The Peter Attia Drive - #374 - The evolutionary biology of testosterone: how it shapes male development and sex-based behavioral differences, | Carole Hooven, Ph.D.

Episode Date: December 1, 2025

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Carole Hooven is a human evolutionary biologist whose research centers on testosterone, sex differences, and behavior. In this episode, she explores how prenatal testosterone orchestrates male development in the body and brain, how early hormonal surges shape lifelong behavioral tendencies, and what rare natural experiments—such as 5-alpha-reductase deficiency—reveal about the biology of sex differentiation. She discusses distinct male and female aggression styles through an evolutionary lens, how modern environments interact with ancient competitive drives, and the implications of attempting to suppress them. The conversation also covers testosterone across the lifespan, the role of hormone therapy in both men and women, and Carole's own experience after surgical menopause, culminating in a broader discussion of masculinity, cultural narratives, and the consequences of denying biological sex differences. We discuss: How Carole became interested in exploring the biological and evolutionary roots of sex differences and the role of testosterone [2:30]; How testosterone and other hormones influence sex differences in aggression and behavior across species [9:45]; How chromosomes, the SRY gene, and early hormones direct embryonic sexual differentiation [12:15]; A stark contrast of male social bonding compared to females, and evolutionary parallels in chimpanzees [19:30]; How hormones like DHT shape sexual differentiation, and how 5⍺-reductase deficiency reveals the distinct roles of these hormones [22:45]; How sex chromosomes and prenatal testosterone shape early brain development and explain sex differences in childhood behavior [31:30]; How gamete differences shape reproductive strategies, energetic costs, and sex-specific behavior [42:30]; How evolutionary biology shapes sex differences in play, aggression, and conflict resolution (and how modern environments and cultural messaging can disrupt those patterns) [49:00]; Why males commit disproportionately more violent crime, and how cultural and environmental forces shape aggression [1:01:00]; Why females evolved different behavioral strategies: nurturing, risk aversion, and the cultural norms that override biology [1:04:00]; Whether male aggression is still necessary in modern society, why the underlying biological drives persist, and how modern society redirects these drives [1:06:30]; How testosterone levels naturally shift to support fatherhood and caregiving [1:13:30]; How testosterone shapes male mating strategies, and why long-term pair-bonding persists even when reproduction is no longer at stake [1:18:30]; The distinct roles of estrogen in male development, mood, libido, and muscle [1:25:00]; How evolution, health, lifestyle, and androgen receptor biology shape modern testosterone replacement therapy (TRT) [1:34:15]; Carole's experience with hormone replacement therapy (HRT), and the risks associated with TRT in younger men [1:45:15]; How Carole rebuilt after controversy: leaving academia and recommitting to scientific honesty [1:51:30,]; Carole's next book: examining masculinity, cultural narratives, and the cost of denying biological sex differences [1:57:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads.

To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you want to learn more about the benefits of our premium membership, head over to peteratia-md.com forward slash subscribe. My guest this week is Carol Hovon. Carol is a human evolutionary biologist, a former Harvard lecturer, and non-resident senior fellow at the American Enterprise Institute.

Her research focuses on testosterone, sex differences, and behavior. She holds a PhD in biological anthropology, now human evolutionary biology, from Harvard University, and is the author of T, the story of testosterone, the hormone that dominates us. In this episode, we discuss how pre-nail testosterone shapes the male body and brain, turning genetic-sicestosterone. into thousands of developmental changes that underlie later sex differences, critical hormone surges and why they matter for lifelong behavior, dh-ht, androgen receptors, and rare natural experiments, for example, 5 alpha reductase deficiency, that reveal how external genitalia and the prostate masculinize, distinct male and female aggression styles, direct physical confrontation versus indirect or relational tactics, and the evolutionary logic behind

each, why modern life changes but doesn't erase ancient drives like male competitiveness and the trade-offs of trying to suppress them, testosterone, aging, and hormone therapy for both sexes, including Carol's personal experience after surgical menopause, and the cultural debate over masculinity and the cost of denying biological sex differences, a theme of Carol's forthcoming book. So without further delay, please enjoy my conversation with Carol Hoovey. Carol, thank you so much for coming out to Austin. Great to meet you in person. Thank you so much for having me.

I'm thrilled to be here. This is a topic that we talk a lot about on the podcast, but usually from a pretty narrow lens, which is in the form of replacement. We talk about hormones, both in men and women, sex hormones, and we talk about how they wax and wane as an individual ages. We obviously then talk about the medical use of them. But I don't think we've spent any time understanding the more basic fundamentals of these hormones, the role they play in our evolution. And anecdotally, I'll just share with you kind of the observation that any parent probably has if they have male and female children.

My first child was a girl. And my wife and I very, very stupidly and arrogantly thought we were the perfect parents because like she was so well behaved. And we were like, what do all of these other parents with their boys running around misbehaving? Like, what are they doing wrong? How could we teach them how to be as good as we are? I mean, we didn't actually say that, but there was undoubtedly an annoying smugness to us. And if you believe in a God, that God smacked us into our place with two boys that followed, who were, for all intents and purposes, treated the same way.

socialize the same way, and there is a level of aggression in them, a fury in them that I've never seen, probably unless I were to go back and hear stories of what my mom said I was like. How old are your boys now? Eight and almost 11. Okay. I wouldn't say they're a different sex. I would say they're a different species. Yeah, I was just going to say that.

Yeah. So all of that is to say, I don't feel we did. anything different, and yet they couldn't be more different. And I appreciate that that's not going to be the case for every parent. What I hope to learn is how much testosterone has to do with that, because I also, I'm under the impression that at this age, the testosterone levels wouldn't be that much different. And I understand and we'll probably talk about the differences in testosterone levels during the embryologic phase, because obviously that led to the differences. But anyway, with that as backdrop, how did you get interested in this topic?

So I want to make sure to come back to everything that you just said. So how did I get interested? I'm going to start at the beginning, which is that I grew up with three older brothers. And I'm assuming that this had something to do with my interest in testosterone. They were different than I was, I am, in some consistent ways. I don't think I thought much about that. And I think that probably made me really want to understand what motivates male behavior in general and why it's different from female behavior. That wasn't sort of an idea that I had when I was in college that I was going to go study this. But I did become intensely interested in the evolutionary origins of human behavior in general and what makes us different from other animals. And that happened, I think because of traveling.

I traveled to a lot of different places in the world, mostly by myself, during and after college. And there were such extreme differences culturally. Your family's Egyptian, that was one of the places I went that really freaked me out because that really shook me. Say more. The cultural differences were so profound in terms of the incredibly important role it sex plays in social life and the segregation and different rules that applied to males and females. I was alone traveling by myself as a young woman totally ignorant of what I was getting into in Egypt.

I was harassed endlessly. Some of that was my fault for not understanding the culture well enough and what I was getting into. So this combination of being immersed in not only different societies that treated sex and sex roles very differently, but also different ecologies. I spent some time in Africa and Kenya and Tanzania and got really interested in all of the animal behavior and why we are different from other animals, et cetera. So I had a whole other career before graduate school and I ended up leaving that career and applying to Harvard to try to do a graduate degree where I could do more to understand the evolutionary basis of human behavior. I ended up getting rejected and I just persisted and then was offered this job out in Uganda studying chimps for what was supposed to be a year.

And that is what really triggered my interest in sex differences and testosterone. Because we, I think to a certain extent, are indoctrinated to believe that most human sex differences are cultural. or if you think that they're not, it's better you don't say that out loud to too many people or in the wrong place. So when I spent time with the chimps, I was really blown away by the ways that the sex differences in the chimps paralleled human sex differences. Of course, not exactly the same, but the very basic things that you just described, even just in terms of energy and aggression, are present in the chimps in terms of being higher in the males and lower in the females. And I'm getting goosebumps because the reasons for that are so profound and far-reaching

and start with sperm and egg. And that's what sex really is about is not just the ability to produce sperm or eggs, but kind of the way that the organism is designed and the reproductive phenotype, including body and behavior. And then that in humans plays out these really complex ways in terms of social systems. So I got interested in testosterone because this is one thing I could grab onto that links very clearly humans, chimpanzees, every other mammal in terms of males having much higher levels than females. And it's not just mammals. There are other forms of steroid hormones that other species have, but this is pervasive and just a very powerful way to understand approximately, that means what's happening here and now in the organism, why the sexes are different. And then

there are these deep evolutionary pressures that have to do with reproductive strategies for organisms that produce sperm versus organisms that produce eggs. And so then I ended up reapplying to Harvard and getting into the grad program there. And I did my dissertation on testosterone and sex differences in cognition, the way we think and process information. And I had men want. much sexy videos and also videos of dental surgery and collected their saliva and measured their testosterone in the lab. And then I just stayed on at Harvard, mostly just teaching. I want to go back to something you said a second ago, which is the distinction between mammals and non-mammals. And I never really thought of it until you said this. But if I were to

look at a male great white shark and a female great white shark, first of all, do they have testosterone in them as the androgen or sex hormone? So vertebrates, most vertebrates will have testosterone or something very, very close to testosterone, yeah. Now, if you, again, go back to the example of great white sharks, typically the females are larger. I would reckon they're just as aggressive as the males. Is that reflected in comparable levels of testosterone in those species? So sharks, I don't know about specifically. First of all, males are not always bigger than females. Males will do whatever they need to do generally to compete for mates, and in many species it's not to be larger. Also, there are differences in the ability to defend a territory or defend mates in

air and water and land. And that's really an interesting way to understand some male competitive strategies. But generally, when in the species, if the female is just as aggressive, often it's maternal aggression and not necessarily mate competition. Maternal aggression tends to be mediated more by estrogen than testosterone, even in hyenas, which are very difficult to tell apart. The females are very difficult to tell apart from the males. They have this clitoris that looks exactly like a penis, and experts often can't even tell the difference. They're highly aggressive. And that seems not to be mediated in the adult, at least, by comparable levels of testosterone. There seems to be potentially something going on in early development. But I don't know of good evidence that testosterone

acts similarly in females to mediate, say mate aggression, we'll say mating aggression. So just make sure I understand, in the hyenas, if you took an adult male and an adult female hyena, would they have similar levels of testosterone and estrogen? No. The males would be higher. The males would be higher. Despite the fact that phenotypically, they look the same and they're both equally aggressive.

I believe they're either just as aggressive, if not more so. I believe that they're dominant to the males. Got it. And there's something going on with potentially maternal adrenal androgens when the fetus is developing. That becomes the aggressive female, but I don't think it's completely worked out. I haven't looked at the literature on that in ages.

So the extent of my recollection for medical school on this topic was, and again, we can come back and talk about the edge cases, but 99.9% of cases are either X, X or X, Y, in terms of humans. In humans, yes. Yeah, right? So we can talk about turners and Klein filters and things like that later. But in the 99.9% of cases of X, X, X, Y, what are the steps and how do they involve sex hormones that create the phenotypic differences in the embryo?

So phenotypic, we'll just stick to the body, and then we can also talk about the behavior. Yes, yes, exactly. That's what I just want to start with. Let's get through the first nine months. Yeah. And then like let's help understand how those two options of chromosomes lead to two different body types. And I just want to say right at the outset that we have a sex determination system that relies on chromosomes, but not every animal does. So chromosomes do not equal sex.

And birds have used chromosomes, but they have a different system where the female is the one that has heterozygotic chromosomes. So there's temperature dependent, sex determination, so people should not confuse the sex hormones themselves with the definition of sex. Chromosomes are the sex hormone? Sorry, chromosomes. Thank you. In mammals, the chromosomes determine sex, but do not define sex. Again, across almost all sexually reproducing organisms, it's the gamete type that the organism

is basically designed around, that the reproductive system is designed around, that defines sex. Other organisms can be hemaphroditic, produce both gamut types at the same time, or they can be sequential hermaphrodite, so I just want to get that out first. So in humans, the mother's egg, the sex chromosome is always going to be an X that it donates in its egg, and it's going to combine with a sperm, 50% of the sperm are going to have a Y sex chromosome, and 50% of the sperm are going to have a X in general. Those two, combine, and the developing embryo is going to be either X, X, X, and X, Y. So let's just start with the X, Y. So you were an X, Y. I had a son who is an X, Y, which is weird for women, because they will

have something inside of them that has testicles that produce testosterone, which I think is interesting. So an XY fetus, around five or six weeks, I should just say that X, X, X, and X, Y, are both, They're almost identical until that time. And the Y chromosome has a gene on it called the sex-determining region of the Y chromosome that produces a protein called the S-R-Y protein. And this is a very important protein because it triggers the differentiation of the undifferenti-gated gonad. So what's really cool and interesting is that before that time, we all,

have a gonad that can become either one. It can become testes or it can become ovaries. And that's sort of an amazing design. That's evolution's way of not wasting energy, not having to have two systems. Two different systems that one develops and the other gets discarded, at least in terms of the gonads. So they come first. So in terms of sexual differentiation, that means that for XY individuals, the gonads are going to develop along the testicle route. And without the SRY gene, they will, by default. When I say by default, that doesn't mean that nothing else has to happen. Other genes have to be expressed. And that's an active process. It's not a passive process. But without the SRY gene, those undifferentiated gonads will differentiate in the

female direction to form ovaries. I remember my overly simplistic, and this is almost 30 years ago, but I could have sworn I used to think about this in the embryology class as by default, we are female, and this gene had to turn on to basically take the X, Y's and make the male phenotypically. But that's obviously oversimplified. Yes. In some ways, that is true. I would not put it that way, but it's by default. The individual will develop, say, female. Because if you have an X, Y, that is missing that region, you will be phenotypically female, but chromosomally male. You will be chromosomally male, sure, but you won't develop functional ovaries because you need two axes to do that. But for all intents and purposes, you would look female, correct?

Yes, yes. So your external genitalia would appear to be. female, we'll get into those cases. Yeah, these are kind of these edge cases. But yeah, if you think about what the genitalia look like in a early developing fetus, it looks female. It doesn't have to change that much. It gets bigger. But if you take what looks like even adult female genitalia, basically you modify the clitoris

and the labia to get what looks like typical male genitalia. So that has to do a lot of growing and changing, and it's like that in the fetus. So if we're going down the male route, you get the expression of S-R-Y, and what that does is it causes certain cells in this undifferentiated gonad to develop into first lading cells and then later Sertoli cells. So that's happening, and then later ovarian differentiation takes place. So two things happen. The lady cells start producing testosterone first, and I'm going to go back and just talk about

the Wolfian ducks and the malarian ducts. Oh, my God, I have not heard that term since medical school. What a blast from the past. Okay, so this is D-U-C-T-S, not duck like quack-quack. So these are duct systems. And so here's another cool thing. So we start out with this two primordial or primitive gonads that can become either. And they're high.

I remember they're in the, almost in the chest. They're high. So obviously the males have to descend into what becomes the scrotum. And the females just stay there. And that seems very sensible. We still don't completely understand why males take all this valuable stuff and keep it outside of their body. That's a whole other. Maybe temperature regulation?

Yeah. I wrote about this at my book. and I researched it pretty thoroughly and came up with no answer because elephants and whales and, but I think elephants, there's a one other vol or something that has their testes inside, but all other mammals it's outside. And yes, there certainly is temperature regulation. But then why don't we have the system, however it is, that the elephants can get away with it. So it's some genetic constraint. I'm just going to take you down a stupid detour for your next book.

We were at my younger son's baseball party at the end of the season. So now picture at the time a bunch of 27-year-old boys running around the pool, playing baseball, playing football, goofing off. Me and the dads were sitting there hanging out. And we were observing their behavior. And I came up with this observation, which is there's estimated to be about 110 billion humans that have lived over the past 250,000 years, inclusive of, of course, the eight or so billion that are alive today.

And just watching this small group of 20, you could already see the number of times one boy would walk up to the other and sort of flick him in the nuts. Okay? And I was like, all right, to the dads. How many times in the history of 250,000 years has one male gone up to another male

to flick him in the nuts? What's that number? So the chimps did this. Well, let me finish the punch line. Yeah, sorry, sorry. The punchline is, whatever that number is, it's enormous. Yeah.

Now, what's the number of females that have gone up to another female and gone, and tried to flick them in the clitoris? Like, zero. There is sometimes a little breast play, I guess, in the teenagers, but nothing like what boys do, what men do. You're talking about a ratio of zero to 87 billion, 432 million. All right, give me your hypothesis about why this happens. I mean, my only hypothesis is males are idiots.

It's such an evolutionary stupid thing to do. That's a very precious part of real estate. That's the point. So why would they do that? So maybe it's threatened. It's like basically, I'm going to make sure you can't reproduce. I'm going to be dominant. I'm going to reduce your probability of reproduction.

So these are kids who are good friends usually. Yes. And only a good friend could do it. Yeah. Well, only a good friend will get away with it. Yes. Like if a stranger did it, then you're going to come to blows. Okay.

So that's the point, I think. Male intimacy involves insults. the harsher the insult somehow, the more intimate, unless it's rejected, like you just described with the flick. So chimps, and this was amazing to see, because I didn't know about it, when they're in a high stress or conflict situation or there has been a conflict, the subordinate will cup the balls of the dominant one. And they also sort of play sex from behind kind of, but it's this intimate, trusting, weird situation where I think it really is saying, I'm down for you. I'm not going to hurt you. I'm holding your testicles and you can trust me. I don't know, but that's interesting. It just blows my mind because, again, the dads, we sat around and we laughed hysterically at this,

because most of us have daughters and we're like, our girls have never once behaved in this way. Yeah. So there's all these things we don't understand. And one of them is, why would you leave this precious real estate outside? your body if you could potentially thermoregulate inside the body. I mean, maybe there's an answer now, and I haven't found it, and someone will write in or something. We'll hear about it in the comment section, yeah. So I'm just going to go through the ducts a little more quickly. There's two different systems.

So the Wolfian ducks become what I'll just say is the male internal plumbing, and the malaria ducks become what is the female internal plumbing. So what's important is that the lading cells produce testosterone, which stabilizes the development of the wolfian ducts. The testicles have to produce two hormones. Leading cells produce testosterone to stabilize the wolf alien ducts to connect the sperm-producing organ to the delivery system ultimately, which is the penis. And they have to cause the dupilip. the degeneration of the malarian ducts. So that's anti-malarian hormone and testosterone. So healthy testes, and this is important when we talk about the disorders or differences of sexual development,

healthy testes will have those effects. And you can also think about what happens if they can't produce anti-malarian hormone or what happens if there's no receptor for testosterone or no receptor for malarian hormone. And by the way, at any point, is any of this testosterone being converted to DHA in any meaningful amount? Not that I know of DHT for sure. That's extremely important. And that comes next. Sorry, I meant DHT.

Yeah. I'm sorry. Yeah, yeah, yeah, yeah. So I want to make sure, maybe I can just talk about it a little bit now. So that conversion is via the enzyme five alpha reductase that's present in high concentrations in the genital tissue. So what's interesting about this is that you have a mechanism to achieve high concentrations of a more potent androgen without that having to circulate through the general circulation,

which you do not want in a developing fetus. You want to be able to control the development of the penis, say, which is one of the things that Dht does. So the genital tubercle can become the clitoris or the penis, essentially, in the presence of testosterone and functional five alpha reductase. It becomes a penis, the labia grow and then fuse to become the scrotum, and also the prostate. DHD is necessary for full prostate development and can later sustain the function of the prostate. So it is interesting because it is this solution to providing very strong androgenic signals in the tissues that need it without wasting energy

on strong androgenic signals in the rest of the body. I've never thought about this until now. Is that why D.HT has such a high affinity for the androgen receptor, you think? Yes. So that you could permit it to only have a local effect during embryologic development. Because otherwise, I don't know that it would matter as much in me at this old age that DHT is that much more potent than testosterone. So I don't think it would matter as much.

I'm okay to be exposed to circulating androgens in a way that the fetus presumably you wouldn't want. I think that DHT is something like two to five times more potent. Oh, I thought it was even more than that. It could be more. But what this means is that it binds the receptor more tightly and it stays on for longer, which means that it produces more of whatever the protein is that it's upregulating because it's a steroid, testosterone is a steroid, estrogen is a steroid, and steroids. this is the way that they typically act is by either inhibiting but generally upregulating

androgenic genes. So yeah, I think that's super interesting. And of course, there's a disorder 5 alpha reductase deficiency where individuals are basically just typical males, but they happen not to be able to produce DHD. We can talk about this later, but it seems not to have any Dht is not what masculinizes the brain, but it does masculineize external genitalia. So without that, you're going to have what look like female genitalia in a male, who's otherwise typical male because the testosterone works and the androgen receptors are present. Unfortunately, these are really, really rare conditions. It's funny.

In medical school, you come away thinking these things occur all the time because of how much time you spend studying these very, very rare disorders. But, again, fortunately, they're not common. I used to teach a lot about these cases because, yes, they really help to understand the typical pathway, but also how powerful even tiny little mutations in little genes, how powerful those mutations can be. And I think it increases compassion when we understand what the pathway is that leads to these differences or disorders. Going back to that specific case, you have an individual that is born that, I assume at birth, looks female. It depends where they're born, if they're born, and this will become relevant. If we talk about this later in terms of sports, if they're born in places without a sort of modern medical care, often they are sexed as female.

But I think it becomes apparent pretty quickly in childhood that they're actually male. Right, because they look male everywhere else, right? Yeah, we should probably talk about that later, but the body will look male once puberty hits. But there is a lack of facial hair and other body hair. But do they have ovaries? No, no, no, they're fully male. No, they're fully male. No, they have testes.

But they haven't descended. They may or may not have. Generally, so the ones that really do appear to be female, and people may believe that they're female until puberty when they start developing male musculature. Yeah. They're producing totally normal testosterone levels. Yes. Just not Dht.

That's right. Yeah. The testosterone at this point is the determining factor. Determining what? Muscle mass, body hair, things like that. Well, it can't. If you don't make DHT, some body hair won't be produced. You won't have full male typical levels.

You certainly won't have any facial hair. Generally, I don't think you have male pattern baldness. So the lack of facial hair really makes a huge. difference because it gives a sort of more feminine appearance to the facial skin. So DHS is important. And part of why five alpha reductase deficiency is relevant now is because there are people who are sexed as female and are legally female who are coming from, say, a rural town in South Africa because they've been running as a female on female sports teams or boxing, for instance. This is obviously the case.

We're all familiar with. brings up complicated social issues about what to do. And that means that we really do need to understand the science there. And the important thing from my point of view is that DHT has been pretty clearly shown not to be necessary for male typical patterns of musculature and other physical features that would give men an advantage over women, which is difficult because sometimes these people have been in a female social role depending on where they were born. Although that's also an easy experiment to do. You could imagine giving a male a 5-valpha reductase inhibitor from birth.

Oh, from birth. Like as a thought experiment. Yeah. If you took a normal, chromosomally, phenotypically normal male, and from the time they were, call it 5 years old, you just gave them 5-valra reductin inhibitor. All you're doing is turning their D.HT down to zero and doing nothing else. You're basically asking the question, will they develop normal musculature? So Bassine, Schallender Bassian and at all have done that experiment and there's no difference between blocking DHS. No, they did it in humans.

How did they get an IRB for that? I think you know his work. They've gotten an IRB for a lot of incredible studies that are totally super rigorous and gold standard. Yeah, interesting. Okay. So you and I are probably the only ones at this point, this excited about this discussion, because we're now so far down the weeds of ember. But bringing it back to the surface, the takeaway here is that XXXY start out for about five weeks, indistinguishable.

At about that five week mark, a gene on the Y chromosome specifically begins to trigger the differentiation pattern. That differentiation pattern triggers the transcription of genes that turn on hormones that are going to further activate and drive sex differentiation. So, yes, thank you for that last piece. That's very important. So the production of testosterone in the testes, this is really important and just fundamental to understanding sex differences. It's not that we have so many different genes. So at the same time, I should say, we're learning more about the role of the 70 to 100 genes on the Y chromosome, many of which are crucial for typical development of male reproduction and reproductive functions. But also, it appears that there's some role even prior to the production and action of testosterone on the body and brain. There may be early expression of genes on the Y chromosome that act in the brain to shape later patterns of behavior. There's a lot of work going on there to understand that.

There are genetic differences. And I also want to say that the genetic differences don't just stop at the differences with those genes on the Y. all the other genes are the same except for the sex chromosomes. But having one X versus two Xs makes a huge difference. It's extremely important. So people think that females completely silence one of their X chromosomes in each cell, which is something that basically does happen so that we don't have a double dose of X chromosome genes compared to males. So that's something called a bar body. But if that were true, it must be more complicated or else you wouldn't have Turner syndrome. Yes, that's right. And we can talk about Turner syndrome, but something like

20%, and here someone might correct me, but I think around 20% of the genes on the silenced X escape inactivation. And that turns out to be important that there are some genes in females where the female needs the double dose of those genes. And if she doesn't have the double dose, as in Turner Syndrome. Which we can define for folks as single X chromosome, which presumably they got from mom, and then they didn't get a chromosome from dad? Or do we know that? They can get it from mom or dad, and that's another rabbit hole.

We could go down. There are imprinted genes depending on the parental origin, meaning certain genes are preferentially expressed or suppressed in the mom's X versus the dads for interesting evolutionary reasons, because the mom and dad have competing interest in what happens to the kid. And phenotypically, a woman with Turner's syndrome does appear phenotypically female. Yes. But I believe she's not able to reproduce. That's correct, as far as I understand.

I think that there's some evidence that there's technology now where they could reproduce. But she's sterile under maybe natural conditions. I think in some rare cases that can happen. But generally the ovaries don't. But her stature is distinctive. It's short. She's going to be shorter, and there's a sort of wider neck

and a few other characteristics. But generally they're typical in other ways. And so something about these 20% were thereabouts of genes on the supposedly silenced X chromosome are clearly making the difference because that would be the biggest difference you would notice.

I don't know if that's the total complete difference. I don't know enough about Turner's, but they turn out to, yes, be important. And I don't even know if it's well understood. I think there is actually. actually some research on exactly which genes are typically escaping. And is it always the same genes? I don't know.

So I just wanted to make the point that, so at this point, we have a high level of testosterone in the fetus that is approaching concentrations in male puberty. So this is not happening in the female. This is a huge difference. And the reason it matters is because testosterone, as a steroid is then going around and acting as a transcription factor when it binds with his receptor to alter gene transcription on thousands of genes. So that is happening in males and not in females. At about what stage of development? How many months or weeks?

I think around eight weeks, it begins peaking around 15 to 20 weeks. And then, of course, after birth. It goes back down. Well, it goes down at birth, but then it goes up peaking at three months after birth, and that's called mini-puberty. So this is— I don't even remember that. Because it's new. You probably didn't learn about it in medical school. Now it's getting a lot of attention.

The point is somewhere in the early second trimester, that level of testosterone in a male fetus is comparable to what— It's lower. It's not exactly as high, but it's very high. If a male in puberty is at 1,200 nanograms per decilator, this could be 600 nanograms per deciliter. Maybe 400, if I remember correctly. But still screaming high. But it's very high. And the point is that this is affecting the development of the brain.

So I'm really interested in behavior. And from an evolutionary point of view, what is going on in this early environment is extremely important. the body is realizing, the male body is realizing that it's going to be a sperm-producing animal. So the brain, and we have very firm evidence, we can't do these experiments in humans. So people don't like it when all the evidence comes from non-human animals, but most of it does. And that's just because we can't manipulate genes and hormones and developing fetuses to see what happens. We have some, quote, natural experiments. But all the evidence shows that testosterone is a post-apeutic.

regulator of neural development and differentiation from females, which is why boys and girls aren't the same. That is why. It is 100% the reason, and it is 100% in my view. This explains the birthday party phenomenon. Yes. There could be new evidence that comes out in humans. All the evidence we have points to testosterone. Socialization matters. If you punish your kid, for not being masculine enough, for being too masculine, which happens, because now toxic masculinity and rough and tumble play is supposed to be toxic. It's not. It's healthy. It's necessary. I didn't know that. I missed that memo, fortunately. Sorry, I get worked up about this because there's

lots of evidence showing that, first of all, it is testosterone. So even in, I'll just go back to the chimps, the males play more roughly than the females. In many mammals, where there is a sex difference, in play, the males are playing more roughly. There's a reason. And just to make sure people are following this logic, there's one part of the swing we didn't finish. And it's because I keep interrupting you, so it's my fault. But I'm going to do my best to synthesize this.

Yeah, bring us back. Testosterone, you have this real peak difference in testosterone during a critical window of development when the brain is developing. And so you have a female brain that is developing in the absence of testosterone. The XX brain is developing in the absence of testosterone. The X, Y brain is developing in the presence of high amounts of testosterone. Testosterone then falls. By the time these two babies are born, they both have really low testosterone.

Then it sounds like you're saying, unbeknownst to me until a few minutes ago, you have this little mini puberty that comes three months later. How high does testosterone get there? Okay. I want to go back to the critical period. This is also extremely important. and has been shown in non-human animals. The critical period in development,

you've got the period where testosterone is being produced in the fetus, and within that there are certain developmental periods where different parts of the brain and body are receptive to testosterone's actions. We know from non-human primates that there are different critical periods for, say, development of the genitalia, other parts of the reproductive system, and potentially for sexual and aggressive behavior separately. That's interesting because when we want to understand certain aspects of male behavior or differences in male behavior, it's helpful to know that possibly aggressive and sexual behavior may have different thresholds for male typical versus female typical,

and that there may be different critical period so that we don't really know inhuman. also in males, once you hit your sort of male typical level of testosterone, we're just talking about male versus female typical patterns of behavior. In males, in adulthood, at any stage, there isn't really a dose response relationship. It's more you're at a level that's like 10 to 20 times more than females. Female have some testosterone exposure in utero, and some females have more than would be typical, and we should talk about that. There, there is a dose response relationship because our levels are so low and we're extremely sensitive to differences. But males have so much more, those differences don't seem to make. And difference. Once you cross this threshold.

Yes, yes. I think the main thing I'm hearing you say, Carol, is that when you observe five-year-old boys and five-year-old girls behaving completely differently, the most obvious explanation for the is a behavioral difference, and the behavioral difference is driven by potentially the way their brains developed during that critical window of being bathed in testosterone, as opposed to the differences in testosterone in a five-year-old boy versus a five-year-old girl, which are de minimis. Okay. Thank you so much. Is that correct? Yes. Okay. And thank you for saying it so clearly, because there's some really important points here. I think what you just said and what we're going to talk about in terms of childhood shows that you cannot judge anyone by their current testosterone

levels. You can't predict that much. You can't attribute all variation in behavior and individual differences in behavior necessarily to current testosterone levels. And even within that, if you do have current levels, often, yeah, you can't predict much in terms of, say, sexual behavior or aggressive behavior. You certainly can't with kids. because they don't have any differences. They hardly have any testosterone at all. What they do have is on average, I should have said this before, but all of this is on average. There is tremendous variation. The only thing that differentiates the sexes cleanly and essentially is the gamete production. Define that again, because I want to make sure the listener understands when you're referring to

gamete, what you're talking about and the production of them. Sperm and eggs, what has evolution designed you for? If you're X, Y, and you're going to be making sperm, there's going to be a suite of characteristics, generally, that are going to be different from the suite of characteristics that a female who has ovaries and eggs will need to maximize reproduction. So all evolution cares about is what portion of your genes are making it into future generations. So the design here is about reproductive strategies that coordinate how your body grows, what your body is like, what physical features you develop,

coordinates the hormones, coordinate that with certain patterns of behavior on average. All of the bodies and the behavior can vary across X, X, X, Y's. But what we're talking about is these broad patterns, mostly to do with sex and aggression, that tend to differ between males. And this is across sexually reproducing organisms for the most part. So all the other stuff can vary. It's not that all X, Y people, are going to have a higher sex drive and be more aggressive. That's just not the case. Bodies vary, behavior varies.

I know you weren't consulted during the design phase, but do you have a sense of why the female gametes are all produced up front? Oh, God. And you basically get your lot at birth, and then you, that's it. It's a rate of attrition versus why the male gamete is just produced on demand. Again, I'm being a bit facetious. Of course, we don't know this. but do you have an insight into why that's the case?

I'm sure there's a better answer, but here's what I think. I hope people will write in with the better answers. Making eggs is expensive, calorically, in terms of time and calories, they're expensive. So what we are designed to do is convert energy into offspring. That's basically what evolution put us here to do. And you want to do that as efficiently as possible. So eggs are energetically expensive. Sperm is less energetically expensive.

And I don't know what happens in terms of how the eggs that go atritic. So we start out with, what is it, 10 million? I know you just had. I know. I just talked about this with Paula. The numbers are staggering how much attrition there is between birth. So and then you end up at birth, you have one million and something like that. Maybe a million to 100,000 to.

Right. Yeah. But most of them just die. So maybe there's some selection process there. There's an overproduction because for females, there's so much that goes into the production of each egg. And time and energy and each egg that you produce is going to limit your ability. If it takes a long time, that means you can only have like eight or ten or however many kids

over a lifetime. So they're very valuable. So we were talking about testes and sperm, testes being not so well protected, but the eggs are extraordinarily well protected if they're made early and then just stored, I think. They resume myosis, of course, when they are ovulated. So maybe there's this store and then there's a selection process that goes on throughout life. That's a very interesting idea, right, which is maybe you make, I mean, let's just pretend we got these numbers right, but directionally. So you make a million, you have the first 18 years of life or whatever it is or 16 years of life to select the best of those. And so it's not a stochastic process that takes you from the

million to the 10,000 or whatever the number is. It's truly a winnowing down of the best of the best. It could be. Again, this is a teleologic BS discussion. I don't know. It is a super interesting question and I should know more about it. But it does, I think, illustrate the reason why we have different strategies. It's because the time and energy that females have to put into reproduction. If, say, imagine we're living as hunter-gatherers, there's no birth control. We're not going through life, getting our periods over and over and going to Whole Foods and having a job. We're having kid after kid after kid.

We're nursing. We're producing the milk with our own bodies. We have to grow the baby in a relatively energy-restricted. the burden for female mammals, the energetic and time burden for female mammals is enormous to produce each offspring. And if you don't have the right egg or the right sperm, you should care about where you're getting the sperm, then you've lost, you know, a huge chunk of your potential reproductive output. Men don't lose a big chunk. That just doesn't happen to them. And this is the sex difference in parental investment that shapes, that's why eggs and sperm matter. in terms of our bodies and our behaviors because we have to do very different things and live in different ways to maximize our reproduction. Okay, I want to come back to what you said about mini-puberty

and the differences in hormones. So I do think it's the differences in the increase in testosterone that males have that explain why they're more likely to have rough and tumble play, more energy. And by the way, how high a peak is this mini-puberty and how long does it last? It starts within a month after birth, but then peaks around three months, and I think then goes down until something like six months. And it appears that it has important effects on brain development and on lengthening the penis.

Does the female do it as well? In other words, does the female experience a rise in estrogen? Yes. There's a lower postnatal peak, but the mini puberty in boys appears to also be, associated with activity levels in the boys and even growth trajectories. So that's interesting. There's a very narrow window of time, right? Three to six months. Yes. Yes. So in terms of the activity levels could be that that postnatal time, that the play in boys has something to do with differences in activity levels, differences in novelty seeking, different temperament, less fear also. But if you think about it from an evolutionary point of view, in male mammals that have to compete for status and operate in a dominance hierarchy. There's a lot of male mammals have

dominance hierarchies which tend to function to reduce aggression overall. Because instead of duking it out every time there's a fertile female or a delicious piece of fruit in a tree, you just signal, I'm not going to take your fruit. I'm subordinate to you. So you can get along as a group, yes, there's infighting just like humans have, but humans have dominance hierarchies. Also, and if you don't learn how to compete physically with other males as a kid, this has been shown in non-human animals, and there's some evidence for this in humans, that you have more trouble, sorry, it just occurred to me that this is obviously happening with social media. People are using their iPhones to compete instead of getting out in the yard and play

fighting or fighting with other boys. That's actually healthy because it ends up reducing aggression. It helps, especially young boys and young men, learn their place in the hierarchy, what they're capable of physically, how to be threatening and when to be threatening, when to signal that they're submitting. All of that happens, and it's fun. So they're driven to do it because it's adaptive for them evolutionarily. So I just wanted to throw that in. And females tend to have have more nurturing play. I had three older brothers. I was climbing trees. I was wrestling with them. But the girls almost never play by choice just with each other. Like they don't have a play date with their tackling each other. My son is 16 now. He's still doing it. And he's six

feet. And his friends are like one of them is like six two. And it makes me very, very nervous. Because they can really hurt each other now. But yeah, they're still doing it. It's such a beautiful thing to watch. If you just stop judging it for a moment and give Just ask yourself the why question. Like, what is driving this behavior, right? So for whatever reasons that are tragic, this has become a political discussion, but it's really not. It's simply a discussion of biology, and it's endlessly fascinating.

Why is it that when I walk into the pantry and I see a candy bar versus a cheese stick or something, I want to eat the candy bar? Well, that's evolution. I can make a choice not to do it, but it would be. silly for me not to appreciate how much my brain looks at the candy bar and sees the sweetness, the energy density, the fat, the sugar. And it's like, yeah, that's what I want. Versus pick the bland, healthier option. And similarly, when we watch kids play, I find it very interesting. I wasn't obviously aware of half of what you're saying, but this idea that if you let

boys duke it out the way we all did, that ultimately it settles them down. Again, because it's probably too soon to tell what the results are of the natural experiment where kids play less. I mean, there's certainly no shortage of discussion about what happens when kids are all the anxiety and things that come from endless social media. But this is kind of a deeper and more interesting question, which is what does it teach us about aggression or lack their of and I'm curious. Have people been studying that as closely as they've been studying the effects of social media on anxiety and some of these other things? I'm not sure what the current literature is on how social media is affecting play other than it's not happening as much,

which I think is obviously bad. You're out there, you're being physical, you're learning about your body, you're developing relationships with other boys in particular that are trusting, but can involve physical aggression. You mentioned something about wanting to have, what did you say, the chocolate bar? What was it? Yeah, yeah. Your knee-jerk reaction is to always eat something

that's sweeter, more calorie-dense. We have a mismatch. We're designed to be motivated to seek out these foods, and we have to expand energy to get high-calorie foods, say like we would have maybe gotten honey. And that would have been super rewarding, and we only would have had a little bit, and then we would have ran around

and spent those. calories and now we have chocolate bar. That's a mismatch situation that's maladaptive. What's interesting is that we've figured out what to do to some degree with the male, any women watching this who are super competitive and aggressive, that's a thing too. It's not that women are not this way. They certainly are. And I see more and more examples on my iPhone from basketball games and stuff recently. But they tend to be less physically competitive than men. On average. On average. So we have sports that ritualize this motivation or this desire, especially on the part of men.

And we have a lot more men who are interested in watching sports because they're kind of getting that need met vicariously. They're like jumping out of their chairs. Often their testosterone is responding also to even the vicarious participation in sports, which is interesting. Now, given that we evolved for the males to get this aggression out physically, what do we say about boys? that play a ton of video games and get their aggression out there. So you could argue, well, if they're playing with their other friends, I don't know enough about video games, I'm going to embarrass myself, but I'm sure there are super aggressive video games where you're killing each other

and doing something in a virtual world that you would do if you were wrestling. Is there a positive to that? Aside from the fact that they're not getting exercise, of course, and not being physically active. Do we know if that serves as even a reasonable proxy? As far as I know, there isn't any getting your aggression out. getting that need met, if it is a need. Some people don't have that. In fact, most men are not terribly, physically aggressive. There's a competitive, I think you could compare it to pornography

and ask, are men getting out their sexual need? I think there's more evidence that maybe they are getting some need met there. But in terms of aggression, I'm not sure it works the same way. So if a parent is listening to this, is there anything that they should be concerned about? In other words, we know that all siblings are a little bit different. So even my two boys are different. So they're clearly both a step function more aggressive and physical than their sister was at a comparable age. But they're quite different themselves. The younger one is still a step ahead in aggression of the middle one, meaning the younger boy is more aggressive than the older boy.

you say what you mean when you say aggressive? So there's three years between them and obviously the older one is larger. The younger one will instigate physically more. Okay. If he's unhappy, he will attack the larger, older boy. And he doesn't have that same. He doesn't respond maybe even aggressively or. He just hits.

He'll hit anything and anyone that stands in his way. Whereas the middle one is not quite that bad. I feel horrible saying all this stuff. My wife's going to kill me. She's like, you make them sound like monsters. They're not monsters, but it's like they're boys, and this is what boys do. But with other kids, they're more in control, but with each other, they're at their worst. And which, of course, I think is normal for male siblings.

But my point being is just even between them, there's quite a difference in aggression. And maybe it's birth order. Maybe when you're the younger one, you have to stand your ground even more. I used to hit my older brother. So it was kind of a big hitter myself. I guess my point is, should a parent just say, look, I'm just going to let these kids do what they're going to do and understand that there are differences.

Some boys are going to be aggressive. Some are going to be less aggressive. Some are going to play rough. Some are not going to play that rough. Is the best thing you can do as a parent from any available evidence? Just let them do their thing? This is an interesting question. I hadn't thought about it in this way.

So I would say the rough play, generally, if they're having fun, if they're smiling and laughing. let him go for it. They need to learn to work their stuff out. And I think the more play, the better. And we are designed to play boys and girls in different ways. And it helps us learn how to be social and have social relationships and respond physically. And all of that is so important. And if we're not doing that, then I think we're going to have more trouble as adults. But where it's not so much fun and people are getting hurt, yeah, then I think the parent, I don't know. Maybe you let them work that out too.

I don't know. Let me give you a specific example. Are boys more likely to bully than girls? I don't think so. There's this difference where boys will say to your face, you fat, F, they'll insult you to your face and bully to your face. Girls are very aggressive also, but what's interesting is that they tend not to do it in a direct confrontational way where they're exposing themselves as the perpetrator so they can hide from physical harm, which is more adaptive, but they can denigrate the reputation, say, of other girls, which they do because they're their competition in terms of mating competition for, say, high status males, so they can denigrate the appearance or behavior, especially sexual behavior. And it's cruel. It's extremely cruel the way that this sort of

feminine aggression. Do we see that kind of behavior amongst other mammals? Well, we certainly see more face-to-face aggression among male mammals. What we do see in female hierarchies sometimes is that there's harassment, say, in some monkeys, there's harassment of a subordinate female by the dominant, so much so that cortisol goes up in the one who is being harassed and it interferes with her capacity to reproduce. So that is not a physical, necessarily confrontation. It's just harassment. But the sex difference in human aggression with females doing more of this passive aggression, I think part of that is that females have not evolved the same skills to resolve conflicts so that the hierarchy can sort of be reinstated. Males can, you know, have a pickup game on the

basketball court, it can get rough, they can insult each other. But by the end, they've sort of worked it out. Maybe there's a change in the status hierarchy, but they've worked it out. It's over. It doesn't go on for weeks. You don't have to talk about it endlessly. Females do not have the same ability to resolve those kinds of complex social. What for us would be very complex social conflicts. That is such an obvious statement the way you make it. I don't think of it that way, but I completely noticed that, even thinking back to high school. Like we would, as boys, get into huge fights, and it would be over by the end of the day. But there's something that feels fair about that and to sort of backstab and not give somebody the opportunity and not to be able to work it out and to gossip behind people's backs.

Yes, there's murder and rape and men are overrepresented in those horrible crimes, but we should. shouldn't glorify feminine ways of interacting necessarily and try to get men to be more feminine because there's a lot of issues also with typical feminine behavior. So let's talk a little bit about the pathology, though. You just alluded to it. There aren't too many female murderers and rapists. And the disproportionate representation of men in violent crime, you don't need statistics to understand that.

But we definitely do have the statistics, like 95% of murders everywhere. where our male and obviously sexual assault is 98% or something. So what role does testosterone play in that? So here again, I think just like with play, people aren't going to like this. So I want to make sure I say it clearly. I do think that the difference, this broad pattern, is similar to what we see in non-human animals where the males are much more likely to kill each other than the females. There's many more violent or physically aggressive.

interactions. If you look at both of us, we have different bodies. You are bigger and stronger. I started lifting weights because of you a year ago, so I'm getting there, but I'll never get to where you are. Also, I'm older. But physically, men are developed for competition, essentially male-male competition for mates. This plays out in this destructive way in society. And I believe that the ultimate reason for the difference is testosterone. However, the murder rates in Canada, men are committing fewer murders in Canada than they are in the U.S. And more- We can't attribute that to testosterone levels. So that's not because of differences in testosterone level. It is because socialization and culture, religion, the laws all have a huge impact on what the values are in any, any

particular society, what is tolerated, what has encouraged some societies, basically allow men to beat and rape their wives. So you have higher rates of those male behaviors where it's not tolerated and the culture is totally different. You have lower rates of those behaviors. But everywhere you will have the sex difference with all of these behaviors higher in men. I'm glad you asked this because I think the main reason people don't like biological explanations for sex differences is because they misinterpret a tendency or a predisposition for a behavior or a biological explanation as suggesting that it's impossible to change behavior. It's not, you know, that there's no variation across the sexes in behavior. There is. Just because there might be a biological

explanation or even a genetic explanation, the important thing to remember is that we develop within an environment, gene environment interactions, we develop within a society, and how we develop, and even how our hormones, say, respond to different kinds of interactions is impacted by the social system and by the ecology and everything else. So it's complicated. But yeah, I think that the ultimate reason is because of the genetic difference, which is the Y chromosome and the hormones, hormonal differences that it leads to. We haven't talked about female behavior. but of course nurturing, if you're going to be growing and producing and holding and feeding and caring for a baby, and you're the one who absolutely has to do it. And that's the female. Of course,

we get help from men. And sometimes men even take over as the primary caregivers, which is extremely unusual in mammals. So men are capable of all of that nurturing if the society values it. Because some societies don't value that. And then they're still capable, but they're not apt to do that. for females, it just doesn't pay reproductively in general to be super aggressive. We need our bodies to be healthy and we have to live a long life. So the longer our lives, the longer our reproductive output. Men can die young and have great reproductive success. Yes, if they take risks and physical risks. And that just doesn't have the same payoff for females. There are some primates, for instance, where the females are relatively aggressive, but it's almost never to the same extent as males.

It's so interesting when you think about how as humans we hold ourselves to a higher standard than we would hold animals. I'll give you a very concrete example. So if we go back in time 500 years, first of all, neither of us would be alive. Forget that part of the discussion. But let's just say 500 years ago, if you had a male that was 25 years old, he would readily reproduce with a 14-year-old female. That would be completely normal and evolutionarily wise. But we've made a decision, at least in our society, that that's unacceptable. And I think most people think that that's a good decision. That's an example of we have made a societal norm that says it's unacceptable for a 14-year-old girl to be reproducing, certainly at the hands of an older man. So if she gets pregnant,

from a 14-year-old boyfriend. That's a different discussion and we can help them both out. Well, in this country, anyway. My point of this story is we've made a decision that this is no longer acceptable, just as we've made a decision that a husband can't rape his wife. We have just decided that maybe that was cool 200 years ago. It's not cool today. So to play the other side of some of these arguments, is there someone watching us who's saying, Peter, Carol, you guys are talking about all this aggression stuff, but we're humans living in the 21st century. We have to change. We have to evolve as a species. Is there a case to be made that men should be less aggressive because all of these evolutionary reasons that you described aren't as necessary? Women and men are going to live

through their reproductive lives. We don't have this urgency. We don't need this competition. Again, I'm not saying I agree with that or anything, but I'm just saying like there's a steel man for the other side of this, just as in those extreme examples of we don't have sex with 14-year-olds and we don't rape our wives. What would it take for you to not eat that chocolate? Well, it's interesting. Food is a really tough one, isn't it? It can be done. It just takes a ton of willpower. Food is a great way to think about it. There's food and sex, and aggression is for ultimately, in a way, for sex. Yeah, well, I mean, but food. But yes. For men more than women, aggression is certainly more about.

To play off that, I don't need to be an alpha male to get as much food as I need today. But you are an alpha male and you have a lot of food. But I don't need to be. We don't need to be an alpha male to get food. No, that's right. That's my point. So you're saying we should get rid of the drive. I'm just exploring this idea, right?

Because there's physical competition, which we certainly do not need. But think about what we get from the male. So there is a sex difference in certain drives. Men tend to be more driven to achieve specific and more narrow goals and like hyper-focused on certain goals and to achieve to be the top of the heap in one thing. Chess, I wrote some article on sex differences in chess and learned a lot because I was like, why are men consistently better at chess than women? and they are. If you only knew of the rabbit hole, we could go down on that front, but I'm

going to refrain. Okay, so I'm really interested in that. And I had, what I suspected appears not to be the case in terms of, doesn't seem to be explained by differences in cognition. At least that's not necessarily the driving force. What is, I think, the driving force is that boys and men are much more willing to spend countless hours studying the moves and practicing and seeing their coach and trying to beat their competition. And for women, there are other things to do that matter in their lives more. Certainly, there are some women who do that kind of focus, but there are way more men. I'm saying this because that competitive drive, chess, I don't know what we're like

getting out of that? You haven't played, have you? No, I have. You have? Okay. I'm not super seriously, but my son was really into it for a while. My brother, I know a lot of people who are obsessed with it. But when I say what we're getting, I mean socially. Competitive men, I'm not saying that women are not competitive or haven't made incredible social advances in all kinds of domains. But what I am saying is that if we want to interfere with the male desire to compete, we are also interfering with whatever products we get or advances we get from that intense drive. Being in academia, as I was for 25 years, there's a lot that is produced because people want to be first. They want to nail finding this gene or be the first to make a certain discovery. It's tremendous.

tremendously productive often that insane drive that men have. And I think women have less of it because we have kids. We are designed to have the kids. We don't have the same. I must do something else have to produce this other thing with the same drive. Again, there's tons of variation here. There's tons of crossover. This is just a pattern. I think men have more of that, potentially because they're not designed to have kids to produce them with their own bodies. Let me play back to you what I think I'm hearing and with a little bit of... I hope you're not going to be in trouble. No, no, no, no, no, with just a little bit of inference looped into it.

What I think you're saying is, look, for most of 250,000 years, male aggression was absolutely essential for males to reproduce and find and forage for food and protect. More so, certainly. Yep, yep. The past 100 years or so has largely done away with that, meaning a couple things have become true. We basically have domesticated crops in agriculture and lives. stock and we're no longer in a food scarce environment, certainly for the last 50 or 60 years.

Lifesans have extended enough that there isn't a race to reproduce. You can actually live through your reproductive years. So it's not like you have to get this done before you die at the hands of a saber-toothed tiger. Third, infant mortality and maternal mortality rates have plummeted. So the success of your offspring skyrockets and basically all of the other reasons that we used to need to be hyper aggressive with each other to compete for mates, again, food and all those other things, have largely dwindled. But that's a fire that's been burning for millennia. So we have to channel into something else. And so in many cases, in the most polished corridors of society, we've channeled that into

professional excellence or things that would have been... There's sports. Their sports are huge. Totally unnecessary and superfluous hundreds of years ago. Nobody thought of discovering genes or trying to be the leading scorer in the pick your favorite sport. And so it's been a easier or maybe more logical transition of aggression from evolutionary needs into gratuitous needs, making more money, being more successful, being more famous, being more respected in some way. And the maternal need of caring for the offspring hasn't,

as it's coming out of my mouth, I'm sure I'm just butchering this, but it hasn't evolved as much in the sense away from its original goal, which was making sure the offspring were perfectly protected. So there's an asymmetry in this evolution of evolution. Yes. That's what I'm hearing. Do you agree with that? Yeah, I think I agree with the general thrust. I mean, what's interesting is thinking about how, say, nurturing, we still need to nurture. My baby was not always with me when I was working. So there are solutions to that. But I think that nurturing drive is still super strong and valuable and that is probably best for the kid if we indulge. And now paternal attention can be given much more to kids.

Yes. Well, it's interesting because even in hunter-gatherers, there's very different traditions across hunter-gatherer societies in terms of expectations for paternal involvement. And when there's high involvement, there's lower testosterone in those males that applies to humans. Sorry, in the father or in the child? In the father. So for fathers to be very attentive, the testosterone generally is suppressed. And that's true in birds where the males are contributing. If you raise it, they neglect their kids. So there is a hormonal support there for parenting. So that's something that men can do to increase their reproductive success. So I just want to say that I think that is not novel.

If you're a man out there listening with low tea, ignore your kids. With low tea? If your tea is low, you should ignore your kids to raise your tea. Is that the implication? Right, right. It doesn't drop by that much. And what matters is that you're in an environment where you see your little kids. Like if you're a guy and you're mated and you have a partner and you're around your baby and you're interacting with your baby, your tea's going to drop a little bit. And that's a good thing. And this is one of the reasons that supplementing with exogenous testosterone, there are so many different ways that male testosterone responds to and influences social dynamics. And this is one of them that's really important. You're a better dad, potentially, if your testosterone does drop. You're potentially a better husband and more attentive to your wife and your kids. I don't know that there's the experiment. Do we know that there's causality here? I mean, this is a pretty bold statement.

We do. I would say, yeah, we do know. By what magnitude are we talking about here? I should have had the data and I don't have the answer. But it's shown across lots of different populations in humans and non-human animals that fatherhood, first of all, mating, being in a pair bond. This is like what birds do when they finally, they're very aggressive when they're setting up their territory, their testosterone is high in the males. When they find the female and establish a territory with her, the testosterone tends to drop

because it's not adaptive to have high testosterone all the time. It's why animals have mating seasons, etc. Because it's expensive metabolically. Because it would make us go out and look for other mates when we don't need to? You're aggressing and fighting for steps. and singing or flexing your muscles or ignoring your kids or being an asshole to your wife. You're also not reinforcing adaptive behaviors with a bit of a testosterone spike. Like if you're around an attractive woman and you're trying to seduce her, there's very possibly going to be a testosterone increase, which stimulates a dopamine surge and reinforces a behavior if you're successful.

How much can that happen? I'm just saying when you shut all that off, it's like when women go on birth control and they don't respond to men necessarily in the same way that they would have because they have just screwed up that entire hormonal birth control. That system, there's a system in women and in men where those sex hormones are giving you signals about what's happening in the environment and what your role is in your potential. Wait, there's a lot for me to unpack here. That's a whole other thing. No, no, no, but I want to talk about this. Everything you're saying is totally new to me. But I don't want to get away from the fatherhood because this is very well established, this drop.

It happens not just in humans, but in other males where paternal investment increases survival of the offspring, which it does in humans. Okay, so let's talk about that first, but then I want to go back to the birth control and stuff like that. So man and wife have baby. Man decides after a few years, I'm going to stay home more and spend more time with my child. and forego, whatever else I was doing. So I used to be working 80 hours a week. I'm now going to work 30 hours a week. Oh, no, he'll keep working 80.

No, men work harder and make more money, tend to do that. But in this experiment, this guy decides to stay home half the time now. Okay. His testosterone will drop. No, because the kid's too old. Kids five at this point. Then he'll start looking for other females. There's serial monogamy where the man is more likely to stay around during the early years.

And that's when maybe a critical period, I'm not sure for this effect. It's really when the offspring is dependent and young and the mother needs to be supplemented. Again, in a hunter-gather situation, the woman is not just going to have one kid. She's going to have several. And she's going to be nursing or weaning and or about to get pregnant. And she's in a situation where she can really benefit from investment from a male. And he benefits reproductively. So I just want to pause.

He benefits reproductively because that's, a critical window in which his protection is producing his survival advantage. And protection. Yeah. So I just want to pause here. And I want to get back to everything else you said. There are different strategies that different men can use to maximize their output, say, in a natural fertility society.

One is pair up forever with one woman. Mait guard her. Be good to her. I'm going to like getting teary-eyed for some reason. Invest in her. Oh, my God. I have no idea what this is about. It's just I have estrogen and estrogen increases crying, which it actually does. Testosterone inhibits it, although I also put on my testosterone gel this

morning. Anyway, so that's one strategy. And he had to compete and have certain status to get that woman. You want a high quality female. You want to keep her. You can do very well reproductively for your lifetime output. And you're not out on the mating market, constantly being vigilant, constantly trying to take down other males, constantly fighting for status. You can have sex with a lot of women, which is what you're designed to want sex with more partners than females are designed to want sex with. But who knows how many of them are going to get pregnant and who knows how many of those babies are going to survive. But that is one strategy where if you're a high status man, you can be very successful. You can have way more than eight kids. But that's a high risk

strategy. A lot of men are going to fail and they won't have the sure thing of the one female where they can invest in her. That seems to be not a lower testosterone man strategy, but we know that when the kid is young, if the guy is physically involved with a small dependent offspring, that there will be suppression in testosterone. And that is a good thing. It doesn't mean that your muscles will be smaller necessarily as far as I know, I'm not sure how big the drop is, but it does facilitate potentially more contentment with that life. If you have higher testosterone, what has been shown in non-human models is that the attention to the mate and the offspring is reduced. There's more attention to status seeking, aggression, getting sex from other partners, etc. I think it's worth trying to understand what the

exogenous testosterone, which shuts down that system does in men who think there are potentially some very important behavioral and social effects that people don't think about because they're so psyched to get jacked and have more social status and have the dopamine hit, you know, it feels good. I think it's worth looking into. There's so much to unpack there. Again, these evolutionary discussions are so interesting because I have to imagine. that most guys who have chosen the path on your right, which is, I'm going to have as many partners as possible, are not doing that because of reproductive fitness.

Oh, no, of course not. They are often choosing not to have kids. How do we reconcile that? From an evolutionary perspective, I get it. The desire to have as many partners as possible increases your probability of six. Or even just serial monogamy where you're in a relationship and then you sort of move on or you divorce your wife and get a younger partner and then divorce your wife again and get a younger partner.

And is that rooted in evolution of reproduction or is that rooted in the evolution of status in a way that is distinct from reproduction? So I don't think status is distinct from reproduction. Do you mean psychologically? Yes. What is the driver? It's not reproduction. It's sex. Which is interesting.

So this is the first time we're basically talking about sex independent of reproduction. Yeah. Ultimately, of course, we have love. and we have relationships and all of that. But that is for reproduction. That whole love thing is just to get your genes into the next generation via the kid. And the love of the wife is to ensure that maximize the chances of that happening. Is there any other species that does what we do as humans, which is, so you and your husband have a 16-year-old and...

That's it. Okay. So in two years or three years, when he's off in college, I know, I know, it's terrible. right? So you guys will have done your job as parents. No, we're going to keep doing it until we die. Okay, but my point is, the love you will have for each other, the support you will have for each other, is really not in the service of making sure your genes survive anymore. Are there other examples of animals that continue in that behavior, which is when they're past the reproductive age, when their offspring are gone, they stay together. Well, there aren't really too many other animals that get past their reproductive age. So elephants and all these other long, mammals? So menopause, you mean? Who has menopause? Yeah. So some whales, rare captive chimp, or maybe there's some wild chimps who have had menopause. It's just very rare. This is kind of another human socialization then. Grandmothers make a massive contribution to their daughters and their daughters' kids in terms of knowledge and support. Someone who is no longer

capable of reproducing, that's valuable. You don't want to be reproducing. In in your 80s because it's a total waste of energy and you're likely to die potentially from trying, you can invest in your genes that are in your daughter and her kids. So that makes a big difference. I'm still not sure what question you're asking exactly. I think you were saying, why do we stay together in a bond? Is there an evolutionary reason for why humans specifically stay monogamous even after it's not necessary for the survival of their offspring. Because it increases the survival of their offspring. So that trust and commitment, even if you don't have kids, you behave as though you do because you would have. There's

no way you wouldn't have kids. So any couple that's having sex would have been having kids. There was no birth control. And they're still acting that way. The same genes are being transcribed as Yes. So even though we only have the one kid, it's as though he's 16, he might have had a kid already. The two of us together with our bond and work, our experience and our relationship with our kid, we're going to help increase the survival of our grandkids. So our genes are really going to potentially do much better if we stay together. But we are liberated from that. People get divorced and find other partners. So again, going back to testosterone and estrogen, I want to talk a little bit about estrogen now. So obviously estrogen is a very important hormone for men and women. It's appreciated more, I think, in women than men. But to cite one study that I've talked about many times in the past, it's about a 13-year-old study that took a large group of men, chemically castrated them all, and then made them replete with different doses of testosterone with and without an astrosol. So this study basically gave men, I think there were five groups

of testosterone and with and without an astrosol. So for folks listening in astrosol would inhibit the conversion of testosterone to estradiol. So it just inhibits aromatase. That's right. It's aerobatase inhibitor. So you have from low to high five levels of tea with and without estrogen. Okay. So it's a pretty elegant study, right? So it was in the New England Journal of Medicine. I don't remember who publishes. We'll link to it in the show notes. The question was, what did these 10 groups? How did they differ with respect to body? body composition, mood, affect, sexual desire, all these sorts of things. I don't remember if bone density was studied.

It might not have been a long enough study. It's been so long since I've looked at it. But here was the big takeaway. The TLDR was by far the best producing outcome was the highest T with high estrogen. Producing outcome for... Everything for body composition, mood, you name it. The learning, to me, it wasn't surprising that higher testosterone was better than lower testosterone for all the metrics that were measured.

the surprising insight at the time, again, we now, I think, understand this much more. But for me, at the time, the surprising insight was more estrogen was better than less for men, not just with respect to how they felt, but even body composition. This was a wake-up call because I think there were a lot of doctors out there who were prescribing aromatase inhibitors to keep estrogen as low as possible in men. In men who were taking testosterone. Who were taking it. Yeah. Within physiologic norms. Okay. So again, yeah, putting aside bodybuilders who are taking a thousand milligrams of testosterone, where you do have to block some of the aromatization. But if you have a guy who's taking 100 or 150 milligrams of testosterone a week, which would put him to a physiologic upper limit of normal, really, it seems to me, you ought to let estrogen go as high as necessary or as high as it goes naturally shy of producing a symptom. And so let's just spend a minute now talking about the role of estrogen and its role in the brain. What do we know about this? And do we know about, for example, why, at a minimum in some of these studies, and even anecdotally, if a male's estrogen level is too low, it has a negative impact

on his mood? So do you know what the specific outcomes were? Was it libido or energy? Libido was definitely one. I don't recall, gosh, I wish I'd looked at the paper recently. So let's just say libido. Yeah. Okay. So this is interesting. And I don't know the paper. What I will say, first of all, is that as far as estrogen in males in rodents, for example, talking about masculinization in very early development, masculinization in rodents clearly occurs via conversion of testosterone once that gets into the brain via aromatase. So if you block aromatase, you get essentially a female rodent brain. Does that mean that you need aromatase to get testosterone in the brain?

Or does it mean that you need the testosterone to become estrogen to go into the brain? The testosterone gets into the brain. Estrogen is actually prevented. The peripheral testosterone is prevented by a protein called alpha-feetoprotein in rodents. So maternal estrogen is bound so that females are not masculinized. So he enters the brain and is aromatized there. produce testosterone from the male testicles is high. That gets into the brain. Once it gets aromatized, yes, gets in there. Once it gets passed because it doesn't have the alpha theta protein. That's a pretty

elegant solution. It is an elegant solution. So it is clear that it's estrogen acting via estrogen receptors that are masculinizing sexual and aggressive behavior, which is just very clear in rodents because you have lordosis in females and mounting in males and you have higher rates of male aggression. etc. This doesn't happen in humans. This does not happen in humans. I know that there's misunderstanding about that. A lot of people just think, of course, that applies also to humans, but it can't apply to humans because our alpha feto protein does not effectively bind estrogen. We also have men who have can't produce aromatase and don't have estrogen, and they are fully typically masculine in their behavior. They have other issues like with bone. And we also have

complete androgen and sensitivity syndrome where you have X, Y individuals who have testicles, but have a defective androgen receptor and essentially develop, they have testicles and X, Y, sex chromosomes, and high testosterone, but they develop as females because their testosterone is converted into estrogen. So they have no testosterone whatsoever, yet they do have estrogen, they're exposed to maternal estrogens, they're very feminine. Wow. What an interesting phenotype. They must have sky-high estrogen given that all of their testosterone, male levels of testosterone are being converted to estradiol. So they go through female, essentially female puberty, and many of them will discover that

they have testes and X, Y, sex chromosomes when they don't get their period. So they're, like, very feminine. But the point here is that we know for sure this is the case in non-human primates. Do they develop with a male pattern of aggression or a female pattern of nurturing? Totally feminine. Totally feminine. So this is interesting because this is a point mutation in the androgen receptor gene. One small mutation.

Everything else is just typical male. You just get the one mutation in the androgen receptor that is disabling it and you take what would have been a typical male and you have someone with testes and X, Y, sex chromosomes. You don't have the double X. You have all the genes on the Y, but you have a totally typical, for all intensive purposes, girl and then a woman. So outside of the sterility, I assume, of this individual, does she go on to be a completely normal woman? Totally. More feminine, I would say, than other women who have testosterone.

So really not a pathologic condition outside of the sterility. No, no. Wow. Never even heard of this. There's incontrovertible evidence. that estrogen is not the masculinizing hormone acting via the estrogen receptor in early development in humans. But then you're raising all these questions about the role of estrogen in adulthood.

And I think, so this one study is interesting, and I think it is important, but I couldn't say with authority exactly how. It's important for bone, you know, it's important for the body. But in terms of behavior, I believe it's important. for sexual behavior, but we do have these guys who don't make estrogen who seem to be normal. They don't have the aromatase capacity. Sorry, yes. And I should mention also that in these women who have complete androgen and sensitivity syndrome, they seem to be sexually normal. There's no differences in sex drive

and orgasmic capacity, even though they have zero testosterone. That's interesting. And there's limited data, I should say, because it's a rare condition. But what we do have suggests that they have estrogen and that the estrogen somehow compensates. And they have the same libido? From the studies that I have seen, yes. I don't know if maybe the peak isn't as high in puberty or something like that. Maybe there are differences there, but I don't see that in the literature. And they presumably they must have a little more difficulty putting on muscle mass.

Well, I have tried. They don't have to. Yeah. They have no acne. They don't have to shave. I worked with a student very closely who had this condition. It's a difficult condition when you're a normal teenager and you learn that's a difficult situation.

A lot of these are very challenging. To me, the most interesting outcome of the study was not, to my recollection, that the men with higher testosterone felt better. it was that they actually put on more muscle mass as well. With the estrogen. Yeah, with the higher estrogen level. Yes, that is my understanding. And I don't know enough about exactly why that is and how it works.

I'm not surprised. I think estrogen is very important in men, in adults. It may be important in early development in some ways that we don't yet understand. So what do you think all of this teaches us about the role of testosterone replacement therapy in both men and women? So let's go back to something you said some time ago. So if we didn't muck around with nature, men would experience a pretty steady decline in testosterone from puberty on down. In Western populations. Because we don't, Hunter Gathers tend not to have that.

Oh, okay. Well, say more about that. Well, they start out with lower testosterone because, again, high testosterone is expensive to maintain. Most animals keep it low and only raise it when females are fertile and they need to compete. So that's why there's the rut. That's the rut. Like the red deer, you know, grow, their testicles grow. They grow weapons on their head.

They become horny. They become aggressive when the females are fertile. If the females aren't fertile, all that stuff goes away. Testosterone drops. Okay. So humans are also designed to keep testosterone low, which is why if there's a situation, a competitive situation, say, testosterone might go up, but generally it's going to be kept low when it can be, but we are overnourished in Western populations. We don't have to worry. We have enough calories

to run our immune system and to do everything else. We need to do. We have the luxury of being able to elevate testosterone over what it would be naturally. In the case of the deer, all of the females go through estrace at the same time. So it's easier for the bucks to say, For these nine months, great point. Great point. I don't need testosterone because all of the doze are infertile. And then bingo, now they're going through S-Trace. We're going to go through the rut and it's a party.

But with humans, I understand there's some literature that says the more women that are together, the more their cycle sinks. But that's got to be weak. And by the way, women are ovulating every month. I'm so glad you brought this up. This is why you guys are the hormonal ones. Let's say that. So everyone says women are hormonal. You're the hormonal one. You have this high testosterone all the time. We just don't notice that you're hormonal because it starts in utero and you're permanently hormonal, basically. Let's just get that out there. But you are hormonal because there's always going to be fertile females around. So that's just an interesting point. But given you have to maintain high testosterone levels throughout your entire life, we, only maintain our high estrogen through a fixed time, our reproductive career, which is when

we're most attractive. If you look at hunter gatherers, they have like a high pathogen load. They have fewer calories coming in. They have high energy expenditure. They have other stressful, energetically stressful situations to deal with that we don't necessarily. So they keep their testosterone levels lower. The peak is significantly lower. I think it's like at least a third lower. And then there's no real drop-off. And they stay active and healthy, relatively healthy throughout the rest of their lives and the testosterone. They don't have that 1% loss, say, per year. And there's no problem with fertility, even though their levels are much, much lower than ours, which makes me skeptical about some of the explanations for the trend that we see

a drop in testosterone levels in men and a drop in fertility because it's definitely, if you look at these natural fertility populations, you see that we are starting out really high. Men should not, I don't really see why there would be a reduction in fertility per se that isn't caused by other health issues, for instance. In other words, you're saying it's hard for us to blame fertility in the Western world on declining testosterone. On just the testosterone. Because I think the testosterone must be declining because of all these other things

that are affecting fertility. Yeah, it could be the inflammation that arises from the metabolic dysfunction. Yes, Thales, you know, that's what. Exactly, but other, exactly. Going back to kind of Western society, so we see this roughly 1% per year drop in testosterone.

And so a guy in his 50s now has, hell, a guy in his third, today has a lower testosterone than a guy in his 50s did 40 years ago. So a guy in his 50s today has pretty low testosterone. And we certainly know that medically it's a completely safe thing to replace. And we know that there are great outcomes with respect to bone health, with respect to frailty and many subjective findings. And we know that it's not increasing the risk of prostate cancer and heart disease and all the things we used to worry about outside of the edge case. of hypertension, which can be managed.

But all of that said, is there a case to be made that we should not be replacing testosterone in men because it turns us backwards in terms of this aggression? And it's more likely to make that 55-year-old guy want to find himself the 20-year-old girlfriend. I don't know that that's been shown. So you're saying testosterone's great. Why shouldn't we give it to people? No, no.

I'm asking the opposite question. Okay. I'm saying, given everything we've just learned about testosterone, is there a negative consequence to take in a 55-year-old guy and restoring his testosterone to what it was when he was 18? Make the argument for why that should happen. Why you should restore it back to when he's 18? Yes. Do you think that should happen?

It totally depends on the symptoms, would be my take. So if a guy is having difficulty putting on muscle mass, if he's complaining of something, see, there are some guys who say, I'd like to have sex once. a week and my wife would like to have sex once a week, and that's what we do, and that's fine. Conversely, there are other guys who say, my wife wants to have sex every day, and I want to have sex once a month. Yeah. Now, this is a problem.

But if my testosterone is what it was when I was 18, I'd like to have sex every day. My wife would like to have sex every day. Now we're happy. There isn't a formula here, but that's one example of how you're trying to match the symptoms and what the patient is saying to what you can do. There are some guys who have no difficulty putting on muscle mass despite having a testosterone of the 20th percentile. It might be that their genetics are such that that was the case, or they put on a lot of muscle

mass when they were younger and it's just easier to maintain it. There's certainly evidence that insulin resistance can be ameliorated by correcting hypogonadism. So there are reasons to consider doing it? What I'm trying to get at is, are there negative consequences of doing it from a behavioral standpoint? And I'm not talking about roid rage and things like that, which has largely been debunked. outside of, again, these edge cases where people are taking superphysiologic doses,

in terms of being a productive non-assholic member of society and not being overly aggressive or engaging in harmful behavior, risky behavior, what's the pro and con case for that in your mind? I imagine that the doses that you're giving, it's, I think, been shown pretty clearly that if men are within the typical range, even at the low end, you don't see changes in sexual or aggressive behavior within the normal range. You see differences in physical parameters. Yeah, the most complicating thing, if I could wave a magic wand, wave one magic wand in medicine right now. What would I have? I would have a PSA equivalent for breast cancer. Come back to why that would be a game-changing solution down the line. The second thing, which would not be nearly as important,

would be I would love to have an assay to measure androgen receptor density. Oh, thank you for bringing that up. Because what we can't, we tell all our patients this, they look at us like, just measure it. And I'm like, no, no, you don't understand. We don't have a test for it. And they're like, how do you not have a test for this? Can you do the CAG repeat? I mean, I guess you could.

That would be, is there a commercial test for that? I mean, and you can do that in the lab. Yeah, I don't know if there's a commercial test. You should get it if there is. Someone should develop a CLIA approved assay for this. Does everybody know what the category? No, they don't. But the point I really want to make is, why is it that one guy can have a testosterone of 400 and feel totally fine?

And another guy can have a testosterone of 400 and feel totally depleted. And if you took both of those guys up to 1,000, the first guy would be like, I don't feel any better. And the second guy would be like, you've changed my life. Can I ask you a question about that? Because you know a lot more about this, I think, than I do. if you have the guy who feels bad on 400, do you eliminate all the other things? Like, how can you eliminate all the other things that could be causing him that are going on in his world or in his body? No, you can't, but you can just change one variable at a time.

But if you change that one variable, is that overriding the potentially negative effects of inflammation or depressing situation in his social life or whatever it is? Typically, T won't fix a lot of those things. The most obvious things you try to fix are sleep, nutrition, and exercise. Regardless of what his testosterone level is, if it's 400, which is very low, especially if his free testosterone is equivalently low. And he's got these vague symptoms. It's like, well, look, if you're not sleeping well, eating well, and exercising well, let's fix those first.

Or obesity, do you have to? Yeah, sure, absolutely. But you can't always fix those things to the nth degree without wanting to at least experiment, especially when it comes to body composition stuff or energy levels. So by making the one variable change at a time, you can say, look, let's do the experiment. If your T is now 900, and we haven't made a change during that period of time other than that T, and you're telling me, I don't really feel that much different. My hypothesis is you have a pretty low density of androgen receptors and they're largely saturated

at 400, and therefore this isn't really the fix. There's something else we need to be looking at. Yeah, I'm glad you brought up the androgen receptors because I think people don't appreciate the fact that one person's 400 is not another person's 400. I know you talk about this a lot, about carrier proteins, but also there's the genetic differences in the receptor itself, which is the CAG repeat, which predict the efficiency of its ability to transcribe the androgen responsive of proteins and just the overall concentration. Where are your androgen receptors and how highly concentrated are there? Of course, it's going to be different in different parts of your brain and

body. So all of that really makes much more complex the interpretation of a single measurement. So that being said, yeah, I don't know. I don't know. I'm coming from a place of thinking about how this all works naturally to promote especially behaviors that are adaptive. I'm on progesterone, testosterone, and estrogen. I'm 59, and I had my ovaries out a couple years ago. And I have to say, I just want to say when that happened, I was 57. So I was already in menopause pretty much, and everything changed after that. It made a huge difference. My hair started falling out, my sex drive plummeted. Sorry, just to be clear, you were on hormone replacement therapy prior to. No. No. Okay. I just want to throw that out there because I'm supposed to be an expert in hormones, and I had my ovaries out at 57, and it had a huge impact. Even though you were already in menopause. Yeah, I mean, I guess I wasn't.

We found out I wasn't actually. I had some fresh corpus luteum in my ovaries, so they said I wasn't actually in menopause. But yeah, it's just amazing, even when they're pumping out low levels of hormones. I think they're still pretty impactful. So why did you decide to only go on? hormone replacement therapy at the age of 57 when presumably you believed you were in menopause prior and didn't go on HRT? It's a good question.

I guess because I felt fine and it wasn't until... It was gradual. It was gradual. Yeah. And I think especially because of you, I started lifting weights a year ago. You looked like you've been at it for years. Oh, thank you. No, I was just a runner and Peloton and biker and all that.

And it's made a huge difference. I just want to say to get into lifting. now I'm addicted to that and now I have a back injury. She'll have to help me with later. So I think the testosterone must be helping in terms of my really getting into the workouts and how much I can lift potentially. I guess I'm saying I myself am on these hormones. And it sounds like you feel better as a result of it.

Yeah, I think so. I think I feel better, but I definitely feel better when I'm working out and the drive. But maybe I would have done that anyway. But I have no issue with people doing what they need to feel better. I just think people don't consider that especially testosterone and I think also estrogen, these are hormones that give us signals about what's going on in our own bodies. Like, are we making eggs? Are we making sperm?

Are we healthy? Are we sick? All of that is communicated. Like if you're sick, those systems are suppressed and your hormone levels are going to be lower, which is adaptive and it will help. you and, you know, and that won't happen if you're taking it all exogenously. And there's a lot of social signaling. So all of that goes away. But yeah, I think that's for each individual to decide. I do think there should be some regulation around testosterone because, from what I understand,

it really is addictive and also can permanently cause someone to become infertile. That's something obviously that I don't know that people, young people in particular, really understand. So I think it's different when people are after the age of 40 or 50, is it different situation from someone who's young and healthy and is doing it and is getting addicted at younger ages. I think we should be much more careful. Yeah, that's an interesting point. Because as you know, but maybe some of the listeners don't, testosterone is a regulated, scheduled drug hormone, whereas estrogen is not.

estrogen can be prescribed without any DEA scheduling testosterone is a schedule. I believe it's a schedule four. But that's an interesting point that you raise, right? Which is one reason to consider scheduling it is the potential for abuse is much more significant in younger men who might not realize. And sadly, a number of them don't realize, hey, if I take this stuff for three years in my 20s, it could significantly and potentially permanently affect my fertility. Yeah.

And it's hard to come off from what I'm. I understand it's very hard to tolerate the transition and the withdrawal where you now, you can't get an erection, your libido tanks. I just don't have experience with it because it's simply not our patient population. So I can't speak to that at all. And my guess is everything you're describing would be more the result of abuse. I don't like using a judgey term like that. I reserve that term for non-medical use that is hyperphysiologic.

Educate me on this. So if you have, or if there is a 25-year-old who's just supplementing to get to the high end of normal range, she's still going to shut down his- He's going to shut his HPA down. But here's the thing. I have a really hard time believing that a 25-year-old should ever be on exogenous testosterone. Okay. Because they are, right? It's really increasing at these younger ages. I assume so. I have to plead ignorance here. I really have no sense of how widely. Yeah. But to be clear, when I was 28, 29, 30. So when I was in my residency, my testosterone level was 220 nanograms per deciliter. Right. I remember saying this on another show. Right. So I was like, I was two X the level of a woman instead of 10x, 5x or whatever, right? But did that mean that I should have been on TRT when I was 30? Definitely not. No, it meant that I needed to get the hell out of residency and actually start sleeping at night. And that's what you did, right? Yeah. And then whatever, like four years later. five years later, I had normal testosterone.

Wow. So again, if a 25-year-old is walking around with a testosterone of three to 400, I would be much more inquisitive about fixing a whole bunch of things and much slower to move towards replacement. And by the way, even if I was going to replace it, I would not be using testosterone. I'd be using HCG. Right. I'd be preserving gonadal function as opposed to completely suppressing it.

I see. Whereas if a guy is 60, if he's fine with testicular shrinkage, which would be the fundamental difference in using exogenous T when you suppresses HPA access, then I think it's less of an issue. I don't want to speak for many authority on treating young people. I simply don't have that experience. I don't have even a sense of how widely used it is. I guess it is a good additional hurdle to have it be DEA mandated, regulated, scheduled. Yeah. So what are you up to right now? So I am trying to finish a book proposal. I'm spending a little more time with my son, which is nice that I'm home when he gets home from school. And I have a part-time job at a DC think tank, which I'm really enjoying. And I do some writing. I have other things that I do, but those are the relevant things. I don't want to go too far down the rabbit hole of what many people, if they Google, you are going to learn about the horrific experiences you had. But how long ago was all of that? That was about three years ago? So that was started in 2021, yeah.

So four years ago. So how has this experience been for you? You're four years on the other side of, I think what any reasonable person would look at and say is just a complete and total injustice. Thank you. A lot of incredibly cowardly people that I'm sure at one point you felt were friends and colleagues completely sat by silently as a minority mob went after you. How were you recovering from that experience? It's been really difficult because I was just reading my acknowledgments in my book on testosterone. And I wrote, you know, I have a great job. I have the privilege of interacting with these amazing young people.

And teaching and advising undergraduates is hard. It's hard. I teach about some really controversial and detailed and intricate top. And I love that. I love putting in the effort and feeling the reward every day. And I love the relationships and changing people's lives and having them change mine. And it's work that is challenging and so deeply rewarding. And it helps to provide a sense of meaning in life and a sense of accomplishment and all these things. So not having that is hard. And it's hard coping with the reason I don't have that. And all the people and the institution I trusted and gave so much to and

feel, yeah, I feel that I was treated pretty horrifically. It's hard. I've had transitions before, but this is a big one. I thought I'd be in that job forever. But what it has done for me is made me much more committed to doing something like what you do. Part of why I'm a huge fan of yours, and I'll probably start to cry again. And I think it's very rare that people get so into the scientific weeds. I don't detect any bias on your part. I detect your very open and honest struggle to understand the evidence and to talk about the evidence and where it points. And that's what I've always tried to do. And I think it is so important, not just for science, but for people to be able to communicate with each other and share facts. Maybe we disagree about the implications.

of the facts, but it's so important to take ideology and bias out of our understanding of reality. Reality's there whether we like it or not. It's always to our benefit to understand it and to try to figure out then to use democratic processes to figure out what to do with reality or how to improve human health or whatever the issue is. So I guess that experience has just made me much more committed to doing that and to advocate for that. isn't always easy. And some of the things I said today are controversial. But, you know, I'd love to hear if people disagree why. And then that's how we learn is by having our views and interpretation of evidence challenged. So given how in many ways successful you were as a professor, how much

your undergraduate students loved you, it's certainly one vehicle through which you can communicate this passion. Do you see yourself going back to that situation? Do you see yourself winding up back at a different university one day, or do you feel like the scars are sufficient that you don't feel like being in that arena again? Yeah, we didn't say what happened. I'll just say that I wrote a book, T, the story of testosterone, the hormone that dominates and divides us. And I went on Fox News and said that there are two sexes, male and female.

And someone who is representing themselves as speaking on behalf of Harvard in my department, accused me of transphobia, and then there was other bad things that happened. And it resulted in me feeling I had no choice but to leave my job that I'd been in for over 20 years and loved. Would you see yourself back? No, because I was traumatized. I was in shock. I could not believe how people were behaving.

And I learned a lot. And one of the things I learned is that I was way too trusting. Whatever I do, I want to throw myself in. into it. And I threw myself into that job. And that's why it hurt so much because that was me. That was like all of me. I kept some of me for other parts of my life, but I really threw myself into it. Everyone who worked with me knows that. And so it feels way too risky. I won't trust an institution like that again. Or I don't know. I'll have trouble. Yeah, academia for me right now, not a fan. Yeah. I think I'm sure a lot of people can relate to that because anybody who's put

every bit of themselves. Take an example like your first love, the first person you fall in love with. If they break your heart, you're going to sit there and say, that wasn't worth it. Like, I'm not doing that again. The bliss of that experience wasn't worth the pain I'm experiencing today. And I'm not going to sit here and suggest that you have to do it again because of look at all the students you were able to help because there's other ways to do it and you're obviously writing another book. And so the truth of the matter is being on a podcast probably reaches more people than you would reach in 10 years of teaching. Right. What is your next book about if you're, are you comfortable talking about what the subject is? Oh, totally. I'm really excited. It's about what's happening with masculinity.

And I'm really interested in the cultural narrative. Here's where I also cry. And that's how I knew I needed to write a book because why am I crying about masculinity and men being denigrated, which I get very upset about that. I wanted to really understand what was happening culturally, why we are in a place where masculinity is not valued and also to explore the interaction between biology and genes and hormones and what's happening culturally. Why is it that these cultural changes that we've had are affecting men in the ways that are different from how they're affecting women, like economic changes, men are falling behind in education, for instance, and what's happening in schools? And why?

our schools may be less hospitable to typical male ways of behaving than typical females. So I really want to dive into that intersection and to explore some of the questions that you were asking today about aggression and we were talking about men's need to compete and how it's different from women and how that plays out socially. So I want to explore those issues really with an eye to understanding what it's called the masculinity crisis and there's a kind of backlash. going on right now, which I think is interesting in that men and their needs and their right to be masculine, I think, has been under attack. And now I think some men are feeling freer to be more

masculine, I would say, today. What I want to explore is the denial of sex differences and how that plays out socially. Because if you believe that men and women are equally interested in engineering, then you don't believe in sex differences. You don't believe there are important, meaningful between the sexes that play out in society that are not all the result of the patriarchy, say. Certainly there are social influences, and that all matters. But there's this denial of real differences that we need to grapple with socially. If you believe that all the differences are the result of society, then you're justified. Potentially, you're more justified in trying to create equal outcomes. But if you deny biological differences, then you have more of a reason to do that. But if

you appreciate that they're real and that we have to grapple with them socially, then it's going to be more complicated. I completely agree. I mean, I joke about this with my wife all the time, right? The reaction she has to a naturally aspirated V8 engine screaming at 10,000 RPM versus my reaction. So you go towards, she goes away, basically. I mean, like, it's the greatest sound I, ever heard. And she is like, what is that awful noise? And there's no socialization that creates that difference. On average, we can only talk in averages here, men are way more hardwired to love that sound. There are incredible... Who to be interested in cars. Sure, sure. But there are incredible YouTube videos where you can

literally listen to every engine. Oh, and it's like ASMR for you? Yeah. The V8 and V10 naturally aspirated engines screaming is the greatest sound ever. I don't know what naturally aspirated. You don't have forced induction of air, so it revs very high. But yes, like if I had my wife listen to that, first of all, she wouldn't hear the difference between any of them. And she would think they all sound awful. They're too loud. And can we just remind your listeners that we are definitely not saying that there are no women interested in cars or that they can't be very enthusiastic. What we're talking about is differences on average, especially those, not with the cars, but a lot of what we've been talking about are differences on average that persist throughout history around the globe and that are shared with non-human animals

and for which we have a mechanism which makes sense, and that is differences in sex hormones. So how do you think as you write this book, you will be able to do the seemingly impossible task, which is to write about this in a manner that is scientifically objective without getting dragged into an ideological political mud pit. I think I did it with my last book. I pulled that off in the writing, in the book. It was being in academia and talking about it in a way, just saying that male and female are real. That was taken as a undermining the rights of a certain group, essentially. And there's just nothing that you can do about that. I think the way to respond is to encourage people to engage with arguments instead of assassinate character. That's part of what is very important to me is encouraging that and teaching people how to do that. And that's what I did in my teaching in my classroom. And it was great. There was really never an issue in my own classes, even though we got into the most controversial subjects.

So I'll just keep trying to stick to the evidence and always remembering these are people's lives, you know, and being compassionate and emphasizing that biology is not destiny. There's a huge amount of variation. And it's perfectly normal to be a little boy who wants to play with dolls. Like that it's even hard for me to talk about because it's heartbreaking that people feel stigmatized for not being sex typical. But that's something where if you understand the science, you understand variation and you understand. what is normal. And there's a spectrum, a huge spectrum of behavior across the sexes. There's just only two sexes and we should learn to deal with that kind of reality. Well, Carol, really appreciate this discussion and appreciate without having experienced it personally what you've been through, which I think is heartbreaking. I know several others who I'm close to who have been similarly just decimated by the mob. Yeah, the mob, the angry mob. So I think the good news is, is virtually all reasonable people can agree on a set of facts, but you can't please everybody and there's going to be certain individuals who are going to have their points of view.

Excited to hear you working on another book and excited that you've got more time at home to do so. Thank you so much for having me. It was great. Thank you for listening to this week's episode of The Drive. Head over to peteratia-md.com forward slash show notes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram, and Twitter, all with the handle Peter Atia MD. You can also leave us review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice

of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very

seriously. For all of my disclosures and the companies I invest in or advise, please visit peteratiamd.com forward slash about where I keep an uption. date an active list of all disclosures.