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

00:00:00.000 Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Atiyah. This podcast,

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00:01:04.160 My guest this week is Carol Hooven. Carol is a human evolutionary biologist, a former Harvard lecturer,

00:01:11.300 and non-resident senior fellow at the American Enterprise Institute. Her research focuses on

00:01:16.320 testosterone, sex differences, and behavior. She holds a PhD in biological anthropology,

00:01:21.260 now human evolutionary biology, from Harvard University, and is the author of T, the story

00:01:27.520 of testosterone, the hormone that dominates and divides us. In this episode, we discuss how

00:01:32.460 prenatal testosterone shapes the male body and brain, turning genetic signals into thousands

00:01:37.620 of developmental changes that underlie later sex differences, critical hormone surges and why

00:01:43.840 they matter for lifelong behavior. DHT, androgen receptors, and rare natural experiments,

00:01:50.100 for example, 5-alpha reductase deficiency, that reveal how external genitalia and the prostate

00:01:56.020 masculinize. Distinct male and female aggression styles, direct physical confrontation versus 1.00

00:02:02.640 indirect or relational tactics, and the evolutionary logic behind each. Why modern life changes,

00:02:09.260 but doesn't erase, ancient drives like male competitiveness, and the trade-offs of trying 0.69

00:02:14.360 to suppress them. Testosterone, aging, and hormone therapy for both sexes, including Carol's personal

00:02:20.660 experience after surgical menopause, and the cultural debate over masculinity and the cost of

00:02:26.080 denying biological sex differences, a theme of Carol's forthcoming book. So, without further delay,

00:02:31.920 please enjoy my conversation with Carol Hooven.

00:02:34.420 Carol, thank you so much for coming out to Austin. Great to meet you in person.

00:02:44.020 Thank you so much for having me. I'm thrilled to be here.

00:02:46.760 This is a topic that we talk a lot about on the podcast, but usually from a pretty narrow lens,

00:02:53.060 which is in the form of replacement. We talk about hormones, both in men and women, sex hormones,

00:02:59.100 and we talk about how they wax and wane as an individual ages. We obviously then talk about

00:03:04.760 the medical use of them, but I don't think we've spent any time understanding the more basic

00:03:10.000 fundamentals of these hormones, the role they play in our evolution. And anecdotally, I'll just share

00:03:16.080 with you kind of the observation that any parent probably has if they have male and female children.

00:03:22.140 My first child was a girl, and my wife and I very, very stupidly and arrogantly thought we were the 0.72

00:03:29.580 perfect parents because she was so well-behaved. And we were like, what do all of these other parents

00:03:36.560 with their boys running around, misbehaving, what are they doing wrong? How could we teach them how to

00:03:44.080 be as good as we are? I mean, we didn't actually say that, but there was undoubtedly an annoying

00:03:50.180 smugness to us. And if you believe in a God, that God smacked us into our place with two boys that

00:03:57.400 followed who were, for all intents and purposes, treated the same way, socialized the same way.

00:04:05.200 And there is a level of aggression in them, a fury in them that I've never seen, probably unless I were

00:04:15.980 to go back and hear stories of what my mom said I was like. How old are your boys now?

00:04:20.180 Eight and almost 11. I wouldn't say they're a different sex. I would say they're a different 1.00

00:04:26.300 species. Yeah. I was just going to say that.

00:04:28.400 So all of that is to say, I don't feel we did anything different and yet they couldn't be more

00:04:35.620 different. And I appreciate that that's not going to be the case for every parent. What I hope to

00:04:39.720 learn is how much testosterone has to do with that. Because I also am under the impression that at

00:04:44.480 this age, the testosterone levels wouldn't be that much different. And I understand, and we'll probably talk

00:04:49.540 about the differences in testosterone levels during the embryologic phase, because obviously that led

00:04:55.420 to the differences. But anyway, with that as backdrop, how did you get interested in this topic?

00:05:01.640 So I want to make sure to come back to everything that you just said. So how did I get interested?

00:05:08.200 I'm going to start at the beginning, which is that I grew up with three older brothers.

00:05:13.040 And I'm assuming that this had something to do with my interest in testosterone. They were different

00:05:20.680 than I was, I am, in some consistent ways. I don't think I thought much about that. And I think that

00:05:28.660 probably made me really want to understand what motivates male behavior in general and why it's

00:05:36.020 different from female behavior. That wasn't sort of an idea that I had when I was in college that I was

00:05:42.420 going to go study this. But I did become intensely interested in the evolutionary origins of human

00:05:50.200 behavior in general and what makes us different from other animals. And that happened, I think,

00:05:56.840 because of traveling. I traveled to a lot of different places in the world, mostly by myself during and

00:06:04.220 after college. And there were such extreme differences culturally. Your family's Egyptian. That was one of the

00:06:11.360 places I went that really freaked me out because that really shook me.

00:06:17.680 Say more.

00:06:18.240 The cultural differences were so profound in terms of the incredibly important role that sex plays in

00:06:26.080 social life and the segregation and different rules that applied to males and females. I was alone

00:06:33.960 traveling by myself as a young woman, totally ignorant of what I was getting into in Egypt.

00:06:39.240 I was harassed endlessly. Some of that was my fault for not understanding the culture

00:06:45.100 well enough and what I was getting into. So this combination of being immersed in not only different

00:06:53.380 societies that treated sex and sex roles very differently, but also different ecologies. I spent

00:06:59.640 some time in Africa and Kenya and Tanzania and got really interested in all of the animal behavior and

00:07:07.460 why we are different from other animals, et cetera. So I had a whole other career before graduate

00:07:12.180 school. And I ended up leaving that career and applying to Harvard to try to do a graduate degree

00:07:19.320 where I could do more to understand the evolutionary basis of human behavior. I ended up getting rejected

00:07:26.520 and I just persisted and then was offered this job out in Uganda studying chimps for what was supposed 0.84

00:07:33.320 to be a year. And that is what really triggered my interest in sex differences and testosterone.

00:07:40.060 Because we, I think to a certain extent, are indoctrinated to believe that most human sex

00:07:47.580 differences are cultural. Or if you think that they're not, it's better you don't say that out loud

00:07:53.440 to too many people or in the wrong place. So when I spent time with the chimps, I was really blown away 1.00

00:07:59.620 by the ways that the sex differences in the chimps paralleled human sex differences. Of course,

00:08:06.260 not exactly the same, but the very basic things that you just described, even just in terms of

00:08:12.120 energy and aggression, are present in the chimps in terms of being higher in the males and lower

00:08:17.620 in the females. And I'm getting goosebumps because the reasons for that are so profound and far-reaching 0.97

00:08:25.300 and start with sperm and egg. And that's what sex really is about, is not just the ability to

00:08:31.900 produce sperm or eggs, but kind of the way that the organism is designed and the reproductive phenotype,

00:08:39.180 including body and behavior. And then that in humans plays out in these really complex ways in terms of

00:08:45.460 social systems. So I got interested in testosterone because this is one thing I could grab onto that

00:08:51.980 links very clearly humans, chimpanzees, every other mammal in terms of males having much higher levels

00:08:59.880 than females. And it's not just mammals, there are other forms of steroid hormones that other species

00:09:05.320 have, but this is pervasive and just a very powerful way to understand proximately, that means what's

00:09:12.500 happening here and now in the organism, why the sexes are different. And then there are these deep

00:09:17.480 evolutionary pressures that have to do with reproductive strategies for organisms that

00:09:22.940 produce sperm versus organisms that produce eggs. And so then I ended up reapplying to Harvard and

00:09:28.880 getting into the grad program there. And I did my dissertation on testosterone and sex differences in

00:09:35.980 cognition, the way we think and process information. And I had men watch sexy videos and also videos of

00:09:43.920 dental surgery and collected their saliva and measured their testosterone in the lab. And then

00:09:49.540 I just stayed on at Harvard, mostly just teaching. I want to go back to something you said a second

00:09:54.580 ago, which is the distinction between mammals and non-mammals. And I never really thought of it until

00:09:59.040 you said this, but if I were to look at a male great white shark and a female great white shark,

00:10:04.920 first of all, do they have testosterone in them as the androgen or sex hormone?

00:10:08.300 Most vertebrates, most vertebrates will have testosterone or something very, very close

00:10:12.360 to testosterone. Yeah.

00:10:14.300 Now, if you, again, go back to the example of great white sharks, typically the females are larger.

00:10:18.760 I would reckon they're just as aggressive as the males. Is that reflected in comparable levels of

00:10:24.940 testosterone in those species?

00:10:26.920 So sharks, I don't know about specifically. First of all, males are not always bigger than females.

00:10:33.000 Males will do whatever they need to do generally to compete for mates. And in many species, it's not 0.97

00:10:39.140 to be larger. Also, there are differences in the ability to defend a territory or defend mates in

00:10:45.100 air and water and land. And that's really an interesting way to understand some male competitive

00:10:51.240 strategies. But generally, when in the species, if the female is just as aggressive, often it's maternal 0.93

00:10:58.980 aggression and not necessarily mate competition. Maternal aggression tends to be mediated more by

00:11:04.840 estrogen than testosterone, even in hyenas, which are very difficult to tell apart. The females are 0.94

00:11:11.800 very difficult to tell apart from the males. They have this clitoris that looks exactly like a penis, 1.00

00:11:16.800 and experts often can't even tell the difference. They're highly aggressive. And that seems not to be 1.00

00:11:22.920 mediated in the adult, at least, by comparable levels of testosterone. There seems to be potentially

00:11:28.460 something going on in early development. But I don't know of good evidence that testosterone

00:11:33.920 acts similarly in females to mediate, say, mate aggression, we'll say mating aggression. 0.98

00:11:42.020 So just make sure I understand, in the hyenas, if you took an adult male and an adult female hyena,

00:11:47.420 would they have similar levels of testosterone and estrogen?

00:11:50.660 No.

00:11:51.380 The males would be higher.

00:11:52.760 The males would be higher.

00:11:54.060 Despite the fact that phenotypically they look the same and they're both equally aggressive.

00:11:57.800 I believe they're either just as aggressive, if not more so. I think they're, I believe that

00:12:02.960 they're dominant to the males. 0.79

00:12:04.540 Got it.

00:12:04.960 And there's something going on with potentially maternal adrenal androgens when the fetus is

00:12:11.220 developing that becomes the aggressive female, but I don't think it's completely worked out. I

00:12:15.940 haven't looked at the literature on that in ages.

00:12:18.200 So the extent of my recollection for medical school on this topic was, and again, we can come back and

00:12:24.680 talk about the edge cases, but 99.9% of cases are either XX or XY in terms of humans.

00:12:32.380 In humans, yes.

00:12:33.040 Yeah, right. So we can talk about turners and Klinefelters and things like that later.

00:12:36.560 But in the 99.9% of cases of XX and XY, what are the steps and how do they involve sex hormones

00:12:47.700 that create the phenotypic differences in the embryo?

00:12:53.220 So phenotypic, we'll just stick to the body and then we can also talk about the behavior.

00:12:58.980 Yes, yes, exactly. That's what I want. I just want to start with. Let's get through the first nine

00:13:02.960 months. Yeah. And then like, let's help understand how those two options of chromosomes lead to two

00:13:09.780 different body types. And I just want to say right at the outset that we have a sex determination

00:13:15.520 system that relies on chromosomes, but not every animal does. So chromosomes do not equal sex and

00:13:22.620 birds have used chromosomes, but they have a different system where the female is the one that has 0.87

00:13:27.740 heterozygotic chromosomes. So there's temperature dependent sex determination. So people should not

00:13:33.800 confuse the sex hormones themselves with the definition of sex.

00:13:38.600 Chromosomes or the sex hormone?

00:13:39.800 Sorry, chromosomes. Thank you. In mammals, the chromosomes determine sex, but do not define sex.

00:13:47.640 Again, across almost all sexually reproducing organisms, it's the gamete type that the organism

00:13:54.360 is basically designed around, that the reproductive system is designed around, that defines sex. 1.00

00:14:01.580 Other organisms can be hermaphroditic, produce both gamete types at the same time, or they can

00:14:07.080 be sequential hermaphrodites. So I just want to get that out first. So in humans, the mother's egg,

00:14:14.260 the sex chromosome is always going to be an X that it donates in its egg, and it's going to combine

00:14:19.680 with a sperm. 50% of the sperm are going to have a Y sex chromosome, and 50% of the sperm are going to

00:14:26.200 have an X in general. Those two combine, and the developing embryo is going to be either XX and XY.

00:14:34.960 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 1.00

00:14:43.360 because they will have something inside of them that has testicles that produce testosterone, 1.00

00:14:48.880 which I think is interesting. So an XY fetus around five or six weeks, I should just say that XX and XY 0.96

00:14:58.240 are both, they're almost identical until that time. And the Y chromosome has a gene on it called the sex

00:15:07.980 determining region of the Y chromosome that produces a protein called the SRY protein. And this is a very

00:15:15.180 important protein because it triggers the differentiation of the undifferentiated gonad.

00:15:23.680 So what's really cool and interesting is that before that time, we all have a gonad that can become

00:15:32.020 either one. It can become testes or it can become ovaries. And that's sort of an amazing design. That's

00:15:39.440 evolution's way of not wasting energy, not having to have two systems, two different systems that one develops

00:15:46.120 and the other gets discarded, at least in terms of the gonads. So they come first. So in terms of sexual

00:15:53.080 differentiation, that means that for XY individuals, the gonads are going to develop along the testicle route. 0.60

00:16:02.020 And without the SRY gene, they will, by default, when I say by default, that doesn't mean that nothing

00:16:09.780 else has to happen. Other genes have to be expressed. And that's an active process. It's not a passive

00:16:16.860 process. But without the SRY gene, those undifferentiated gonads will differentiate in the 0.81

00:16:24.060 female direction to form ovaries. 1.00

00:16:26.300 I remember my overly simplistic, and this is almost 30 years ago, but I could have sworn I used to think

00:16:33.380 about this in the embryology class as by default, we are female. And this gene had to turn on to 0.99

00:16:42.380 basically take the XYs and make them male phenotypically. But that's obviously oversimplified.

00:16:47.500 Yes. In some ways that is true. I would not put it that way, but it's by default. The individual will

00:16:54.980 develop, say, female... Because if you have an XY that is missing that region, you will be 1.00

00:17:00.960 phenotypically female, but chromosomally male. You will be chromosomally male, sure, but you won't

00:17:10.520 develop functional ovaries because you need two Xs to do that. Correct. You won't be able to reproduce,

00:17:13.100 to do that. But for all intents and purposes, you would look female, correct?

00:17:16.820 Yes. Yes. So your external genitalia would appear to be female. We'll get into those cases. 0.83

00:17:23.860 Again, these are kind of these edge cases.

00:17:25.080 But yeah, if you think about what the genitalia look like in an early developing fetus, it looks

00:17:33.440 female. It doesn't have to change that much. It gets bigger. But if you take what looks like even 1.00

00:17:39.980 adult female genitalia, basically you modify the clitoris and the labia to get what looks like 1.00

00:17:48.420 typical male genitalia. So that has to do a lot of growing and changing. And it's like that 0.82

00:17:52.920 in the fetus. So if we're going down the male route, you get the expression of SRY. And what that does

00:18:00.100 is it causes certain cells in this undifferentiated gonad to develop into first

00:18:08.120 Leydig cells and then later Sertoli cells. So that's happening. And then later ovarian

00:18:14.880 differentiation takes place. So two things happen. The Leydig cells start producing testosterone

00:18:22.900 first. And I'm going to go back and just talk about the Wolfian ducts and the Malarian ducts.

00:18:30.900 Oh my God. I have not heard that term since medical school. What a blast from the past.

00:18:36.080 Okay. So this is D-U-C-T-S, not duct like quack quack. So these are duct systems.

00:18:42.920 Duct, yeah. 0.91

00:18:43.660 And so here's another cool thing. So we start out with this two primordial or primitive

00:18:50.700 gonads that can become either.

00:18:53.280 And they're high. I remember they're almost in the chest.

00:18:56.540 Yes. They're high. So obviously the males have to descend into what becomes the scrotum

00:19:00.960 and the females just stay there. And that seems very sensible. We still don't completely understand 1.00

00:19:07.060 why males take all this valuable stuff and keep it outside of their body. That's a whole other...

00:19:12.820 Maybe temperature regulation?

00:19:14.400 Yeah. I wrote about this in my book and I researched it pretty thoroughly and came up with

00:19:19.240 no answer because elephants and whales and... But I think elephants, there's a one other vole

00:19:24.900 or something that has their testes inside, but all other mammals, it's outside. And yes,

00:19:29.480 there certainly is temperature regulation, but then why don't we have the system, however it is,

00:19:35.940 that the elephants can get away with it.

00:19:37.240 Yeah, to just be able to regulate.

00:19:37.960 So it's some genetic constraint. 0.99

00:19:39.980 I'm just going to take you down a stupid detour for your next book. We were at my younger son's 0.99

00:19:46.620 baseball party at the end of the season. So now picture at the time, a bunch of 27-year-old

00:19:52.400 boys running around the pool, playing baseball, playing football, goofing off. Me and the dads

00:19:57.860 were sitting there hanging out and we were observing their behavior. And I came up with

00:20:03.040 this observation, which is there's estimated to be about 110 billion humans that have lived

00:20:08.760 over the past 250,000 years, inclusive of, of course, the eight or so billion that are alive

00:20:13.840 today. And just watching this small group of 20, you could already see the number of times one boy

00:20:19.880 would walk up to the other and sort of flick him in the nuts. Okay. And I was like, all right, 0.63

00:20:25.040 to the dads, how many times in the history of 250,000 years has one male gone up to another male 0.59

00:20:32.440 to flick him in the nuts? What's that number?

00:20:34.260 So the chimps did this.

00:20:35.560 Well, so let me finish the punchline.

00:20:37.120 The punchline is whatever that number is, it's enormous. Now, what's the number of females that 1.00

00:20:45.360 have gone up to another female and gone and tried to flick them in the clitoris? Like zero. 1.00

00:20:50.320 There is sometimes a little breast play, I guess, in the teenagers, but nothing like what boys do,

00:20:56.960 what men do.

00:20:57.840 You're talking about a ratio of zero to 87,432,000,000.

00:21:03.320 All right. Give me your hypothesis about why this happens.

00:21:06.680 I mean, my only hypothesis is males are idiots. It's such an evolutionary, stupid thing to do. 1.00

00:21:14.020 Yeah. 1.00

00:21:14.180 Like that's a very precious part of real estate.

00:21:16.820 That's the point. So why would they do that?

00:21:18.460 So maybe it's threatened. It's like, basically, I'm going to make sure you can't reproduce.

00:21:21.800 I'm going to be dominant. I'm going to reduce your probability of reproduction. 0.97

00:21:25.320 So these are kids who are good friends usually, right?

00:21:27.560 Yes.

00:21:27.920 And only a good friend could do it.

00:21:29.760 Yeah. Well, only a good friend will get away with it. Like if a stranger did it,

00:21:33.740 then you're going to come to blows.

00:21:34.960 Okay. So that's the point, I think. Male intimacy involves insults. The harsher the insult somehow,

00:21:43.200 the more intimate, unless it's rejected, like you just described with the flick. So chimps, 0.98

00:21:49.300 and this was amazing to see because I didn't know about it. When they're in a high stress or

00:21:54.180 conflict situation, or there has been a conflict, the subordinate will cup the balls of the dominant 0.96

00:22:02.640 one. And they also sort of play sex from behind kind of, but it's this intimate, trusting, 0.99

00:22:11.240 weird situation where I think it really is saying, I'm down for you. I'm not going to hurt you. I'm 0.66

00:22:18.620 holding your testicles and you can trust me. I don't know, but that's interesting. 0.99

00:22:25.300 It just blows my mind because again, the dads, we sat around and we laughed hysterically at this

00:22:29.300 because most of us have daughters and we're like, our girls have never once behaved in this way.

00:22:34.300 Yeah.

00:22:35.060 So there's all these things we don't understand.

00:22:37.060 Yes.

00:22:37.380 And one of them is why would you leave this precious real estate outside your body

00:22:40.800 if you could potentially thermoregulate inside the body?

00:22:44.120 I mean, maybe there's an answer now and I haven't found it and someone will

00:22:47.400 write in or something.

00:22:48.400 We'll hear about it in the comment section, yeah.

00:22:50.400 So I'm just going to go through the ducts a little more quickly. There's two different systems.

00:22:56.860 So the Wolfian ducts become what I'll just say is the male internal plumbing and the 0.83

00:23:01.860 Malarian ducts become what is the female internal plumbing. So what's important is that the 1.00

00:23:10.040 Leydig cells produce testosterone, which stabilizes the development of the Wolfian ducts. 0.82

00:23:16.560 The testicles have to produce two hormones. Leydig cells produce testosterone to stabilize 1.00

00:23:22.300 the Wolfian ducts to connect the sperm producing organ to the delivery system ultimately, which 0.97

00:23:31.140 is the penis. And they have to cause the degeneration of the Malarian ducts. So that's

00:23:38.780 anti-malarian hormone and testosterone. So healthy testes, and this is important when

00:23:44.040 we talk about the disorders or differences of sexual development, healthy testes will 0.54

00:23:50.100 have those effects. And you can also think about what happens if they can't produce anti-malarian 0.99

00:23:55.640 hormone or what happens if there's no receptor for testosterone or no receptor for malarian

00:24:00.940 hormone.

00:24:01.840 And by the way, at any point, is any of this testosterone being converted to DHEA in any

00:24:06.760 meaningful amount?

00:24:08.500 Not that I know of. DHT for sure. That's extremely important. And that comes next.

00:24:16.080 Sorry, I meant DHT.

00:24:17.480 Yeah.

00:24:17.600 I'm sorry. I'm sorry.

00:24:18.400 Yeah, yeah, yeah, yeah.

00:24:18.840 So I want to make sure, maybe I can just talk about it a little bit now. So that conversion

00:24:24.640 is via the enzyme 5-alpha reductase that's present in high concentrations in the genital tissue.

00:24:31.540 So what's interesting about this is that you have a mechanism to achieve high concentrations

00:24:37.820 of a more potent androgen without that having to circulate through the general circulation,

00:24:43.760 which you do not want in a developing fetus. You want to be able to control the development

00:24:50.340 of the penis, say, which is one of the things that DHT does. So the genital tubercle can become 0.84

00:24:57.680 the clitoris or the penis, essentially in the presence of testosterone and functional 5-alpha 0.85

00:25:03.900 reductase. It becomes a penis. The labia grow and then fuse to become the scrotum and also the 0.99

00:25:11.240 prostate. DHT is necessary for full prostate development and can later sustain the function

00:25:16.980 of the prostate. So it is interesting because it is this solution to providing very strong

00:25:24.640 androgenic signals in the tissues that need it without wasting energy on strong androgenic

00:25:31.300 signals in the rest of the body. I've never thought about this until now. Is that why DHT has

00:25:37.180 such a high affinity for the androgen receptor, you think? Yes. Is so that you could permit it to

00:25:42.540 only have a local effect during embryologic development? Because otherwise, I don't know

00:25:47.160 that it would matter as much in me at this old age that DHT is that much more potent than

00:25:53.060 testosterone. So I don't think it would matter as much. I'm okay to be exposed to circulating

00:25:59.140 androgens in a way that the fetus presumably you wouldn't want. I think that DHT is something like

00:26:05.480 two to five times more potent. Oh, I thought it was even more than that. It could be more.

00:26:10.240 But what this means is that it binds the receptor more tightly and it stays on for longer, which means

00:26:16.260 that it produces more of whatever the protein is that it's upregulating because it's a steroid.

00:26:23.420 Testosterone is a steroid. Estrogen is a steroid. And steroids, this is the way that they typically

00:26:28.660 act is by either inhibiting but generally upregulating androgenic genes. So yeah, I think that's super

00:26:37.980 interesting. And of course, there's a disorder, 5-alpha reductase deficiency, where individuals are

00:26:44.420 basically just typical males, but they happen not to be able to produce DHT. We can talk about this

00:26:51.560 later, but it seems not to have any. DHT is not what masculinizes the brain, but it does masculinize

00:26:57.300 external genitalia. So without that, you're going to have what look like female genitalia in a male 1.00

00:27:02.640 who's otherwise typical male because the testosterone works and the androgen receptors are present.

00:27:09.280 And fortunately, these are really, really rare conditions. It's funny, in medical school,

00:27:13.480 you come away thinking these things occur all the time because of how much time you spend studying

00:27:17.340 these very, very rare disorders. But again, fortunately, they're not common.

00:27:22.800 I used to teach a lot about these cases because, yes, they really help to understand the typical pathway,

00:27:30.000 but also how powerful, even tiny little mutations in little genes, how powerful those mutations can be.

00:27:40.620 And I think it increases compassion when we understand what the pathway is that leads to these

00:27:48.300 differences or disorders.

00:27:50.400 Going back to that specific case, you have an individual that is born that I assume at birth

00:27:57.540 looks female. 0.99

00:27:58.780 It depends where they're born. If they're born, and this will become relevant if we talk about this later

00:28:03.380 in terms of sports, if they're born in places without a sort of modern medical care, often they

00:28:09.460 are sexed as female. But I think it becomes apparent pretty quickly in childhood that they're actually

00:28:16.180 male.

00:28:17.060 Right, because they look male everywhere else, right?

00:28:19.800 Yeah, we should probably talk about that later. But the body will look male once puberty hits. 0.87

00:28:26.000 But there is a lack of facial hair and other body hair.

00:28:30.580 But do they have ovaries? 1.00

00:28:32.000 No, no, no.

00:28:32.780 They're fully male. 0.94

00:28:33.120 No testes, no ovaries?

00:28:34.440 No, they have testes. 0.91

00:28:35.420 But they haven't descended?

00:28:36.600 They may or may not have. Generally, so the ones that really do appear to be female, and

00:28:42.060 people may believe that they're female until puberty when they start developing male musculature.

00:28:48.320 Yeah, they're producing totally normal testosterone levels.

00:28:51.180 Yes.

00:28:51.460 Just not DHT.

00:28:52.540 That's right.

00:28:53.060 Yeah, the testosterone at this point is the determining factor.

00:28:57.780 Determining what?

00:28:58.580 Muscle mass, body hair, things like that.

00:29:01.220 Well, it can't. If you don't make DHT, some body hair won't be produced. You won't have

00:29:06.860 full male typical levels. You certainly won't have any facial hair. Generally, I don't think

00:29:12.860 you have male pattern baldness. So the lack of facial hair really makes a huge difference

00:29:18.960 because it gives a sort of more feminine appearance to the facial skin. 1.00

00:29:22.360 So DHT is important. And part of why 5-alpha reductase deficiency is relevant now is because

00:29:30.800 there are people who are sexed as female and are legally female who are coming from, say,

00:29:37.260 a rural town in South Africa because they've been running as a female on female sports teams

00:29:44.040 or boxing, for instance.

00:29:45.520 Yeah, yeah. This is obviously the case we're all familiar with.

00:29:47.780 So it brings up complicated social issues about what to do. And that means that we really do need

00:29:54.020 to understand the science there. And the important thing from my point of view is that DHT has been

00:30:00.060 pretty clearly shown not to be necessary for male typical patterns of musculature and other physical

00:30:07.480 features that would give men an advantage over women, which is difficult because sometimes these 0.81

00:30:12.320 people have been in a female social role depending on where they were born. 1.00

00:30:15.920 It's also an easy experiment to do. You could imagine giving a male a 5-alpha reductase inhibitor

00:30:22.160 from birth.

00:30:23.260 Oh, from birth.

00:30:24.120 Like as a thought experiment.

00:30:25.200 Yeah.

00:30:25.480 If you took a normal, chromosomally, phenotypically normal male, and from the time they were,

00:30:31.040 call it five years old, you just gave them 5-alpha reductase inhibitor. All you're doing is

00:30:35.580 turning their DHT down to zero and doing nothing else. You're basically asking the question,

00:30:40.360 will they develop normal musculature?

00:30:43.040 So Best Seen, Challenger, Best Seen, and et al. have done that experiment and there's

00:30:48.980 no difference between blocking DHT and-

00:30:52.340 No, they did it in humans.

00:30:53.320 How did they get an IRB for that?

00:30:55.300 I think you know his work. They've gotten an IRB for a lot of incredible studies that are-

00:31:00.540 Would never be done today.

00:31:01.800 Super rigorous and gold standard.

00:31:04.320 Yeah. Interesting. Okay. So you and I are probably the only ones at this point this excited about

00:31:09.560 this discussion because we're now so far down the weeds of embryology, but bringing it back to

00:31:14.220 the surface, the takeaway here is that XXXY start out for about five weeks indistinguishable.

00:31:22.760 At about that five-week mark, a gene on the Y chromosome specifically begins to trigger the

00:31:29.920 differentiation pattern. That differentiation pattern triggers the transcription of genes that

00:31:36.460 turn on hormones that are going to further activate and drive sex differentiation.

00:31:41.700 So yes, thank you for that last piece. That's very important. So the production of testosterone

00:31:47.560 in the testes, this is really important and just fundamental to understanding sex differences.

00:31:54.220 It's not that we have so many different genes. So at the same time, I should say,

00:31:58.200 we're learning more about the role of the 70 to 100 genes on the Y chromosome, many of which are

00:32:06.200 crucial for typical development of male reproduction and reproductive function. But also it appears that

00:32:13.800 there's some role even prior to the production and action of testosterone on the body and brain,

00:32:21.020 there may be early expression of genes on the Y chromosome that act in the brain to shape

00:32:27.080 later patterns of behavior. There's a lot of work going on there to understand that.

00:32:32.520 There are genetic differences. And I also want to say that the genetic differences don't just stop

00:32:38.700 at the differences with those genes on the Y. All the other genes are the same except for the sex

00:32:44.520 chromosomes. But having one X versus two Xs makes a huge difference. It's extremely important.

00:32:51.920 So people think that females completely silence one of their X chromosomes in each cell, which is 0.99

00:32:59.940 something that basically does happen so that we don't have a double dose of X chromosome genes

00:33:05.400 compared to males. So that's something called a bar body. But if that were true, it must be more

00:33:10.500 complicated or else you wouldn't have Turner syndrome. Yes, that's right. And we can talk about

00:33:15.120 Turner syndrome. But something like 20%, and here someone might correct me, but I think around 20%

00:33:22.040 of the genes on the silenced X escape inactivation. And that turns out to be important that there are

00:33:31.360 some genes in females where the female needs the double dose of those genes. And if she doesn't have 1.00

00:33:37.180 the double dose as in Turner syndrome. Which we can define for folks as single X chromosome,

00:33:43.580 which presumably they got from mom and then they didn't get a chromosome from dad. Or do we know

00:33:48.720 that? They can get it from mom or dad. And that's another rabbit hole we could go down. There are

00:33:54.060 imprinted genes depending on the parental origin, meaning certain genes are preferentially expressed

00:34:02.140 or suppressed in the mom's X versus the dad's for interesting evolutionary reasons because the mom

00:34:08.300 and dad have competing interests in what happens to the kid. And phenotypically, a woman with Turner's 1.00

00:34:15.380 syndrome does appear phenotypically female. Yes. But I believe she's not able to reproduce. 0.91

00:34:21.660 That's correct. As far as I understand, I think that there's some evidence that there's technology now

00:34:27.500 where they could reproduce. But she's sterile under maybe natural conditions. I think in some rare 0.70

00:34:32.540 cases that can happen. But generally the ovaries don't. But her stature is distinctive. It's short. 0.75

00:34:37.920 She's going to be shorter, wider neck, and a few other characteristics. But generally they're 1.00

00:34:42.960 typical in other ways. And so something about these 20% or thereabouts of genes on the supposedly

00:34:51.440 silenced X chromosome are clearly making the difference because that would be the biggest

00:34:56.380 difference you would notice. I don't know if that's the total complete difference. I don't

00:34:59.900 know enough about Turner's, but they turn out to, yes, be important. And I don't even know if it's

00:35:05.420 well understood. I think there is actually some research on exactly which genes are typically

00:35:10.680 escaping. And is it always the same genes? I don't know. So I just wanted to make the point that

00:35:16.940 so at this point we have a high level of testosterone in the fetus that is approaching concentrations

00:35:25.540 in male puberty. So this is not happening in the female. This is a huge difference. And the reason 0.98

00:35:33.440 it matters is because testosterone as a steroid is then going around and acting as a transcription

00:35:41.220 factor when it binds with a receptor to alter gene transcription on thousands of genes. So that is

00:35:50.860 happening in males and not in females. At about what stage of development? How many

00:35:55.660 months or weeks? I think around eight weeks, it begins peaking around 15 to 20 weeks. And then of

00:36:04.760 course, after birth, it goes back down. Well, it goes down at birth, but then it goes up peaking at

00:36:10.440 three months after birth. And that's called mini puberty. So this is- I don't even remember this.

00:36:16.060 Because it's new. You probably didn't learn about it in medical school. Now it's getting a lot of

00:36:20.120 attention. The point is somewhere in the early second trimester, that level of testosterone in

00:36:26.980 a male fetus is comparable to what- It's lower. It's not exactly as high, but it's very high.

00:36:33.300 If a male in puberty is at 1,200 nanograms per deciliter, this could be 600 nanograms per deciliter.

00:36:39.180 Maybe 400. Okay. If I remember correctly. But still screaming high. But it's very high. And the

00:36:45.540 point is that this is affecting the development of the brain. So I'm really interested in behavior.

00:36:52.580 And from an evolutionary point of view, what is going on in this early environment is extremely

00:37:00.480 important. The body is realizing, the male body is realizing that it's going to be a sperm producing

00:37:08.560 animal. So the brain, and we have very firm evidence, we can't do these experiments in humans.

00:37:15.500 So people don't like it when all the evidence comes from non-human animals, but most of it does.

00:37:19.660 And that's just because we can't manipulate genes and hormones and developing fetuses to see what

00:37:23.960 happens. We have some, quote, natural experiments. But all the evidence shows that testosterone is a

00:37:30.920 potent regulator of neural development and differentiation from females, which is why 0.58

00:37:37.680 boys and girls aren't the same. That is why. It is 100% the reason. And it is 100% in my view.

00:37:47.480 This explains the birthday party phenomenon.

00:37:49.980 Yes. There could be new evidence that comes out in humans. All the evidence we have points to

00:37:56.100 testosterone. Socialization matters. If you punish your kid for not being masculine enough,

00:38:04.560 for being too masculine, which happens because now toxic masculinity and rough and tumble play is

00:38:10.020 supposed to be toxic. It's not. It's healthy. It's necessary.

00:38:13.640 I didn't know that. I missed that memo, fortunately.

00:38:16.120 Sorry, I get worked up about this because there's lots of evidence showing that, first of all,

00:38:21.140 it is testosterone. So even in, I'll just go back to the chimps, the males play more roughly than the

00:38:28.020 females. In many mammals, where there is a sex difference in play, the males are playing more

00:38:33.680 roughly. There's a reason. And just to make sure people are following this logic, there's one part of

00:38:39.380 the swing we didn't finish. And it's because I keep interrupting you, so it's my fault. But I'm going

00:38:43.640 to do my best to synthesize this. Yeah, bring us back.

00:38:46.520 Testosterone, you have this real peak difference in testosterone during a critical window of

00:38:51.940 development when the brain is developing. And so you have a female brain that is developing in the 1.00

00:38:57.420 absence of testosterone. The XX brain is developing in the absence of testosterone. The XY brain is 0.96

00:39:03.780 developing in the presence of high amounts of testosterone. Testosterone then falls. By the time

00:39:09.120 these two babies are born, they both have really low testosterone. Then it sounds like you're saying

00:39:15.140 unbeknownst to me until a few minutes ago, you have this little mini puberty that comes three months

00:39:20.240 later. How high does testosterone get there? Okay. I want to go back to the critical period.

00:39:26.420 This is also extremely important and has been shown in non-human animals. The critical period in

00:39:32.360 development, you've got the period where testosterone is being produced in the fetus. And within that, there

00:39:40.500 are certain developmental periods where different parts of the brain and body are receptive to

00:39:47.160 testosterone actions. We know from non-human primates that there are different critical periods for,

00:39:55.020 say, development of the genitalia, other parts of the reproductive system, and potentially for sexual

00:40:02.420 and aggressive behavior separately. That's interesting because when we want to understand certain aspects

00:40:09.400 of male behavior or differences in male behavior, it's helpful to know that possibly aggressive and

00:40:16.840 sexual behavior may have different thresholds for male typical versus female typical, and that there

00:40:23.100 may be different critical periods so that we don't really know in humans. Also, in males, once you hit

00:40:30.140 your sort of male typical level of testosterone, we're just talking about male versus female typical

00:40:36.940 patterns of behavior. In males, in adulthood, at any stage, there isn't really a dose-response

00:40:43.900 relationship. It's more you're at a level that's like 10 to 20 times more than females. Female have 1.00

00:40:50.660 some testosterone exposure in utero, and some females have more than would be typical, and we

00:40:56.700 should talk about that. There is a dose-response relationship because our levels are so low and

00:41:02.320 we're extremely sensitive to differences. But males have so much more, those differences don't seem to

00:41:08.740 make a difference. Once you cross this threshold. Yes, yes. I think the main thing I'm hearing you

00:41:13.740 say, Carol, is that when you observe five-year-old boys and five-year-old girls behaving completely

00:41:21.760 differently, the most obvious explanation for the why is a behavioral difference. And the behavioral

00:41:29.140 difference is driven by potentially the way their brains developed during that critical window of being

00:41:34.780 bathed in testosterone as opposed to the differences in testosterone in a five-year-old boy versus a

00:41:41.860 five-year-old girl, which are de minimis. Okay. Thank you so much. Is that correct? Yes. Okay. And thank

00:41:46.660 you for saying it so clearly because there are some really important points here. I think what you just

00:41:52.820 said and what we're going to talk about in terms of childhood shows that you cannot judge anyone by their

00:42:01.000 current testosterone levels. You can't predict that much. You can't attribute all variation in behavior

00:42:08.220 and individual differences in behavior necessarily to current testosterone levels. And even within that,

00:42:14.940 if you do have current levels, often, yeah, you can't predict much in terms of, say, sexual behavior

00:42:21.120 or aggressive behavior. You certainly can't with kids because they don't have any differences. They hardly

00:42:26.720 have any testosterone at all. What they do have is on average, I should have said this before, but all

00:42:32.240 of this is on average. There is tremendous variation. The only thing that differentiates the sexes 0.98

00:42:37.640 cleanly and essentially is the gamete production. Define that again, because I want to make sure the

00:42:44.280 listener understands when you're referring to gamete, what you're talking about and the production of them.

00:42:48.800 Sperm and eggs. What has evolution designed you for? If you're X, Y, and you're going to be making

00:42:55.480 sperm, there's going to be a suite of characteristics generally that are going to be different from the 0.56

00:43:01.440 suite of characteristics that a female who has ovaries and eggs will need to maximize reproduction.

00:43:08.100 So all evolution cares about is what portion of your genes are making it into future generations.

00:43:13.600 So the design here is about reproductive strategies that coordinate how your body grows, what your body

00:43:21.800 is like, what physical features you develop, coordinates the hormones, coordinate that with

00:43:28.000 certain patterns of behavior on average. All of the bodies and the behavior can vary across XX and XYs. 0.91

00:43:37.260 But what we're talking about is these broad patterns, mostly to do with sex and aggression,

00:43:42.020 that tend to differ between males. And this is across sexually reproducing organisms for the most part.

00:43:48.600 So all the other stuff can vary. It's not that all XY people are going to have a higher sex drive and be

00:43:57.120 more aggressive. That's just not the case. Bodies vary, behavior varies.

00:44:02.880 I know you weren't consulted during the design phase, but do you have a sense of why the female gametes are all

00:44:10.460 produced up front? Oh God. And you basically get your lot at birth and then you, that's it. It's a rate of

00:44:16.520 attrition versus why the male gamete is just produced on demand. Again, I'm being a bit facetious. Of course,

00:44:22.940 we don't know this, but do you have an insight into why that's the case?

00:44:26.300 I'm sure there's a better answer, but here's what I think. I hope people will write in with the better

00:44:32.440 answers. Making eggs is expensive. Calorically, in terms of time and calories, they're expensive.

00:44:40.900 So what we are designed to do is convert energy into offspring. That's basically what evolution

00:44:46.240 put us here to do. And you want to do that as efficiently as possible. So eggs are energetically

00:44:53.540 expensive. Sperm is less energetically expensive. And I don't know what happens in terms of how the

00:45:02.340 eggs that go atritic. So we start out with, what is it? 10 million? I know you just had.

00:45:07.740 I know. I just talked about this with Paula. The numbers are staggering how much attrition there is

00:45:12.300 between birth and. So, and then you end up at birth, you have 1 million and something like that.

00:45:16.960 Maybe a million to a hundred thousand to. Right. Yeah. But most of them just die. So maybe there's

00:45:22.720 some selection process there. There's an overproduction because for females, there's so much that goes into 1.00

00:45:29.280 the production of each egg and time and energy and each egg that you produce is going to limit your

00:45:36.520 ability. If it takes a long time, that means you can only have like eight or 10 or however many kids

00:45:41.920 over a lifetime. So they're very valuable. So we're talking about testes and sperm, testes being not so

00:45:51.660 well protected, but the eggs are extraordinarily well protected if they're made early and then just

00:45:59.340 stored. I think they resume meiosis, of course, when they are ovulated. So maybe there's this store

00:46:06.780 and then there's a selection process that goes on throughout life. That's a very interesting idea,

00:46:11.740 right? Which is maybe you make, I mean, let's just pretend we got these numbers right, but directionally,

00:46:16.300 you know, let's say you make a million, you have the first 18 years of life or whatever it is,

00:46:21.160 or 16 years of life to select the best of those. And so it's not a stochastic process that takes you

00:46:28.220 from the million to the 10,000 or whatever the number is. It's truly a winnowing down of the best

00:46:34.320 of the best of the best. It could be. I don't know. I don't know. It is a super interesting question

00:46:41.160 and I should know more about it. But it does, I think, illustrate the reason why we have different

00:46:48.960 strategies. It's because the time and energy that females have to put into reproduction, 1.00

00:46:56.260 if, say, imagine we're living as hunter-gatherers, there's no birth control. We're not going through

00:47:00.660 life getting our periods over and over and going to Whole Foods and having a job. We're having kid

00:47:06.120 after kid after kid. We're nursing. We're producing the milk with our own bodies. We have to grow the

00:47:12.340 baby in an energy, relatively energy-restricted environment. The burden for female mammals, 0.89

00:47:18.980 the energetic and time burden for female mammals is enormous to produce each offspring. And if you 1.00

00:47:25.380 don't have the right egg or the right sperm, you should care about where you're getting the sperm,

00:47:29.900 then you've lost, you know, a huge chunk of your potential reproductive output. Men don't lose a

00:47:36.880 big chunk. That just doesn't happen to them. And this is the sex difference in parental investment

00:47:42.820 that shapes, that's why eggs and sperm matter in terms of our bodies and our behaviors, because we

00:47:48.600 have to do very different things and live in different ways to maximize our reproduction. Okay,

00:47:54.160 I want to come back to what you said about mini puberty and the differences in hormones. So I do

00:48:01.460 think it's the differences in the increase in testosterone that males have that explain why

00:48:08.000 they're more likely to have rough and tumble play, more energy. And by the way, how high a peak is this

00:48:13.860 mini puberty and how long does it last? It starts within a month after birth, but then peaks around

00:48:20.720 three months and I think then goes down until something like six months. And it appears that

00:48:27.620 it has important effects on brain development and on lengthening the penis. Does the female do it as 1.00

00:48:34.060 well? In other words, does the female experience a rise in estrogen? Yes, there's a lower postnatal peak, 0.96

00:48:39.980 but the mini puberty in boys appears to also be associated with activity levels in the boys and even

00:48:50.080 growth trajectories. So that's interesting. There's a very narrow window of time, right? Three to six

00:48:55.360 months. Yes, yes. So in terms of the activity levels, could be that that postnatal time that

00:49:03.300 the play in boys has something to do with differences in activity levels, differences in novelty seeking,

00:49:09.860 different temperament, less fear also. But if you think about it from an evolutionary point of view,

00:49:15.620 in male mammals that have to compete for status and operate in a dominance hierarchy. There's a

00:49:22.620 lot of male mammals have dominance hierarchies, which tend to function to reduce aggression overall,

00:49:29.100 because instead of duking it out every time there's a fertile female or a delicious piece of 0.99

00:49:34.560 fruit in a tree, you just signal, I'm not going to take your fruit. I'm subordinate to you. So you can

00:49:40.560 get along as a group. Yes, there's infighting just like humans have, but humans have dominance

00:49:45.640 hierarchies also. And if you don't learn how to compete physically with other males as a kid,

00:49:52.960 this has been shown in non-human animals, and there's some evidence for this in humans,

00:49:57.120 that you have more trouble. Sorry, it just occurred to me that this is obviously happening with social

00:50:02.260 media. People are using their iPhones to compete instead of getting out in the yard and play fighting

00:50:08.960 or fighting with other boys. That's actually healthy because it ends up reducing aggression.

00:50:14.340 It helps especially young boys and young men learn their place in the hierarchy, what they're capable

00:50:21.300 of physically, how to be threatening and when to be threatening, when to signal that they're submitting.

00:50:28.780 All of that happens, and it's fun. So they're driven to do it because it's adaptive for them

00:50:33.980 evolutionarily. So I just wanted to throw that in. And females tend to have more nurturing play. 1.00

00:50:40.840 I had three older brothers. I was climbing trees. I was wrestling with them. But the girls almost never

00:50:45.740 play by choice just with each other. Like they don't have a play date where they're tackling each

00:50:51.480 other. My son is 16 now. He's still doing it. And he's six feet and his friends are like one of them

00:50:57.240 is like six, two. And it makes me very, very nervous because they can really hurt each other now. But

00:51:02.940 yeah, they're still doing it. It's such a beautiful thing to watch if you just stop judging it for a

00:51:07.920 moment and just ask yourself the why question. Like what is driving this behavior, right? So for whatever

00:51:13.860 reasons that are tragic, this has become a political discussion, but it's really not. It's simply a

00:51:19.140 discussion of biology and it's endlessly fascinating. Why is it that when I walk into the pantry

00:51:25.340 and I see a candy bar versus a cheese stick or something, I want to eat the candy bar? Well,

00:51:34.400 that's evolution. I can make a choice not to do it, but it would be silly for me not to appreciate

00:51:40.420 how much my brain looks at the candy bar and sees the sweetness, the energy density, the fat,

00:51:48.220 the sugar. And it's like, yeah, that's what I want versus pick the bland, healthier option.

00:51:53.440 And similarly, when we watch kids play, I find it very interesting. I wasn't obviously aware of half

00:52:00.720 of what you're saying, but this idea that if you let boys duke it out the way we all did,

00:52:08.800 that ultimately it settles them down. Again, because it's probably too soon to tell what the results are

00:52:14.340 of the natural experiment where kids play less. I mean, there's certainly no shortage of discussion

00:52:20.740 about what happens when kids are all the anxiety and things that come from endless social media.

00:52:26.900 But this is kind of a deeper and more interesting question, which is what does it teach us about

00:52:32.280 aggression or lack thereof? And I'm curious, have people been studying that as closely as they've

00:52:37.740 been studying the effects of social media on anxiety and some of these other things?

00:52:41.900 I'm not sure what the current literature is on how social media is affecting play,

00:52:48.460 other than it's not happening as much, which I think is obviously bad. You're out there,

00:52:54.640 you're being physical, you're learning about your body, you're developing relationships with other

00:52:59.520 boys in particular that are trusting, but can involve physical aggression. You mentioned something

00:53:06.260 about wanting to have, what did you say? The chocolate bar? What was it?

00:53:09.640 Yeah, yeah. Your knee-jerk reaction is to always eat something that's sweeter, more calorie-dense.

00:53:15.500 We have a mismatch. We're designed to be motivated to seek out these foods and we have to expend

00:53:20.680 energy to get high-calorie foods, say like we would have maybe gotten honey. And that would have been

00:53:25.860 super rewarding and we only would have had a little bit and then we would have ran around and spent those

00:53:31.480 calories and now we have chocolate bar. That's a mismatch situation that's maladaptive.

00:53:36.700 What's interesting is that we've figured out what to do to some degree with the male. Any women watching 0.87

00:53:43.620 this who are super competitive and aggressive, that's a thing too. It's not that women are not this way. 1.00

00:53:50.080 They certainly are. And I see more and more examples on my iPhone from basketball games and stuff recently.

00:53:55.460 But they tend to be less physically competitive than men on average. So we have sports that

00:54:02.880 ritualize this motivation or this desire, especially on the part of men. And we have

00:54:08.660 a lot more men who are interested in watching sports because they're kind of getting that

00:54:12.700 need met vicariously. They're like jumping out of their chairs. Often their testosterone

00:54:16.680 is responding also to even the vicarious participation in sports, which is interesting.

00:54:22.360 Now, given that we evolved for the males to get this aggression out physically, what do we say

00:54:29.420 about boys that play a ton of video games and get their aggression out there? So you could argue,

00:54:35.840 well, they're playing with their other friends. I don't know enough about video games, so I'm going

00:54:39.740 to embarrass myself, but I'm sure there are super aggressive video games where you're killing each

00:54:43.660 other and doing something in a virtual world that you would do if you were wrestling. Is there a

00:54:49.040 positive to that, aside from the fact that they're not getting exercise, of course, and not being

00:54:52.580 physically active? Do we know if that serves as even a reasonable proxy?

00:54:56.660 As far as I know, there isn't any getting your aggression out, getting that need met,

00:55:02.320 if it is a need. Some people don't have that. In fact, most men are not terribly physically

00:55:09.180 aggressive. There's a competitive, I think you could compare it to pornography and ask,

00:55:16.880 are men getting out their sexual need. I think there's more evidence that maybe they are getting

00:55:24.060 some need met there. But in terms of aggression, I'm not sure it works the same way.

00:55:31.560 So if a parent is listening to this, is there anything that they should be concerned about? In

00:55:36.820 other words, we know that all siblings are a little bit different. So even my two boys are different.

00:55:41.640 So they're clearly both a step function more aggressive and physical than their sister was

00:55:47.240 at a comparable age, but they're quite different themselves. The younger one is still a step ahead

00:55:54.140 in aggression of the middle one, meaning the younger boy is more aggressive than the older boy.

00:56:00.700 Can you say what you mean when you say aggressive?

00:56:03.060 So there's three years between them. And obviously the older one is larger. The younger

00:56:10.320 one will instigate physically more. If he's unhappy, he will attack the larger, older boy.

00:56:20.120 And he doesn't have that same, he doesn't respond maybe even aggressively or...

00:56:25.600 He just hits. He'll hit anything and anyone that stands in his way. Whereas the middle one is

00:56:30.880 not quite that bad. I feel horrible saying all of this stuff. My wife's going to kill me. She's

00:56:35.660 like, you make them sound like monsters. They're not monsters, but it's like they're boys and this

00:56:39.520 is what boys do. But with other kids, they're more in control, but with each other, they're at their

00:56:45.480 worst. And which of course I think is normal for male siblings. But my point being is just even 0.78

00:56:50.220 between them, there's quite a difference in aggression and maybe it's birth order. Maybe when

00:56:53.540 you're the younger one, you have to stand your ground even more.

00:56:56.740 I used to hit my older brother. So I was kind of a big hitter myself.

00:57:00.840 I guess my point is, should a parent just say, look, I'm just going to let these kids

00:57:03.640 do what they're going to do and understand that there are differences. Some boys are going

00:57:07.240 to be aggressive. Some are going to be less aggressive. Some are going to play rough.

00:57:12.480 Some are not going to play that rough. Is the best thing you can do as a parent from any

00:57:15.880 available evidence, just let them do their thing?

00:57:18.960 This is an interesting question. I hadn't thought about it in this way. So I would say the rough

00:57:24.700 play generally, if they're having fun, if they're smiling and laughing, let them go for it. They

00:57:30.920 need to learn to work their stuff out. And I think the more play, the better. And we are designed to

00:57:37.360 play boys and girls in different ways. And it helps us learn how to be social and have social

00:57:45.180 relationships and respond physically. And all of that is so important. And if we're not doing that,

00:57:51.600 then I think we're going to have more trouble as adults. But where it's not so much fun and people

00:57:56.600 are getting hurt. Yeah. Then I think the parent, I don't know, maybe you let them work that out too.

00:58:01.100 I don't know.

00:58:02.000 Let me give you a specific example. Are boys more likely to bully than girls?

00:58:06.740 I don't think so. There's this difference where boys will say to your face, you fat F. 1.00

00:58:14.260 They'll insult you to your face and bully to your face. Girls are very aggressive also. But what's 1.00

00:58:23.040 interesting is that they tend not to do it in a direct confrontational way where they're exposing

00:58:28.840 themselves as the perpetrator. So they can hide from physical harm, which is more adaptive. But they

00:58:36.020 can denigrate the reputation, say, of other girls, which they do because they're their competition in 1.00

00:58:41.960 terms of mating competition for, say, high status males. So they can denigrate the appearance or

00:58:47.980 behavior, especially sexual behavior. And it's cruel. It's extremely cruel the way that this sort

00:58:54.100 of feminine aggression. Do we see that kind of behavior amongst other mammals? 0.98

00:59:01.180 Well, we certainly see more face-to-face aggression among male mammals. What we do see in female

00:59:08.220 hierarchies sometimes is that there's harassment, say, in some monkeys, there's harassment of a subordinate

00:59:16.520 female by the dominant, so much so that cortisol goes up in the one who is being harassed, and it interferes 0.98

00:59:23.660 with her capacity to reproduce. So that is not a physical, necessarily, confrontation. It's just harassment.

00:59:32.080 But the sex difference in human aggression with females doing more of this passive aggression, 0.90

00:59:39.640 I think part of that is that females have not evolved the same skills to resolve conflicts so 1.00

00:59:47.660 that the hierarchy can sort of be reinstated. Males can, you know, have a pickup game on the basketball

00:59:53.360 court. It can get rough. They can insult each other. But by the end, they've sort of worked it out.

00:59:58.520 Maybe there's a change in the status hierarchy, but they've worked it out. It's over. It doesn't

01:00:03.000 go on for weeks. You don't have to talk about it endlessly. Females do not have the same ability 1.00

01:00:08.300 to resolve those kinds of complex social, what for us would be very complex social conflicts.

01:00:14.620 That is such an obvious statement, the way you make it. I don't think of it that way,

01:00:19.060 but I completely noticed that even thinking back to high school. Like we would, as boys,

01:00:23.920 get into huge fights and it would be over by the end of the day.

01:00:29.940 But there's something that feels fair about that and to sort of backstab and not give somebody the

01:00:36.400 opportunity and not to be able to work it out and to gossip behind people's backs. Yes, there's murder

01:00:43.320 and rape and men are overrepresented in those horrible crimes, but we shouldn't glorify feminine ways of 1.00

01:00:52.520 interacting necessarily and try to get men to be more feminine because there's a lot of 0.93

01:00:58.040 issues also with typical feminine behavior. 1.00

01:01:01.900 So let's talk a little bit about the pathology though. You just alluded to it.

01:01:05.120 There aren't too many female murderers and rapists and the disproportionate representation of men 1.00

01:01:11.160 in violent crime. You don't need statistics to understand that.

01:01:14.660 Definitely do have the statistics like 95% of murders everywhere are male and obviously sexual

01:01:21.320 assault is 98% or something.

01:01:25.040 So what role does testosterone play in that?

01:01:28.000 So here again, I think just like with play, people aren't going to like this. So I want to

01:01:33.140 make sure I say it clearly. I do think that the difference, this broad pattern is similar to what

01:01:40.040 we see in non-human animals where the males are much more likely to kill each other than the females.

01:01:46.340 There's many more violent or physically aggressive interactions. If you look at both of us, we have

01:01:52.280 different bodies. You are bigger and stronger. I started lifting weights because of you a year ago,

01:01:57.100 so I'm getting there, but I'll never get to where you are. Also, I'm older, but physically men are

01:02:03.620 developed for competition, essentially male-male competition for mates. This plays out in this

01:02:10.840 destructive way in society. And I believe that the ultimate reason for the difference is

01:02:18.920 testosterone. However, the murder rates in Canada, men are committing fewer murders in Canada than they

01:02:26.940 are in the U.S.

01:02:27.680 We can't attribute that to testosterone levels.

01:02:29.980 So that's not because of differences in testosterone level. It is because socialization

01:02:36.440 and culture, religion, the laws all have a huge impact on what the values are in any particular

01:02:46.120 society, what is tolerated, what is encouraged. Some societies basically allow men to beat and

01:02:52.220 rape their wives. So you have higher rates of those male behaviors. Where it's not tolerated and the 0.98

01:02:58.180 culture is totally different. You have lower rates of those behaviors. But everywhere, you will have

01:03:04.140 the sex difference with all of these behaviors higher in men. I'm glad you asked this because I

01:03:09.520 think the main reason people don't like biological explanations for sex differences is because they

01:03:15.840 misinterpret a tendency or a predisposition for a behavior or a biological explanation as suggesting that

01:03:26.020 it's impossible to change behavior. It's impossible to change behavior. It's not. You know, that there's no

01:03:30.980 variation across the sexes in behavior. There is. Just because there might be a biological explanation or even a

01:03:38.220 genetic explanation. The important thing to remember is that we develop within an environment. It's gene-environment

01:03:47.360 interactions. We develop within a society. And how we develop and even how our hormones, say, respond to

01:03:55.060 different kinds of interactions is impacted by the social system and by the ecology and everything else.

01:04:01.820 So it's complicated. But yeah, I think that the ultimate reason is because of the genetic difference,

01:04:07.640 which is the Y chromosome and the hormones, hormonal differences that it leads to. We haven't talked about

01:04:13.260 female behavior, but of course, nurturing. If you're going to be growing and producing and holding 1.00

01:04:19.040 and feeding and caring for a baby, and you're the one who absolutely has to do it, and that's the

01:04:24.060 female, of course, we get help from men. And sometimes men even take over as the primary caregivers, which is 0.99

01:04:29.960 extremely unusual in mammals. So men are capable of all of that nurturing if the society values it, because

01:04:36.880 some societies don't value that, and then they're still capable, but they're not apt to do that.

01:04:42.340 For females, it just doesn't pay reproductively in general to be super aggressive. We need our 1.00

01:04:50.420 bodies to be healthy, and we have to live a long life. So the longer our lives, the longer our

01:04:56.660 reproductive output. Men can die young and have great reproductive success. Yes, if they take risks

01:05:03.760 and physical risks. And that just doesn't have the same payoff for females. There are some primates, 1.00

01:05:10.060 for instance, where the females are relatively aggressive, but it's almost never to the same 0.98

01:05:14.820 extent as males. It's so interesting when you think about how, as humans, we hold ourselves to

01:05:20.740 a higher standard than we would hold animals. I'll give you a very concrete example. So if we go back

01:05:25.960 in time 500 years, first of all, neither of us would be alive. Forget that part of the discussion. But

01:05:31.500 let's just say 500 years ago, if you had a male that was 25 years old, he would readily reproduce

01:05:40.700 with a 14-year-old female. That would be completely normal and evolutionarily wise. But we've made a 0.94

01:05:47.420 decision, at least in our society, that that's unacceptable. And I think most people think that

01:05:53.280 that's a good decision. That's an example of we have made a societal norm that says it's unacceptable

01:06:02.480 for a 14-year-old girl to be reproducing, certainly at the hands of an older man. So if she gets

01:06:09.660 pregnant from her 14-year-old boyfriend, that's a different discussion and we can help them both out.

01:06:13.860 Well, in this country anyway.

01:06:15.480 My point of this story is we've made a decision that this is no longer acceptable. Just as we've made

01:06:21.740 a decision that a husband can't rape his wife, we have just decided that maybe that was cool 1.00

01:06:27.480 200 years ago. It's not cool today. So to play the other side of some of these arguments,

01:06:33.680 is there someone watching us who's saying, Peter, Carol, you guys are talking about all this

01:06:38.060 aggression stuff, but we're humans living in the 21st century. We have to change. We have to evolve

01:06:44.860 as a species. Is there a case to be made that men should be less aggressive because all

01:06:51.680 of these evolutionary reasons that you described aren't as necessary. Women and men are going to 0.98

01:06:57.380 live through their reproductive lives. We don't have this urgency. We don't need this competition.

01:07:02.900 Again, I'm not saying I agree with that or anything, but I'm just saying like there's a steel man for

01:07:06.680 the other side of this, just as in those extreme examples of we don't have sex with 14-year-olds and 0.93

01:07:12.220 we don't rape our wives. 1.00

01:07:13.960 What would it take for you to not eat that chocolate? 0.93

01:07:15.880 Well, it's interesting. Food is a really tough one, isn't it? It can be done. It just takes

01:07:22.100 a ton of willpower.

01:07:23.880 Food is a great way to think about it. There's food and sex and aggression is for ultimately,

01:07:29.780 in a way, for sex.

01:07:31.100 For both. Yeah. Well, I mean, 0.85

01:07:31.720 but also for both.

01:07:32.460 But yes, for men more than women, aggression is certainly more about.

01:07:37.020 To play off that, I don't need to be an alpha male to get as much food as I need today.

01:07:41.700 But you are an alpha male and you have a lot of food.

01:07:45.540 But I don't need to be.

01:07:46.780 Certainly, were you competitive?

01:07:47.080 We don't need to be an alpha male to get food.

01:07:49.360 No, that's right.

01:07:50.060 That's my point.

01:07:50.740 So you're saying we should get rid of the drive.

01:07:55.000 I'm just exploring this idea, right?

01:07:56.320 No, and I'm glad you are exploring because there's physical competition, which we certainly

01:08:01.560 do not need. But think about what we get from the male. So there is a sex difference in

01:08:08.740 certain drives. Men tend to be more driven to achieve specific and more narrow goals and

01:08:16.520 like hyper-focused on certain goals and to achieve, to be the top of the heap in one thing,

01:08:22.500 chess. I wrote some article on sex differences in chess and learned a lot because I was like,

01:08:27.120 why are men consistently better at chess than women? And they are. 0.99

01:08:31.840 If you only knew of the rabbit hole, we could go down on that front, but I'm going to refrain.

01:08:35.940 So I'm really interested in that. And I had what I suspected appears not to be the case

01:08:41.520 in terms of doesn't seem to be explained by differences in cognition. At least that's not

01:08:47.600 necessarily the driving force. What is, I think, the driving force is that boys and men are much

01:08:53.280 more willing to spend countless hours studying the moves and practicing and seeing their coach and

01:09:01.580 trying to beat their competition. And for women, there are other things to do that matter in their 1.00

01:09:09.820 lives more. Certainly, there are some women who do that kind of focus, but there are way more men.

01:09:17.100 I'm saying this because that competitive drive, chess, I don't know what we're like getting out of that.

01:09:24.260 You haven't played, have you?

01:09:25.360 No, I have.

01:09:26.080 You have? Okay.

01:09:26.800 I'm not super seriously, but my son was really into it for a while. My brother,

01:09:31.300 I know a lot of people who are obsessed with it. But when I say what we're getting, I mean,

01:09:36.400 socially. Competitive men, I'm not saying that women are not competitive or haven't made incredible

01:09:42.760 social advances in all kinds of domains. But what I am saying is that if we want to interfere

01:09:50.520 with the male desire to compete, we are also interfering with whatever products we get

01:09:56.740 or advances we get from that intense drive. Being in academia, as I was for 25 years,

01:10:06.040 there's a lot that is produced because people want to be first. They want to nail finding this gene or be

01:10:14.340 the first to make a certain discovery. It's tremendously productive, often, that insane

01:10:20.640 drive that men have. And I think women have less of it because we have kids. We are designed to have 0.99

01:10:27.100 the kids. We don't have the same, I must do something else, have to produce this other thing

01:10:33.980 with the same drive. Again, there's tons of variation here. There's tons of crossover.

01:10:39.180 This is just a pattern. I think men have more of that potentially because they're not designed to

01:10:44.640 have kids, to produce them with their own bodies. Let me play back to you what I think I'm hearing

01:10:49.960 and with a little bit of- I'm in trouble. I hope you're not going to be in trouble. No, no, no, no.

01:10:52.540 With just a little bit of inference looped into it. What I think you're saying is, look,

01:10:56.680 for most of 250,000 years, male aggression was absolutely essential for males to reproduce

01:11:02.980 and find and forage for food and protect. More so, certainly.

01:11:06.320 Yep, yep. The past 100 years or so has largely done away with that, meaning a couple things have

01:11:12.740 become true. We basically have domesticated crops and agriculture and livestock, and we're no longer

01:11:18.600 in a food-scarce environment, certainly for the last 50 or 60 years. Lifespans have extended enough

01:11:24.680 that there isn't a race to reproduce. You can actually live through your reproductive years.

01:11:31.160 So it's not like you have to get this done before you die at the hands of a saber-toothed tiger.

01:11:37.840 Third, infant mortality and maternal mortality rates have plummeted. So the success of your

01:11:45.620 offspring skyrockets. And basically, all of the other reasons that we used to need to be hyper

01:11:53.800 aggressive with each other to compete for mates, again, food and all those other things, 0.94

01:11:57.960 have largely dwindled. But that's a fire that's been burning for millennia. So we have to channel

01:12:05.180 into something else. And so in many cases, in the most polished corridors of society,

01:12:11.980 we've channeled that into professional excellence or things that would have been-

01:12:16.720 Their sports. Their sports are huge.

01:12:18.120 Totally unnecessary and superfluous hundreds of years ago. Nobody thought of discovering genes or

01:12:23.620 trying to be the leading scorer in the pick your favorite sport. And so it's been an easier or maybe

01:12:31.340 more logical transition of aggression from evolutionary needs into gratuitous needs, making more money,

01:12:40.300 being more successful, being more famous, being more respected in some way. And the maternal need

01:12:48.220 of caring for the offspring hasn't, as it's coming out of my mouth, I'm sure I'm just butchering this,

01:12:55.620 but it hasn't evolved as much in the sense away from its original goal, which was making sure the

01:13:02.100 offspring were perfectly protected. So there's an asymmetry in this evolution of evolution.

01:13:07.600 Yes.

01:13:08.240 That's what I'm hearing. Do you agree with that?

01:13:09.920 Yeah, I think I agree with the general thrust. I mean, what's interesting is thinking about how,

01:13:16.260 say, nurturing, we still need to nurture. My baby was not always with me when I was working,

01:13:23.280 so there are solutions to that. But I think that nurturing drive is still super strong and valuable,

01:13:30.780 and that is probably best for the kid if we indulge.

01:13:34.720 And now paternal attention can be given much more to kids.

01:13:38.620 Yes. Well, it's interesting, because even in hunter-gatherers, there's very different

01:13:43.420 traditions across hunter-gatherer societies in terms of expectations for paternal involvement.

01:13:49.900 And when there's high involvement, there's lower testosterone in those males that applies to

01:13:56.420 humans.

01:13:56.880 Sorry, in the father or in the child?

01:13:59.040 In the father. So for fathers to be very attentive, the testosterone generally is suppressed,

01:14:05.460 and that's true in birds where the males are contributing. If you raise it, they neglect

01:14:10.180 their kids. So there is a hormonal support there for parenting. So that's something that

01:14:15.720 men can do to increase their reproductive success. So I just want to say that I think that is not

01:14:19.900 novel.

01:14:21.200 If you're a man out there listening with low T, ignore your kids.

01:14:24.740 With low T?

01:14:25.720 If your T is low, you should ignore your kids to raise your T. Is that the implication?

01:14:29.280 Right, right. It doesn't drop by that much. And what matters is that you're in an environment

01:14:34.980 where you see your little kids. Like if you're a guy and you're mated and you have a partner and

01:14:40.060 you're around your baby and you're interacting with your baby, your T is going to drop a little

01:14:43.920 bit. And that's a good thing. And this is one of the reasons that supplementing with exogenous

01:14:49.440 testosterone, there are so many different ways that male testosterone responds to and influences

01:14:55.620 social dynamics. And this is one of them that's really important. You're a better

01:15:00.100 dad, potentially, if your testosterone does drop. You're potentially a better husband and

01:15:06.420 more attentive to your wife and your kids. I don't know that there's the experiment.

01:15:10.720 Do we know that there's causality here? I mean, this is a pretty bold statement.

01:15:13.940 We do. I would say, yeah, we do know.

01:15:16.580 By what magnitude are we talking about here?

01:15:19.140 I should have had the data and I don't have the answer, but it's shown across lots of different

01:15:23.760 populations in humans and non-human animals that fatherhood, first of all, mating, being in a pair

01:15:31.020 bond. This is like what birds do when they finally, they're very aggressive when they're

01:15:35.020 setting up their territory, their testosterone is high in the males. When they find the female and

01:15:40.380 establish a territory with her, the testosterone tends to drop because it's not adaptive to have

01:15:46.180 high testosterone all the time. It's why animals have mating seasons, et cetera, because it's

01:15:51.300 expensive metabolically. Because it would make us go out and look for other mates when we don't need 1.00

01:15:56.220 to. You're aggressing and fighting for status and singing or flexing your muscles or ignoring your

01:16:03.560 kids or being an asshole to your wife. You're also not reinforcing adaptive behaviors with a bit of a 0.99

01:16:12.020 testosterone spike. Like if you're around an attractive woman and you're trying to seduce her,

01:16:17.440 there's very possibly going to be a testosterone increase, which stimulates a dopamine surge and

01:16:23.760 reinforces a behavior if you're successful. How much can that happen? I'm just saying when you

01:16:30.000 shut all that off, it's like when women go on birth control and they don't respond to men necessarily 1.00

01:16:37.320 in the same way that they would have because they have just screwed up that entire hormonal birth

01:16:42.360 control. That system, there's a system in women and in men where those sex hormones are giving you 1.00

01:16:50.360 signals about what's happening in the environment and what your role is in your potential.

01:16:56.120 Wait, there's a lot for me to unpack here.

01:16:57.680 But that's a whole other thing.

01:16:57.920 No, no, no. But I want to talk about this. Everything you're saying is totally new to me.

01:17:01.200 But I don't want to get away from the fatherhood because this is very well established,

01:17:04.680 this drop. It happens not just in humans, but in other males where paternal investment

01:17:10.680 increases survival of the offspring, which it does in humans.

01:17:13.740 Okay, so let's talk about that first, but then I want to go back to the birth control and stuff

01:17:16.540 like that. So man and wife have baby. Man decides after a few years, I'm going to stay home more

01:17:24.160 and spend more time with my child and forego whatever else I was doing. So I used to be

01:17:31.440 working 80 hours a week. I'm now going to work 30 hours a week.

01:17:33.980 Oh no, he'll keep working 80. No, men work harder and make more money, tend to do that when they 0.86

01:17:38.860 have a kid. But in this experiment, this guy decides to stay home half the time now.

01:17:43.620 Okay.

01:17:44.200 His testosterone will drop.

01:17:46.000 No, because the kid's too old.

01:17:49.140 The kid's five at this point.

01:17:50.140 Then he'll start looking for other females. There's serial monogamy where the man is more 1.00

01:17:55.420 likely to stay around during the early years. And that's when maybe a critical period, I'm not sure

01:18:01.380 for this effect. It's really when the offspring is dependent and young and the mother needs to be 0.59

01:18:06.600 supplemented. Again, in a hunter-gatherer situation, the woman is not just going to have 0.99

01:18:10.940 one kid. She's going to have several and she's going to be nursing or weaning and or about to

01:18:17.280 get pregnant. And she's in a situation where she can really benefit from investment from a male and

01:18:22.840 he benefits reproductively. So I just want to pause.

01:18:26.240 He benefits reproductively because that's a critical window in which his protection is producing his

01:18:31.580 survival advantage.

01:18:32.240 And protection. Yeah. So I just want to pause here and I want to get back to everything else

01:18:36.900 you said. There are different strategies that different men can use to maximize their output, 0.92

01:18:42.800 say, in a natural fertility society. One is pair up forever with one woman. Mate guard her. Be good 1.00

01:18:50.540 to her. I'm going to like getting teary-eyed for some reason. Invest in her. Oh my God, I have no idea

01:18:57.840 what this is about. It's just I have estrogen and estrogen increases crying, which it actually does.

01:19:03.480 Testosterone inhibits it. Although I also put on my testosterone gel this morning. Anyway, so that's

01:19:09.420 one strategy. And he had to compete and have certain status to get that woman. You want a high quality 0.99

01:19:16.020 female. You want to keep her. You can do very well reproductively for your lifetime output. And you're 1.00

01:19:22.540 not out on the mating market constantly being vigilant, constantly trying to take down other males,

01:19:27.980 constantly fighting for status. You can have sex with a lot of women, which is what you're designed 0.96

01:19:32.860 to want sex with more partners than females are designed to want sex with. But who knows how many of 1.00

01:19:38.900 them are going to get pregnant and who knows how many of those babies are going to survive. But that is one 0.98

01:19:44.260 strategy where if you're a high status man, you can be very successful. You can have way more than eight

01:19:49.480 kids. But that's a high risk strategy. A lot of men are going to fail and they won't have the sure

01:19:57.040 thing of the one female where they can invest in her. That seems to be not a lower testosterone man 1.00

01:20:05.160 strategy. But we know that when the kid is young, if the guy is physically involved with a small

01:20:13.040 dependent offspring, that there will be suppression in testosterone. And that is a good thing.

01:20:19.480 It doesn't mean that your muscles will be smaller necessarily. As far as I know, I'm not sure how

01:20:24.260 big the drop is, but it does facilitate potentially more contentment with that life. If you have higher

01:20:32.000 testosterone, what has been shown in non-human models is that the attention to the mate and the

01:20:38.680 offspring is reduced. There's more attention to status seeking, aggression, getting sex from other

01:20:45.580 partners, et cetera. I think it's worth trying to understand what the exogenous testosterone,

01:20:52.440 which shuts down that system, does in men who think there are potentially some very important

01:20:58.080 behavioral and social effects that people don't think about because they're so psyched to get jacked

01:21:05.440 and have more social status and have the dopamine hit. You know, it feels good. I think it's worth

01:21:11.540 looking into. There's so much to unpack there. Again, these evolutionary discussions are so

01:21:17.620 interesting because I have to imagine that most guys who have chosen the path on your right, which is

01:21:26.620 I'm going to have as many partners as possible, are not doing that because of reproductive fitness.

01:21:34.880 Oh, no, of course not. They are often choosing not to have kids. That's right. How do we reconcile

01:21:39.280 that? From an evolutionary perspective, I get it. The desire to have as many partners as possible

01:21:44.100 increases your probability of sex. Or even just serial monogamy where you're in a relationship and

01:21:48.580 then you sort of move on or you divorce your wife and get a younger partner and then divorce your wife

01:21:52.920 again and get a younger partner. And is that rooted in evolution of reproduction or is that rooted in

01:21:58.760 the evolution of status in a way that is distinct from reproduction? So I don't think status is

01:22:04.160 distinct from reproduction. Do you mean psychologically? What is the driver? It's not

01:22:09.260 reproduction. It's sex. Which is interesting. So this is the first time we're basically talking

01:22:13.820 about sex independent of reproduction. Yeah. Ultimately, of course, we have love and we have

01:22:20.100 relationships and all of that. But that is for reproduction. That whole love thing is just to get

01:22:26.900 your genes into the next generation via the kid. And the love of the wife is to ensure that 0.93

01:22:33.600 it maximizes the chances of that happening. Is there any other species that does what we do

01:22:39.300 as humans, which is... So you and your husband have a 16-year-old and... That's it. Okay. So in two

01:22:45.880 years or three years when he's off in college... Oh, boo-hoo. Don't talk about it. I know. I know.

01:22:49.220 It's terrible, right? So you guys will have done your job as parents. No, we're going to keep doing it

01:22:54.260 until we die. Okay. But my point is the love you will have for each other, the support you will have for

01:23:00.020 each other is really not in the service of making sure your genes survive anymore. Are there other

01:23:05.540 examples of animals that continue in that behavior? Which is when they're past their reproductive age,

01:23:10.540 when their offspring are gone, they stay together. Well, there aren't really too many other animals

01:23:15.480 that get past their reproductive age. So elephants and all these other long-lived mammals...

01:23:20.480 So menopause, you mean? Who has menopause? Yeah. So some whales, rare captive chimp, 0.96

01:23:26.880 or maybe there's some wild chimps who have had menopause. It's just very rare.

01:23:29.940 This is kind of another human socialization then.

01:23:33.380 Okay. Grandmothers make a massive contribution to their daughters and their daughter's kids in 0.66

01:23:40.640 terms of knowledge and support. Someone who is no longer capable of reproducing, that's valuable.

01:23:47.980 You don't want to be reproducing in your 80s because it's a total waste of energy and you're likely to

01:23:53.880 die potentially from trying. You can invest in your genes that are in your daughter and her kids.

01:24:01.600 So that makes a big difference. I'm still not sure what question you're asking exactly. I think you

01:24:07.460 were saying, why do we stay together in a bond? Yes. Is there an evolutionary reason for why

01:24:13.400 humans specifically stay monogamous even after it's not necessary for the survival of their offspring?

01:24:21.880 Because it increases the survival of their offspring. So that trust and commitment,

01:24:28.520 even if you don't have kids, you behave as though you do because you would have. There's no way you

01:24:34.040 wouldn't have kids. So any couple that's having sex would have been having kids. There was no birth 0.99

01:24:40.600 control. And they're still acting that way. The same genes are being transcribed as though they had

01:24:44.760 kids. So even though we only have the one kid, it's as though he's 16, he might've had a kid

01:24:50.960 already. The two of us together with our bond and work, our experience and our relationship with our

01:24:56.440 kids, we're going to help increase the survival of our grandkids. So our genes are really going to

01:25:02.080 potentially do much better if we stay together, but we are liberated from that. People get divorced

01:25:09.040 and find other partners. So again, going back to testosterone and estrogen, I want to talk a little

01:25:14.420 bit about estrogen now. So obviously estrogen is a very important hormone for men and women. It's

01:25:20.240 appreciated more, I think, in women than men. But to cite one study that I've talked about many times

01:25:25.400 in the past, it's about a 13-year-old study that took a large group of men, chemically castrated them

01:25:29.920 all, and then made them replete with different doses of testosterone with and without an astrazole.

01:25:36.940 So this study basically gave men, I think there were five groups of testosterone and with and

01:25:44.380 without an astrazole. So for folks listening, an astrazole would inhibit the conversion of

01:25:48.760 testosterone to estradiol. So it just inhibits aromatase. That's right. It's an aromatase

01:25:52.940 inhibitor. So you have from low to high five levels of T with and without estrogen. So it's a pretty

01:26:00.340 elegant study, right? It was in the New England Journal of Medicine. I don't remember who published

01:26:04.160 it. We'll link to it in the show notes. The question was, what did these 10 groups, how did

01:26:09.660 they differ with respect to body composition, mood, affect, sexual desire, all these sorts of

01:26:16.080 things? I don't remember if bone density was studied. It might not have been a long enough

01:26:19.200 study. It's been so long since I've looked at it. But here was the big takeaway. The TLDR was by far

01:26:25.320 the best producing outcome, was the highest T with high estrogen. Producing outcome for?

01:26:31.580 Everything for body composition, mood, you name it. The learning to me, it wasn't surprising that

01:26:36.900 higher testosterone was better than lower testosterone for all the metrics that were

01:26:40.260 measured. The surprising insight at the time, again, we now I think understand this much more,

01:26:46.380 but for me at the time, the surprising insight was more estrogen was better than less for men,

01:26:51.820 not just with respect to how they felt, but even body composition. This was a wake-up call because I

01:26:57.260 think there were a lot of doctors out there who were prescribing aromatase inhibitors to keep

01:27:03.040 estrogen as low as possible in men.

01:27:05.200 In men who were?

01:27:06.360 Who were taking testosterone.

01:27:07.800 Who were taking it.

01:27:08.560 Yep. Within physiologic norms.

01:27:10.340 Yeah.

01:27:10.460 Okay.

01:27:10.860 So again, yeah, putting aside bodybuilders who were taking-

01:27:13.660 Yeah.

01:27:14.120 A thousand milligrams of testosterone-

01:27:15.700 Gynecomastia, et cetera.

01:27:16.180 Where you do have to block some of the aromatization. But if you have a guy who's taking

01:27:20.320 100 or 150 milligrams of testosterone a week, which would put him to a physiologic

01:27:24.800 upper limit of normal, really, it seems to me you ought to let estrogen go as high as necessary

01:27:30.100 or as high as it goes naturally shy of producing a symptom. And so let's just spend a minute now

01:27:36.060 talking about the role of estrogen and its role in the brain. What do we know about this? And do we

01:27:42.440 know about, for example, why at a minimum in some of these studies and even anecdotally,

01:27:48.100 if a male's estrogen level is too low, it has a negative impact on his mood.

01:27:54.040 So do you know what the specific outcomes were? Was it libido or energy?

01:27:59.700 Libido was definitely one. I don't recall. Gosh, I wish I'd looked at the paper recently.

01:28:04.580 So let's just say libido.

01:28:06.000 Yeah.

01:28:06.400 Okay. So this is interesting. And I don't know the paper. What I will say, first of all,

01:28:12.140 is that as far as estrogen in males, in rodents, for example, talking about masculinization in

01:28:20.680 very early development, masculinization in rodents clearly occurs via conversion of testosterone once

01:28:29.840 that gets into the brain via aromatase. So if you block aromatase, you get essentially a female 1.00

01:28:37.900 rodent brain. Does that mean that you need aromatase to get testosterone in the brain?

01:28:42.620 Or does it mean that you need the testosterone to become estrogen to go into the brain?

01:28:47.160 The testosterone gets into the brain. Estrogen is actually prevented. The peripheral testosterone

01:28:52.760 is prevented by a protein called alpha-fetoprotein in rodents. So maternal estrogen is bound

01:29:00.080 so that females are not masculinized. 1.00

01:29:04.860 So he enters the brain and is aromatized there.

01:29:08.020 The testicular produced testosterone from the male testicles is high. That gets into the brain.

01:29:14.140 That gets aromatized.

01:29:15.020 Once it passes the blood. Yes. Gets in there.

01:29:16.560 Once it gets passed because it doesn't have the alpha-fetoprotein. That's a pretty elegant solution.

01:29:20.060 It is an elegant solution. So it is clear that it's estrogen acting via estrogen receptors that

01:29:27.000 are masculinizing sexual and aggressive behavior, which is just very clear in rodents because you

01:29:32.300 have lordosis in females and mounting in males and you have higher rates of male aggression, etc.

01:29:38.280 This doesn't happen in humans.

01:29:39.740 This does not happen in humans. I know that there's misunderstanding about that. A lot of

01:29:43.920 people just think, of course, that applies also to humans, but it can't apply to humans because

01:29:49.160 our alpha-fetoprotein does not effectively bind estrogen. We also have men who have

01:29:56.540 can't produce aromatase and don't have estrogen, and they are fully typically masculine in their

01:30:03.920 behavior. They have other issues like with bone. And we also have complete androgen insensitivity 0.92

01:30:09.200 syndrome where you have XY individuals who have testicles but have a defective androgen receptor 0.70

01:30:16.680 and essentially develop. They have testicles and XY sex chromosomes and high testosterone, 0.92

01:30:21.140 but they develop as females because their testosterone is converted into estrogen. So they have no 0.97

01:30:28.380 testosterone whatsoever, yet they do have estrogen. They're exposed to maternal estrogens. They're very

01:30:32.680 feminine.

01:30:33.660 Wow. What an interesting phenotype. They must have sky-high estrogen given that all of their

01:30:40.720 testosterone, male levels of testosterone, are being converted to estradiol.

01:30:44.420 So they go through female, essentially female puberty, and many of them will discover that they 0.99

01:30:50.940 have testes and XY sex chromosomes when they don't get their period. So they're like very feminine. 1.00

01:30:56.840 But the point here is that we know for sure this is the case in non-human primates.

01:31:03.680 Do they develop with a male pattern of aggression or a female pattern of nurturing? 0.61

01:31:08.880 Totally feminine. Totally feminine. So this is interesting because this is a point mutation 0.89

01:31:13.660 in the androgen receptor gene, one small mutation. Everything else is just typical male. You just

01:31:21.380 get the one mutation in the androgen receptor that is disabling it, and you take what would have been

01:31:28.000 a typical male, and you have someone with testes and XY sex chromosomes. You don't have the double X.

01:31:34.140 You have all the genes on the Y. But you have a totally typical, for all intents and purposes,

01:31:39.720 girl and then a woman. So outside of the sterility, I assume, of this individual,

01:31:46.180 does she go on to be a completely normal woman? Totally. More feminine, I would say, than other 1.00

01:31:52.440 women who have testosterone. So really not a pathologic condition outside of the sterility? 0.67

01:31:57.440 No. Wow. Never even heard of this. There's incontrovertible evidence that estrogen is not

01:32:04.500 the masculinizing hormone acting via the estrogen receptor in early development in humans. But then

01:32:12.220 you're raising all these questions about the role of estrogen in adulthood. And I think,

01:32:19.280 so this one study is interesting, and I think it is important, but I couldn't say with authority

01:32:25.500 exactly how. It's important for bone, you know, it's important for the body. But in terms of behavior,

01:32:30.840 I believe it's important for sexual behavior. But we do have these guys who don't make estrogen,

01:32:38.240 who seem to be normal. They don't have the aromatase capacity.

01:32:43.060 Sorry, yes. And I should mention also that in these women who have complete androgen insensitivity 1.00

01:32:50.160 syndrome, they seem to be sexually normal. There's no differences in sex drive and orgasmic

01:32:57.980 capacity, even though they have zero testosterone. That's interesting. And there's limited data,

01:33:03.580 I should say, because it's a rare condition. But what we do have suggests that they have estrogen

01:33:10.020 and that the estrogen somehow compensates. And they have the same libido?

01:33:14.660 From the studies that I have seen, yes. I don't know if maybe the peak isn't as high in puberty or

01:33:20.840 something like that. Maybe there are differences there, but I don't see that in the literature.

01:33:26.200 And they, presumably, they must have a little more difficulty putting on muscle mass?

01:33:31.200 Well, I have tried.

01:33:31.800 Do they shave their legs?

01:33:33.200 They don't have to.

01:33:34.160 Yeah.

01:33:34.920 They have no acne.

01:33:35.660 They have no, yeah.

01:33:36.960 They don't have to shave. I worked with a student very closely who had this condition. It's a difficult

01:33:42.640 condition when you're a normal teenager and you learn that's a difficult situation. A lot of these

01:33:50.060 are very challenging.

01:33:50.920 To me, the most interesting outcome of the study was not, to my recollection, that the men with

01:33:57.080 higher testosterone felt better. It was that they actually put on more muscle mass as well.

01:34:02.300 With the estrogen?

01:34:03.240 Yeah. With the higher estrogen level?

01:34:04.340 Yes. That is my understanding. And I don't know enough about exactly why that is and how it works.

01:34:10.360 I'm not surprised. I think estrogen is very important in men, in adults. It may be important

01:34:16.580 in early development in some ways that we don't yet understand.

01:34:20.660 So what do you think all of this teaches us about the role of testosterone replacement therapy

01:34:26.480 in both men and women? So let's go back to something you said some time ago. So if we didn't

01:34:34.220 muck around with nature, men would experience a pretty steady decline in testosterone from puberty

01:34:43.460 on down?

01:34:44.880 In Western populations. Because we don't, hunter-gatherers tend not to have that.

01:34:48.620 Oh, okay. Well, say more about that.

01:34:50.380 Well, they start out with lower testosterone because, again, high testosterone is expensive

01:34:56.140 to maintain. Most animals keep it low and only raise it when females are fertile and they need

01:35:01.060 to compete. So that's why there's-

01:35:02.580 So that's the rut.

01:35:03.500 That's the rut. 0.61

01:35:04.180 Like the red deer, you know, grow, their testicles grow, they grow weapons on their head,

01:35:09.840 they become horny, they become aggressive when the females are fertile. If the females aren't

01:35:14.500 fertile, all that stuff goes away, testosterone drops. Okay. So humans are also designed to keep

01:35:20.440 testosterone low, which is why if there's a situation, a competitive situation, say testosterone

01:35:28.400 might go up, but generally it's going to be kept low when it can be. But we are overnourished in

01:35:35.080 Western populations. We don't have to worry. We have enough calories to run our immune system and

01:35:40.080 to do everything else we need to do. We have the luxury of being able to elevate testosterone over

01:35:45.040 what it would be naturally.

01:35:47.360 In the case of the deer, all of the females go through esterase at the same time. So it's easier

01:35:53.820 for the bucks to say, for these nine months, I don't need testosterone because all of the does

01:36:01.580 are infertile. And then bingo, now they're going through esterase. We're going to go through the

01:36:06.260 rut and it's a party. But with humans, I understand there's some literature that says the more women 1.00

01:36:11.700 that are together, the more their cycle sinks, but that's got to be weak. And by the way, women are 1.00

01:36:17.440 ovulating every month. I'm so glad you brought this up. This is why you guys are the hormonal ones.

01:36:24.240 Let's say that. So everyone says women are hormonal. You're the hormonal one. You have this high 1.00

01:36:30.140 testosterone all the time. We just don't notice that you're hormonal because it starts in utero

01:36:35.060 and you're permanently hormonal, basically. Let's just get that out there. But you are hormonal

01:36:41.000 because there's always going to be fertile females around. So that's just an interesting point. But 0.96

01:36:48.860 given you have to maintain high testosterone levels throughout your entire life, we only maintain

01:36:55.760 our high estrogen through a fixed time or reproductive career, which is when we're most

01:37:00.620 attractive. If you look at hunter-gatherers, they have like a high pathogen load. They have fewer

01:37:06.000 calories coming in. They have high energy expenditure. They have other stressful, energetically stressful

01:37:13.220 situations to deal with that we don't necessarily. So they keep their testosterone levels lower. The peak

01:37:19.740 is significantly lower. I think it's like at least a third lower. And then there's no real drop-off.

01:37:27.200 And they stay active and healthy, relatively healthy, throughout the rest of their lives. And the

01:37:33.220 testosterone, they don't have that 1% loss, say, per year. And there's no problem with fertility,

01:37:40.240 even though their levels are much, much lower than ours, which makes me skeptical about some of the

01:37:47.140 explanations for the trend that we see of a drop in testosterone levels in men and a drop in

01:37:54.820 fertility. Because it's definitely, if you look at these natural fertility populations, you see that 0.52

01:38:01.100 we are starting out really high. Men should not, I don't really see why there would be a reduction

01:38:07.240 in fertility per se that isn't caused by other health issues, for instance.

01:38:13.700 In other words, you're saying it's hard for us to blame fertility in the Western world on declining

01:38:20.220 testosterone. On just the testosterone. Because I think the testosterone must be declining because

01:38:24.420 of all these other things that are affecting fertility. Yeah. It could be the inflammation that

01:38:29.500 arises from the metabolic dysfunction, the- Yes. Phthalates. Yeah, yeah, yeah. Exactly. What

01:38:34.760 other, yeah, exactly. Going back to kind of Western society. So we see this roughly 1% per year drop in

01:38:42.180 testosterone. And so a guy in his 50s now has, hell, a guy in his 30s today has a lower testosterone than

01:38:50.120 a guy in his 50s did 40 years ago. So a guy in his 50s today has pretty low testosterone. And we

01:38:58.900 certainly know that medically, it's a completely safe thing to replace. And we know that there are

01:39:04.860 great outcomes with respect to bone health, with respect to frailty and subjective, many subjective

01:39:11.860 findings. And we know that it's not increasing the risk of prostate cancer and heart disease and all

01:39:15.740 the things we used to worry about outside of the edge case of hypertension, which can be managed.

01:39:19.920 But all of that said, is there a case to be made that we should not be replacing testosterone in men

01:39:26.520 because it turns us backwards in terms of this aggression. And it's more likely to make that

01:39:34.260 55-year-old guy want to find himself the 20-year-old girlfriend. Yeah, I don't know about that.

01:39:39.540 I don't know that that's been shown. So you're saying testosterone's great. Why shouldn't we give

01:39:44.740 it to people? No, no. I'm asking the opposite question. Okay. I'm saying given everything we've

01:39:50.740 just learned about testosterone, is there a negative consequence to taking a 55-year-old guy

01:39:56.340 and restoring his testosterone to what it was when he was 18? Make the argument for why that should

01:40:01.900 happen. Why you should restore it back to when he's 18? Yes. Do you think that should happen?

01:40:06.840 It totally depends on the symptoms, would be my take. So if a guy is having difficulty putting

01:40:10.960 on muscle mass, if he's complaining of something, see, there are some guys who say, I'd like to have

01:40:16.420 sex once a week, and my wife would like to have sex once a week, and that's what we do, and that's 1.00

01:40:21.340 fine. Conversely, there are other guys who say, my wife wants to have sex every day, 0.96

01:40:25.300 and I want to have sex once a month. Now this is a problem. But if my testosterone is what it was 0.71

01:40:30.940 when I was 18, I'd like to have sex every day. My wife would like to have sex every day. Now we're 0.99

01:40:35.540 happy. There isn't a formula here, but that's one example of how you're trying to match the symptoms

01:40:41.080 and what the patient is saying to what you can do. There are some guys who have no difficulty

01:40:46.240 putting on muscle mass despite having a testosterone of the 20th percentile. It might be that their

01:40:51.300 genetics are such that that was the case, or they put on a lot of muscle mass when they were

01:40:54.780 younger and it's just easier to maintain it. There's certainly evidence that insulin resistance

01:40:58.900 can be ameliorated by correcting hypogonadism. So there are reasons to consider doing it. What

01:41:04.580 I'm trying to get at is, are there negative consequences of doing it from a behavioral

01:41:08.880 standpoint? And I'm not talking about roid rage and things like that, which has largely been

01:41:13.620 debunked outside of, again, these edge cases where people are taking super physiologic doses.

01:41:19.120 In terms of being a productive non-asholic member of society and not being overly aggressive or 0.88

01:41:26.860 engaging in harmful behavior, risky behavior, what's the pro and con case for that in your mind?

01:41:32.960 I imagine that the doses that you're giving, it's, I think, been shown pretty clearly that if men are 0.99

01:41:39.840 within the typical range, even at the low end, you don't see changes in sexual or aggressive behavior

01:41:47.400 within the normal range. You see differences in physical parameters.

01:41:50.900 Yeah. The most complicating thing, if I could wave a magic wand, wave one magic wand in medicine

01:41:56.900 right now, what would I have? I would have a PSA equivalent for breast cancer. Come back to why

01:42:02.380 that would be a game-changing solution down the line. The second thing, which would not be nearly as

01:42:08.240 important, would be I would love to have an assay to measure androgen receptor density.

01:42:13.340 Oh, thank you for bringing that up.

01:42:15.000 Because what we can't, we tell all our patients this, they look at us like, just measure it. And

01:42:20.820 I'm like, no, no, you don't understand. We don't have a test for it. And they're like,

01:42:24.480 how do you not have a test for this?

01:42:25.740 Can you do the CAG repeat?

01:42:27.500 I mean, I guess you could. That would be, is there a commercial test for that? I mean,

01:42:31.040 you can do that in the lab.

01:42:32.460 Yeah. I don't know if there's a commercial test. You should get it if there is.

01:42:36.200 Someone should develop a CLIA-approved assay for this.

01:42:38.600 Does everybody know what the CAG repeat is?

01:42:39.780 No, they don't. But the point I really want to make is why is it that one guy can have a

01:42:43.700 testosterone of 400 and feel totally fine? And another guy can have a testosterone of 400

01:42:48.440 and feel totally depleted. And if you took both of those guys up to a thousand,

01:42:54.340 the first guy would be like, I don't feel any better. And the second guy would be like,

01:42:58.380 you've changed my life.

01:42:59.380 Can I ask you a question about that? Because you know a lot more about this,

01:43:02.360 I think, than I do. If you have the guy who feels bad on 400, do you eliminate all the other

01:43:11.520 things? Like, how can you eliminate all the other things that could be causing him

01:43:16.060 that are going on in his world or in his body?

01:43:18.320 No, you can't, but you can just change one variable at a time.

01:43:20.680 But if you change that one variable, is that overriding the potentially negative effects of

01:43:28.480 inflammation or depressing situation in his social life or whatever it is?

01:43:33.560 Typically, T won't fix a lot of those things. The most obvious things he's trying to fix are sleep,

01:43:37.800 nutrition, and exercise.

01:43:38.680 Yeah.

01:43:39.280 Regardless of what his testosterone level is, if it's 400, which is very low,

01:43:43.480 especially if his free testosterone is equivalently low.

01:43:46.380 And he's got these vague symptoms. It's like, well, look, if you're not sleeping well,

01:43:51.020 eating well, and exercising well, let's fix those first.

01:43:54.220 Or obesity, do you have to?

01:43:55.660 Yeah, sure. Absolutely. But you can't always fix those things to the nth degree without

01:44:00.560 wanting to at least experiment, especially when it comes to body composition stuff or energy levels.

01:44:06.000 So by making the one variable change at a time, you can say, look, let's do the experiment.

01:44:10.620 If your T is now 900, and we haven't made a change during that period of time,

01:44:16.220 other than that T, and you're telling me, I don't really feel that much different.

01:44:20.380 My hypothesis is you have a pretty low density of androgen receptors, and they're largely saturated

01:44:24.840 at 400. And therefore, this isn't really the fix. There's something else we need to be looking at.

01:44:30.800 Yeah. I'm glad you brought up the androgen receptors because I think people don't appreciate

01:44:35.220 the fact that one person's 400 is not another person's 400. I know you talk about this a lot,

01:44:42.560 about carrier proteins, but also there's the genetic differences in the receptor itself,

01:44:49.440 which is the CAG repeat, which predict the efficiency of its ability to transcribe the

01:44:57.360 androgen responsive proteins. And just the overall concentration, where are your androgen receptors

01:45:03.500 and how highly concentrated are there? Of course, it's going to be different in different parts of

01:45:08.640 your brain and body. So all of that really makes much more complex the interpretation of a single

01:45:15.200 measurement. So that being said, yeah, I don't know. I don't know. I'm coming from a place of

01:45:21.480 thinking about how this all works naturally to promote, especially behaviors that are adaptive.

01:45:27.980 I'm on progesterone, testosterone, and estrogen. I'm 59, and I had my ovaries out a couple years ago.

01:45:34.780 And I have to say, I just want to say when that happened, I was 57. So I was already in menopause

01:45:41.860 pretty much. And everything changed after that. It made a huge difference. My hair started falling

01:45:47.540 out. My sex drive plummeted. Sorry, just to be clear, you were on hormone replacement therapy prior

01:45:52.020 to? No, I was not. No. No. Okay. I just want to throw that out there because I'm supposed to be an

01:45:56.380 expert in hormones. And I had my ovaries out at 57 and it had a huge impact. Even though you were

01:46:03.600 already in menopause. Yeah. I mean, I guess I wasn't. We found out I wasn't actually. I had some

01:46:08.220 fresh corpus luteum in my ovaries. So they said I wasn't actually in menopause. But yeah, it's just

01:46:14.460 amazing. Even when they're pumping out low levels of hormones, I think they're still pretty impactful.

01:46:20.820 So why did you decide to only go on hormone replacement therapy at the age of 57 when presumably

01:46:26.880 you believed you were in menopause prior and didn't go on HRT?

01:46:31.180 That's a good question. I guess because I felt fine and it wasn't until...

01:46:35.220 It was gradual.

01:46:35.900 It was gradual. Yeah. And I think especially because of you, I started lifting weights a year ago.

01:46:42.700 You look like you've been at it for years.

01:46:44.320 Oh, thank you. No, I was just a runner and Peloton and biker and all that. And it's made a huge

01:46:49.740 difference. I just want to say to get into lifting. Now I'm addicted to that. And now I have a back

01:46:54.520 injury. She'll have to help me with later. So I think the testosterone must be helping

01:47:00.040 in terms of my really getting into the workouts and how much I can lift potentially. I guess I'm

01:47:06.820 saying I myself am on these hormones.

01:47:10.180 And it sounds like you feel better as a result of it.

01:47:12.360 Yeah, I think so. I think I feel better, but I definitely feel better when I'm working out and

01:47:17.620 the drive to it. But maybe I would have done that anyway. But I have no issue with people doing what

01:47:23.100 they need to feel better. I just think people don't consider that, especially testosterone and

01:47:30.740 I think also estrogen. These are hormones that give us signals about what's going on in our own

01:47:36.100 bodies. Like, are we making eggs? Are we making sperm? Are we healthy? Are we sick? All of that is

01:47:42.260 communicated. Like, if you're sick, those systems are suppressed and your hormone levels are going to

01:47:47.180 be lower, which is adaptive and will help you. And that won't happen if you're taking it all

01:47:52.180 exogenously. And there's a lot of social signaling. So all of that goes away. But yeah, I think that's

01:47:59.240 for each individual to decide. I do think there should be some regulation around testosterone because

01:48:05.720 from what I understand, it really is addictive and also can permanently cause someone to become

01:48:11.960 infertile. That's something that I don't know that people, young people in particular, really

01:48:17.620 understand. So I think it's different when people are after the age of 40 or 50. Is it a different

01:48:23.800 situation from someone who's young and healthy and is doing it and is getting addicted? At younger

01:48:29.620 ages, I think we should be much more careful. Yeah, that's an interesting point. Because as you know,

01:48:35.580 but maybe some of the listeners don't, testosterone is a regulated scheduled drug hormone,

01:48:40.680 whereas estrogen is not. Estrogen can be prescribed without any DEA scheduling. Testosterone is a

01:48:47.540 schedule. I believe it's a schedule four. But that's an interesting point that you raise, right?

01:48:50.940 Which is one reason to consider scheduling it is the potential for abuse is much more significant in

01:48:57.040 younger men who might not realize. And sadly, a number of them don't realize, hey, if I take this

01:49:03.400 stuff for three years in my twenties, it could significantly and potentially permanently affect my

01:49:08.420 fertility. Yeah. And it's hard to come off. From what I understand, it's very hard to tolerate the

01:49:15.860 transition and the withdrawal where you now you can't get an erection, your libido tanks.

01:49:21.620 I just don't have experience with it because it's simply not our patient population.

01:49:25.020 Yeah. I can't speak to that at all. And my guess is everything you're describing would be

01:49:29.160 more the result of abuse. I don't like using a judgy term like that. I reserve that term for

01:49:36.280 non-medical use that is hyperphysiologic. Educate me on this. So if you have or if there

01:49:44.040 is a 25-year-old who's just supplementing to get to the high end of normal range, he's still

01:49:51.420 going to shut down his... He's going to shut his HPA down. But here's the thing. I have a really hard

01:49:56.640 time believing that a 25-year-old should ever be on exogenous testosterone. Okay. Because they are,

01:50:02.240 right? It's really increasing at these younger ages. I assume so. I have to plead ignorance here.

01:50:05.960 I really have no sense of how widely... No, I think social media. Yeah. But to be clear,

01:50:11.520 when I was 28, 29, 30, so when I was in my residency, my testosterone level was 220 nanograms

01:50:21.960 per deciliter. Right. I remember you saying this on another show.

01:50:23.840 Right. So I was like... So you were not sleeping, totally stressed out.

01:50:26.960 Level of a woman instead of 10X, 5X or whatever, right? But did that mean that I should have been 0.99

01:50:32.080 on TRT when I was 30? Definitely not.

01:50:34.540 No. It meant that I needed to get the hell out of residency and actually start sleeping at night.

01:50:38.740 And that's what you did, right? Yeah. And then whatever, like four years later,

01:50:42.200 five years later, I had normal testosterone. Wow.

01:50:45.120 So again, if a 25-year-old is walking around with a testosterone of 300 to 400,

01:50:50.300 I would be much more inquisitive about fixing a whole bunch of things and much slower to move

01:50:58.000 towards replacement. And by the way, even if I was going to replace it, I would not be using

01:51:02.140 testosterone. I'd be using HCG. Right.

01:51:04.800 I'd be preserving gonadal function as opposed to completely suppressing it.

01:51:08.380 I see.

01:51:10.000 Whereas if a guy is 60, if he's fine with testicular shrinkage, which would be

01:51:14.640 the fundamental difference in using exogenous T when you suppress his HPA access, then I think

01:51:21.040 it's less of an issue. I don't want to speak from any authority on treating young people. I simply

01:51:24.500 don't have that experience. I don't have even a sense of how widely used it is. I guess it is a

01:51:30.100 good additional hurdle to have it be DEA mandated, regulated, scheduled.

01:51:35.560 Yeah.

01:51:35.980 So what are you up to right now?

01:51:37.860 So I am trying to finish a book proposal. I'm spending a little more time with my son,

01:51:44.100 which is nice that I'm home when he gets home from school. And I have a part-time job at a DC

01:51:51.580 think tank, which I'm really enjoying. And I do some writing. I have other things that I do,

01:51:57.460 but those are the relevant things.

01:51:59.720 I don't want to go too far down the rabbit hole of what many people, if they Google you,

01:52:03.820 are going to learn about the horrific experiences you had. But how long ago was all of that? That

01:52:08.840 was about three years ago?

01:52:09.780 So that was, it started in 2021. Yeah.

01:52:13.020 So four years ago.

01:52:14.100 So how has this experience been for you? You're four years on the other side of,

01:52:19.420 I think what any reasonable person would look at and say is just a complete and total injustice.

01:52:24.580 Thank you.

01:52:25.100 A lot of incredibly cowardly people that I'm sure at one point you felt were friends and colleagues

01:52:31.400 completely sat by silently as a minority mob went after you. How were you recovering from that

01:52:37.600 experience?

01:52:38.040 It's been really difficult because I was just reading my acknowledgements in my book on testosterone and

01:52:47.580 I wrote, you know, I have a great job. I have the privilege of interacting with these amazing young

01:52:52.700 people and teaching and advising undergraduates is hard. It's hard. I teach about some really

01:53:01.580 controversial and detailed and intricate topics. And I love that. I love putting in the effort and feeling

01:53:09.420 the reward every day. And I love the relationships and changing people's lives and having them change

01:53:17.520 mine. And it's work that is challenging and so deeply rewarding. And it helps to provide a sense of

01:53:25.760 meaning in life and a sense of accomplishment and all these things. So not having that is hard. And

01:53:32.300 it's hard coping with the reason I don't have that and all the people and the institution I trusted and

01:53:38.380 gave so much to and feel, yeah, I feel that I was treated pretty horrifically. It's hard. I've had

01:53:44.580 transitions before, but this is a big one. I thought I'd be in that job forever. But what it has done

01:53:51.740 for me is made me much more committed to doing something like what you do, part of why I'm a

01:54:00.140 huge fan of yours, and I'll probably start to cry again. And I think it's very rare that people get so

01:54:06.900 into the scientific weeds. I don't detect any bias on your part. I detect your very open and honest

01:54:14.620 struggle to understand the evidence and to talk about the evidence and where it points. And that's what

01:54:20.120 I've always tried to do. And I think it is so important, not just for science, but for people

01:54:26.360 to be able to communicate with each other and share facts. Maybe we disagree about the implications of

01:54:31.300 the facts, but it's so important to take ideology and bias out of our understanding of reality.

01:54:38.700 Reality is there whether we like it or not. It's always to our benefit to understand it and to try to

01:54:44.260 figure out then to use democratic processes to figure out what to do with reality or how to improve

01:54:50.460 human health or whatever the issue is. So I guess that experience has just made me much more committed

01:54:55.800 to doing that and to advocate for that, which isn't always easy. And some of the things I said

01:55:03.960 today are controversial. But, you know, I'd love to hear if people disagree, why? And then that's how

01:55:09.720 we learn is by having our views and interpretation of evidence challenged.

01:55:15.280 So given how in many ways successful you were as a professor, how much your undergraduate students

01:55:21.780 loved you, it's certainly one vehicle through which you can communicate this passion. Do you see

01:55:27.500 yourself going back to that situation? Do you see yourself winding up back at a different university

01:55:32.780 one day? Or do you feel like the scars are sufficient that you don't feel like being in that arena again?

01:55:38.920 Yeah, we didn't say what happened. I'll just say that I wrote a book, T, the story of testosterone,

01:55:45.300 the hormone that dominates and divides us. And I went on Fox News and said that there are two sexes,

01:55:52.220 male and female. And someone who's representing themselves as speaking on behalf of Harvard and my

01:55:58.100 department accused me of transphobia. And then there was other bad things that happened. And it resulted

01:56:04.700 in me feeling I had no choice but to leave my job that I'd been in for over 20 years and loved.

01:56:11.080 Would you see yourself back?

01:56:13.260 No, because I was traumatized. I was in shock. I could not believe how people were behaving.

01:56:20.980 And I learned a lot. And one of the things I learned is that I was way too trusting.

01:56:25.780 Whatever I do, I want to throw myself into it. And I threw myself into that job. And that's why

01:56:32.180 it hurt so much. Because that was me. That was like all of me. I kept some of me for other parts

01:56:37.560 of my life. But I really threw myself into it. Everyone who worked with me knows that. And so

01:56:42.540 it feels way too risky. I won't trust an institution like that again. Or I don't know,

01:56:48.440 I'll have trouble. Yeah, academia for me right now, not a fan.

01:56:54.040 Yeah. I think I'm sure a lot of people can relate to that. Because anybody who's put every bit of

01:56:59.300 themselves, take an example like your first love. The first person you fall in love with,

01:57:03.920 if they break your heart, you're going to sit there and say, that wasn't worth it. Like,

01:57:08.500 I'm not doing that again. The bliss of that experience wasn't worth the pain I'm experiencing today.

01:57:13.380 Right. And I'm not going to sit here and suggest that you have to do it again because of, look at

01:57:18.760 all the students you were able to help. Because there's other ways to do it. And you're obviously

01:57:21.900 writing another book. And so the truth of the matter is being on a podcast probably reaches

01:57:26.360 more people than you would reach in 10 years of teaching. Right.

01:57:29.800 What is your next book about? Are you comfortable talking about what the subject is?

01:57:33.020 Totally. I'm really excited. It's about what's happening with masculinity. And I'm really

01:57:40.120 interested in the cultural narrative. Here's where I also cry. And that's how I knew I needed

01:57:45.020 to write a book. Because why am I crying about masculinity and men being denigrated? Which I get

01:57:51.260 very upset about that. I wanted to really understand what was happening culturally, why we are in a place

01:57:57.780 where masculinity is not valued. And also to explore the interaction between biology and genes and

01:58:07.480 hormones and what's happening culturally. Why is it that these cultural changes that we've had

01:58:12.920 are affecting men in the ways that are different from how they're affecting women? Like economic

01:58:18.420 changes, men are falling behind in education, for instance. And what's happening in schools and why

01:58:25.680 are schools maybe less hospitable to typical male ways of behaving than typical females? So I really want

01:58:32.480 to dive into that intersection and to explore some of the questions that you were asking today about

01:58:40.480 aggression. And we were talking about men's need to compete and how it's different from women and how 0.82

01:58:45.840 that plays out socially. So I want to explore those issues really with an eye to understanding what's

01:58:51.620 called the masculinity crisis. And there's a kind of backlash going on right now, which I think is

01:58:57.060 interesting in that men and their needs and their right to be masculine, I think has been under

01:59:03.120 attack. And now I think some men are feeling freer to be more masculine, I would say today. What I want

01:59:09.780 to explore is the denial of sex differences and how that plays out socially. Because if you believe that

01:59:16.640 men and women are equally interested in engineering, then you don't believe in sex differences. You don't 0.80

01:59:22.320 believe there are important, meaningful differences between the sexes that play out in society that

01:59:29.360 are not all the result of the patriarchy, say. Certainly there are social influences, and that all

01:59:36.640 matters. But there's this denial of real differences that we need to grapple with socially. If you believe

01:59:44.700 that all the differences are the result of society, then you're justified. Potentially you're more

01:59:49.860 justified in trying to create equal outcomes. But if you deny biological differences, then you have

01:59:56.700 more of a reason to do that. But if you appreciate that they're real, and that we have to grapple with

02:00:01.540 them socially, then it's going to be more complicated. I completely agree. I mean, I joke about this with

02:00:06.760 my wife all the time, right? The reaction she has to a naturally aspirated V8 engine screaming at 1.00

02:00:13.940 10,000 RPM versus my reaction. So you go towards, she goes away, basically. I mean, like, it's the

02:00:19.900 greatest sound I've ever heard. And she is like, what is that awful noise? And there's no socialization 0.97

02:00:29.000 that creates that difference. On average, we can only talk in averages here, men are way more hardwired

02:00:36.060 to love that sound. There are incredible- Or to be interested in cars. Sure, sure. But there are

02:00:41.780 incredible YouTube videos where you can literally listen to every engine. Oh, and it's like ASMR for

02:00:49.080 you? Yeah. The V8 and V10 naturally aspirated engine screaming is the greatest sound I've ever-

02:00:54.960 Okay, I don't know what naturally aspirated. You don't have forced induction of air, so it revs very

02:00:59.520 high. Okay. But yes, like if I had my wife listen to that, first of all, she wouldn't hear the

02:01:04.340 difference between any of them, and she would think they all sound awful. They're too loud.

02:01:07.620 And can we just remind your listeners that we are definitely not saying that there are no women

02:01:12.560 interested in cars or that they can't be very enthusiastic. What we're talking about is

02:01:18.660 differences on average, especially those, not with the cars, but a lot of what we've been talking about

02:01:24.900 are differences on average that persist throughout history around the globe and that are shared with

02:01:31.260 non-human animals and for which we have a mechanism which makes sense, and that is differences in sex

02:01:37.440 hormones. So how do you think, as you write this book, you will be able to do the seemingly impossible

02:01:45.960 task, which is to write about this in a manner that is scientifically objective without getting dragged

02:01:56.400 into an ideological political mud pit? I think I did it with my last book. I pulled that off in the

02:02:05.840 writing, in the book. It was being in academia and talking about it in a way, just saying that male and

02:02:13.380 female are real. That was taken as undermining the rights of a certain group, essentially. And there's 1.00

02:02:20.480 just nothing that you can do about that. I think the way to respond is to encourage people to engage

02:02:26.880 with arguments instead of assassinate character. That's part of what is very important to me is

02:02:33.640 encouraging that and teaching people how to do that. And that's what I did in my teaching

02:02:36.960 in my classroom. And it was great. There was really never an issue in my own classes, even though we got

02:02:42.600 into the most controversial subjects. So I'll just keep trying to stick to the evidence and always

02:02:48.620 remembering these are people's lives, you know, and being compassionate and emphasizing that biology

02:02:54.000 is not destiny. There's a huge amount of variation. And it's perfectly normal to be a little boy who

02:03:00.580 wants to play with dolls like that. It's even hard for me to talk about because it's heartbreaking that

02:03:04.940 people feel stigmatized for not being sex typical. But that's something where if you understand the

02:03:11.320 science, you understand variation and you understand what is normal. And there's this spectrum,

02:03:16.360 a huge spectrum of behavior across the sexes. There's just only two sexes and we should learn to deal 1.00

02:03:23.620 with that kind of reality.

02:03:26.080 Well, Carol, really appreciate this discussion and appreciate without having experienced it personally

02:03:31.560 what you've been through, which I think is heartbreaking. I know several others who I'm close to who have

02:03:37.180 been similarly just decimated by...

02:03:40.360 The mob.

02:03:41.280 Yeah, the mob, the angry mob. So I think the good news is virtually all reasonable people can agree

02:03:47.160 on a set of facts, but you can't please everybody. And there's going to be certain individuals who are

02:03:51.220 going to have their points of view. Excited to hear you working on another book and excited that you've

02:03:55.700 got more time at home to do so.

02:03:57.500 Thank you so much for having me. It was great.

02:03:59.360 Thank you for listening to this week's episode of The Drive. Head over to peteratiamd.com forward slash

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The Peter Attia Drive - December 01, 2025

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

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