How Hormones Shape Sexual Orientation & Behavior | Dr. Marc Breedlove

The larger the number of older brothers that a male has, the higher the probability that he is gay. It's been seen over and over. I mean, it's it's really one of the u rock solid findings in human sexuality. So, the way to emphasize the difference is if a baby boy is born today, um if if he has no older brothers, his odds of being gay when he grows up is about 2%. Right? Pretty low. But if he had one older brother, his odds go up by a third. Okay, 2.6. And if he has two older brothers, they go up a third again. All right, now we're at 3.5. It turns out you got to have like a dozen older brothers just to have a 50/50 chance. Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stanford School of Medicine. My guest today is Dr. Mark Breedlove. Dr. Mark Breedlove is a professor of neuroscience at Michigan State University, and he is an expert in how hormones shape the developing brain, in particular, how they influence sexual orientation. As you'll learn today, the amount of testosterone that a fetus is exposed to while in the mother has a profound impact not only on the ratio of finger lengths, yes, you heard that right, but it also plays a meaningful role in sexual orientation. And in fact, there's a correlation there between finger length ratios and sexual orientation. Now, as wild as that may seem, that result has now been confirmed many times over in humans and in animals. And today, you'll understand why. You'll also learn that every time a woman is pregnant with a male, there's a biological trace of that which biases the likelihood that her next male offspring will be either heterosexual or homosexual. Now, I know this sounds really out there, but these are extremely solid biological findings for which the mechanisms are now understood for both animals and humans. It turns out that the hormones we are exposed to while we are in the womb shape not only the preference for whether somebody is attracted to males or females, but also an aversion to the opposite. Meaning there appears to be the formation of circuits for being attracted to one sex and not attracted to the other. Today you'll also learn how hormones impact the amount of rough and tumble or social play that kids engage in, the interplay between nature and nurture in shaping male versus female differences and sexual orientation. Dr. Breedlove is one of the long-standing pioneers in this field of how hormone shape brain development and psychology. We approach these questions through the lens of biology and statistics. So today's is not a political discussion. Instead, it's a discussion about what is known and what is still not known about this profound aspect of our species. Oh, and we also talk about gay rams. Yes, that's a real thing and it has important implications for everything we've mentioned thus far. By the end of today's episode, you'll surely think differently about the relationship between hormones and brain development, nature and nurture, and romantic partner choice. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Mark Breedlove. Dr. Mark Breedlove, welcome. Thank you. I'm delighted to be here. It's very exciting. Been 25 years since we stood in the same physical space. I know. How can that How can that be possible when I I feel like, you know, just saw you a few days ago, but then Well, you look great. Uh you look the same. So, uh we can talk longevity protocols at the end, but I'm trying to have a blonde look in my hair apparently. So, well, um, I've wanted to have you on this podcast since I launched it because you work on one of the most interesting things in the world, which is how and why people become who they are and how hormones play a role there, how genes play a role there. If you're willing, I'd like to jump from the high dive to the deep end first. Right off, let's talk about this fingerlength ratios sexual orientation study that you published and somehow I landed on that paper. That's not why I want to talk about it. I want to talk about because it's an incredibly interesting set of findings. Other people have done the sameish experiments and there's a whole context there about how hormones influence sexual orientation independent of behavior. We need to step back a little bit for the context. Uh, one thing that your listeners might not know is, you know, in the year 2000, there was still a lot of people who regarded um, same-sex orientation as a choice, a lifestyle choice. That was the the political combination of words that meant you could disapprove of people u because they were attracted to the same sex. Of course, I'm I'm at Berkeley. I I didn't have any truck with such notions at all. and and and I've always been convinced that sexual orientation is not a choice. And there's a exercise I do in class where I ask so I'm going to put you to it now. So remember the first time you had a crush, right? It might have been someone on TV, might have been someone a playground, etc. So think about it and I I want you to tell me about how old you were at the time in a moment. My guess is it was before puberty. Yeah, I was six. So and I hit puberty somewhere starting around 14. So, so it had nothing to do with puberty, right? It was this thing that happened and and I'll I'll share my experience. So, so I'm about six or seven. I couldn't have been more than seven. Uh, and Marilyn Monroe is on TV. I'm dating myself. And there's a closeup, you know, with that face and the and the mole, etc. And afterwards, I'm just so agitated. I don't, you know, I don't I and I know nothing about sex. I remember I had a hard time going to sleep. So, it was like something about this was really agitating me and I didn't choose to have that reaction and my guess is that whatever sex you had your first crush on, that's the one you were going to be attracted to the rest of your life. Yeah. It's been constant. Yeah. Well, so so so this idea that it was a choice that always just seems so absurd to me. On the other hand, um, even though, you know, I' I've been doing animal research with giving hormones early in life and seeing what it did to the nervous system, etc. Um, and every time I wrote an NIH grant, I said, well, you know, the effect of early hormones may be important for human behavior. But to tell you the truth, I never actually believe that, right? It was just I I just wanted to justify be because it seemed to me that we are so sensitive to social influences and we have this long stretch of time where we're, you know, our brains are still growing at a fetal rate of growth until at like 9 or 10 years of age and we're taking in so much information and and think of what a what a heterosexual world it is, right? I mean, all those Disney movies with Prince Charming and etc. Uh, and so it always seemed to me that that social learning would be more than enough to explain why 95% of people are straight. But that doesn't mean that was a choice. And it doesn't mean that they would even be aware of what the social influence was. So, so my example is I speak English. It's, you know, I'm hopelessly monilingual only language I speak. Well, I don't remember learning English and I certainly didn't choose to learn English, but I'm sure that it's English because of social influences, right? So that was where I stood on the question of sexual orientation until 1998 1999 when this fellow at University of Texas Dennis McFaden came out with a paper where it really made me think that prenatal testosterone might have an effect after all despite my expectations. And this was looking at oto acoustic emissions. Do you want you want to talk about those? These are uh people's ears making noise. Yeah. I mean, right now, in this studio, if if I if I shut up for a moment, your ears will continue to make little popping sounds that you're not aware of because having grown up with it, the the brain stops you from perceiving those long ago. Well, but if Dennis puts you in a soundproof room and puts a very sensitive microphone in your ear, he'll he'll hear these pops. And uh and I I won't get into the acoustics of why that's a good thing, right? It helps you to focus on the sounds you want to hear, but what Dennis knew is there's a sex difference in how many of these oto acoustic emissions are being made. Girls make more and it's present at birth. So Dennis comes out with a strange study. I mean, who would do such a thing where he he proposes, well, since the sex difference is present at birth, it might reflect prenatal testosterone. And so he measured the oto acoustic emissions in straight men and gay men and straight women and lesbians. And he reports that that the compared to straight women, the lesbians have fewer of these oto acoustic emissions than straight women. It's like, well, what what how would that happen? Um, how I I I couldn't think of any way to explain that except that, well, well, the lesbians might have been exposed to more prenatal testosterone than straight women before birth. And I don't know how to explain that except to say, well, maybe prenatal testosterone, maybe if you're exposed to that before birth, you're more likely to be attracted to women when you grow up. which oh well that might explain why 95% of men are attracted to women right because they're all exposed to prenatal testosterone. So this oddball study really gets me to thinking that maybe there's you know something to that but but I'll forget it. You know I'm still working with my rats and and paramiscus and siberian hamsters and stuff. I'm happily doing that. And then and I remember it so well and I I in 1999 I'm in my office at Berkeley and I read this paper that says there's a sex difference in the the ratio of fingers that's present in 9-year-old children. What? I've studied sex differences my whole adult life. How do I not know about this? And and it turns out that that if you if you measure the length of the second digit, the pointer finger, the pointer finger for those just listening. Yeah. Right. And the the length of the ring finger and you can you can do a simple ratio. Divide the length of the second digit by the fourth digit so-called 2d4 ratio. And a guy named John Manning was reporting that there's a sex difference there, that it's that that ratio tends to be smaller in men than in women, and that it's present in children. It's like, well, wait a minute. A sex difference in the body that's present before puberty. I know enough about sexual differentiation of the body, it's almost certainly due to prenatal testosterone. Forgive me for interrupting you, but people are probably looking at their hands right now. Yes. And um I just want to point out that these are averages but it's I think the 2D 4D thing for people that aren't familiar even though you explained it quite clearly can be a little confusing. Basically in men the finger lengths are more different than they are in women and there are some differences in uh in that statement according to sexual orientation that we'll get into. When you say uh the the in other words the typical heterosexual male pattern is that the pointer finger right is shorter than the ring finger. Right. Right. Whereas in women they tend to be more similar. Again these are averages and not to give it away but this is because people are looking at their fingers right now. Let me just say don't panic. Yeah. Right. We're we're going to walk you through this. You're going to be fine. And uh the difference between men and women is more pronounced on the right hand as I recall. That that's true too. Uh did I earn my authorship on the paper? Well, that and and the fact that you persuaded so many people to answer our weird questions and let us see rocks their hands. Yeah. Okay. So, please continue. But I know that the moment that came out, you know, hopefully there were no car accidents that people were driving. But but um uh these are averages. Um but that's the pattern that was observed. That's the pattern we Well, I'd never worked with humans before, but I'm sitting in the Bay Area. We have loads of gay people around. You you know, so it's like, well, let's I guess we could try to do this. And so, we started going out to street fairs. You were you were with us uh going out to street fairs and giving people asking people questions, asking them to fill out a questionnaire anonymously. And um and I remember it it was one of the organizers of one of the street fair, but I said, "Well, what should we do as an incentive to get people?" And they said, "Well, offer them scratcher tickets, lottery tickets, lottery tickets." So So we we asked people, "Will you please answer these very personal questions about about who you have sex with, who you want to have sex with, etc., and tell us everything about yourself anonymously, and we'll give you a $1 lottery scratcher people ticket." Andy, people will do anything for a $1 lottery scratcher ticket. I mean, it was just a which is weird because you do the math and they're they're worth like 27 cents, right? But but but people want them. Um and oh, and by the way, can we xerox your hands? And the last two questions we asked about handedness, but it was really just to to keep them from panicking. Um, so you know, and it, by the way, it was it was the least expensive experiment I'd ever done in my life because really, you know, compared to to any experiment with rat where step one, buy a rat for 20 bucks, right? So it's um so uh and it was an odd experience going in the 7-Eleven that morning and saying, "Please, I'd like 750 $1 lottery scratcher tickets." 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Again, that's r o r a.com/huberman. Well, as long as we're getting into the context, it's interesting because you said there there are a lot of uh gay people in the Bay Area, but it was very clear, as I recall when doing the study, that if we wanted to get a a large sample population of uh gay men, we would need to go to the Castro District in San Francisco. If we needed to get a large cohort of gay women, we need to go to the Solano Street Fair in Berkeley and and in Oakland. So there there was a there was a brand new Oakland gay festival that got started and yeah there Oakland is a wonderful place to find lesbians. So u one of one of the charms of the place. I thought the whole idea was kind of crazy actually. I mean I didn't think we'd come up with anything. And I insisted on measuring all the all the digits myself which I did twice. Boring as hell. I recall when we were on what was like third floor of Tolman Hall uh and you came running in. I was talking to my adviser, our good friend Zucker, one of the pioneers of circadian biology, discovered the super chaos nucleus with Bob Moore and others. But um and you came running in with with a ruler and you said, "Give me your hands." And you grabbed my hands and you measured them and you go, "Well, that's weird cuz it's like different on one hand than the other." And then you go, "Okay." and you took the notes and you measured his hands and he left and I thought, "What in the world is he doing?" It turns out that was the early origins of the study. Yeah. No, no. And uh anyway, so so I I measure these hands and um and I'm doing the the the math at the end of the day and lo and behold, I mean, I don't I don't see any difference in the digit ratios of gay and straight men, right? Okay. Between gay and straight men. Yeah. Yeah. I didn't see any difference there. which itself is interesting because it implies more or less equivalent amounts of prenatal testosterone exposure which I think is the case. Yes. And and right now just forgive me but um you know might some people might say well that's not surprising but in the 80s and 90s the Hollywood stereotype of gay men was that they were all very effeminite. Yep. Um since then there's been an evolution. In fact, I haven't seen it, but many people I know are very excited about this recent show about these two gay hockey players where so the whole context is these guys that are very masculine but are gay, right? So for people hearing this that are younger than 40, they're going to think, well, duh. But for people that grew up in my generation or your generation, it was a bit of a shocker to a lot of people. Um because depending on their level of exposure to the gay community, they may or may not have realized that not all gay men are uh affeminite. Exactly. No. And and and you know that idea that gay men might have been under androenized, there was always a part of it that was that always seems strange to me. So the big sex differences in human behavior are not in, you know, math skills and the verbal skill. Those are tiny, right? The really big sex differences in human behavior are in sexual attitudes. And the biggest sex difference is one sex is much more interested in multiple partners and younger partners than the other. Right? Everyone knows which sex that is. One uh sex is much more interested in casual sex than the other. Everyone knows one sex is much more interested in visual pornography than the other sex. Those are huge sex differences compared to any, you know, cognitive things. Uh, and in all those ways, gay men are totally masculine. So, how would that work that that, you know, they were underroenized and yet they have all these sex differences in in sexual attitude? I I think the difference between gay and straight men isn't in how much prenatal testosterone they got. I think it's in how their brains responded to the testosterone that they got. We'll we can talk about that some more um later. But back to the digit ratios, the lesbians had more masculine digit ratios than the straight women on average. And and as you say, that's been replicated by many different labs. Dave Puts at at Penn State and uh uh and Ashlin Swift Gant and I recently published a like the third meta analysis and I mean it's clear so many people have seen it. It's there. And and as with Dennis's oto acoustic emissions, I don't know how to explain that. Why why would lesbians have a more masculine digit ratio than straight women? Unless on average they were exposed to more women. And why would that matter? Unless being exposed to prenatal testosterone makes you more inclined to be attracted to women when you grow up. What's really weird about it, think about the time lag, your first crush, this sudden, this mysterious, for me, it was like a visitation, right? It's like, where'd this come from? Um, that happened six years after you were out of the womb, right? And so it's really strange to think that something that happened to you before you were born would have an influence on who you're going to be attracted to 6 10 years later uh when you have your first crush. Um so it it was uh and I can tell you that when we published that in 2000 um it it did quite cause quite an uproar. I heard from a lot of strangers that I'd never heard from before. Um and it was pretty interesting. Um, of of course there were several people wrote who I did had and told me that they were gay and they were very positive, very supportive. Um, but I got lots of, you know, emails from people saying, I know you're lying. You know, you're making this up to justify your gay lifestyle. Uh, you know, it's like, well, okay, except I don't happen to be gay. I mean, we we had a nice mix of orientations on the research team, but people were having a hard time with it. and to assure your your your listeners about if they're looking at their hands. If if they're a woman and they looked at the hands and they see that the index finger is quite a bit shorter than the ring finger and they're thinking I thought I was straight, etc. So, here's a joke that I tell which is if you want I'm going to teach you right now. I'm going to you gather a big sample of people and I'm going to teach you how to look at their hands, look at their right hand and guess their sexual orientation and you're going to be right 95% of the time. Okay? You want to learn how? So, so look at the right hand, pay really careful attention to whether the index finger is shorter than the ring finger and no matter what you see, guess straight and you will be right 95% of the time if it was a random sample of people. So um so the important thing to to get across is that while these average differences across group are theoretically important because they do indeed indicate that lesbians are more likely to have been exposed to slightly more testosterone before birth. That doesn't mean you can predict how much testosterone one person was exposed to from their digit ratio because other things influence the diger ratios. Fascinating study. I got made fun of quite a lot, but you know, I I I thought it was a blast. I mean, I mean, some of the more outrageous things that people have asked me about the study over the years, uh, were, and by the way, they all came from men, uh, were if I cut off my, uh, index finger, um, you know, will that raise my testosterone? Someone actually asked that. No, it's not reverse causality. I would have said, well, let's try it and see. again now most people I realize there are differences across the country and the world on this stance but I think most people would say yeah like okay there's a biological variable um associated with sexual orientation the fact that it's linked to prenatal testosterone is very interesting um and the question that then comes up is is there anything about behaviors associated with gay or straight men gay or straight women that change hormone levels independent of all this, right? Because um put differently, I think for a number of years, people were interested in whether or not gay men, as you pointed out, um would have higher or lower levels of testosterone. The the hypothesis was lower based on the affeminate stereotype. Turned out probably the opposite outcome. If if anything, you're right. Anyone that went to gyms in the 1980s and '90s uh would would also realize that that the low androgen argument was wrong. Although steroids become a problem in gyms too but you know it gets confounded but am I correct in remembering that this effect is also present in frogs or in mice the sex difference is present in mice that's D2D4 ratio difference I find that amazing well I I did too so so uh Wendy Brown and I did that first and you know I'd worked with mice and rats all my life but you know I'd never noticed that that that that this is that that the first digit is the shortest and that the third digit is the longest and that sometimes the second digit is longer than I you know it's like I mean it's you know evolution is real right that it happened uh and so yeah there's a sex difference there and a group looked at mice and did lots of genetic manipulations and it turns out that if you if you make the androceptor dysfunctional the sex difference goes away and they showed that in mice at least there's more androceptor in the the growing bones of the fourth digit than the second digit. And then they showed that um that that's why the fourth digit grows a little bit more than the second digit. Beautiful. So the me and we I should have said this earlier. Androgens are things like testosterone um DHT other other androgens. Um men and women both have them other animals have them. Um incredible. So let's talk about effects of testosterone when we're in the womb. Yeah, obviously it's having an organizing effect on the body plan. This D4 D2 ratio, right? What about in the brain? What is known about brain differences between men and women that identify as straight or um gay? Well, in in terms of prenatally, we don't know. But but the very famous study from Simon Ley, who was already a highly respected neuroscientist, lots of wonderful papers in development of the visual system. Um, Simon Ley got everyone's attention well before we did when he looked at a brain region in the hypothalamus, a specific region called the preoptic area or POA. And he looked there and compared uh the the size of the POA in the brains of gay men versus straight men. And he looked in the preoptic area because in rats there's a very prominent sexual difference or sex dimmorphism and a nucleus in in the rat brain in the preoptic area and the the nucleus got named the sexually dimorphic nucleus of the preoptic area of the SD and POA. And Simon knew there was a huge sex difference there in rats. And so he looked at the brains of gay and straight men and found a nucleus there that may or may not be the same as the SDPA, but is larger in men than in women. And what he found was that the the nucleus in gay men was smaller than in straight men and in fact not significantly different from the size of the nucleus in women. So it wasn't hyper male like the finger length ratio was. No. No. that in that case it indicated less either less and exposure or less of a response to the ant and antigen that was there. And uh Simon got even more of an uproar than I did. Uh published his paper in science and uh there were lots of people that were very skeptical including some neuroscientists but but eventually another group replicated it. You know that's what I was going to ask because I recall that the two major critiques of the paper um one was fair in my opinion. it was that some of the post-mortem samples were from people who had died of AIDS and so AIDS has some known neurodeenerative effects that may or may not have impacted the samples although hopefully they control for that and then as I recall he also got some push back because he is openly gay and people accused him of g uh agended I didn't say gendered I said agended science yeah that that that he was part of some conspiracy a gay agenda to to to to force Americans to regard people with samesex orientation as somehow okay. But a replication of the study from an independent group that presumably has no reason to be biased whatsoever. They were very skeptical of it. So that was William Bler who u eventually it it and there's an interesting aspect of it. It took him a long time to get a sample big enough because you know Simon it was such a horrible time in AIDS epidemic. there were so many young men dying um that uh Simon had no trouble finding enough brains to do the sample and and then as treatment got better the the death rates of HIV started going down u and so it took longer for William Ber to gather the samples but but eventually did and even though he was skeptical of it he saw it too. the the a the question about AIDS. I mean, Simon was able to address that in that um he also had some straight men who had AIDS and and he didn't, you know, they didn't they weren't significantly different from other straight men. Um but but and so it was widely interpreted as proof that sexual orientation is not a choice, that it's something that happens to you. And of course, I don't think sexual orientation is a choice. That's true. But Simon himself made it clear that he could only look at this nucleus in adults, right? You can only look, it's so tiny, the sexual dimmorphic nucleus, the preoptic area in humans. It's it's about the size of a grain of sand, right? So you got to have a microscope and you can only there there's no non-invasive way to look at it. And he pointed out that he didn't know if what what the order of causation was. He doesn't know if those men had been born with a smaller SD and POA and that's why they became gay or did something else cause them to become gay and also cause the SDNPA to get smaller and and for the public the idea that a nucleus might change its size in adulthood maybe that seems kind of like you know unlikely but as neuroscientists we know you know that adult brains are changing all the time. uh in in fact e even in animals Brad Cook showed that you know there's a nucleus the medial amydala um there's sex difference there but if you take away the testosterone in males sex difference goes away in just a matter of a few weeks so Simon's work on the sdnoa also known asina 3 I won't bother with why unfortunately I remember the full name because my brain it's the intercal nucleus of the anterior hypothalamus sub region I'm not saying that to impress saying when you get to be 50, which I can now say that you wonder why your hippocampus remembers certain things that are like basically totally useless to remember. I we waste so many synapses on on totally useless crap. But but that's not that's that's that's worth holding on to. You did well. So um but uh so so we don't know u it's a chicken and egg problem. We don't know if um if that happened um if if they were gay because they had a small line of three or do they have a small line of three because they're gay. So what what I liked about Dennis's oto acoustic emissions and is pretty good evidence that that happened well before they they had a sexual orientation. And and the other thing I always liked about it is that what well I mean you can't imagine there's a social influence on on dig and and and nobody nobody knew about this. So I wasn't worried that there were some little girls out there that looked at their hand to say gee that looks kind of masculine. Maybe I should be a lesbian, right? Because nobody knew this until your paper was published. Yes. Yeah. I mean, as I recall, there w there was some like schoolyard stuff of kids looking at each other's hands and trying to decide who was gay and who was straight. And you know, every once in a while to this day on on the internet, I'll look at and there'll be a little ad over there other claiming to to tell me something about my personality based on the on on on digit ratio length and it's just like, you know, please uh yeah, there's nothing to it don't waste your money, gang. And there's an aspect of this this this fact that that the group differences were there, but you can't tell about differences between individuals that that I think is the hardest thing for scientists to communicate to the public at large. You you have a really good way of explaining this to people because and it's an important lesson just in reading statistics and and making sense of data that um I'd love for you to give an example of how this plays out perhaps in a separate example. psychologist they like to talk about how a way of measuring how big a difference is between two groups. So this difference in digit ratios between men and women it's it's a relatively small difference. It's like well we measure it in terms of how many standard deviations apart are the two means of the populations the two averages the two averages. And uh to give an example of that everyone knows about the sex difference in human height right among adults. So that's a huge sex difference. It's one where we're all aware of it. And if if nobody had told us it was such a thing, we'd notice it after a while, right? And that that's because those two averages and those two populations are about two standard deviations apart. The standard deviation being a measure of how much variability there is in something. So that's a huge sex difference. And to give you an idea of what that means, if I had you grab a a sample of a thousand people and I'm going to tell you one thing about each one of them, and that's their height. That's all. And now I give you the job. You've got to guess what sex they are. And I can tell you what you want to do to to maximize your hit rate. Everyone who is 5' 5 and a half, you're going to say those are men. And if they're less than that, you're going to say they're women. and you'll be right about 80% of the time, which means you'll be wrong almost 20% of the time, right? And so everyone you you can you can see that that there's some predictive power there, but not it's far from perfect. Well, this sex difference in digit ratios is half a standard deviation, so a quarter that. And so that means there's much more overlap. and that and and we know that other things influence digit ratios too, not just prenatal testosterone. And so, uh, this is why there's no predictive value. I mean, so anyone who looked at their hand while we were talking about this and got worried, um, I don't know anything about your particular prenatal testosterone level, no matter what your digit ratio is. What about bisexuality? People who identify as attracted to both men and women. And maybe we ask about first bisexual women, then bisexual men. Is there a pattern in digit ratios that leads anywhere? I mean, in those days, we didn't have enough people that identified as bisexual to to have a reasonable sample. And it's interesting, and that's something that's changed, right? I mean, if you do surveys now, especially for among younger people, there are more people who report that they are bisexual than there were then. So, so I I don't really have anything to say about them. The one thing I will say is I'm sure that even among lesbians, there's more than one pathway, more than one developmental pathway to to to become a lesbian or to become a gay man, right? I I don't think there's just one thing. That's not how human behavior, but you do think it's based on the data that it's biological. Based on that data, I think testosterone has a say, right? That it not doesn't mean it's the whole package. Prenatal testosterone. Prenatal testosterone. And the reason I asked that is I mean there are conditions that are not uncommon where um someone has a particularly stressful long phase of development where there's every reason to believe that their androgens are impacted negatively. Yes. There's also every reason to believe that there are stretches of development where androgens are increased. Like we know that people who do a sort of a a contact sport um or engage in anything that requires like deliberate aggression I realize that real martial artist no competitive aggression know how to you know sort of um gate their levels of aggression so that they're not they're not like in in a fury right um like but we know that certain types of activities competition etc. I mean, there's no question that those can increase androgen. So, you can imagine there's some plasticity postnatally and that could be before puberty. It could be during puberty and and so that's testosterone there. the body as you you said you said something that even as a developmental neurobiologist I don't think I'd ever um heard uh stated so clearly and it's so important that that the the rate of brain development from birth until age 12 is at least as fast as it was before we're born. Yeah. That I mean the the way to really bring that home is to compare human brain growth and chimpanzeee brain growth. So up until birth, the rate at which the brain size increases compared to body size is about the same in humans and chimps. And shortly after birth, the chimpanzeee brain stops growing as fast and eventually asmmptotes right away. The human brain continues that feverish fetal rate of growth until at least six years of age, maybe out there to 10 years of age. So, uh, people have pointed out that in in a real sense, human beings, children are fetuses that are outside learning a whole bunch of stuff from other people. That's the real distinctiveness of our species is, you know, we have this protracted childhood and really intense social learning and, as you say, a fetal rate of growth even though we're not in the fetus anymore. So I guess for me the the idea that behavior exposure to things uh you know and I don't want to get into veilance of negative positive but sure pesticides but also you know schoolyard activities um if you have and we'll get to this you know uh five siblings and it's very competitive who gets how much pizza I've been you know I had one sibling so it was a little bit you know there was competition but it was different right you know these things change hormones hormones change the brain the brain, as you're explaining, can impact sexual preference. What's great about studying hormones and behavior, right, is is that sometimes you can control the hormone in animals at least. But the hard thing about hormones and behavior that people don't understand is that behavior can affect hormones, as you say. In in competitions, the winners afterwards are more likely to have higher testosterone and the losers will have lower. In elections, it's been shown that people whose candidate won the presidential election, they their testosterone levels went up a little bit and the people whose whose candidate lost went down a little. And so you'll always have this cycle where the the hormone alters the behavior and then the behavior alters the hormone and and you always have to look for ways to try to pin down u the order of of of effects. Um and you know, not always easy. The only thing I know for sure is is that the brain remains plastic all of our lives. Well, that statement is a significant one because I I also believe that the brain remains plastic throughout our lives. It's always surprising to me that the hypothalamus remains plastic throughout our lives. And I think that's worth perhaps um double clicking on so to speak because you know the idea that you can learn another language and your neoortex changes um or you can learn to juggle and your you know your neoort your motor cortex changes your cerebellum changes okay like there's a lot of beautiful studies demonstrating that but when I think about the hypothalamus I think about it as something that's pretty hardwired by time puberty wraps up but the more I learn and the more data that get published, the more surprised I am. I saw a paper just the other day that um the neurons that control suppression of appetite, these palm C neurons in the arcuate nucleus, there's a population of them that are sort of undifferentiated that can become, let's just call it pro- hunger, and by expressing some a different peptide, neuropeptide Y, and that there's a lot of latestage plasticity. And this may explain why people who reach a certain level of obesity may actually find that they're hungrier despite not needing food. So it's fascinating to me how these deeper brain structures may actually remain plastic. I think both your statements are true. I I I think it's probably true that the neoortex is more plastic than the hypothalamus, but it's a matter of relativity. And so as you say, the one thing we know is that there's plenty plasticity there. The the other thing I noticed, so I I' I've gone to society for neuroscience meetings pretty regularly every year since 1977. And after a while, I noticed something. Every year when I went to the neuroscience meeting, the brain was more plastic than it was the year before, right? I mean, because there more and more of these demonstrations and it's like um I I you know, I think synapses can come and go just about anywhere. Um and so hardwired let let's let's say there's might be less plasticity in the hypothalamus surely. So um but that doesn't mean there's none. As many of you know, I've been taking AG1 for nearly 15 years now. I discovered it way back in 2012, long before I ever had a podcast, and I've been taking it every day since. The reason I started taking it, and the reason I still take it, is because AG1 is, to my knowledge, the highest quality and most comprehensive of the foundational nutritional supplements on the market. It combines vitamins, minerals, prebiotics, probiotics, and adaptogens into a single scoop that's easy to drink, and it tastes great. It's designed to support things like gut health, immune health, and overall energy. And it does so by helping to fill any gaps you might have in your daily nutrition. Now, of course, everyone should strive to eat nutritious whole foods. I certainly do that every day. But I'm often asked, if you could take just one supplement, what would that supplement be? And my answer is always AG1 because it has just been oh so critical to supporting all aspects of my physical health, mental health, and performance. I know this from my own experience with AG1, and I continually hear this from other people who use AG1 daily. If you would like to try AG1, you can go to drinkaga AG1.com/huberman to get a special offer. For a limited time, AG1 is giving away six free travel packs of AG1 and a bottle of vitamin D3 K2 with your subscription. Again, that's drink AG1 with the numeral one.com/huberman to get six free travel packs and a bottle of vitamin D3 K2 with your subscription. What are some of the other effects in human studies of behavior impacting hormones that come to mind for you? I mean, it's been a while since we've touched into this and we haven't done it much on this podcast. I mean, obviously competition, winners, losers. You explained the data there. Um, what are some other scenarios, just studies that that have been striking to you or that have stood out over the years? No, I think for testosterone, I think the big ones have been have have been competition, you know, between males. Um, and no, I don't, you know, I mean, there there's a stress response, but that's a whole other thing. What about sex behavior itself? In animals, at least, we know that that there's a relationship there that that in in males, in males of most species, let's take rats, uh, if you take away the testosterone, within a few weeks, they'll they'll stop mounting altogether. And if you give them testosterone, after a few weeks, they they start mounting again, right? So, we know that that um plasticity is is there and we know that it's driven by testosterone. But, uh in in animals where they're in charge of their own testosterone, we've known for a long time that if a male is exposed to the odors of a receptive female, that causes a spike in their testosterone. And so, uh that's kind of preparing them for maybe maybe some maybe I'll be lucky. Maybe there's something coming down the pike. Uh and so we know that that's a reciprocal relationship uh when the animal's in charge of the of the hormone. For the longest time, thanks to your textbooks, and by the way, folks, uh Mark has um authored some of the most important textbooks on hormones and behavior, developmental neurobiology. He's a he's a true scholar of the whole field. And so immensely grateful to him that those textbooks have formed the backbone of a lot of uh solo episodes of the podcast. So um you know the textbook version of male versus female sexual behavior has been a story about females having a circuit that goes from brain to body to control this thing they call lordosis the arching of the lower back the receptivity the willingness to mate and the males having a circuit that goes from brain to spinal cord to body um involving uh arousal erection mount counting, um, insertion, ejaculation. I mean, your lab and others has really parsed this, uh, right down to the the details. And yet, of course, people have sex that way, but also other ways. And so, for a lot of people who aren't familiar with hormones and neural circuits and behavior, the sort of strict context kind of is is still forms the framework, you know. I mean, I I've learned and I'm now fortunate that this podcast has been around more than five years, so I no longer have to tap dance around things, right? So, people will say, "Oh, well, you know, there's this lordosis behavior in the female. She's she's receptive um or not. Um he mounts, etc." And then there's gay men who have to have sex a certain way that mimics the female sex pattern of behavior. And so, people do this onetoone, right? And I think that it's understandable why they do that if they're not educated. But how should we make sense of these biological circuits that are in the textbooks that define stereotyped literally motor behavior? It's almost like saying like like females have sex this way with males, males have sex this way with females. But then the caveat is always like, oh, but in humans all that goes away and there's these like bonabos that are a little bit more like humans. So did we waste all our time um studying that stuff? I mean really and you're getting at exactly what every textbook author has to deal with, right? which is, you know, uh, as the old joke go, you you you you look where the light is, right? So, we know so much more about the circuits that are involved in the motor behaviors because they're relatively easy to trace and relatively easy to manipulate and relatively easy to to study. We know lots about the motor patterns in animals. We know a lot less about the motivational patterns in animals which in human sexual behavior is I mean in many ways that's the whole show you know that's that's really what's uh and and we don't really have good animal models of of libido right and this was brought home to me many years ago now I I was on a session of 60 Minutes the CBS news program and uh Leslie Stall was there in our lab. I mean, the producers had called me up and said, you know, can you show us a way that that early testosterone exposure changes behavior permanently. And I said, "Sure, I can do that. Give me some time." So, I went to the lab and castrated a bunch of rats on the day of birth. I know how to do that. I'm not proud of it, but I I know how to do that. Um, and they came three months later, and uh, so I I showed them those motor patterns you talk about. So, here's a typical female. I've given her hormones, estrogen, progesterone, so I know she's going to be receptive. And here's a male rat that I know has had lots of experience copulating. And uh Leslie immediately dubbed him Romeo. Okay. Well, this is Romeo. And she hates rats, by the way. So, she she was she was very brave. And so, I I drop a female on top of Romeo and he starts mounting and she shows the Lordosis posture. And it's all beautiful and easy. And we do that several. I said, "Now I'm I'm going to drop a male, a control male in." And Romeo, of course, you know, you don't know unless you try. He mounts several times and the male rat acts like nothing's going on. I mean, it's just a bored thing on Earth. And Romeo eventually gives up. Now I drop into the cage a a male rat who I castrated on the day of birth 90 days before and I've given him the same hormones I gave the female to make her receptive. Romeo hops on and sure enough a beautiful lordosis right that of the sort that the that the control male never showed. So here this pre this this neonataly castrated male is showing very female-like patterns and Miss Stall kept asking me would you say this is a gay rat and it's you know I'm sitting there and I'm definitely in a tough spot because I don't think my rats have an orientation. I mean we we just saw Romeo happily mount any rat I he threw in the cage because what do you know? You know try your luck. Um, and so, uh, you know, she asked me several and I I knew she wanted me to say that, but I said, "What I would say, I don't remember exactly what ended up in the final." What I would say is that this is a rat whose sexual behavior has been permanently changed because of something that happened to him a long time ago at the very beginning of development. And, and really, that's the best I can do in terms of any rat model of sexual orientation. I don't think my rats have a sexual orientation. If I give the female those hormones, she's going to show ordosis to whoever mounts her. And my male rat, he he will mount any rat he comes across just in case he gets a word ordosis out of them. Well, good on you for not um getting uh coralled into giving a particular answer. Uh I've recently joined CBS as a correspondent. If we have this conversation on 60 Minutes, I promise to not try and force an answer. Romeo is an interesting um case because I think for most people, including myself, um I thought that you were going to say that Romeo was willing to um try to mount a female if she was receptive, he would mate. If not, he wouldn't. Um but I was surprised that he would try to mount a male as well. That doesn't align, at least with my experience, of of male human behavior. Well, certainly not. That's right. This is the thing that's distinctive about humans is we're not actually that particular about what particular behaviors we engage in, what motor behaviors, and we're overwhelmingly interested in who our partner is. Right? That is an overriding concern that that I don't think my rats have. I think I think few animals do. Here's the you're the anthropologist from Mars and um and I tell you here's a person that 50% here's whoever's the sexiest man alive this year. People magazine or I don't know who that happens to be. Well, this is an interesting discussion alto together because there's this people have been lining up the images of these people and claiming that they're sort of like this eff like effeminite drift that takes us back to a time in the early 90s when there was this sort of revision about male male facial. We can get back to that. But yeah, yeah, it's not the point being that it's not fixed. Who? Yes. Yeah. Well, well, whoever, let's say it's George Clooney. So, uh, so here's someone that half the planet believes is an ideal sexual partner, right? But the other half of the planet finds him totally unacceptable, even if the behaviors they engaged in would be pretty much the same. And so, you know, in terms of positions and who's doing what to whose genitalia, etc. I mean for for for most people it it isn't that there has to be one particular act. I suppose there's some but for most people there maybe a variety of acts that they that they want to be engaged in with that other person and their overwhelming concern is the the gender of that other person or the sex of that other person. Um you know it's it's hard to have an animal model of that. I I actually do know of one example in sheep if you want to talk about this of all things. Yes. Oh, I I I I noticed it. So, um so, uh Chuck Rosselli out at Oregon, he's the one that studied this very carefully. I guess shepherds have known for ages, um that in any herd, there are some rams who will not mount a female ever and keep mounting other males. And of course, to maintain a shepherd, to maintain a herd, you don't need every male to reproduce. So, but in the old days, they got those males got sent off to solder, right? Well, um, hearing these rumors, uh, Chuck did these tests where he would put a bunch of females that are in stocks, so they can't move and they're all ready for mating. And he put a ram in with them. And most rams, of course, will mount the females. He he puts in these rams that that prefer males. If there's a variety of sheep's butts sticking at him out at him, uh he'll mount males, including sometimes, you know, having intermission through the anus and all the way to ejaculation and and he never mounts a female. In some cases, they'll have one of these I'm going to call them gay rams. I think I think they have an orientation. He'll put the gay ram where there's a dozen females and he might be in that paddic for 12 hours and never mount a single female. Highly unusual for male rams. And these are not typical ram there. It's like a small percentage of the population. And um and I don't know how to explain that. I mean, you would think that the that these gay rams that well, you know, an ejaculation is an ejaculation, right? An orgasm is an orgasm. I presume they have or you you would think that at some point that well there's nothing else to do in here. I'll mount one of these and they never do. And I don't know how you can explain that except that there's some aversive component that that that that rams do care about the sex of their partner and that and that for these gay rams um there's some aversive component to that. By the way, Chuck told me uh not too long ago, there's a company that has identified these gay rams and decided that instead of sending them off to slaughter, they're going to harvest their wool and sell them as and and make them into clothing. So, you you can buy you can buy um wool clothing that came from gay rams and and know that you saved them from the slaughterhouse. There's no response that's appropriate to to that statement. And apparently they apparently they they you know they they're out of stock. So it's it's been a big success. Actually I can think of about 50 different responses to that. None none of which are are appropriate or have any real conceptual uh importance. So I I I won't I won't say fascinating because rams while of course they have sociodnamics um presumably there isn't pressure uh independent of reproductive pressure to um to be a gay ram or a straight ram. And I I guess I I left off the kicker, which is uh Chuck eventually dissected the preoptic areas of these various rams. And he found a difference between the preoptic area of gay rams and and straight rams, a difference in how they process testosterone in in exactly that part of the brain, the preoptic area where Simon saw a difference between gay and straight men. So there may be something about the hypothalamus, the preoptic area, uh that has something to do with orientation if if we're talking about an organism as complicated enough to have an orientation, including sheep. This is a particularly um nice moment uh not just for this episode but for the entire podcast arc uh because there are these moments that come up every once in a while where a larger principle shows up in a new way that I think um is really important for people to understand. Across neuroscience we see this pushpull right a flexor muscle like the bicep when it flexes the tricep relaxes. When the tricep flexes, the the bicep relaxes these antagonistic relationships. You see this in the hunger circuit. I mentioned one earlier. Like hunger and feeling full are they're like a pushpull. They're like a seessaw. And um uh and you see this over and over and over again. It's it's a it's a very consistent theme of of brain function. And you said something that I was not aware of, but makes perfect sense. I just wasn't aware that there were, you know, data um at the level you described, which is clearly there's an a pettitive aspect to sex behavior. Heterosexual males wanting to have sex with females, heterosexual females wanting to have sex with males, and and so on. Every derivation there, there's a desire. In species where there's strong pheromone and odor determination and and receptivity stuff gets played out that way, it looks one way. In humans, it may have some of that, but it plays out different way. Receptivity is communicated differently, although odor may be very important in ways we don't quite fully understand. But this idea that there's an aversive aspect to it, right? I think this is important and it's something that I have not heard discussed before. And I think that sociologically it has relevance because I think that um there's so many different aspects to the notion that our species, humans, um come in gay and straight and perhaps bisexual varieties. We know that's true clearly. But there is this um not uncommon theme whereby many people I I'm only you know say many people, right? not all um that the concept of mating with same sex is aversive to them and that has shaped a lot of the the landscape around this and I'm I'm not trying to get political here. It's just I think it's it's worth acknowledging that that may be a real phenomenon, too. I'm not trying to justify mistreatment of anybody, but I think that we're never going to get where we want to go as a as a species um society until we really at least understand the biology and how to work with it. And so the idea that same-sex sex, right, um would be aversive as an idea to people, some people like, oh, they haven't been educated. Okay, perhaps, you know, but there may be a biological basis for that. I think the data is still out and I but I think it's to me at least it's pretty clear that for men at least for there's an asymmetry here that that that experiment where I said you know who wants to have sex with George Clooney half the population says sure the other half population never. If we reverse the experiment, what percentage want to have sex with Margot Roby? And yeah, half the population, the men would see her as a very desirable sexual um partner, but you know, the women too would many women would also would at least consider the idea of having sex with her. And and we know there are plenty of women who are straight in one part of their lives and later they fall in love with a woman and now they feel like they're they're gay. Right? So females, women are more plastic in terms of their sexual longings and sexual orientation than men are. I'll be a little more specific. I I think it's among males where sometimes for many males, not all, uh there's an aversive idea that that the idea of having sex with the same-sex partner is aversive. Now, of course, context matters, right? There's same sex happening in prisons all the time when, you know, if the conditions are are enough and and I don't know where that aversive component came from. It could be that our society maybe it's all socially inculcated, you know, again before we're aware of it at all. Um, but I I think there's also at least the possibility that there's a biological component to it. And I think that's what uh Chuck was getting at in that here's this difference in the brain. He he doesn't know when the difference happened uh in their pre-optic areas. Um, but it seems to correlate with this idea that maybe these gay rams um, no, they they they're not interested in having sex with her. They're, you know, only it's aversive to them. It's aversive. Yeah. There's no other way to I can't I don't know any other way to explain uh how they choose never to never once mount a female. Yeah. I feel like that the acknowledgement of a of an aversive pathway for sexual partner choice is as important as the acknowledgement of biological uh coralates of homosexuality. Yeah. Because if this sort of conversation is ever to advance past the sort of like okay what's okay to say now that we're willing to say now trust in science disappears. I really believe that. Now, of course, the problem is that people leverage fragments of what they hear in order to make arguments in in favor of whatever stance they have. And that that's the complication. That's why I like long form because no matter what gets pulled out, we can go back to the full conversation. And this makes you old-fashioned because this that's not the world. I mean, our world seems to be hurtling towards this. Yeah. I mean, world of snippets. People will notice that we have not used the word gender. We're talking about biological sex and sex, the act. And we're talking about male versus female partner choice. And we're talking about a desire for one or the other. And an aversion to one or the other. And I think the aversion piece is an important theme. So here's a hypothesis if I can come to a sbatical. I'm due for a sbatical at some point. It may be that in male humans that there's a pathway or a molecule that serves as an aversive to sex with other men circuit, peptides, neurons, etc. that suppresses um sexual desire and activates some level of disgust. Let me just say it bluntly. Might not be the same disgust that they would experience to something more aversive, but okay. And that in women there is no such pathway. There's either desire for women or desire for men. But as you said, you know, stati stat statistically women are more open on average to samesex a interactions. And it may be because there's no aversive signal or the aversive signal has a less robust circuit. to me that that would explain these differences that these sex differences and who people are willing to have sex with. Your hypothesis fits the data. I mean, it is true that in the like the early 90s, for instance, when the first gay characters were on television, like the real first real world, I'm really dating myself here, and subsequent characters started to dismantle some of the stereotypes that had been seen in like comedies in the 80s and things like that of the affeminite gay man, right? What you saw was indeed that heterosexual women, as far as we know, seem to be more like generally accepting of gay men before heterosexual men embrace that as as typical. That's my impression, too. I think I think it's pretty clear. Yeah. And then and then there's a societal shift and then it sort of becomes like, you know, uh like if you like I spend some time on X, formerly known as Twitter, right? And there's some um gay political uh accounts and um and you just kind of notice like it's just people are like comfortable with it. Men and women seem to be comfortable with that, right? I mean, of course, you don't see a lot of attacks now. That's very different than what you would have observe would have observed for instance in like the late 80s, early 90s, right? Anyway, I think these are important biological uh phenomenon. this notion of an aversive pathway. You could imagine where societal standards or community standards or household standards might, you know, amplify or reduce like the the the sort of expression of these things. I'm I'm sure they do. And and I'm sure, you know, cultures, you know, can amplify or uh reduce that component. Um the question is, you know, to what extent? I mean, and and I don't I don't think we know. One thing that we haven't talked about and it is a small percentage of people but it's something that um people think about um is this notion of sort of um neither here nor there kind of mixed sex right is there a biological coralate of that um a graduate student my year when you were my professor um Nikki Oipka Nola Oipka um who was already famous for dog training dogs for the beast master show. She's amazing. Um, and had very well- behaved dogs uh that she would bring everywhere with her. Studied a species of mole in Tilden Park that could transiate its testes into ovaries and back again. And I thought, well, that's like alien weird levels of stuff. But she would occasionally go over to UCSF when babies were born that were sort of back then they called them, no one uses this language now, pseudo hermaphrodite. What is the deal with exposure to prenatal androgens and neither clearly here nor there a genitalia? Yeah. So in most of those cases we're talking about congenital adrenal hyperplasia also known as cah. And the congenital means it's present at birth. And the adrenal hyperplasia is referring to the fact that the adrenal glands are slightly larger. And the reason they're slightly larger in this case is because these are individuals where the the the fetus itself is not able to make some of the adrenal steroids that are important for staying healthy. And so the brain detecting, hey, where's the where are the adrenal steroids that we need here? Drives the pituitary to tell the the adrenal gland, hey, we need more steroids. The adrenal gland gets the message. It hypertrophies, but the machinery isn't there to make those steroids. And so instead, the adrenal gland makes testosterone and other androgens. And actually, this can happen in either XX or XY individuals. And in XY individuals, u people might not notice, but in XX individuals, what that means is that prenatally her genitalia being exposed to more testosterone than is typical. And so uh under the influence of this extra testosterone the clitoris may grow to be bigger than the typical clitoris. In some cases in extreme cases um the the phalus looks like a penis and the skin around that area that would normally form the labia again there might be enough testosterone that it starts to look like a scrotum except of course there are no there are no testes inside there because this is an XX individual. So these individuals are identified at birth typically especially in XX uh individuals and there's a there's an easy treatment which is oh they can't make you you know you do the test and you oh they can't make adrenal steroids so we'll give them some and so for the rest of their lives they take adrenal steroids orally and get the benefits of that and that shuts off the hyperactive adrenal gland so that it shuts off the the role of the output of testosterone. So this is an what's known as an interex phenotype. And yes, you're right. And in the older literature, they were sometimes known as pseudoh hermaphrodite. Huh? With the idea being well that a hermaphrodite is some is an individual that can that can function and reproduce either as a male or female. And so supposedly they were pseudo because they can't do that because they have only ovaries. Well, uh, you can imagine, uh, first of all, um, being called hermaphrodite, nobody liked that. And if you ask them, well, does it better if I put this pseudo at the beginning? Does that that make you feel like you're being less stigmatized? No. But a much more accurate uh description is to say that it's intersects. They have a a fallus that's somewhere between a clitoris and a penis. And the skin around there is sort of like a scrotum and sort of like a sort of like labia. So uh in the old days once this got recognized it was standard procedure to tell the parents oh uh this is an emergency. We need to do cosmetic surgery. We need to do surgery to make this little girl look like all the other little girls. You know sometimes the surgery was you know there could sometimes be successful or not. And indeed, they knew how to make her look like other girls. Um, but many of those interex folks when they grew up were pretty angry that someone had done this surgery on them that wasn't needed medically, right? They were already taking care of the problem with the exogenous adrenal steroids. And so, who asked you to to deal with my, you know, to do surgery on my clitoris? In some cases, uh, the tip of the clitoris was missing and so these women grew up and were an orgasmic because they couldn't get the stimulation that they normally would have had. These days, um, there's much more thanks to the activists like Cheryl Chase and others who started getting the pediatricians attention. Hey, you you need to think about that. You're you're doing elective surgery on an infant who cannot possibly have informed consent. And so these days they're more of a wait and see attitude which which I think is absolutely that. So wait till they're grown up and ask them then if they want to have surgery and my guess is most will will say no. I think that's been the pattern so far. So these are females who were exposed to more testosterone than other females. So does that mean that they're going to be attracted to women when they grow up? And and the answer is well interestingly uh if you look at groups of women with CA they are more likely to be same-sex attracted to be lesbians than the than the population at large but most of them are straight. But what's interesting about that is the older they get as you keep surveying them the higher the percentage of them that report having a lesbian orientation. M so it's possible first of all that indicates that yeah maybe prenatal testosterone increases the the odds of them uh being lesbians when they grow up. Uh, and and you also wonder, well, how many of them always had that same-sex attraction, but, you know, were following the pathway society laid out for them, and then as they get older, they said, well, no, screw this. I, you know, I I know who I'm attracted to. I don't have to fit the heterosexual mold. And so, it it's, you know, that's entirely consistent with the idea that prenatal testosterone makes you more likely to be attracted to women when you grow up. There's another syndrome that I know you've talked about um which is androgen insensitivity syndrome sometimes abbreviated AIS and it turns out the gene for the androen receptor that responds to testosterone and other androgens is on the X chromosome and it may sometimes be that a woman will have an X chromosome that has a copy of the androceptor gene that doesn't work and if she passes that X chromosome onto a daughter then she's sort of duplicated herself. What's interesting is when that X chromosome is given to a son, in other words, that egg with an X chromosome that has a dysfunctional copy of the Andraceptor gene, if it gets fertilized by a Y-bearing sperm, now we have an XY individual. And as you've explained clearly in your in your basics podcast, uh we know what'll happen in development. The Y chromosome will mean that the indifferent gonad will develop his testes. The testes will secrete two hormones that are going to guide sexual differentiation in the periphery. One of them being antimmalarian hormone which is going to suppress the development of the malarian ducts and therefore no ovduct no uterus will form and the testus will also release testosterone which normally would masculinize the body. But in this case, because there's no functional androceptor to respond to it, the testosterone goes round and round, but the body doesn't respond. And so the wolfie and ducks don't develop. The periphery looks like a typical female. And these individuals when they're born often are not identified because the baby's born. The doctor does that very careful analysis by looking between the legs and says, "Congratulations, you have a girl." and they grow up to to be girls un undetected and they come to a doctor's attention when puberty happens and all their classmates are having their period but she's not and so she'll eventually go to an OBGYn who will first do an exam a vaginal exam and he'll notice that the vagina is relatively short because the inner part of the vagina is normally derived from the malarian ducts. Well, in this woman, in this teenage girl, um the malarian ducts never develop because of antimmalarian hormone. So, there'll be no cervix that can be seen in the exam. And if he takes blood plasma levels, he'll see that this very feminine looking girl, teenage girl, has very high levels of testosterone and presumably testes. And if he does a carotype, he'll see that she has an XY carotype. And yes, there are testes in there typically in the abdomen. And they're releasing lots of testosterone because there's no negative feedback to tell the brain, you know, hey, you can stop sending signals to the testes. Now, in these cases, you can ask, well, what's the sexual orientation of these women? And the vast majority of them grow up to be straight. They are attracted to men and they might be very they're often very interested in having a family and of course they can't carry children themselves but they can you know adopt and things like that and so they're very much feminine very straight women but they're exy but they're ex so the question is and unfortunately in terms of understanding whether prenatal testosterone alters our sexual orientation these individuals aren't aren't useful to us because we I don't know if they're straight women because their brains could never respond to the prenatal testosterone or are they straight women because they were raised as girls and socialized to to be attracted to men. It's a fascinating syndrome and there's at least one woman with AIS who's self-identified who's a successful model. Uh and there's another woman who wrote a memoir that's quite uh it's quite good. And what's interesting about when there's no testosterone response, uh, they have very feminine faces, very feminine bodies. U and, and so they're, you know, they're frankly quite attractive, uh, as women. I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over 160 advanced lab tests to give you a clear snapshot of your bodily health. This snapshot gives insights into your heart health, hormone health, autoimmune function, nutrient levels, and much more. They've also recently added access to advanced MRI and CT scans. Function not only provides testing of over 160 biomarkers key to your physical and mental health, it also analyzes these results and provides recommendations for improving your health from top doctors. 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I'm realizing I'm drawing a model over here whereby we've got again accelerators and breaks and and I think we've got different axes. um not you know I'm not trying to um split hairs here but I think for people who want to understand how hormones sex and behavior sexual orientation fit together it's very useful to think about okay you've got chromosomes that drive you know our typical notions of male versus female and you're providing some important caveats where the the body appears one way but it's an XY you know and and there's almost every derivation of this has been observed although not at a very high frequency Um, and then you've got choice of same versus other, uh, in terms of orientation, a key role of prenatal testosterone there. Um, maybe some cultural or other types of plasticity that might be biased more toward the female side. It seems that way based on what you're saying, if I'm, you know, I'm willing to say it. If you're not, it does seem that way. um there's an aversive signal that kind of that certainly in male sheep and um other species and that you know matches my observations uh as a 50-year-old male who grew up in Northern California and you know I mean again in this era and the joke being that I'm I can only speak for my own reference point on this and then we have a bunch of different things about um partner preference And and that at some point it almost seems like it departs from well it certainly departs from our sort of linear like okay uh girls like boys, boys like girls, testosterone makes boys, estrogen makes we're we're we're nowhere near there. We're we're we've left that station a long time ago. Exactly. Um and at the same time we we arrive at a place where I think we need better languaging to separate these axes because it is very confusing for people. Um, and so that would be very useful if if the fields of neuroscience and psychology would start to embrace the real world uh realities of of because I actually think the lack of of specificity of talking about orientation versus biological sex and and these and these other aspects have have led I think that's the source of a lot of conflict actually. Anyway, that's a that's an editorial for another time. Um, in terms of biological impact on sexual orientation, one of the more striking findings that you've been talking about for a number of years that just kind of shocks at first, but then you get a lot of nods from people is this idea that the larger the number of older brothers it's it's really one of the uh rock solid findings in human sexuality that that was first noticed by Ray Blanchard at Toronto and has been seen in many populations all over the world. So, the way to emphasize the difference is if a baby boy is born today, um if if he has no older brothers, his odds of being gay brothers just to have a 50/50 chance from the same mother, right? So we know that it's not, you know, in, you know, what they call now blended family or so this is we'll get to those in a moment, but but but this is what you see. So you get a big population of men. Here's here's a big population that have one older brother. How many are gay? And it's a small number. And and the number that have two, still a small number, but more. And you know, how do you explain that? We saw it when when we did those surveys. We I I don't know if you remember, we also asked people how many older brothers and sisters they had and how many younger brothers and sisters they had. So it it turns out in the general population, there about 105 boys born for every 100 girls, right? That's also very consistent. 105 boys born for every hundred girls. That's right. So there's or put it another way, uh, if you want, I can I can guess the sex of any baby that's going to be born and I can be right more than 50% of the time because I'm always going to guess boy, right? Because 51% of the time it'll be a boy. For straight men, you total up all the older brothers they have and all the older sisters. And there's a ratio of about 105 older brothers to 100 older sisters. For the gay men, it it turned out there were 140 older brothers for every 100 sisters. Help frame that statistic for people. So, so you gave us the one older brother, what the probability was, right? Uh it's a third increase. You go from 2% to 2.6. Is it a linear increase as you increase the number of older brothers? Do you just start um increasing the probability at every with every older brother or are there is it sort of a step function? It is in fact a linear progression. So at at that rate so Ray's worked that out. Of course it's hard to find men that had more than four or five older brothers especially these days. But uh but it turns out in the Kinsey surveys Ry went to the Kinsey surveys way back then. you know, those c those interviews were incredibly thorough. And so they have a record of how many siblings of each sex every one of those men had. And and you can see it there, too. And it's another one of these cases where I tell you this and you tell me, well, I know somebody who has two older brothers and they're gay. Is that why? Or I know somebody with three older brothers and they're not gay. This absolutely. So you tell me, oh, I know he's gay. Is that why he's gay? And I I really can't tell you. There's no way to know because in fact most men with two older brothers are straight. Right? Again, it's one of these instances where it gives you no predictive power…

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