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

View the Show Notes Page for This Episode https://peterattiamd.com/carolehooven/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251201-pod-carolehooven&utm_content=251201-pod-antoniobianco-podfeed Become a Member to Receive Exclusive Content https://peterattiamd.com/subscribe/?utm_source=podcast-feed&carolehooven%20=referral&utm_campaign=251201-pod-carolehooven&utm_content=251201-pod-antoniobianco-podfeed Sign Up to Receive Peter's Weekly Newsletter https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251201-pod-carolehooven&utm_content=251201-pod-carolehooven-podfeed 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 https://twitter.com/PeterAttiaMD, Instagram https://www.instagram.com/peterattiamd/, Facebook https://www.facebook.com/peterattiamd/ and YouTube https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg

• 0:11Speaker 00

  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 a subscription.

• 0:54Speaker 00

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• 1:04Speaker 00

  My guest this week is Carol Hooven. Carol is a human evolutionary biologist, 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 and Divides Us." In this episode, we discuss how prenatal testosterone shapes the male body and brain, turning genetic signals into thousands of developmental changes that underlie later sex differences, critical hormone surges and why they matter for lifelong behavior, DHT, androgen receptors, and rare natural

• 1:49Speaker 00

  experiments, for example, five 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 erupt. Race, 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 Hooven.

• 2:40Speaker 00

  Carol, thank you so much for coming out to Austin. Great to meet you in person.

• 2:43Speaker 01

  Thank you so much for having me. I'm thrilled to be here.

• 2:46Speaker 00

  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

• 3:31Speaker 00

  because 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, socialized 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

• 4:16Speaker 00

  and hear stories of what my mom said I was like.

• 4:18Speaker 01

  How old are your boys now?

• 4:20Speaker 00

  Eight and almost 11.

• 4:22Speaker 01

  Okay.

• 4:23Speaker 00

  I wouldn't say they're a different sex. I would say they're a different species.

• 4:26Speaker 01

  Yeah, I was just gonna say that.

• 4:27Speaker 00

  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 am 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?

• 5:01Speaker 01

  So I want to make sure to come back to everything that you just said. So how did I get interested? I'm gonna 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 gonna go study this. But I did become intensely interested

• 5:46Speaker 01

  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.

• 6:17Speaker 00

  Say more.

• 6:18Speaker 01

  The cultural differences were so profound in terms of the incredibly important role that sex plays in social life, and the segregation.

• 6:30Speaker 01

  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.

• 7:10Speaker 01

  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.

• 7:49Speaker 01

  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,

• 8:33Speaker 01

  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 in 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 proximally. That means what's happening here and now in the organism, why the sexes are different. And then there are these deep evolutionary pressures

• 9:18Speaker 01

  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 watch 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.

• 9:52Speaker 00

  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?

• 10:08Speaker 01

  So vertebrates, most vertebrates will have testosterone or something very, very close to testosterone. Yep.

• 10:14Speaker 00

  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?

• 10:26Speaker 01

  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.

• 11:11Speaker 01

  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.

• 11:41Speaker 00

  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?

• 11:50Speaker 01

  No.

• 11:51Speaker 00

  The males would be higher?

• 11:52Speaker 01

  The males would be higher.

• 11:54Speaker 00

  Despite the fact that phenotypically, they look the same and they're both equally aggressive?

• 11:58Speaker 01

  I believe they're either just as aggressive, if not more so. I think they're, I believe that they're dominant to the males.

• 12:04Speaker 00

  Got it.

• 12:04Speaker 01

  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.

• 12:18Speaker 00

  So the extent of my recollection from 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 XX or XY in terms of humans.

• 12:32Speaker 01

  In humans, yes.

• 12:33Speaker 00

  Yeah, right. So we can talk about Turners and Kleinfelter's and things like that later. But in the 99.9% of cases of XX and XY, what are the steps? And how do they involve sex hormones that create the phenotypic differences in the embryo?

• 12:52Speaker 01

  So phenotypic, we'll just stick to the body and then we can also talk about the behavior.

• 12:58Speaker 00

  Yes, yes, exactly. That's what I want. I just want to start with, let's get through the first nine months.

• 13:03Speaker 01

  Yeah.

• 13:04Speaker 00

  And then like, let's help understand how those two options of chromosomes lead to two different body types.

• 13:10Speaker 01

  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.

• 13:38Speaker 00

  Chromosomes or the sex hormone?

• 13:39Speaker 01

  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 hermaphroditic, produce both gamete types at the same time, or they can be sequential hermaphrodites. 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 the sperm.

• 14:20Speaker 01

  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 XX and XY. So let's just start with the XY. So you were an XY, I had a son who is an XY, 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 XX and XY are both, they're almost identical until that time.

• 15:02Speaker 01

  And the Y chromosome has a gene on it called the sex determining region of the Y chromosome that produces a protein called the SRY protein. And this is a very important protein because it triggers the differentiation of the undifferentiated 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

• 15:43Speaker 00

  Two systems.

• 15:43Speaker 01

  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.

• 16:26Speaker 00

  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 XYs and make them male phenotypically. But that's obviously oversimplified.

• 16:47Speaker 01

  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.

• 16:57Speaker 00

  Because if you have an XY that is missing that region, you will be phenotypically female, but chromosomally male.

• 17:06Speaker 01

  You will be chromosomally male, sure, but you won't develop functional ovaries.

• 17:11Speaker 00

  Correct.

• 17:12Speaker 01

  Because you need two axes to do that.

• 17:13Speaker 00

  But for all intents and purposes, you would look female, correct?

• 17:16Speaker 01

  Yes, yes. So your external genitalia would appear to be female. We'll get into those cases.

• 17:24Speaker 00

  Yeah, yeah. Again, these are kind of these edge cases.

• 17:25Speaker 01

  But yeah, if you think about what the genitalia look like in an 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 SRY. And what that does is it causes certain cells in this undifferentiated gonad

• 18:05Speaker 01

  to develop into first Leydig cells and then later Sertoli cells. So that's happening, and then later ovarian differentiation takes place. So two things happen. The Leydig cells start producing testosterone first. And I'm going to go back and just talk about the Wolfian ducts and the Malarian ducts.

• 18:30Speaker 00

  Oh, my God. I have not heard that term since medical school. What a blast from the past.

• 18:36Speaker 01

  OK, so this is DUCTS, not duck like quack-quack. So these are duct systems.

• 18:43Speaker 00

  Duct, yeah.

• 18:43Speaker 01

  And so here's another cool thing. So we start out with this two primordial or primitive gonads that can become either.

• 18:53Speaker 00

  And they're high. I remember.

• 18:55Speaker 01

  Yes.

• 18:55Speaker 00

  They're in the, almost in the chest.

• 18:57Speaker 01

  They're high, so obviously the males have to descend into what becomes the scrotum, and the females just stay there.

• 19:03Speaker 00

  They stay there.

• 19:03Speaker 01

  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.

• 19:12Speaker 00

  Maybe temperature regulation?

• 19:14Speaker 01

  Yeah, I wrote about this in 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 vole 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?

• 19:37Speaker 00

  To just be able to regulate.

• 19:38Speaker 01

  Some genetic constraint.

• 19:40Speaker 00

  I'm just gonna 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.

• 20:22Speaker 00

  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?

• 20:34Speaker 01

  So the chimps did this.

• 20:35Speaker 00

  Well, so finish the punchline.

• 20:37Speaker 01

  Yeah, sorry, sorry.

• 20:37Speaker 00

  Punchline is whatever that number is, it's enormous.

• 20:41Speaker 01

  Yeah.

• 20:42Speaker 00

  Now, what's the number of females that have gone up to another female and gone bing and tried to flick them in the clitoris like zero?

• 20:50Speaker 01

  There is sometimes a little breast play, I guess.

• 20:53Speaker 00

  But it's like.

• 20:54Speaker 01

  To the teenagers, but nothing like but what boys do, what men do.

• 20:57Speaker 00

  You're talking about a ratio of zero to 87 billion, 432 million.

• 21:03Speaker 01

  All right. Give me your hypothesis about why this happens.

• 21:06Speaker 00

  I mean, my only hypothesis is males are idiots. It's such an evolutionary stupid thing to do.

• 21:13Speaker 01

  Yeah.

• 21:14Speaker 00

  Like, that's a very precious part of real estate.

• 21:16Speaker 01

  That's the point. So why would they do that?

• 21:18Speaker 00

  So maybe it's threatened. It's like, basically, I'm gonna make sure you can't reproduce. I'm gonna be dominant. I'm gonna reduce your probability of reproduction.

• 21:25Speaker 01

  So these are kids who are good friends, usually, right?

• 21:27Speaker 00

  Yes.

• 21:27Speaker 01

  And only a good friend could do it.

• 21:29Speaker 00

  Yeah. Well, only a good friend will get away with it.

• 21:32Speaker 01

  Yes.

• 21:32Speaker 00

  Like, if a stranger did it, then you're gonna come to blows.

• 21:34Speaker 01

  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,

• 22:15Speaker 01

  "I'm down for you. I'm not gonna hurt you. I'm holding your testicles, and you can trust me." I don't know, but that's interesting.

• 22:25Speaker 00

  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."

• 22:34Speaker 01

  Yeah.

• 22:35Speaker 00

  So there's all these things we don't understand.

• 22:37Speaker 01

  Yes.

• 22:37Speaker 00

  And one of them is, why would you leave this precious real estate outside your body if you could potentially thermo-regulate inside the body?

• 22:44Speaker 01

  I mean, maybe there's an answer now, and I haven't found it, and someone will write in or something.

• 22:48Speaker 00

  We'll hear about it in the comment section, yeah.

• 22:50Speaker 01

  So I'm just gonna go through the ducts a little more quickly. That's, there's two different systems. So the Wolfian ducts become, what I'll just say is, the male internal plumbing. And the Malarian ducts become what is the female internal plumbing.

• 23:07Speaker 01

  So what's important is that the Leydig cells produce testosterone, which stabilizes the development of the wolfy inducts. The testicles have to produce two hormones. Leydig cells produce testosterone to stabilize the wolfly inducts to connect the sperm-producing organ to the delivery system ultimately, which is the penis, and they have to cause 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.

• 23:52Speaker 01

  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.

• 24:01Speaker 00

  And by the way, at any point is any of this testosterone being converted to DHEA in any meaningful amount?

• 24:08Speaker 01

  Not that I know of, DHT for sure. That's extremely important, and that comes next.

• 24:16Speaker 00

  Sorry, I meant DHT. I'm sorry.

• 24:17Speaker 01

  Okay.

• 24:18Speaker 00

  Yeah, yeah, yeah.

• 24:18Speaker 01

  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,

• 24:59Speaker 01

  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. DHT 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.

• 25:32Speaker 00

  I've never thought about this until now. Is that why DHT has such a high affinity for the androgen receptor, you think?

• 25:40Speaker 01

  Yes.

• 25:41Speaker 00

  Is 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.

• 25:54Speaker 01

  So I don't think it would matter as much.

• 25:57Speaker 00

  I'm OK to be exposed to circulating androgens in a way that the fetus presumably you wouldn't want.

• 26:03Speaker 01

  I think that DHT is something like two to five times more potent.

• 26:07Speaker 00

  I thought it was even more than that.

• 26:09Speaker 01

  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, five alpha reductase deficiency, where individuals are basically just typical males, but they happen not to be able to produce DHT. We can talk about this later, but it seems not to have any.

• 26:53Speaker 01

  DHT is not what masculinizes the brain, but it does masculinize 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.

• 27:09Speaker 00

  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, these very, very rare disorders. But again, fortunately, they're not common.

• 27:22Speaker 01

  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.

• 27:50Speaker 00

  Going back to that specific case, you have an individual that is born that, I assume, at birth, looks female.

• 27:58Speaker 01

  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.

• 28:16Speaker 00

  Right, because they look male everywhere else, right?

• 28:19Speaker 01

  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.

• 28:30Speaker 00

  But do they have ovaries?

• 28:31Speaker 01

  No, no, no, they're fully male.

• 28:33Speaker 00

  No testes, no ovaries?

• 28:34Speaker 01

  No, they have testes.

• 28:35Speaker 00

  But they haven't descended?

• 28:36Speaker 01

  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.

• 28:48Speaker 00

  Yeah, they're producing totally normal testosterone levels.

• 28:51Speaker 01

  Yes.

• 28:51Speaker 00

  Just not DHT.

• 28:52Speaker 01

  That's right.

• 28:53Speaker 00

  Yeah, the testosterone at this point is the determining factor.

• 28:57Speaker 01

  Determining what?

• 28:58Speaker 00

  Muscle mass.

• 28:59Speaker 01

  Yes.

• 28:59Speaker 00

  Body hair, things like that.

• 29:01Speaker 01

  Well, it can't, if you don't make DHT, some body hair won't be produced. You won't have full

• 29:07Speaker 00

  Okay.

• 29:08Speaker 01

  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 DHT 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.

• 29:45Speaker 00

  Yeah, this is obviously the case. We're all familiar with.

• 29:47Speaker 01

  It 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.

• 30:15Speaker 00

  Although that's also an easy experiment to do. You could imagine giving a male a five alpha reductase inhibitor from birth.

• 30:23Speaker 01

  Oh, from birth.

• 30:24Speaker 00

  Like as a thought experiment.

• 30:25Speaker 01

  Yeah.

• 30:25Speaker 00

  If you took a normal chromosomally, phenotypically normal male, and from the time they were, call it five years old, you just gave them five alpha reductase inhibitor. All you're doing is turning their DHT down to zero and doing nothing else. You're basically asking the question, will they develop normal musculature?

• 30:42Speaker 01

  So Bessin, Challenger, Bessin and et al. have done that experiment. And there's no difference between blocking DHT.

• 30:51Speaker 00

  They've done this in animals?

• 30:52Speaker 01

  No, they did it in humans.

• 30:53Speaker 00

  How did they get an IRB for that?

• 30:55Speaker 01

  I think you know his work. They've gotten an IRB for a lot of incredible studies that are

• 31:00Speaker 00

  Would never be done today.

• 31:01Speaker 01

  super rigorous and gold standard.

• 31:04Speaker 00

  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 embryology. 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.

• 31:41Speaker 01

  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 function. 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

• 32:26Speaker 01

  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 X's 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 the bar body.

• 33:08Speaker 00

  But if that were true, it must be more complicated, or else you wouldn't have Turner syndrome.

• 33:12Speaker 01

  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.

• 33:40Speaker 00

  Which we can define for folks as single X chromosome.

• 33:43Speaker 01

  That's right.

• 33:44Speaker 00

  Which presumably they got from mom and then they didn't get a chromosome from dad? Or do we know that?

• 33:48Speaker 01

  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 dad's for interesting evolutionary reasons, because the mom and dad have competing interests in what happens to the kid.

• 34:12Speaker 00

  And phenotypically, a woman with Turner's syndrome does appear phenotypically female.

• 34:18Speaker 01

  Yes.

• 34:19Speaker 00

  But I believe she's not able to reproduce?

• 34:21Speaker 01

  That's correct, as far as I understand. I think that there's some evidence that there's technology now where they could reproduce.

• 34:29Speaker 00

  But she's sterile under maybe natural conditions?

• 34:31Speaker 01

  I think in some rare cases that can happen, but generally the ovaries don't.

• 34:35Speaker 00

  But her stature is distinctive.

• 34:37Speaker 01

  It's short.

• 34:37Speaker 00

  She's going to be shorter.

• 34:38Speaker 01

  And there's those sort of.

• 34:39Speaker 00

  Wider neck and a few other characteristics.

• 34:42Speaker 01

  But generally, they're typical in other ways.

• 34:44Speaker 00

  And so, something about these 20% or thereabouts of genes on the supposedly silenced X chromosome are clearly making the difference, because that would be the biggest difference you would notice.

• 34:57Speaker 01

  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 underst-- I think there is actually some research on exactly which genes are typically escaping.

• 35:11Speaker 00

  And is it always the same genes?

• 35:14Speaker 01

  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 a receptor to alter gene transcription on thousands of genes. So that is happening in males and not in females.

• 35:53Speaker 00

  At about what stage of development? How many months or weeks?

• 35:57Speaker 01

  I think around eight weeks. It begins peaking around 15 to 20 weeks. And then, of course, after birth.

• 36:06Speaker 00

  It goes back down.

• 36:07Speaker 01

  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.

• 36:14Speaker 00

  I don't even remember this.

• 36:15Speaker 01

  Because it's new. You probably didn't learn about it in medical school. Now it's getting a lot of attention.

• 36:21Speaker 00

  The point is, somewhere in the second, early second trimester, that level of testosterone in a male fetus is comparable to what.

• 36:29Speaker 01

  It's lower. It's not exactly as high, but it's very high.

• 36:33Speaker 00

  If a male in puberty is at 1,200 nanograms per deciliter, this could be 600 nanograms per deciliter.

• 36:39Speaker 01

  Maybe 400.

• 36:40Speaker 00

  Okay.

• 36:41Speaker 01

  If I remember correctly.

• 36:42Speaker 00

  But still screaming high.

• 36:44Speaker 01

  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."

• 37:27Speaker 01

  But all the evidence shows that testosterone is a potent 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.

• 37:47Speaker 00

  This explains the birthday party phenomenon.

• 37:49Speaker 01

  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, or 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.

• 38:13Speaker 00

  I didn't know that. I missed that memo, fortunately.

• 38:16Speaker 01

  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.

• 38:35Speaker 00

  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.

• 38:45Speaker 01

  Yeah, bring us back.

• 38:46Speaker 00

  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 XY 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?

• 39:23Speaker 01

  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

• 40:08Speaker 01

  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 periods. So that we don't really know in humans. 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,

• 40:53Speaker 01

  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 a difference.

• 41:10Speaker 00

  Once you cross this threshold.

• 41:11Speaker 01

  Yes, yes.

• 41:12Speaker 00

  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 why 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.

• 41:43Speaker 01

  Okay, thank you so much.

• 41:45Speaker 00

  Is that correct?

• 41:45Speaker 01

  Yes.

• 41:46Speaker 00

  Okay.

• 41:46Speaker 01

  And thank you for saying it so clearly, because there are 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.

• 42:28Speaker 01

  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.

• 42:41Speaker 00

  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.

• 42:48Speaker 01

  Sperm and eggs. What has evolution designed you for? If you're XY 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.

• 43:32Speaker 01

  All of the bodies and the behavior can vary across XX and XY'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 XY people are going to have a higher sex drive and be more aggressive. That's just not the case. Bodies vary, behavior varies.

• 44:02Speaker 00

  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?

• 44:11Speaker 01

  Oh, God.

• 44:12Speaker 00

  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?

• 44:26Speaker 01

  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 atretic. So we start out with, what is it, 10 million? I know you just had-

• 45:07Speaker 00

  I know, I just talked about this with Paula. The numbers are staggering how much attrition there is between birth and-

• 45:13Speaker 01

  So and then you end up at birth, you have 1 million and something like that.

• 45:16Speaker 00

  Maybe a million to 100,000 to-

• 45:18Speaker 01

  Right. 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 10 or however many kids. Over a lifetime. So they're very valuable. So we're 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 meiosis, of course,

• 46:02Speaker 01

  when they are ovulated. So maybe there's this store and then there's a selection process that goes on throughout life.

• 46:10Speaker 00

  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, let's say 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 of the best.

• 46:35Speaker 01

  It could be.

• 46:36Speaker 00

  Again, this is a telelogic BS discussion.

• 46:37Speaker 01

  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 an energy, relatively energy restricted environment. The burden for female mammals, the energetic and time burden for female mammals

• 47:21Speaker 01

  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. 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

• 48:06Speaker 01

  that explain why they're more likely to have rough and tumble play, more energy.

• 48:12Speaker 00

  And by the way, how high a peak is this mini puberty and how long does it last?

• 48:16Speaker 01

  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.

• 48:33Speaker 00

  Does the female do it as well? In other words, does the female experience a rise in estrogen?

• 48:36Speaker 01

  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.

• 48:53Speaker 00

  There's a very narrow window of time, right? Three to six months?

• 48:56Speaker 01

  Yes, yes. So in terms of the activity levels, it 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.

• 49:40Speaker 01

  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,

• 50:25Speaker 01

  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 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 playdate where they're 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 6'2". And it makes me very, very nervous because they can really hurt each other now. But yeah, they're still doing it.

• 51:04Speaker 00

  It's such a beautiful thing to watch. If you just stop judging it for a moment and 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.

• 51:48Speaker 00

  And it's like, yeah, that's what I want. Versus pick the bland, healthier option.

• 51:54Speaker 00

  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 thereof? And I'm curious, have people been studying that as closely as they've been studying

• 52:38Speaker 00

  the effects of social media on anxiety and some of these other things?

• 52:42Speaker 01

  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?

• 53:09Speaker 00

  Yeah, yeah. Just your knee jerk reaction is to always eat something that's sweeter, more calorie dense.

• 53:15Speaker 01

  We have a mismatch. We're designed to be motivated to seek out these foods and we have to expend 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.

• 53:59Speaker 00

  On average.

• 54:00Speaker 01

  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 vicarious participation in sports, which is interesting.

• 54:22Speaker 00

  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, they're playing with their other friends. I don't know enough about video games, so 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?

• 54:56Speaker 01

  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.

• 55:31Speaker 00

  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 of The younger boy is more aggressive than the older boy.

• 56:00Speaker 01

  Can you say what you mean when you say aggressive?

• 56:03Speaker 00

  So there's three years between them and obviously the older one is larger. The younger one will instigate physically more.

• 56:13Speaker 01

  Okay.

• 56:14Speaker 00

  If he's unhappy.

• 56:16Speaker 01

  Yeah.

• 56:16Speaker 00

  He will attack the larger, older boy.

• 56:20Speaker 01

  And he doesn't have that same, he doesn't respond maybe even aggressively or?

• 56:25Speaker 00

  He just hits. He'll hit anything and anyone that stands in his way. Whereas the middle one is not quite that bad.

• 56:32Speaker 01

  Yeah, that's funny.

• 56:33Speaker 00

  I feel horrible saying all of this stuff. My wife's gonna 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.

• 56:56Speaker 01

  I used to hit my older brother, so I was kind of a big hitter myself.

• 57:00Speaker 00

  I guess my point is, should a parent just say, look, I'm just gonna let these kids do what they're gonna do and understand that there are differences? Some boys are gonna be aggressive, some are gonna be less aggressive, some are going to play rough, some are not gonna play that rough. Is the best thing you can do as a parent from any available evidence, just let them do their thing?

• 57:18Speaker 01

  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 them 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 gonna 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.

• 58:01Speaker 00

  Let me give you a specific example. Are boys more likely to bully than girls?

• 58:06Speaker 01

  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.

• 58:19Speaker 01

  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.

• 58:56Speaker 00

  Do we see that kind of behavior amongst other mammals?

• 59:01Speaker 01

  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

• 59:40Speaker 01

  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.

• 1:00:14Speaker 00

  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.

• 1:00:30Speaker 01

  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 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.

• 1:01:01Speaker 00

  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.

• 1:01:14Speaker 01

  Right, but we definitely do have the statistics, like 95% of murders everywhere are male and obviously sexual assault is 98% or something.

• 1:01:24Speaker 00

  So what role does testosterone play in that?

• 1:01:27Speaker 01

  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.

• 1:02:08Speaker 01

  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 US.

• 1:02:27Speaker 00

  Right, we can't attribute that to testosterone levels.

• 1:02:30Speaker 01

  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 particular society, what is tolerated, what is 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

• 1:03:12Speaker 01

  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. It's gene environment interactions. We develop within a society. And how we develop and even how our hormones, say, respond to different kinds of interactions

• 1:03:56Speaker 01

  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

• 1:04:40Speaker 01

  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.

• 1:05:16Speaker 00

  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

• 1:06:00Speaker 00

  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 her 14 year old boyfriend, that's a different discussion and we can help them both out.

• 1:06:13Speaker 01

  Well, in this country, anyway.

• 1:06:15Speaker 00

  My point of the 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.

• 1:07:00Speaker 00

  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.

• 1:07:13Speaker 01

  What would it take for you to not eat that chocolate?

• 1:07:16Speaker 00

  Well, it's interesting. Food is a really tough one, isn't it? It can be done. It just takes a ton of willpower.

• 1:07:23Speaker 01

  Food is a great way to think about it. There's food and sex. And aggression is for, ultimately, in a way, for sex.

• 1:07:31Speaker 00

  Yeah, well, I mean, but also for both, yeah.

• 1:07:32Speaker 01

  Or food. But yes, for men more than women, aggression is certainly more about.

• 1:07:37Speaker 00

  To play off that, I don't need to be an alpha male to get as much food as I need today.

• 1:07:42Speaker 01

  But you are an alpha male and you have a lot of food.

• 1:07:45Speaker 00

  But I don't need to be.

• 1:07:46Speaker 01

  Certainly, were you competitive?

• 1:07:47Speaker 00

  We don't need to be an alpha male to get food.

• 1:07:49Speaker 01

  No, that's right.

• 1:07:50Speaker 00

  That's my point.

• 1:07:50Speaker 01

  So you're saying we should get rid of the drive.

• 1:07:55Speaker 00

  I'm just exploring this, this idea, right?

• 1:07:57Speaker 01

  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.

• 1:08:31Speaker 00

  If you only knew of the rabbit hole, we could go down on that front, but I'm gonna refrain.

• 1:08:36Speaker 01

  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.

• 1:09:17Speaker 01

  I'm saying this because that competitive drive chess, I don't know what we're like getting out of that.

• 1:09:24Speaker 00

  You haven't played, have you?

• 1:09:25Speaker 01

  No, I have.

• 1:09:26Speaker 00

  You have?

• 1:09:26Speaker 01

  Yes.

• 1:09:27Speaker 00

  Okay, alright.

• 1:09:27Speaker 01

  I'm not super seriously, but my son was really into it for a while and 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.

• 1:10:11Speaker 01

  They want to nail finding this gene or be the first to make a certain discovery. It's 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.

• 1:10:47Speaker 00

  Let me play back to you what I think I'm hearing and with a little bit of-

• 1:10:51Speaker 01

  I'm in trouble.

• 1:10:51Speaker 00

  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.

• 1:11:05Speaker 01

  More so, certainly.

• 1:11:06Speaker 00

  Yep, yep. The past 100 years or so has largely done away with that, meaning a couple of things have become true. We basically have domesticated crops and agriculture and livestock and we're no longer in a food scarce environment, certainly for the last 50 or 60 years. Lifespans 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.

• 1:11:48Speaker 00

  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

• 1:12:16Speaker 01

  Their sports, their sports are huge.

• 1:12:18Speaker 00

  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,

• 1:13:00Speaker 00

  which was making sure the offspring were perfectly protected. So there's an asymmetry in this evolution of evolution.

• 1:13:07Speaker 01

  Yes.

• 1:13:08Speaker 00

  That's what I'm hearing. Do you agree with that?

• 1:13:10Speaker 01

  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.

• 1:13:34Speaker 00

  And now paternal attention can be given much more to kids.

• 1:13:38Speaker 01

  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.

• 1:13:56Speaker 00

  Sorry, in the father or in the child?

• 1:13:58Speaker 01

  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.

• 1:14:21Speaker 00

  If you're a man out there listening with low T, ignore your kids.

• 1:14:24Speaker 01

  With low T?

• 1:14:25Speaker 00

  If your T is low, you should ignore your kids to raise your T. Is that the implication?

• 1:14:29Speaker 01

  Oh, right, right. It doesn't drop by that much.

• 1:14:32Speaker 00

  All right.

• 1:14:32Speaker 01

  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 T is 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.

• 1:15:10Speaker 00

  Do we know that there's causality here? I mean, this is a pretty bold statement.

• 1:15:13Speaker 01

  We do. I would say, yeah, we do know.

• 1:15:16Speaker 00

  By what magnitude are we talking about here?

• 1:15:19Speaker 01

  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, et cetera. Because it's expensive metabolically.

• 1:15:53Speaker 00

  Because it would make us go out and look for other mates when we don't need to?

• 1:15:56Speaker 01

  You're aggressing and fighting for status 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.

• 1:16:27Speaker 00

  How much can that happen?

• 1:16:28Speaker 01

  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 and your potential.

• 1:16:55Speaker 00

  Wait, there's a lot for me to unpack here.

• 1:16:57Speaker 01

  But that's a whole other thing.

• 1:16:57Speaker 00

  No, no, but I want to talk about this. Everything you're saying is totally new to me.

• 1:17:01Speaker 01

  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.

• 1:17:13Speaker 00

  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.

• 1:17:33Speaker 01

  Oh, no, he'll keep working 80. No, men work harder and make more money, tend to do that.

• 1:17:38Speaker 00

  Right, but in this experiment,

• 1:17:40Speaker 01

  Yes.

• 1:17:40Speaker 00

  this guy decides to stay home half the time now.

• 1:17:43Speaker 01

  Okay.

• 1:17:44Speaker 00

  His testosterone will drop.

• 1:17:45Speaker 01

  No, because the kid's too old.

• 1:17:49Speaker 00

  Kid's five at this point.

• 1:17:50Speaker 01

  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 gatherer 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.

• 1:18:26Speaker 00

  He benefits reproductively because that's a critical window in which

• 1:18:29Speaker 01

  Yes.

• 1:18:30Speaker 00

  his protection is producing his survival advantage.

• 1:18:32Speaker 01

  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. Mate 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.

• 1:19:16Speaker 01

  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.

• 1:20:00Speaker 01

  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.

• 1:20:40Speaker 01

  There's more attention to status seeking, aggression, getting sex from other partners, et cetera. 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.

• 1:21:13Speaker 00

  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 gonna have as many partners as possible, are not doing that because of reproductive fitness.

• 1:21:35Speaker 01

  Oh, no, of course not.

• 1:21:36Speaker 00

  Choosing not to have kids.

• 1:21:37Speaker 01

  That's right.

• 1:21:38Speaker 00

  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.

• 1:21:45Speaker 01

  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.

• 1:21:54Speaker 00

  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?

• 1:22:02Speaker 01

  So I don't think status is distinct from reproduction. Do you mean psychologically?

• 1:22:07Speaker 00

  Yes.

• 1:22:08Speaker 01

  What is the driver?

• 1:22:08Speaker 00

  Yes.

• 1:22:08Speaker 01

  It's not reproduction. It's sex.

• 1:22:11Speaker 00

  Which is interesting. So this is the first time we're basically talking about sex independent of reproduction.

• 1:22:16Speaker 01

  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.

• 1:22:36Speaker 00

  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?

• 1:22:44Speaker 01

  That's it.

• 1:22:44Speaker 00

  Okay. So in two years or three years, when he's off in college?

• 1:22:48Speaker 01

  Oh, boo hoo. Don't talk about it.

• 1:22:49Speaker 00

  I know, I know. It's terrible, right? So you guys will have done your job as parents.

• 1:22:52Speaker 01

  No, we're gonna keep doing it until we die.

• 1:22:55Speaker 00

  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?

• 1:23:13Speaker 01

  Well, there aren't really too many other animals that get past their reproductive age.

• 1:23:18Speaker 00

  So elephants and all these other long-lived mammals?

• 1:23:20Speaker 01

  So menopause, you mean? Who has menopause?

• 1:23:22Speaker 00

  Yeah.

• 1:23:23Speaker 01

  So some whales, rare captive chimp, or maybe there's some wild chimps who have had menopause. It's just very rare.

• 1:23:30Speaker 00

  This is kind of another human socialization then.

• 1:23:33Speaker 01

  Okay. 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 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?

• 1:24:10Speaker 00

  Yes. Is there an evolutionary reason for why humans specifically stay monogamous even after it's not necessary for the survival of their offspring?

• 1:24:22Speaker 01

  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.

• 1:24:40Speaker 00

  And they're still acting that way. The same genes are being transcribed as though they had kids.

• 1:24:45Speaker 01

  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 our experience and our relationship with our kids, 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.

• 1:25:11Speaker 00

  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 AstraZeneca. So this study basically gave men, I think there were five groups of testosterone and with and without an AstraZeneca. So for folks listening, an AstraZeneca would inhibit the conversion of testosterone to estradiol.

• 1:25:50Speaker 01

  So it just inhibits aromatase.

• 1:25:52Speaker 00

  That's right, some aromatase inhibitor. So you have from low to high, five levels of T with and without estrogen.

• 1:25:59Speaker 01

  Okay.

• 1:26:00Speaker 00

  So it's a pretty elegant study, right? It was in the New England Journal of Medicine. I don't remember who published it. 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 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.

• 1:26:30Speaker 01

  Producing outcome for?

• 1:26:31Speaker 00

  Everything, for body composition, mood, you name it. The learning, to me, it wasn't. Isn'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.

• 1:27:05Speaker 01

  In men who were?

• 1:27:06Speaker 00

  Who were taking testosterone.

• 1:27:07Speaker 01

  Who were taking it.

• 1:27:08Speaker 00

  Yep. Within physiologic norms. Yeah.

• 1:27:10Speaker 01

  Okay.

• 1:27:10Speaker 00

  So again, yeah, putting aside bodybuilders who were taking

• 1:27:13Speaker 01

  Yeah.

• 1:27:14Speaker 00

  A thousand milligrams of testosterone.

• 1:27:16Speaker 01

  Gynecomastia, etc.

• 1:27:16Speaker 00

  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?

• 1:27:54Speaker 01

  So, do you know what the specific outcomes were? Was it libido or energy?

• 1:27:59Speaker 00

  Libido is definitely one. I don't recall. Gosh, I wish I'd looked at the paper recently.

• 1:28:04Speaker 01

  So let's just say libido.

• 1:28:05Speaker 00

  Yeah.

• 1:28:06Speaker 01

  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.

• 1:28:39Speaker 00

  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?

• 1:28:47Speaker 01

  The testosterone gets into the brain. Estrogen is actually prevented. The peripheral testosterone is prevented by a protein called alpha fetoprotein in rodents. So maternal estrogen is bound so that females are not masculinized.

• 1:29:04Speaker 00

  So he enters the brain and is aromatized there.

• 1:29:07Speaker 01

  The testicular produce testosterone from the male testicles is high. That gets into the brain.

• 1:29:14Speaker 00

  That gets aromatized.

• 1:29:15Speaker 01

  Yes, gets in there.

• 1:29:16Speaker 00

  Once it gets passed because it doesn't have the alpha fetoprotein.

• 1:29:18Speaker 01

  That's right.

• 1:29:19Speaker 00

  That's a pretty elegant solution.

• 1:29:20Speaker 01

  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, et cetera.

• 1:29:38Speaker 00

  This doesn't happen in humans?

• 1:29:39Speaker 01

  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 fetoprotein 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 insensitivity syndrome where you have XY individuals who have testicles but have a defective androgen receptor and essentially develop, they have testicles and XY sex chromosomes and high testosterone, but they develop as females

• 1:30:23Speaker 01

  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.

• 1:30:33Speaker 00

  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.

• 1:30:44Speaker 01

  So they go through female, essentially female puberty and many of them will discover that they have testes and XY 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.

• 1:31:03Speaker 00

  Do they develop with a male pattern of aggression or a female pattern of nurturing?

• 1:31:08Speaker 01

  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 XY 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.

• 1:31:42Speaker 00

  So outside of the sterility, I assume, of this individual, does she go on to be a completely normal woman?

• 1:31:48Speaker 01

  Totally. More feminine, I would say, than

• 1:31:51Speaker 00

  That's incredible.

• 1:31:52Speaker 01

  Other women who have testosterone.

• 1:31:54Speaker 00

  So really, not a pathologic condition outside of the sterility?

• 1:31:57Speaker 01

  No, no.

• 1:31:58Speaker 00

  Wow. Never even heard of this.

• 1:32:00Speaker 01

  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.

• 1:32:40Speaker 00

  They don't have the aromatase capacity?

• 1:32:42Speaker 01

  Sorry, that, yes. And I should mention also that in these women who have complete androgen insensitivity 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, but because it's a rare condition. But what we do have suggests that they have estrogen and that the estrogen somehow compensates.

• 1:33:12Speaker 00

  And they have the same libido?

• 1:33:14Speaker 01

  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.

• 1:33:26Speaker 00

  And they, presumably, they must have a little more difficulty putting on muscle mass?

• 1:33:31Speaker 01

  Well, I have tried.

• 1:33:32Speaker 00

  Do they shave their legs?

• 1:33:33Speaker 01

  They don't have to.

• 1:33:34Speaker 00

  Yeah.

• 1:33:34Speaker 01

  They have no acne.

• 1:33:36Speaker 00

  Yeah.

• 1:33:37Speaker 01

  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.

• 1:33:51Speaker 00

  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.

• 1:34:02Speaker 01

  With the estrogen.

• 1:34:03Speaker 00

  Yeah, with the higher estrogen level.

• 1:34:04Speaker 01

  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's very important in men, in adults. It may be important in early development in some ways that we don't yet understand.

• 1:34:20Speaker 00

  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.

• 1:34:44Speaker 01

  In Western populations. Because we don't, hunter-gatherers tend not to have that.

• 1:34:48Speaker 00

  Oh, OK, well, say more about that.

• 1:34:50Speaker 01

  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.

• 1:35:02Speaker 00

  So that's the rut. Like, we're animals, basically.

• 1:35:04Speaker 01

  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. OK. So humans are also designed to keep testosterone low, which is why.

• 1:35:23Speaker 01

  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.

• 1:35:47Speaker 00

  In the case of the deer, all of the females go through estrase at the same time. So it's easier for the bucks to say, for these nine months,

• 1:35:57Speaker 01

  Great point, great point.

• 1:35:58Speaker 00

  I don't need testosterone because all of the does are infertile. And then bingo, now they're going through estrase. 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.

• 1:36:15Speaker 01

  No, it is.

• 1:36:16Speaker 00

  And by the way, women are ovulating every month.

• 1:36:19Speaker 01

  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.

• 1:37:01Speaker 01

  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,

• 1:37:44Speaker 01

  which makes me skeptical about some of the explanations for the trend that we see of 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.

• 1:38:14Speaker 00

  In other words, you're saying it's hard for us to blame fertility in the Western world on declining testosterone.

• 1:38:20Speaker 01

  On just the testosterone. Because I think the testosterone must be declining because of all these other things that are affecting fertility.

• 1:38:27Speaker 00

  Yeah, it could be the inflammation that arises from the metabolic dysfunction, the...

• 1:38:32Speaker 01

  Yes, phalates, who knows what.

• 1:38:34Speaker 00

  Exactly. What other, yeah, 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 30s 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 subjective, 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.

• 1:39:19Speaker 00

  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?

• 1:39:39Speaker 01

  I don't know that that's been shown. So you're saying testosterone's great, why shouldn't we give it to people?

• 1:39:46Speaker 00

  No, no, I'm asking the opposite question.

• 1:39:48Speaker 01

  Okay.

• 1:39:48Speaker 00

  I'm saying, given everything we've just learned about testosterone, is there a negative consequence to taking a 55-year-old guy and restoring his testosterone to what it was when he was 18?

• 1:40:00Speaker 01

  Make the argument for why that should happen.

• 1:40:02Speaker 00

  Why you should restore it back to when he's 18?

• 1:40:04Speaker 01

  Yes. Do you think that should happen?

• 1:40:06Speaker 00

  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 some things, he... 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."

• 1:40:27Speaker 01

  Yeah.

• 1:40:27Speaker 00

  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,

• 1:41:12Speaker 00

  which has largely been debunked outside of, again, these edge cases where people are taking supraphysiologic doses. In terms of being a productive, non-assholic member of society

• 1:41:24Speaker 01

  Yeah.

• 1:41:24Speaker 00

  and not being overly aggressive or engaging in harmful behavior, risky behavior, what's the pro and con case for that in your mind?

• 1:41:32Speaker 01

  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.

• 1:41:50Speaker 00

  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.

• 1:42:13Speaker 01

  Oh, thank you for bringing that up.

• 1:42:14Speaker 00

  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?

• 1:42:25Speaker 01

  Can you do the CAG repeat?

• 1:42:27Speaker 00

  I mean, I guess you could. That would be, is there a commercial test for that? I mean, you can do that in the lab.

• 1:42:32Speaker 01

  Yeah, I don't know if there's a commercial test. You should get it if there is.

• 1:42:36Speaker 00

  Someone should develop a CLIA-approved assay for this.

• 1:42:38Speaker 01

  Does everybody know what the CAG repeat is?

• 1:42:39Speaker 00

  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.

• 1:42:59Speaker 01

  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?

• 1:43:18Speaker 00

  No, you can't. But you can just change one variable at a time.

• 1:43:20Speaker 01

  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?

• 1:43:33Speaker 00

  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.

• 1:43:54Speaker 01

  Or obesity, do you have to?

• 1:43:55Speaker 00

  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.

• 1:44:30Speaker 01

  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 proteins and just the overall concentration. Where are your androgen receptors and how highly concentrated are they? 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

• 1:45:12Speaker 01

  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 of 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.

• 1:45:49Speaker 00

  Sorry, just to be clear, you were on hormone replacement therapy prior to?

• 1:45:52Speaker 01

  No.

• 1:45:52Speaker 00

  No, okay.

• 1:45:53Speaker 01

  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.

• 1:46:03Speaker 00

  Even though you were already in menopause?

• 1:46:04Speaker 01

  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.

• 1:46:20Speaker 00

  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?

• 1:46:31Speaker 01

  It's a good question. I guess because I felt fine and it wasn't until-

• 1:46:35Speaker 00

  It was gradual.

• 1:46:35Speaker 01

  It was gradual. Yeah. And I think especially because of you, I started lifting weights a year ago.

• 1:46:42Speaker 00

  You look like you've been at it for years.

• 1:46:44Speaker 01

  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.

• 1:47:10Speaker 00

  And it sounds like you feel better as a result of it.

• 1:47:12Speaker 01

  Yeah, I think so. I think I feel better, but I definitely feel better when I'm working out and the drive to- 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 will help you. 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.

• 1:47:57Speaker 01

  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 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. It's a 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.

• 1:48:32Speaker 00

  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- 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 twenties, it could significantly and potentially permanently affect my fertility.

• 1:49:09Speaker 01

  Yeah, and it's hard to come off. From what 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.

• 1:49:21Speaker 00

  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 judgy term like that. I reserve that term for non-medical use that is hyperphysiologic.

• 1:49:40Speaker 01

  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 gonna shut down his...

• 1:49:52Speaker 00

  He's gonna shut his HP eight down. But here's the thing, I have a really hard time believing that a 25-year-old should ever be on exogenous testosterone.

• 1:50:00Speaker 01

  Okay, because they are, right? It's really increasing at these younger ages.

• 1:50:04Speaker 00

  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.

• 1:50:22Speaker 01

  I remember saying this on another show, yeah.

• 1:50:23Speaker 00

  So I was like...

• 1:50:24Speaker 01

  So you were not sleeping, totally stressed out.

• 1:50:26Speaker 00

  I was 2X 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?

• 1:50:33Speaker 01

  Definitely not.

• 1:50:34Speaker 00

  No, it meant that I needed to get the hell out of residency and actually start sleeping at night.

• 1:50:38Speaker 01

  And that's what you did, right?

• 1:50:39Speaker 00

  Yeah, and then whatever, like four years later, five years later, I had normal testosterone.

• 1:50:44Speaker 01

  Wow.

• 1:50:45Speaker 00

  So again, if a 25-year-old is walking around with a testosterone of 300 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.

• 1:51:04Speaker 01

  Right.

• 1:51:04Speaker 00

  I'd be preserving gonadal function as opposed to completely suppressing it.

• 1:51:08Speaker 01

  I see.

• 1:51:10Speaker 00

  Whereas if a guy's 60, if he's fine with testicular shrinkage, which would be the fundamental difference in using exogenous T when you suppress his HPA axis, then I think it's less of an issue. I don't want to speak for any 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.

• 1:51:35Speaker 01

  Yeah.

• 1:51:35Speaker 00

  So what are you up to right now?

• 1:51:37Speaker 01

  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.

• 1:51:59Speaker 00

  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?

• 1:52:09Speaker 01

  So that was, it started in 2021. Yeah.

• 1:52:13Speaker 00

  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.

• 1:52:24Speaker 01

  Thank you.

• 1:52:25Speaker 00

  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 are you recovering from that experience?

• 1:52:38Speaker 01

  It's been really difficult because I was just reading my acknowledgements in my book on testosterone and

• 1:52:48Speaker 01

  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 topics 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

• 1:53:33Speaker 01

  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

• 1:54:16Speaker 01

  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

• 1:54:57Speaker 01

  that and to advocate for that, which 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.

• 1:55:15Speaker 00

  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?

• 1:55:39Speaker 01

  Yeah, we didn't say what happened. I'll just say that I wrote a book, Tea, 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 was 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.

• 1:56:10Speaker 00

  Would you see yourself back?

• 1:56:12Speaker 01

  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 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. So...

• 1:56:53Speaker 00

  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 gonna 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 gonna 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.

• 1:57:29Speaker 01

  Right.

• 1:57:29Speaker 00

  What is your next book about? Are you comfortable talking about what the subject is?

• 1:57:32Speaker 01

  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?

• 1:58:17Speaker 01

  Like economic changes, men are falling behind in education, for instance. And what's happening in schools and why are schools maybe 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's called the masculinity crisis.

• 1:58:53Speaker 01

  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 differences between the sexes that play out in society that are not all the result of the patriarchy, say.

• 1:59:34Speaker 01

  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.

• 2:00:04Speaker 00

  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.

• 2:00:16Speaker 01

  So you go towards, she goes away, basically?

• 2:00:18Speaker 00

  I mean, like, it's the greatest sound I've 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-

• 2:00:38Speaker 01

  Or to be interested in cars.

• 2:00:40Speaker 00

  Sure, sure. But there are incredible YouTube videos where you can literally listen to every engine.

• 2:00:47Speaker 01

  Oh, and it's like ASMR for you?

• 2:00:49Speaker 00

  Yeah. The V8 and V10 naturally aspirated engine screaming is the greatest sound I've ever-

• 2:00:54Speaker 01

  I don't know what naturally aspirated.

• 2:00:57Speaker 00

  You don't have forced induction of air, so it revs very high.

• 2:01:00Speaker 01

  Okay.

• 2:01:00Speaker 00

  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.

• 2:01:07Speaker 01

  And can we just remind your listeners that we are definitely not saying that there are no women interested in cars or that they're-

• 2:01:14Speaker 00

  I know plenty of them, but on average, that's right.

• 2:01:17Speaker 01

  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.

• 2:01:38Speaker 00

  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?

• 2:02:01Speaker 01

  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 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.

• 2:02:44Speaker 01

  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.

• 2:03:25Speaker 00

  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-

• 2:03:40Speaker 01

  The mob.

• 2:03:41Speaker 00

  Yeah, the mob, the angry mob. So I think the good news 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're working on another book and excited that you've got more time at home to do so.

• 2:03:57Speaker 01

  Thank you so much for having me. It was great.

• 2:04:00Speaker 00

  Thank you for listening to this week's episode of The Drive. Head over to peterattiamd.com/shownotes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram, and Twitter, all with the handle Peter Attia MD. You can also leave us a 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

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