and ⁓ and that could be relevant to sexual differentiation of the brain and behavior. And so far what we found is it seems to influence attraction to females in humans. There's a lot of evidence that androgen binding to androgen receptors makes you more gynephilic, makes you more attracted to females. speaker-0: I read one of your papers looking at women with ⁓ PCOS, which is now called PMOS, because they're recognizing that it's ⁓ really a metabolic syndrome, and ⁓ finding that that there tends to be a co-occurrence between having PCOS, which is something that's related to increased ⁓ androgen production and obviously then androgen exposure. ⁓ and preference for women, so essentially women who are are either ⁓ bisexual or lesbian. Do you think that that's part of the this whole picture that's unfolding about the ⁓ sort of development of things like ⁓ sexual orientation? speaker-1: I had seen a few studies before that had found some relationship, and some that didn't, find a relationship between PMOS or PCOS and sexual orientation. And so we did this review paper ⁓ in the journal Adaptive Human Behavior and Physiology, where we just wanted to look at all the literature that had linked early hormone exposure to sexual orientation, but just to see. In this highly sexual i like if you're interested in does sexual differentiation of the reign and behavior and psychology in humans, does it seem like it's the way it is in other mammals, which is that it's you know strongly related to hormone exposure? You could hardly do better than sexual orientation in terms of picking a trait that's highly sexually differentiated, that you know ought ought to be responsive to hormones if if they if they play a role. And so we just reviewed all the evidence across we looked at C A I S, C A H and IHH and all these different And so we did a meta analysis where we got data from every study that we could find, w and they were all PCOS at the time, that was the the terminology. And, you know, across all those studies, and I don't remember the total number of participants across all studies, but it was like, I don't know, in the tens of thousands or something. And yes, I mean there seems to be that, you know, females with PMOS or PCOS have an elevated probability of being attracted to females, but it's not a big effect. ⁓ and that's why some studies found it and some didn't. But as we know, you know, there's evidence of elevated androgens in in females with that condition. Now we don't know if they had it during early development, like the, you know, prenatally or early postnatally, and that affected their sexual orientation, or maybe it's that their moms, because it's highly heritable, their moms are likely to have it. So maybe their mom's, you know, exposure to their mom's androgen levels affected their brain development during fetal development. But we did find an association across. ⁓ w in a big statistical analysis across all studies that have been conducted so far. speaker-0: So, given that all of these different lines of evidence really seem to support the idea that sex hormone exposure during development, like the uterine environment, plays an important role in the development of ⁓ sex differentiation. And so, like one of those things is, you know, gender identity, one of those things is sexual orientation. So some of the other things are, yeah, just like the ⁓ tendency toward aggression or rough and tumble play and and these kinds of things. What do you think? You know, given that we live in a world right now where there's so much exposure to things like endocrine disrupting compounds, are there special things? And I know that you're not a clinician and so you're not in the business of making recommendations about what people should do, but do you think that people are right to be a little bit cautious, like if they're pregnant moms, ⁓ about exposure to these types of compounds? Like is there an impact of xenoestrogens or that that sort of thing potentially on could that have long term developmental effects on a developing fetus? speaker-1: My answer to this question will be ⁓ it's plausible. I d I haven't conducted research on that myself and so I'm not an expert and on that particular question. But certainly, you know, hormones can enter the bloodstream through the skin th through a variety of of modes. I don't know how much ingestion has an effect because ⁓ you know your body's gonna break these things down during during digestion, but th there could be, you know, we know that taking p the pill orally gets into the bloodstream, right? That's the whole point of it. ⁓ and so yeah, I think that exposing yourself to different hormone levels during development gets into the bloodstream, your blood goes to your fetus, and so yeah, it makes sense to do your research on it, and I don't mean get on Facebook or or Twitter or whatever, but rather, you know, reputable medical sites or better yet, consult your physician. But yeah, it makes sense that, you know, these hormones can can affect the development of your fetus in some way, yeah, for sure. Yeah, and there have been studies in in non human animals where that's how the researchers influenced, like they wanted to manipulate sex hormones in rhesus monkeys, so they treated their moms when they were pregnant. speaker-0: Yeah. And I think that there's been ⁓ different, you know, studies where they found that there's feminized male frogs in certain ponds where they have a greater exposure to things like phthalates and other forms of endocrine disrupting compounds. And I think that there's been these like little natural experiments that suggest that there's a developmental effect. But yeah, as you noted, like the studies and I actually I think that just heard about a study where they looked at exposure to endocrine disrupting compounds. And I think this was done like cross sectionally across the US, looking at I think it was like just based on pollution levels, like water pollution levels. And then looking at the distance of length between the anus and do you know what this measure that I'm talking about? Yeah. So can you tell listeners? speaker-1: Absolutely. Yeah. Anogenital distance. It's speaker-0: Yeah, so so yeah. Yeah, so tell us what that is and and what it is a marker of because I think people will be totally fascinated by this. speaker-1: Distance between the anus and the genitals, and ⁓ it's highly sexually differentiated, higher in males, and responsive to sex hormones. So, and that's true in humans too. And it's interesting because there's this whole literature on, you know, because we can't manipulate sex hormones early on, it's nice to have some kind of information about early hormone exposure. And one trait that we've looked at and lots of other researchers have looked at is is finger length ratios, that there's a sex difference in males tend to have a a shorter index finger than ring finger. And it's not a big sex difference. It's like about half of a standard deviation. I don't know how I'm trying to think of what percentage. Anyway, there's a lot of overlap, but males if you if you measured a hundred women and a hundred men, you'd find a, you know, a a s a sex difference there. And so people have used that as a retrospective marker of early hormone signaling to say, okay, So we've got this biomarker. What does that relate to? Like it does it relate to sexual orientation and so on. And people have found that it does. But it would be better to have a measure that was more responsive to sex hormones that showed a bigger sex difference. And this kind of thing has been done in rodents, but to my knowledge, and I probably would know, nobody's looked at it in people as a biomarker, because for obvious reasons. You know, you could scan people's hands on a scanner in the lab. Do you have them sit on your scanner? ⁓ you know, no IOB is gonna approve this if you'd even want to do that. But it would be kind of amazing. Maybe you could like they measure speaker-0: So this was a study Yeah, well I'm measuring home. speaker-1: Like just tell us the number. We don't wanna know. ⁓ anything else? speaker-0: We'll send you a kit. Yeah, we'll send you a kit. Like do not take pictures. Well, so in this study, they actually looked at this with babies. Yeah, and so and so they measure it. Yeah, so so they measured it in babies and essentially found that boys have shorter speaker-1: Someone you're very close to all these simple instructions. Okay, yeah, yeah. Okay, that's all behavior, but you speaker-0: Anogenital distance. So yeah, so a more feminized that in more ⁓ polluted areas. ⁓ Where essentially where they would get greater exposure to ⁓ endocrine disrupting compounds, which ⁓ yeah, which I thought was was was really interesting. And also just ⁓ just another reminder of just how sensitive we are to sex hormones ⁓ during development. And that's true whether it's the sex hormones that are supposed to be there or those that are being introduced to the system on the outside. So one of the the things that evolutionary scientists are are particularly interested in are some of the hormonal changes that begin to happen during puberty. So we're gonna move now beyond the womb and start looking at the second big influx of sex hormones. And this is something where Both men and women each experience a big surge in sex hormones that we all know about that leads to ⁓ the development of postsecondary sexual characteristics. So, like for men, it's like the you know, the deepening of the voice and lengthening of the penis. And for girls, it's you develop the waist, the lower waist hip ratio, right? Where you start to put fat on around your button thighs at breast development, et cetera. Are there also things that happen to the brain? Like is there further sex differentiation of the brain during this time? speaker-1: Almost certainly. But we also don't know a whole lot about it. And part of the reason is because it's an important time in social development as well. And so you see changes, of course, in psychology and behavior across puberty, but how much of that is because of sort of maturation that happens through changes in your social behavior and how much of that is in of influence of of hormones. And you know, when I was a A postdoc, a postdoctoral fellow in Michigan State University in the neuroscience program there, the director of the program at the time, Cheryl Sisk, her lab was looking at puberty and actually caught caused me to then look at puberty later because I was looking at the research that she and her lab were doing and thinking, this is amazing, this is cool, I wonder if it's true in people. They were manipulating the timing of sex hormone exposure in rodents by castrating males at birth, and then they could control the timing of when they instead of normally the testes start to produce androgens during puberty and they they could manipulate that by treating males with testosterone at the normal time of puberty, a little earlier, a little later. And what they found was that earlier treatment resulted in a more masculine brain, more male typical brain and behavior. So more, you know, male aggr male aggression and sexual behavior and stuff if they treated them earlier. So looked like the brain had a like a decreasing sensitivity to the effects of testosterone across the time window around puberty. Cool experiments, which you can't do in people. But one of the reasons why I started looking at IHH is because it's kind of a natural experiment here, because what you can do is, you know, they're not gonna produce hormones on their own. They get on hormone replacement therapy. So it's kind of like an experimenter treating people with hormones. It's exactly what they're doing, only it's a physician saying, you you're not going through puberty, here's what we can do. We can give you this hormone. And so we I could look at whether if they took it if they started treatment earlier, were they more sex typical than if they took it later. And we found some effects. There's smaller effects and so sort of less exciting because they seem to be there, but they're not very big effects on cognition and some aspects of sexual behavior that sexual psychology that that earlier exposure seems to relate to ⁓ to more sort of sex typical psychology. But that also indicates then that hormones are having an effect across the, you know, the time window surrounding puberty. And, you know, it also makes like logical sense that that would be true because we know that the brain has sex hormone receptors all over it. And that, you know, we we also know that there are some psychological changes around puberty, that some of these things it makes sense to to have them be driven by hormones at puberty. Caterpillars are a good example. Like you know, for butterflies and moths, they have a part of their life that is just for like growing it's just eating. They just their their first part of their life is just I'm I just eat. You know, that's what a cater caterpillar does. Their whole point in life is consumption of nutrition, resources, calories, so that later they can develop and then have babies, you know, so they develop then they go through metamorphosis and and become a butterfly or a moth. And that's the sexual part. That's the reproductive part of their life. And puberty for us is kind of the same thing that like when you're a kid, you know, yes, you're socially developing, you're learning, you're interacting, but it's a lot about sort of your your body development. ⁓ you know, just sort of getting the resources, getting the calories, grow larger. And then you go through puberty and that's sexual development to then be enter the reproductive phase of your life, right? And during that time, then people get more interested in sex and in mates and in social things related to social status that could affect your meeting opportunities and things like that. So we know that psychology and behavior also change in a way that's totally consistent with hormones having an influence on these important things that change your sort of life phase from being the developmental to the reproductive. speaker-0: Yeah, one of the things that I think is so ⁓ interesting, and it's also, I mean, it's it's sad, but it ⁓ again just goes to show like how much more complex psychologically we become as we go through the pubertal transition is what happens with ⁓ depression and anxiety risk, especially in girls and women, is that you'll see that boys and girls are kind of on the same page, and then all of a sudden it's like. Age 12 hits, which is the average age of pubertal development in girls. And it's like all of a sudden, it's just like girls just rise, rise, rise, rise, rise. Boys go up too, but not to the same extent as girls. And then all of a sudden the menopausal transition, and then the sexes start to converge again. And it goes to show that our like our sex hormones during this, during these years when ⁓ you know, so after our our sex hormones ⁓ have this these, you know, create these developmental changes during the pubertal transition. That make us more sensitive to social information, more sort of attuned to social comparisons. And like you notice, like you noted, like things like interest in status seeking and mate seeking, and then also becoming more self-critical because you're trying to attract a partner. And so you're thinking about yourself and then yourself relative to other people and how do you stack up and all these different things. And then it creates this vulnerability for mental health-related conditions that doesn't resolve until menopause. speaker-1: Yeah, I mean that's a an important reason to study some of these things. I mean, we can study them because we're just sort of intellectually interested in like how people, you know, become the way that they are. But then, you know, a lot of this research has real applications for ⁓ for our health, including our mental health. Almost every disease has some sex difference in its expression, severity, frequency, and some much more than others. And so understanding how the sexes differentiate, like what causes that to happen, then can lead us to understand the factors that play a role. And, you know, anxiety and depression are higher in females. It's some ev there's some evidence that, well, maybe males are really experiencing depression, but it's just coming out in a different way, like, you know, aggression or something. Males are more susceptible to, you know, substance abuse disorders and ⁓ also sort of risk taking behavior. I mean, they get themselves killed ⁓ at a much higher rate and lots of other diseases too, right? I mean in general males are more susceptible to Yeah, right. Yeah, and males are more sort of susceptible to ⁓ to most diseases, but not all. And as you pointed out, some of these things seem to have a life course that suggest and and some research also suggests that circulating hormones play a role. That if if the disease, if the disorder of whatever we want to call it, gets worse when sex hormone levels are high and then it gets better when they get lower, then that suggests that it's an activational effect. That and as you ⁓ you know mentioned before, activational effects of hormones are ones that exist when the hormones are in the bloodstream and then they go away as the hormone is metabolized out of the bloodstream and and activational effects are ones it's a more permanent effect on the brain and behavior. And so you know that suggests that that it's actually circulating hormones that play a role ⁓ in some of these traits. And we've got some data on that, but I have they haven't yet been analyzed, but ⁓ I I've been interested in studying exactly those sorts of questions like how do steroid hormones influence our our mental health? speaker-0: Well, we'll have to have you back on to talk about that once you have those data analyzed. Cause I know there's a lot of people who'd be really interested in ⁓ learning more about that because I I think that for a lot of different mental health related conditions that there that you do see these hormonal effects. And so it'll be really interesting to learn more about that and get your hot take. On what's going on there. Before we leave puberty, and then I want to talk about these ⁓ activational effects of hormones and sort of like some of the cool research that you've done looking at shifts across women's menstrual cycles, which we started to talk a little bit about. I want to circle back to a little a few of those issues. I want to talk about pubertal effects of testosterone on masculinizing male traits and what is known as in the evolutionary world as like the good genes hypothesis. Right. And so there's this idea that exists in the world of evolutionary biology and evolutionary psychology that, you know, masculinized male voices and faces, right, are the result of exposure to relatively high levels of androgens during puberty. Right. And it is hypothesized that these kinds of qualities are markers of like good immune genes. Right. So essentially that you have fewer mutations in your immune system than other folks do. Because ⁓ there's and there's a good research evidence that suggests that ⁓ you know, it androgens tend to trade off against immune function. And so what we tend to see, for example, is like during the summer months, androgens are higher than they are in the winter and immunological ex ⁓ gene expression is lower. And and it seems like there's generally a trade-off between these things. And we actually, my lab published a paper ⁓ like three or four years ago. ⁓ with Jeff Gasson as the lead author, he was one my former ⁓ PhD students, looking at the relationship between testosterone and immune function. And lo and behold, they are negatively correlated. And so the hypothesis is that boys who during puberty, like only boys whose bodies are so well put together and whose immune systems are so well functioning, it's only these boys that will release relative, like super high levels of androgen during development or during puberty. Because they're the ones who can afford to do it. Right. So if you can afford to have your immune system suppressed to release high levels of androgen, that suggests that your immune genes are super smart and thrifty and can like take care of business even when they have their hands tied behind their back. Right. And so there's there's this idea out there. We call this a good genes hypothesis. ⁓ and this is like the immunosuppressive hypothesis of testosterone or something to that effect. And so, so is there truth to this? So it's like, do so one. Do things like masculinize male ⁓ voices, faces, ⁓ behaviors, so just like, you know, social dominance orientation and that sort of thing, are these things related to testosterone? Right. And does this do women like this? Like, is this, does this seem to be attractive to women? as has been proposed by people who argue that women should like these things because essentially they're trying to choose partners who have the best immune genes on the market. speaker-1: You might have to remind me of ⁓ parts of those questions. Okay, so sometimes this is called the immunocompetence handicap hypothesis. And if we go way back, to start at sort of the beginning of this question, it was evolutionary biologists weren't even thinking about people. They were just thinking about mate choice in non-human animals. And let's say you've got a species where males all congregate in an area and they advertise to females. They're doing strutting displays and making calls and things like that. And females are clearly choosing certain males. And you know, they're like they have a preference and certain males get a lot more mating opportunities. And you can manipulate things in the in the lab and show, ⁓ sure enough, females prefer this male's, you know, typical trait. And evolutionary biologists are like, why though? Because they're what are they getting? Like that's not they're just copulating with the male and then leaving. It's not like he's a good dad or anything like that. They're just having sex. And so the idea is, well, it must they must be getting good genes because Every in every sexually reproducing organism, half the DNA, so in some species have weird genetics, but all but lots of them, including all mammals and all humans, half the DNA of every of one of your offspring comes from somebody else. So it completely makes sense that that selection would shape the mating psychology of sexually reproducing organisms to prefer mates with good quality genes, right? So that was the hypothesis that okay, maybe females are preferring males with good genes so that their offspring are healthier and have those genes themselves. And then evolutionary biologists were like, yeah, but how does this make sense? Because if females are converging in their choices and they're preferring the same males generation after generation, males who have traits, bright coloration, extravagant ornamentation, you know, color ⁓ displays, energetic displays, ⁓ that under that indicate underlying they're correlated with underlying good genes, then those are the males, the good genes males that have the offspring. Those good genes get passed on. The males with lower quality genes don't have those traits, so they don't mate, so they don't have offspring. So pretty soon the whole population should have whatever those good genes were, and the and the the bad genes are the are selected out. And so then why are females still paying this cost of choosing some males over others and not just mating with whatever male was available if there's no benefit? So then. evolutionary biologists got to thinking, well, maybe there's always an injection of new genetic variability in the population because what constitutes good genes is constantly being redefined by co-evolution between these organisms like birds or mammals and their parasites and pathogens. That those parasites and pathogens are evolving very rapidly. They're the things that make us sick. They're the the things that we need an immune system for. That those evolve very fast because they're little microscopic, have or or tiny, depending on what kind of parasite we're talking about, have very short generation times, and so they evolve very rapidly. And maybe that's what's going on, is that females are preferring genes that that give you a strong immune system that make you able to survive and reproduce in an environment with lots of parasites and pathogens. And that could maintain that genetic variability that constitutes the basis for mate choice. What are good genes now, like allele A, gene A is being favored by selection because it gives you immun Competence now, but those parasites and pathogens are evolving, and now in the next generation, B is preferred. And so you're always just preferring whatever makes you healthy, and that those genes are contributing to the expression of these traits. So that's way that's the the intro to the thing. And then in the early 90s, some researchers said, and here's a mechanism: testosterone. There's some evidence that testosterone suppresses the immune system. And so maybe. You can only afford to produce these extravagant traits, these male traits, if you have a well-functioning immune system, then you can afford to suppress your your immune system to produce these traits. So it's like an honest advertisement of your underlying immunocompetence, especially your genes that would produce a strong immune system. And, you know, there have been enough studies in mammals now that it does seem like testosterone and other androgens do suppress. some components of immune function. The the the actually the causality goes both ways. That when you're sick, that also suppresses hormone production, you know, sex hormone production, and sex hormone production suppresses immune function. So there's some reason to think that's true. And that's all the the background to it. But then you ask me like what do I think? I don't know. The evidence is not great. speaker-0: So what are some of the qualities that are related in humans? Like what are some of the cause we don't croak and and have feathers, but we do wave sort of, you know, like there's facial masculinization, there's vocal masculinization. Are those things yeah, body behavioral? Yeah. Like are those things related to testosterone levels in puberty? speaker-1: They absolutely are. I mean, so you don't you don't develop, you know, facial hair or the deep voice until I mean the the mechanism is well known. Like there the vocal folds, that's a trait that I've studied as sort of a you know, a model trait for understanding like a lot of things related to mating competition and and sexual differentiation because it's shows a huge sex difference. Like there's in one one study I we min we measured over six hundred men and women ⁓ their voice pitch and there was no overlap. The highest pitch guy's average speaking fundamental frequency of voice pitch was lower than the lowest pitched woman's in o you know. speaker-0: That's really interesting. That's very rare. So just like for li like that is very rare. speaker-1: Yeah, like height we can recognize there's a sex difference. Yeah. So height, the standard there's like a a two standard deviation sex difference in height. So most men are taller than most women, but we all know of lots of cases of really tall women, really short guys, you know. ⁓ but voice pitch is like there's the sex difference is like five or six standard deviations, so that you can measure hundreds of people and see no overlap. But anyway, okay. We know how this happens. Testosterone at puberty goes all over the body doing its things. It makes facial hair grow, it makes mu you know, more lean muscle mass. So and The vocal folds are skeletal muscle, the vocalis thyroidinoid muscles, they're like biceps and triceps and whatever, they do the same thing. Testosterone makes the vocal folds grow longer and thicker. And then we push air past those during phonation, they vibrate more slowly, just like if you ever looked inside of a piano. What are the low notes? They're the long, thick strings. And the and the shorter, thinner ones are the high notes, right? So because they vibrate faster, and we perceive that as higher pitch and lower vibrational frequency, lower pitch. So anyway. All those things are driven by by a testosterone, especially at puberty. Now, do women prefer them? ⁓ kind of. I would say that the typical result you get across studies is that women don't like feminine. So they w they wouldn't like a really high pitched voice they don't like. But they pre they prefer around the male average, but for some traits a little bit more than the male average, but it's a curvilinear. Like if you get really masculine, it's like, ooh. You know, something it's either gross or it's scary or it's just you know. ⁓ of course there's a ton of variation. ⁓ you know, I would say that y females, there's less convergence in their preferences than there is for males. There's tons of variation. But if you look at on average across females, they prefer around the male average but a little bit more, like a little bit taller than the male average, maybe a voice pitch that's a little bit lower than the male average, but they don't care that much. And for facial hair, that's gonna be weird. Most studies ⁓ that manipulate facial hair find that Women prefer the not a full beard. And the studies that have looked at five o'clock shadows say they prefer a little bit of stubble, but not but I but these things are gonna vary especially facial hair across cultures and over time. And between women. Like my mom and her t two sisters demand facial hair and their husbands. they're just all the same in that regard. I think that these traits were shaped by female preferences over our evolution, but mainly shaped by other selective pressures. They don't look like sexual ornaments, like some species males have a trait that's like it's clearly an ornament, like bright tail feathers that females are like scrutinize these to say, mmm, good, but not good enough. Humans like females have preferences for males, and that's ⁓ almost certainly been an important factor in shaping the development of the traits, but some of them look like they function way better For males to intimidate their c male competitors, you know, like deep voices make guys seem big, scary, and like better fighters. Facial hair makes you seem older and s and more dominant, things like that. And things like musculature, I mean, they actually help win fights, which, you know, in our ancestors was probably quite relevant. speaker-0: That's so interesting. So so you're saying that some of these traits that ⁓ are essentially make men and women different from one another, that men have like the deep voice or whatever, may actually serve more of a function in terms of like just essentially ascending the status hierarchy and avoiding getting your ass kicked, like so sort of ⁓ intimidating other men rather than direct mate attraction and that ultimately they're kind of all funneling into the female preference for status, right? And power. speaker-1: It'll work both ways. So just to give you an example, when I as a as a grad student manipulated voice pitch, actually I manipulate manipulated pitch and and timbre, like two different acoustic parameters, but both are highly sexually differentiated, make a voice seem deep and male typical or high and female typical. And I manipulated those and I looked at, you know, do women prefer the the more masculinized voice? And and I looked at it seemed to matter whether they were rating for sexual attractiveness or a long-term relationship. And in that data set, whether they were in the fertile part of the cycle or not, and I found that sh they did. They preferred, you know, a more masculine voice, but it was a small effect. And I also did the same manipulation, but I had guys rate like, how good of a fighter would this guy be? And the effect was fifteen times as great on how scary a guy seemed or how good of a fighter he was, than whether women, you know, it affected attractiveness to women. And so that's actually what got me thinking, because I was I was reading the evolutionary psychology literature at the time. which seemed to be like, you know, male tra males must be like all these other species that bird species really that people had studied. And, you know, that these are ornaments, you know, I would have thought, ⁓ beards must be sexual ornaments to attract females and so on. And so I went in thinking that voices were probably like that too. Like it's an ornament to attract females. And I got this result. I was like, whoa. I mean, if we think about, you know, form follows function, what does it look like it evolved for? It looks like it it's way better at intimidating other males than it is at attracting females. And so it's not that both weren't important, but you know, looking at male traits, they they look like they're like you said, you know, intimidating other guys, ascend ascend the status hierarchy. Some of that can work through while women prefer a guy's high in status. And some of it can work through just males limiting females' ability to choose by excluding other males by intimidation. Like I'm talking to her and you're not gonna at a bar or at a party. And certain guys, you're not gonna try to interfere with that. And so it can be just like guys having an influence on other guys that gives them the opportunity to to attract a female or whatever that other guys won't try to interfere with. speaker-0: That's so interesting because I've I've you know, aggression kind of works the same way where it's like, you know, women don't generally find men, like aggressive men more attractive, right? It's like not something that women like, wow, like that's great. But as Doug Kenrick, ⁓ our mutual friend once said, like women don't want to see the fight, but they do care about who won. speaker-1: That's that's right. Yeah, the aggressive the aggression itself. And and you know, sometimes ⁓ women are okay with a guy being aggressive if he's defending her, you know. Right. ⁓ that that's okay. We did one study where we with ⁓ with Dave Geary at University of Missouri, where we looked at the effect of different vignettes. ⁓ so we showed women pictures of different things and we wanted to see if we could affect their masculinity preferences. And so we manipulated voice masculinity, we manipulated facial masculinity. And it was actually back to your point about immunocompetence handicap hypothesis, we manipulated these things. And then we also showed women different kinds of images. One was like meant to evoke like high parasite pathogen environment. Like, you know, it was like, I don't know, dirty toilets or something. I don't know, something that would like exposure to pathogens that that pr prior research would indicate, ⁓ women should prefer really masculine traits because it's an indicator of good genes that'll make my offspring healthy. in environments with high pathogen loads. We found no effect there, by the way. And we did a a couple of other manipulations. And the one that had an effect, I think one was like males fighting each other or something. That basically across trials you see women perform more masculine things and v faces and voices. And I think it's just that they maybe subconsciously like learn what's manipulated. And so then they attune to that more across trials. But there was one vignette where they did not increase their preference for masculinity. And it was male and female violence. That if if there was an image of a guy being aggressive, that yeah, w women did not show that pattern that they actually preferred a less masculine male. Which is another indicator that, you know, these masculine traits, what what do they evolve for? ⁓ they don't make guys seem like better they actually make guys seem more aggressive, really. You know, some of that can be functional if it's for protecting you. ⁓ but some of it can be yeah, harmful in a relationship too. So speaker-0: Right. Yeah. Yeah. I think that there's probably sort of a stabilizing selection, you know, where there's like it's like there's definitely selection against somebody who's gonna be a complete pushover and then also against, you know, the super aggressive Neanderthal and that we sort of converge somewhere in that middle point, especially given how important male caretaking has played to, you know, the survival of offspring in our species. Yeah. speaker-1: Yeah, s social status and and confidence are highly attractive, for sure. speaker-0: Yeah, yeah, exactly. But like a prison record and ⁓ and a felony speaker-1: They're into that. I mean they're like you know, have like fans that are like emailing ⁓ or mailing sending letters to to guys in prison. But anyway, that might be the fame of it. I don't know. Some guys are you know, if it's all over the news or something. I don't know. speaker-0: I wanna talk a little bit about your work on women's mating psychology and how it changes across the cycle as we sort of begin to wrap up our time here. Because we've done a lot of work in this area and it's an area and we talked a little bit about it, and we don't need to rehash the things we've already spoken about. But there's, you know, there's a lot of research in this area. And ⁓ and so for those of you who want just to reorient you to the earlier part of the conversation. ⁓ there's research, ⁓ people in neuroendocronology and and and the evolutionary sciences in particular have have hypothesized that women, when they're in the fertile point of the menstrual cycle, when estrogen levels are relatively high, progesterone levels are relatively low, that this should be related to both psychological and behavioral changes that would essentially help to promote successful conception. Right. So essentially during this time when sex can lead to conception that we should want more sex, have more sex, and ⁓ potentially be really zeroed in on qualities that are related to good genes and some of these other things. So that way you can have the healthiest offspring possible. Based on your research that you've done, and then also just your understanding of the literature as it's unfolded, because it's been a little bit of a saga, I think, in the in the last 30 years. ⁓ like what do you think is real? And what do you think is questionable when it comes to the effects of ovarian hormones on women's sexual psychology and mate preferences and so on? Yeah. speaker-1: And I I will say that my thinking on this has has evolved. You know, ⁓ that you know intended. Yeah, pun intended. That when I that's a that's an old one. But yeah, when I was a grad student looking at this stuff and found that result that, you know, women seem to prefer more masculine voices at the fertile time of the cycle. And then other studies that have looked at preferences for facial masculinity and that have been replicated by other labs and body and behavioral and stuff, it all seemed to converge. And, you know, I ten years ago I was teaching this stuff like it was the gospel truth, you know. I mean, any everything that I teach in my class, I I like preface with like the tension between data and theory and saying that like scientists never know anything for certain. Like we can be very, very confident in something, and then later on more data accumulate, and we're like, actually, probably not, you know? ⁓ and so you know, that's just the nature of you know good science is that we're gonna discover new things later that change our way of thinking about things. But of all the sort of effects in psychology that evolutionary psychology had led us to, I was confident in that one. Because of the number of studies across a number of domains and century domains, old faction, you know, s a sense of smell and vision and an audition that these things were just seeming to converge unlike women prefer more prefer more masculine traits during the fertile time of the cycle. I found it in my own data. And when you see it in your own data, you're like, it's real. You know, you it's easy to discount like something. Somebody else's lab, they had some kind of, you know, methodological issue, but you see it in your own data. And then some studies who were that were better designed were not that even ones that had found something earlier were not finding things later. And I still don't I'm still not confident. I'm still now I'm closer to fifty fifty. But we didn't see it in a well-designed study of our own and a well-designed study by our collaborators and and a paper on those things. So like preferences for masculine male traits changing over the cycle, I still think it's plausible. There's some evidence for it. I'm still looking. Like I said, we did a study that I that will make me a lot more confident one way or the other, w whether this is real, but it it makes sense that it would be true. But then other things, you said, well, you know, you the only time you can actually conceive is the late follicular. Like this, maybe it's a six day window. That's how people normally talk about it. I don't know how much of that is measurement error. Maybe it's a four day window, given how long sperm actually survive in the reproductive tract and things, but whatever. It's a s it's a window that conception is possible. Doesn't it make sense that psychology then would be more mating oriented during this phase? And then you spend your effort, your energy and time doing other things. You wouldn't do, you know, those other things during the rest of the cycle, maybe focus taking care of your kids or or eating, you know, something you don't like, it will help you taking a nap. Yeah. ⁓ other things that will you know that would have helped our female ancestors' reproductive success. And that is highly plausible, that there are ⁓ changes in what Jim Roney calls motivational priorities. That like what are the things that you most spend your time and energy doing? And do those vary across the cycle? And we've seen it in our data and I've seen it in other well-designed studies that there is more sexual interest during the fertile phase, during the late follicular phase, and it and it seems to relate to ovarian hormones. But it does make sense that there are some other things that would change along with that, other mo you know, motivational priorities. and speaker-0: Was it about preferences or was it about serious sexual attraction? speaker-1: ⁓ I know. Just that some of this this idea that women pr would prefer good genes males during the fertile part of the cycle, and males who putatively, you know, have traits that indicate underlying good genes, it sort of assumes that ancestral female mating was like I'll mate with males who are g in high in genetic quality during the fertile phase and other males outside of the fertile phase. And you know We don't have a mating system that's so much like that, you know, that like in chimpanzees, for example, I mean females are mating acros like once they're in the an estrus and their their genitals are swollen actually for longer than the fertile window. It's actually be starts before that and ends after the fertile window. But they're copulating during the fertile phase with the with the alpha male, the highest ranking male. And a lot of that has to do with some of it is female preferences, but some of it is just males. alpha status that he's able to bully his way into getting those highly fertile matings whereas the other males aren't. Females are mating with all the males in the group. And so there is that scope for like, you know, mating with certain males during this time of the cycle and other males outside of the fertile window and stuff. But human mating, you know, almost all human reproduction occurs within long term relationships. It's mostly monogamous relationships in, you know, most even in societies with polygyny. And if we if you're an anthropologist, you know that like polygyny is There are lots of societies that have polygynous meaning. Most of the little small scale societies that anthropologists study have polygynous meaning. speaker-0: Right. And just just a polygyny just for people who don't know, right? That's like where you have the ⁓ single man, multiple women. Right. speaker-1: Exactly. And but even in those societies, most marriages are monogamous. And so anyway, based on what we see and the way we know human mating works, yes, there's cheating. And that's that's the theory, is that women who have a long-term mate who's investing in them, during the fertile phase, they might have ideas about this other guy that I thought was pretty attractive and kinda was interested in, maybe more sexually attracted to than my lo my husband or long-term partner. more likely to cheat with this a attractive male who has good genes during the fertile part of the cycle. That's possible. There's a huge risk to cheating. You know, you could lose all the investment from the male that you had. You know, you were married, you had an you know, but that was the theory. And you know, the extent to which that really applied in our ancestry, I and the you know, the the role that it played, I'm I'm not sure about that. So, you know, I'm I'm not saying it's not it wasn't true, but just, you know, how important was it? I don't know. speaker-0: Yeah, well, given, you know, what you found with ⁓ estrogen and its role in sort of just like increasing women's atr like, what do you call androphily, just sort of like this like attraction toward men, right? So something that's male typical. I mean, it you could clearly see how like there is a relationship both organizationally and then sort of on a day-to-day basis, just like how your hormones influence you, is that estrogen essentially amplifies interest in males. Right. And that almost as a byproduct of this, although I I would assume it's also maintained by selection, because that's also going to just orient you toward men during a time when sex can lead to conception, that things that are sort of distinctly male might be more likely to kind of pluck the right strings when estrogen is high in the cycle. Where you might still appreciate those things, but maybe just not to the same degree when you're outside of that window, with with essentially estrogen orienting you toward maleness. Right. And then that means that when estrogen is rising toward the cycle, it's just like the maleness things are just even more enticing to the female brain. speaker-1: Yeah, and you're right. And and that's one of the reasons why I'm sort of you know holding out on maybe these maybe preferences really are changing across the cycle. And maybe one of the reasons why you see you tended to see an effect early on in those between subject studies is because so each female just tested once. It is whatever time in the cycle she happened to be in, is maybe s let's imagine that cycle phase really does matter. That whether you're in the fertile part, let's imagine that you're in the fertile part of the cycle, you tend to, it's a small effect, but you tend to prefer more masculine male traits or something like that. It's a within subject study, where you're testing the same woman over time. If you're using the same stimuli each time, we know there are effects of of trial of how many times you've done this. And it could be that preferences just sort of crystallize over time for a particular set of stimuli, which then makes your preferences less susceptible to changes in ovarian hormones. And so what we did in our most recent study was we tested women's preferences every day of the cycle, but we used entirely different stimuli every day. We I think it was maybe 15 male faces or something like that. But it was a random selection of male faces. And so then we can say we can measure it wasn't faces in this one, it was voices. We we can measure the masculinity of the voices and then say how how strongly did she prefer this trait and see if that changes Over the cycle and with estrogen and with progesterone, but using different stimuli, so there's no opportunity for a preferences for a particular set of stimuli to crystallize over time. That's why I said we have data from 70 women every day of the cycle with estrogen and progesterone measured from urine and prep yeah, preferences every day with different stimuli every day. If we find something cool, if we don't, then I'll be like, you know what, maybe there's something, but I'm not investing any more diet. speaker-0: I think about estrogen as sort of like ⁓ kind of like rather than like shifting, I think of it deepening the preference for masculinity. Does that make sense? Where it's like I I cause I don't know that it like leads you to prefer this to, you know, to this, right? It's just like this to this, right? And it's almost like deepening the like sort of attraction to that in interesting ways. And so I've I've got some ideas about ways to look at that and that we'll talk about off camera. speaker-1: You can actually measure preference a couple of ways. I mean, one of them is just what's the effect of the trait on how attractive you find it? And so, ⁓ then it's like you you prefer a different thing. And another one is how tightly constrained are your evaluations? So they're all around the same thing, you know, like the precision increases, you know? It's not that it's not that the bullseye moves, it's that all the all the ⁓ darts are f are around around the same place now. And so that's like what you're saying, the strengthening of the preference. speaker-0: Yeah, well, and so just to give you I'll I'll give you a little preview of what we'll talk about off camera, but we did a study and we were looking at the ability to detect tiny differences in facial masculinity based on cycle phase. And what we found was that women at high fertility were able to tell the difference between very low levels of difference of masculinity that we didn't find. Yeah, and I th and we didn't end up doing anything with it. And I wanna replicate that. And so this other idea I have is kind of going into that idea because ul ultimately what I think happens is that it's just like we become very we become more attuned to these really tiny differences and all of a sudden we start to notice them. And if there, you know, the masculinity or whatever is there that we just appreciate it more, that it's a noticing issue. And when you look at what happens in the brain with ⁓ estrogen, I mean it's very consistent with the idea that our sensory acuity is gonna be upregulated just because you get a lot more fi neural firing. And so, you know, there's a lot mechanistically that would is consistent with this as well, which is kind of why we thought that this might be what's going on. But I think that there's something to that. And it's also consistent with what you see, you know, like developmentally with estrogen, where it's like just sort of increases your interest in I love this word and I already forgot it. or no, what is Androphily. Yeah, androphily. Where it's essentially like speaker-1: And endophilia? speaker-0: Like makes you more attuned to these things that essentially make men and women different visually or vocally or, you know, acoustically, et cetera. And so I think that it just kind of increases our attunement and then kind of like our preference comes from that heightened attunement. Yeah. My hypothesis. speaker-1: No, I love it. And so you you know, then you might want to see how general that effect is. Like are there, you know, non human stimuli that you could see actually, yeah, there's better visual ⁓ acuity during the fur yeah. And actually, yeah, go ahead. speaker-0: Yeah, well, no, what I was gonna say, what's also really interesting to me, because like so I'm forty-eight, right? And so like my my hormone levels are much lower than what they were when I was a younger woman. And my son, who's sixteen now, his vo because I I don't think that I'm ⁓ you know, acoustically or visually attuned as much to testosterone as I used to, because you know, we we talk about like, you know, the visual cues of testosterone or acoustic cu cues to testosterone. But that also so that requires the cue, but it also requires the receiver to have the adaptations to be able to pick up on those things. And like my son's voice sometimes is so low, I can't even pick it up. Like I can't hear what he's saying because his voice is so low. And I'm like, I'm not acoustically attuned to you anymore. Like you're gonna have to try to try to find a way to, you know, articulate this a little bit louder because your low voice, like my old ears aren't picking up on it anymore. speaker-1: I get that a lot from my wife too, that you know, like ⁓ you're you're a low talker. So if you look at the the range of frequencies that humans are good at hearing, female voices are are closer to the, you know, optimal ⁓ in terms of what we can hear. speaker-0: Right. Yeah. It's it's so funny to think about ⁓ because you know, one of the things when we're talking about the way that sex hormones change. And one thing that's like occurred to me the other day, I was reading a paper about sex differences, and it occurred to me that sex differences are gonna be at their apex during pr peak reproductive years and then start to really decrease over time. And, you know, I just thought that was so fascinating because it hadn't occurred to me before, but of course it's true, right? That men and women are gonna be maximally different from one another during peak reproductive years, and then as we get older. We all look like our Aunt Mildred, you know. speaker-1: Yeah, yeah. W once you get past, you know, eighty it's like they all look the same. speaker-0: They all like the same. It's yeah, it's just so interesting. And I was like, God I know, but it's also like it's trying as I'm entering that age where I'm like looking increasingly like more like my dad. Yeah. And then I was you know, I'm just like, God, you know, this is just where this is just where where I'm at with, you know, with life folks. speaker-1: That's so offensive. I I saw something posted recently about when it is when when is it okay to stop caring about, you know, how attractive you're like, Can you just relax now? You know? speaker-0: Yeah, exactly. It's like, come on. That's so funny. So just ⁓ to close out, I'm just curious about like, you know, what is one thing? So you've done all of this work on hormones and you've studied hormones in women, you've studied hormones in men, you've studied developmental hormones, you've studied adult hormones. Like what is I wanna know what is like one thing that you know, for example, about men or women that that you just think everybody like is like the most interesting, juicy thing that most people don't know about. Or is it could even be something that we talked about that people don't appreciate. Like what what is like one of the most important lessons that you've learned in the work that you've done? I mean speaker-1: I think the big the big picture is that some of the most sexually differentiated psychological and behavioral traits are the ones that are probably the most strongly tied to early sex hormone exposure. And so, you know, we talked about sexual orientation and there's a sex difference in who people are attracted to. There's also within sex variation. Some of that within sex variation is probably caused by differences in sex hormone exposure, but other other of that variation we really don't know. You know, there's not good evidence that ⁓ gay men are gay because they had like lower androgen exposure. If they had general lower androgen exposure, then their genitals would be like less male typical and they're not. So, you know, it's possible that it was localized in the brain, or that there were some parts of the brain that were more or less sensitive, or that there's a a little peak during in in production or valley in production or something. It could be it could be related to estrogens. But probably the sex difference is driven. Like the reason why. Males tend to be attracted to females is because of androgen exposure. And the reason why females don't is because of low lower androgen exposure. And then some of their attraction to males, their androphilia, as we've said. So gynephilia, attraction to females, androphilia, attraction to males. Some of that could be due to estrogen exposure. But I think that that's kind of an interesting and important lesson to pull out is that. You know, goanyl steroid hormone exposure seems to be important in human brain sexual differentiation and behavior and psychology. And one of the areas that that's most evident is in who we're attracted to later in life. But there are other things as well, but that one is such a su you know, such a pronounced sex difference. And there's so many different converging lines of evidence that suggest that's the case in a species ourselves where we can't do the same kinds of experiments that we can in rodents or something, and we can actually demonstrate experimentally. ⁓ There are probably other things that I'm gonna think of as soon as we get off it. I'm like, ⁓ I should have said that really cool thing or that important thing. But this isn't really hormone related. But I think one of the things that has come out of my research on sort of mate choice and mating competition and things like that on voice that I've thought this is important for us to know about is manipulating, you know, I went into, you know, studying voice. I I was sitting on a bus in Pittsburgh thinking ⁓ gr grad school is going great. This is socially, ⁓ academically, I'm loving this time in my life, but I should probably write a dissertation. And I thought, okay, we'll start from the beginning. What what component should it have? ⁓ number one, like do real good in the world, like have some medical relevance or r y ⁓ importance to people's lives. Number two, and or be a new area that hasn't really been done yet. And so I was thinking about voices and thinking, you know, that's gotta be related to mating competition, it develops this big sex difference develops at sexual maturity, probably related to something like attracting females or intimidating guys or something. And one of the things that, you know, I've discovered as we've talked about, and other labs have as well, is that a low voice makes somebody seem dominant, intimidating, high status, and that may be completely irrelevant to our lives now. It may have been relevant to our ancestors when I think the evidence indicates that Our lives that's 10,000, 20,000, 50,000 years ago were a lot more violent and and there weren't police and there weren't laws and things like that. And so but they may be completely irrelevant. The the voice pitch of a person may be like low pitch may be negatively related to your leadership abilities and your competence and so on, right? But we act like it's actually re positively related to that. And so being aware of those biases, and you can imagine that then that would bias things so that like, ⁓ maybe guys tend to prefer a male voice than a female voice for certain kinds of high status positions. Well, we should be aware of that bias because it could be either completely irrelevant or actually maybe even go the opposite direction. And so studying that and making making people aware that you've got this bias that you should be paying attention to so that you don't make a bad decision or an unfair decision. I think that's been something that I, you know, has come out of this that I think actually can can help us, you know, and we make better decisions about hiring and and political candidates and things like that by just being aware of this unconscious bias that we speaker-0: Love that. Yeah. I think that's so I think that's so interesting. And I think that especially with the work that we do, we have a lot of colleagues who study things that are kind of unsavory, like unsavory aspects of human nature and how important it is to understand our the biases that we have or or the different types of ⁓ environmental contingencies that can lead people to do terrible things to understand them so that way you can overcome them. And it yeah, even with something like the biases that we have with ⁓ with voices. And on the other side of that, I actually just had this. conversation with my my low voiced son about this issue because he's ⁓ he's shy and so he's tall on top so he's like you he's like six three and tall and has this really deep voice and I was telling him because of these biases, I'm like, you're gonna have to overcome like being shy and and be, you know, sort of not have that, you know, resting bitch face when you're meeting people because people are gonna be into like it it's it's intimidating. Just your physical and the way you sound is intimidating. And so you have to Yeah, you have to be extra friendly to try to overcome that because people are going to have this tendency to think this and you don't want to be getting into fights, for example, that you know, with with people who think that you're trying to provoke them or whatever just by virtue of the way that you look and sound. Yeah. Right and and so understanding these things is important. The first speaker-1: Extra friendly. important step is just to be realistic about, you know, like st study things as they are and then use that useful information to then, you know, help improve our lives. You know, yeah. Not not view things the way we want them to be, but how they are, so then that we can actually we don't have ⁓ you know, the blind leading the blind as my my great grandfather wrote and ⁓ he was a an economist and he I I love this introduction to a book that he wrote. He said something about that, you know, that you even with the greatest goodwill in the world You know, if you don't first start with the science, then you know, we'll have only blind leaders of the blind or something. speaker-0: I love that. And I think that that's is so true, right? Understanding the truth then allows us to ⁓ be able to create the world that we want by using the laws of the those truths to try to set parameters that are going to lead to the behaviors that we want. Thank you so much. This was so much fun for me. I'm so sorry that I I ⁓ kept you on for as long as I did, but there was so much fun stuff to cover. I ⁓ wanted to make sure we were able to get to at least most of it. speaker-1: Yeah though. ⁓ really a pleasure. It was really fun talking. Okay. Yeah. speaker-0: All right, thank.