The larger the number of older brothers

that a male has, the higher the

probability that he is gay.

>> It's been seen over and over. I mean,

it's it's really one of the u rock solid

findings in human sexuality. So, the way

to emphasize the difference is if a baby

boy is born today, um if if he has no

older brothers, his odds of being gay

when he grows up is about 2%. Right?

Pretty low. But if he had one older

brother, his odds go up by a third.

Okay, 2.6. And if he has two older

brothers, they go up a third again. All

right, now we're at 3.5. It turns out

you got to have like a dozen older

brothers just to have a 50/50 chance.

Welcome to the Huberman Lab podcast,

where we discuss science and

science-based tools for everyday life.

I'm Andrew Huberman and I'm a professor

of neurobiology and opthalmology at

Stanford School of Medicine. My guest

today is Dr. Mark Breedlove. Dr. Mark

Breedlove is a professor of neuroscience

at Michigan State University, and he is

an expert in how hormones shape the

developing brain, in particular, how

they influence sexual orientation. As

you'll learn today, the amount of

testosterone that a fetus is exposed to

while in the mother has a profound

impact not only on the ratio of finger

lengths, yes, you heard that right, but

it also plays a meaningful role in

sexual orientation. And in fact, there's

a correlation there between finger

length ratios and sexual orientation.

Now, as wild as that may seem, that

result has now been confirmed many times

over in humans and in animals. And

today, you'll understand why. You'll

also learn that every time a woman is

pregnant with a male, there's a

biological trace of that which biases

the likelihood that her next male

offspring will be either heterosexual or

homosexual. Now, I know this sounds

really out there, but these are

extremely solid biological findings for

which the mechanisms are now understood

for both animals and humans. It turns

out that the hormones we are exposed to

while we are in the womb shape not only

the preference for whether somebody is

attracted to males or females, but also

an aversion to the opposite. Meaning

there appears to be the formation of

circuits for being attracted to one sex

and not attracted to the other. Today

you'll also learn how hormones impact

the amount of rough and tumble or social

play that kids engage in, the interplay

between nature and nurture in shaping

male versus female differences and

sexual orientation. Dr. Breedlove is one

of the long-standing pioneers in this

field of how hormone shape brain

development and psychology. We approach

these questions through the lens of

biology and statistics. So today's is

not a political discussion. Instead,

it's a discussion about what is known

and what is still not known about this

profound aspect of our species. Oh, and

we also talk about gay rams. Yes, that's

a real thing and it has important

implications for everything we've

mentioned thus far. By the end of

today's episode, you'll surely think

differently about the relationship

between hormones and brain development,

nature and nurture, and romantic partner

choice. Before we begin, I'd like to

emphasize that this podcast is separate

from my teaching and research roles at

Stanford. It is however part of my

desire and effort to bring zero cost to

consumer information about science and

science related tools to the general

public. In keeping with that theme,

today's episode does include sponsors.

And now for my discussion with Dr. Mark

Breedlove. Dr. Mark Breedlove, welcome.

>> Thank you. I'm delighted to be here.

It's very exciting.

>> Been 25 years since we stood in the same

physical space.

>> I know. How can that How can that be

possible when I I feel like, you know,

just saw you a few days ago, but then

>> Well, you look great. Uh you look the

same. So, uh we can talk longevity

protocols at the end, but

>> I'm trying to have a blonde look in my

hair apparently. So,

>> well, um, I've wanted to have you on

this podcast since I launched it because

you work on one of the most interesting

things in the world, which is how and

why people become who they are and how

hormones play a role there, how genes

play a role there.

>> If you're willing, I'd like to jump from

the high dive to the deep end first.

Right off,

>> let's talk about this fingerlength

ratios sexual orientation study that

>> you published and somehow I landed on

that paper. That's not why I want to

talk about it. I want to talk about

because it's an incredibly interesting

set of findings. Other people have done

the sameish experiments and there's a

whole context there about how hormones

influence sexual orientation independent

of behavior.

>> We need to step back a little bit for

the context. Uh, one thing that your

listeners might not know is, you know,

in the year 2000, there was still a lot

of people who regarded um, same-sex

orientation as a choice, a lifestyle

choice. That was the the political

combination of words that meant you

could disapprove of people u because

they were attracted to the same sex. Of

course, I'm I'm at Berkeley. I I didn't

have any truck with such notions at all.

and and and I've always been convinced

that sexual orientation is not a choice.

And there's a exercise I do in class

where I ask so I'm going to put you to

it now. So remember the first time you

had a crush,

>> right? It might have been someone on TV,

might have been someone a playground,

etc. So think about it and I I want you

to tell me about how old you were at the

time in a moment.

>> My guess is it was before puberty.

>> Yeah, I was six. So and I hit puberty

somewhere starting around 14. So, so it

had nothing to do with puberty, right?

It was this thing that happened and and

I'll I'll share my experience. So, so

I'm about six or seven. I couldn't have

been more than seven. Uh, and Marilyn

Monroe is on TV. I'm dating myself. And

there's a closeup, you know, with that

face and the and the mole, etc. And

afterwards, I'm just so agitated. I

don't, you know, I don't I and I know

nothing about sex. I remember I had a

hard time going to sleep. So, it was

like something about this was really

agitating me and I didn't choose to have

that reaction and my guess is that

whatever sex you had your first crush

on, that's the one you were going to be

attracted to the rest of your life.

>> Yeah. It's been constant.

>> Yeah. Well, so so so this idea that it

was a choice that always just seems so

absurd to me. On the other hand, um,

even though, you know, I' I've been

doing animal research with giving

hormones early in life and seeing what

it did to the nervous system, etc. Um,

and every time I wrote an NIH grant, I

said, well, you know, the effect of

early hormones may be important for

human behavior. But to tell you the

truth, I never actually believe that,

right? It was just I I just wanted to

justify be because it seemed to me that

we are so sensitive to social influences

and we have this long stretch of time

where we're, you know, our brains are

still growing at a fetal rate of growth

until at like 9 or 10 years of age and

we're taking in so much information and

and think of what a what a heterosexual

world it is, right? I mean, all those

Disney movies with Prince Charming and

etc. Uh, and so it always seemed to me

that that social

learning would be more than enough to

explain why 95% of people are straight.

But that doesn't mean that was a choice.

And it doesn't mean that they would even

be aware of what the social influence

was. So, so my example is I speak

English. It's, you know, I'm hopelessly

monilingual only language I speak. Well,

I don't remember learning English and I

certainly didn't choose to learn

English, but I'm sure that it's English

because of social influences, right? So

that was where I stood on the question

of sexual orientation until 1998 1999

when this fellow at University of Texas

Dennis McFaden came out with a paper

where it really made me think that

prenatal testosterone might have an

effect after all despite my

expectations.

And this was looking at oto acoustic

emissions. Do you want you want to talk

about those? These are uh people's ears

making noise.

>> Yeah. I mean, right now, in this studio,

if if I if I shut up for a moment, your

ears will continue to make little

popping sounds that you're not aware of

because having grown up with it, the the

brain stops you from perceiving those

long ago. Well, but if Dennis puts you

in a soundproof room and puts a very

sensitive microphone in your ear, he'll

he'll hear these pops. And uh and I I

won't get into the acoustics of why

that's a good thing, right? It helps you

to focus on the sounds you want to hear,

but what Dennis knew is there's a sex

difference in how many of these oto

acoustic emissions are being made. Girls

make more and it's present at birth. So

Dennis comes out with a strange study. I

mean, who would do such a thing where he

he proposes, well, since the sex

difference is present at birth, it might

reflect prenatal testosterone. And so he

measured the oto acoustic emissions in

straight men and gay men and straight

women and lesbians.

And he reports that that the compared to

straight women, the lesbians have fewer

of these oto acoustic emissions than

straight women. It's like, well, what

what how would that happen? Um, how I I

I couldn't think of any way to explain

that except that, well, well, the

lesbians might have been exposed to more

prenatal testosterone than straight

women before birth. And I don't know how

to explain that except to say, well,

maybe prenatal testosterone, maybe if

you're exposed to that before birth,

you're more likely to be attracted to

women when you grow up. which oh well

that might explain why 95% of men are

attracted to women right because they're

all exposed to prenatal testosterone. So

this oddball study really gets me to

thinking that maybe there's you know

something to that but but I'll forget

it. You know I'm still working with my

rats and and paramiscus and siberian

hamsters and stuff. I'm happily doing

that. And then and I remember it so well

and I I in 1999 I'm in my office at

Berkeley and I read this paper that says

there's a sex difference in the the

ratio of fingers that's present in

9-year-old children.

What? I've studied sex differences my

whole adult life. How do I not know

about this? And and it turns out that

that if you if you measure the length of

the second digit,

>> the pointer finger, the pointer finger

>> for those just listening. Yeah.

>> Right. And the the length of the ring

finger and you can you can do a simple

ratio. Divide the length of the second

digit by the fourth digit so-called 2d4

ratio. And a guy named John Manning was

reporting that there's a sex difference

there, that it's that that ratio tends

to be smaller in men than in women, and

that it's present in children. It's

like, well, wait a minute. A sex

difference in the body that's present

before puberty. I know enough about

sexual differentiation of the body, it's

almost certainly due to prenatal

testosterone.

>> Forgive me for interrupting you, but

people are probably looking at their

hands right now. Yes. And um I just want

to point out that these are averages but

it's I think the 2D 4D thing for people

that aren't familiar even though you

explained it quite clearly can be a

little confusing. Basically in men the

finger lengths are more different than

they are in women and there are some

differences in

uh in that statement according to sexual

orientation that we'll get into. When

you say uh the the in other words the

typical heterosexual male pattern is

that the pointer finger right is shorter

than the ring finger.

>> Right. Right.

>> Whereas in women

>> they tend to be more similar. Again

these are averages and

>> not to give it away but this is because

people are looking at their fingers

right now.

>> Let me just say don't panic.

>> Yeah. Right.

>> We're we're going to walk you through

this. You're going to be fine. And uh

the difference between men and women is

more pronounced on the right hand as I

recall.

>> That that's true too.

>> Uh

>> did I earn my authorship on the paper?

>> Well, that and and the fact that you

persuaded so many people to answer our

weird questions and let us see rocks

their hands. Yeah.

>> Okay. So, please continue. But I know

that the moment that came out, you know,

hopefully there were no car accidents

that people were driving. But but um uh

these are averages. Um but that's the

pattern that was observed. That's the

pattern we Well, I'd never worked with

humans before, but I'm sitting in the

Bay Area. We have loads of gay people

around. You you know, so it's like,

well, let's I guess we could try to do

this. And so, we started going out to

street fairs. You were you were with us

uh going out to street fairs and giving

people asking people questions, asking

them to fill out a questionnaire

anonymously. And um and I remember it it

was one of the organizers of one of the

street fair, but I said, "Well, what

should we do as an incentive to get

people?" And they said, "Well, offer

them scratcher tickets,

>> lottery tickets,

>> lottery tickets." So So we we asked

people, "Will you please answer these

very personal questions about about who

you have sex with, who you want to have

sex with, etc., and tell us everything

about yourself anonymously, and we'll

give you a $1 lottery scratcher people

ticket." Andy, people will do anything

for a $1 lottery scratcher ticket. I

mean, it was just a which is weird

because you do the math and they're

they're worth like 27 cents, right? But

but but people want them. Um and oh, and

by the way, can we xerox your hands? And

the last two questions we asked about

handedness, but it was really just to to

keep them from panicking. Um, so you

know, and it, by the way, it was it was

the least expensive experiment I'd ever

done in my life because really, you

know, compared to to any experiment with

rat where step one, buy a rat for 20

bucks, right? So it's um so uh and it

was an odd experience going in the

7-Eleven that morning and saying,

"Please, I'd like 750 $1 lottery

scratcher tickets."

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Well, as long as we're getting into the

context, it's interesting because you

said there there are a lot of uh gay

people in the Bay Area, but it was very

clear, as I recall when doing the study,

that if we wanted to get a a large

sample population of uh gay men, we

would need to go to the Castro District

in San Francisco. If we needed to get a

large cohort of gay women, we need to go

to the Solano Street Fair in Berkeley

>> and and in Oakland. So there there was a

there was a brand new Oakland gay

festival that got started and yeah there

Oakland is a wonderful place to find

lesbians. So u one of one of the charms

of the place. I thought the whole idea

was kind of crazy actually. I mean I

didn't think we'd come up with anything.

And I insisted on measuring all the all

the digits myself which I did twice.

Boring as hell. I recall when we were on

what was like third floor of Tolman Hall

uh and you came running in.

>> I was talking to my adviser, our good

friend Zucker, one of the pioneers of

circadian biology, discovered the super

chaos nucleus with Bob Moore and others.

But um and you came running in with with

a ruler and you said, "Give me your

hands." And you grabbed my hands and you

measured them and you go, "Well, that's

weird cuz it's like different on one

hand than the other." And then you go,

"Okay." and you took the notes and you

measured his hands and he left and I

thought, "What in the world is he

doing?" It turns out that was the early

origins of the study.

>> Yeah. No, no. And uh anyway, so so I I

measure these hands and um and I'm doing

the the the math at the end of the day

and lo and behold, I mean, I don't I

don't see any difference in the digit

ratios of gay and straight men, right?

Okay.

>> Between gay and straight men.

>> Yeah. Yeah. I didn't see any difference

there. which itself is interesting

because it implies

>> more or less equivalent amounts of

prenatal testosterone exposure

>> which I think is the case. Yes.

>> And and right now just forgive me but um

you know might some people might say

well that's not surprising but in the

80s and 90s the Hollywood stereotype of

gay men was that they were all very

effeminite.

>> Yep.

>> Um since then there's been an evolution.

In fact, I haven't seen it, but many

people I know are very excited about

this recent show about these two gay

hockey players where so the whole

context is these guys that are very

masculine but are gay, right? So

>> for people hearing this that are younger

than 40, they're going to think, well,

duh. But for people that grew up in my

generation or your generation, it was a

bit of a shocker to a lot of people. Um

because depending on their level of

exposure to the gay community, they may

or may not have realized that not all

gay men are uh affeminite.

>> Exactly. No. And and and you know that

idea that gay men might have been under

androenized, there was always a part of

it that was that always seems strange to

me. So the big sex differences in human

behavior are not in, you know, math

skills and the verbal skill. Those are

tiny, right? The really big sex

differences in human behavior are in

sexual attitudes. And the biggest sex

difference is one sex is much more

interested in multiple partners and

younger partners than the other. Right?

Everyone knows which sex that is. One uh

sex is much more interested in casual

sex than the other. Everyone knows one

sex is much more interested in visual

pornography than the other sex. Those

are huge sex differences compared to

any, you know, cognitive things. Uh, and

in all those ways, gay men are totally

masculine.

So, how would that work that that, you

know, they were underroenized and yet

they have all these sex differences in

in sexual attitude? I I think the

difference between gay and straight men

isn't in how much prenatal testosterone

they got. I think it's in how their

brains responded to the testosterone

that they got. We'll we can talk about

that some more um later. But back to the

digit ratios, the lesbians had more

masculine digit ratios than the straight

women on average. And and as you say,

that's been replicated by many different

labs. Dave Puts at at Penn State and uh

uh and Ashlin Swift Gant and I recently

published a like the third meta analysis

and I mean it's clear so many people

have seen it. It's there. And and as

with Dennis's oto acoustic emissions, I

don't know how to explain that. Why why

would

lesbians have a more masculine digit

ratio than straight women? Unless on

average they were exposed to more

prenatal testosterone than straight

women. And why would that matter? Unless

being exposed to prenatal testosterone

makes you more inclined to be attracted

to women when you grow up. What's really

weird about it, think about the time

lag, your first crush, this sudden, this

mysterious, for me, it was like a

visitation, right? It's like, where'd

this come from? Um, that happened six

years after you were out of the womb,

right? And so it's really strange to

think that something that happened to

you before you were born would have an

influence on who you're going to be

attracted to 6 10 years later uh when

you have your first crush. Um so it it

was uh and I can tell you that when we

published that in 2000 um it it did

quite cause quite an uproar. I heard

from a lot of strangers that I'd never

heard from before. Um and it was pretty

interesting. Um, of of course there were

several people wrote who I did had and

told me that they were gay and they were

very positive, very supportive. Um, but

I got lots of, you know, emails from

people saying, I know you're lying. You

know, you're making this up to justify

your gay lifestyle. Uh, you know, it's

like, well, okay, except I don't happen

to be gay. I mean, we we had a nice mix

of orientations on the research team,

but people were having a hard time with

it. and to assure your your your

listeners about if they're looking at

their hands. If if they're a woman and

they looked at the hands and they see

that the index finger is quite a bit

shorter than the ring finger and they're

thinking I thought I was straight, etc.

So, here's a joke that I tell which is

if you want I'm going to teach you right

now. I'm going to you gather a big

sample of people and I'm going to teach

you how to look at their hands, look at

their right hand and guess their sexual

orientation and you're going to be right

95% of the time. Okay? You want to learn

how? So, so look at the right hand, pay

really careful attention to whether the

index finger is shorter than the ring

finger and no matter what you see, guess

straight and you will be right 95% of

the time if it was a random sample of

people. So um so the important thing to

to get across is that while these

average differences across group are

theoretically important because they do

indeed indicate that lesbians are more

likely to have been exposed to slightly

more testosterone before birth. That

doesn't mean you can predict how much

testosterone one person was exposed to

from their digit ratio because other

things influence the diger ratios.

>> Fascinating study. I got made fun of

quite a lot, but you know, I I I thought

it was a blast.

>> I mean, I mean, some of the more

outrageous things that people have asked

me about the study over the years, uh,

were, and by the way, they all came from

men, uh, were if I cut off my, uh, index

finger, um, you know, will that raise my

testosterone? Someone actually asked

that.

>> No, it's not reverse causality.

>> I would have said, well, let's try it

and see. again now most people I realize

there are differences across the country

and the world on this stance but I think

most people would say yeah like okay

there's a biological variable um

associated with sexual orientation the

fact that it's linked to prenatal

testosterone is very interesting um and

the question that then comes up is is

there anything about behaviors

associated with gay or straight men gay

or straight women that change hormone

levels

independent of all this, right? Because

um put differently, I think for a number

of years, people were interested in

whether or not gay men, as you pointed

out, um would have higher or lower

levels of testosterone. The the

hypothesis was lower based on the

affeminate stereotype. Turned out

>> probably the opposite outcome.

>> If if anything, you're right.

>> Yeah. Right.

>> Anyone that went to gyms in the 1980s

and '90s uh would would also realize

that that the low androgen argument was

wrong. Although steroids become a

problem in gyms too but you know it gets

confounded but

>> am I correct in remembering that this

effect is also present in frogs or in

mice

>> the sex difference is present in mice

>> that's D2D4 ratio difference I find that

amazing

>> well I I did too so so uh Wendy Brown

and I did that first and you know I'd

worked with mice and rats all my life

but you know I'd never noticed that that

that that this is that that the first

digit is the shortest and that the third

digit is the longest and that sometimes

the second digit is longer than I you

know it's like I mean it's you know

evolution is real right that it happened

uh and so yeah there's a sex difference

there and a group looked at mice and did

lots of genetic manipulations and it

turns out that if you if you make the

androceptor dysfunctional the sex

difference goes away and they showed

that in mice at least there's more

androceptor in the the growing bones of

the fourth digit than the second digit.

And then they showed that um that that's

why the fourth digit grows a little bit

more than the second digit.

>> Beautiful. So the me and we I should

have said this earlier. Androgens are

things like testosterone um DHT other

other androgens. Um men and women both

have them other animals have them. Um

incredible. So let's talk about

effects of testosterone when we're in

the womb.

>> Yeah,

>> obviously it's having an organizing

effect on the body plan. This D4 D2

ratio, right?

>> What about in the brain? What is known

about brain differences between men and

women that identify as straight or um

gay? Well, in in terms of prenatally, we

don't know. But but the very famous

study from Simon Ley, who was already a

highly respected neuroscientist, lots of

wonderful papers in development of the

visual system. Um, Simon Ley got

everyone's attention well before we did

when he looked at a brain region in the

hypothalamus, a specific region called

the preoptic area or POA. And he looked

there and compared uh the the size of

the POA in the brains of gay men versus

straight men. And he looked in the

preoptic area because in rats there's a

very prominent sexual difference or sex

dimmorphism and a nucleus in in the rat

brain in the preoptic area and the the

nucleus got named the sexually dimorphic

nucleus of the preoptic area of the SD

and POA. And Simon knew there was a huge

sex difference there in rats. And so he

looked at the brains of gay and straight

men and found a nucleus there that may

or may not be the same as the SDPA, but

is larger in men than in women. And what

he found was that the the nucleus in gay

men was smaller than in straight men and

in fact not significantly different from

the size of the nucleus in women.

>> So it wasn't hyper male like the finger

length ratio was.

>> No. No. that in that case it indicated

less either less and exposure or less of

a response to the ant and antigen that

was there. And uh Simon got even more of

an uproar than I did. Uh published his

paper in science and uh there were lots

of people that were very skeptical

including some neuroscientists but but

eventually another group replicated it.

You know

>> that's what I was going to ask because I

recall that the two major critiques of

the paper um one was fair in my opinion.

it was that some of the post-mortem

samples were from people who had died of

AIDS and so AIDS has some known

neurodeenerative effects that may or may

not have impacted the samples although

hopefully they control for that and then

as I recall he also got some push back

because he is openly gay and people

accused him of g uh agended I didn't say

gendered I said agended science

>> yeah that that that he was part of some

conspiracy a gay agenda to to to to

force Americans to regard people with

samesex orientation as somehow okay.

>> But a replication of the study from an

independent group that presumably has no

reason to be biased whatsoever.

>> They were very skeptical of it. So that

was William Bler who u eventually it it

and there's an interesting aspect of it.

It took him a long time to get a sample

big enough because you know Simon it was

such a horrible time in AIDS epidemic.

there were so many young men dying um

that uh Simon had no trouble finding

enough brains to do the sample and and

then as treatment got better the the

death rates of HIV started going down u

and so it took longer for William Ber to

gather the samples but but eventually

did and even though he was skeptical of

it he saw it too. the the a the question

about AIDS. I mean, Simon was able to

address that in that um he also had some

straight men who had AIDS and and he

didn't, you know, they didn't they

weren't significantly different from

other straight men. Um but but and so it

was widely interpreted as proof that

sexual orientation is not a choice, that

it's something that happens to you. And

of course, I don't think sexual

orientation is a choice. That's true.

But Simon himself made it clear that he

could only look at this nucleus in

adults, right? You can only look, it's

so tiny, the sexual dimmorphic nucleus,

the preoptic area in humans. It's it's

about the size of a grain of sand,

right? So you got to have a microscope

and you can only there there's no

non-invasive way to look at it. And he

pointed out that he didn't know if what

what the order of causation was. He

doesn't know if those men had been born

with a smaller SD and POA and that's why

they became gay or did something else

cause them to become gay and also cause

the SDNPA to get smaller and and for the

public the idea that a nucleus might

change its size in adulthood maybe that

seems kind of like you know unlikely but

as neuroscientists we know you know that

adult brains are changing all the time.

uh in in fact e even in animals Brad

Cook showed that you know there's a

nucleus the medial amydala um there's

sex difference there but if you take

away the testosterone in males sex

difference goes away in just a matter of

a few weeks so Simon's work on the sdnoa

also known asina 3 I won't bother with

why

>> unfortunately I remember the full name

because my brain it's the intercal

nucleus of the anterior hypothalamus sub

region I'm not saying that to impress

saying when you get to be 50, which I

can now say that you wonder why your

hippocampus remembers certain things

that are like basically totally useless

to remember.

>> I we waste so many synapses on on

totally useless crap. But but that's not

that's that's that's worth holding on

to. You did well. So um but uh so so we

don't know u it's a chicken and egg

problem. We don't know if um if that

happened um if if they were gay because

they had a small line of three or do

they have a small line of three because

they're gay. So what what I liked about

Dennis's oto acoustic emissions and is

pretty good evidence that that happened

well before they they had a sexual

orientation. And and the other thing I

always liked about it is that what well

I mean you can't imagine there's a

social influence on on dig and and and

nobody nobody knew about this. So I

wasn't worried that there were some

little girls out there that looked at

their hand to say gee that looks kind of

masculine. Maybe I should be a lesbian,

right? Because nobody knew this

>> until your paper was published.

>> Yes. Yeah. I mean, as I recall, there w

there was some like schoolyard stuff of

kids looking at each other's hands and

trying to decide who was gay and who was

straight. And

>> you know, every once in a while to this

day on on the internet, I'll look at and

there'll be a little ad over there other

claiming to to tell me something about

my personality based on the on on on

digit ratio length and it's just like,

you know, please uh yeah, there's

nothing to it don't waste your money,

gang. And there's an aspect of this this

this fact that that the group

differences were there, but you can't

tell about differences between

individuals that that I think is the

hardest thing for scientists to

communicate to the public at large.

>> You you have a really good way of

explaining this to people because and

it's an important lesson just in reading

statistics and and making sense of data

that um I'd love for you to give an

example of how this plays out perhaps in

a separate example. psychologist they

like to talk about how a way of

measuring how big a difference is

between two groups. So this difference

in digit ratios between men and women

it's it's a relatively small difference.

It's like well we measure it in terms of

how many standard deviations apart are

the two means of the populations

>> the two averages

>> the two averages. And uh to give an

example of that everyone knows about the

sex difference in human height right

among adults. So that's a huge sex

difference. It's one where we're all

aware of it. And if if nobody had told

us it was such a thing, we'd notice it

after a while, right? And that that's

because those two averages and those two

populations are about two standard

deviations apart. The standard deviation

being a measure of how much variability

there is in something. So that's a huge

sex difference. And to give you an idea

of what that means, if I had you grab a

a sample of a thousand people and I'm

going to tell you one thing about each

one of them, and that's their height.

That's all. And now I give you the job.

You've got to guess what sex they are.

And I can tell you what you want to do

to to maximize your hit rate. Everyone

who is 5' 5 and a half, you're going to

say those are men. And if they're less

than that, you're going to say they're

women. and you'll be right about 80% of

the time, which means you'll be wrong

almost 20% of the time, right? And so

everyone you you can you can see that

that there's some predictive power

there, but not it's far from perfect.

Well, this sex difference in digit

ratios is half a standard deviation, so

a quarter that. And so that means

there's much more overlap. and that and

and we know that other things influence

digit ratios too, not just prenatal

testosterone. And so, uh, this is why

there's no predictive value. I mean, so

anyone who looked at their hand while we

were talking about this and got worried,

um, I don't know anything about your

particular prenatal testosterone level,

no matter what your digit ratio is.

>> What about bisexuality? People who

identify as attracted to both men and

women. And maybe we ask about first

bisexual women, then bisexual men. Is

there a pattern in digit ratios that

leads anywhere?

>> I mean, in those days, we didn't have

enough people that identified as

bisexual to to have a reasonable sample.

And it's interesting, and that's

something that's changed, right? I mean,

if you do surveys now, especially for

among younger people, there are more

people who report that they are bisexual

than there were then. So, so I I don't

really have anything to say about them.

The one thing I will say is I'm sure

that even among lesbians, there's more

than one pathway, more than one

developmental pathway to to to become a

lesbian or to become a gay man, right? I

I don't think there's just one thing.

That's not how human behavior,

>> but you do think it's based on the data

that it's biological.

>> Based on that data, I think testosterone

has a say,

>> right? That it not doesn't mean it's the

whole package.

>> Prenatal testosterone.

>> Prenatal testosterone. And the reason I

asked that is I mean there are

conditions that are not uncommon where

um someone has a particularly stressful

long phase of development where there's

every reason to believe that their

androgens are impacted negatively.

>> Yes.

>> There's also every reason to believe

that there are stretches of development

where androgens are increased. Like we

know that people who do a sort of a a

contact sport um or engage in anything

that requires like deliberate aggression

I realize that real martial artist no

competitive aggression know how to you

know sort of um gate their levels of

aggression so that they're not they're

not like in in a fury right um like but

we know that certain types of activities

competition etc. I mean, there's no

question that those can increase

androgen. So, you can imagine there's

some plasticity postnatally and that

could be before puberty. It could be

during puberty and and so that's

testosterone there. the body as you you

said you said something that even as a

developmental neurobiologist I don't

think I'd ever um heard uh stated so

clearly and it's so important that that

the the rate of brain development from

birth until age 12 is at least as fast

as it was before we're born.

>> Yeah. That I mean the the way to really

bring that home is to compare human

brain growth and chimpanzeee brain

growth. So up until birth, the rate at

which the brain size increases compared

to body size is about the same in humans

and chimps. And shortly after birth, the

chimpanzeee brain stops growing as fast

and eventually asmmptotes right away.

The human brain continues that feverish

fetal rate of growth until at least six

years of age, maybe out there to 10

years of age. So, uh, people have

pointed out that in in a real sense,

human beings, children are fetuses that

are outside learning a whole bunch of

stuff from other people. That's the real

distinctiveness of our species is, you

know, we have this protracted childhood

and really intense social learning and,

as you say, a fetal rate of growth even

though we're not in the fetus anymore.

So I guess for me the the idea that

behavior exposure to things uh you know

and I don't want to get into veilance of

negative positive but sure pesticides

but also you know schoolyard activities

um

>> if you have and we'll get to this you

know uh five siblings and it's very

competitive who gets how much pizza I've

been you know I had one sibling so it

was a little bit you know there was

competition but it was different right

you know these things change hormones

hormones change the brain the brain, as

you're explaining, can impact sexual

preference.

>> What's great about studying hormones and

behavior, right, is is that sometimes

you can control the hormone in animals

at least. But the hard thing about

hormones and behavior that people don't

understand is that behavior can affect

hormones, as you say. In in

competitions, the winners afterwards are

more likely to have higher testosterone

and the losers will have lower. In

elections, it's been shown that people

whose candidate won the presidential

election, they their testosterone levels

went up a little bit and the people

whose whose candidate lost went down a

little. And so you'll always have this

cycle where the the hormone alters the

behavior and then the behavior alters

the hormone and and you always have to

look for ways to try to pin down u the

order of of of effects. Um and you know,

not always easy. The only thing I know

for sure is is that the brain remains

plastic all of our lives.

>> Well, that statement is a significant

one because I I also believe that the

brain remains plastic throughout our

lives. It's always surprising to me that

the hypothalamus remains plastic

throughout our lives. And I think that's

worth perhaps um double clicking on so

to speak because you know the idea that

you can learn another language and your

neoortex changes um or you can learn to

juggle and your you know your neoort

your motor cortex changes your

cerebellum changes okay like there's a

lot of beautiful studies demonstrating

that but when I think about the

hypothalamus I think about it as

something that's pretty hardwired

by time puberty wraps up

>> but the more I learn and the more data

that get published, the more surprised I

am. I saw a paper just the other day

that um the neurons that control

suppression of appetite,

>> these palm C neurons in the arcuate

nucleus, there's a population of them

that are sort of undifferentiated that

can become, let's just call it pro-

hunger, and by expressing some a

different peptide, neuropeptide Y, and

that there's a lot of latestage

plasticity. And this may explain why

people who reach a certain level of

obesity may actually find that they're

hungrier despite not needing food. So

it's fascinating to me how these deeper

brain structures may actually remain

plastic.

>> I think both your statements are true. I

I I think it's probably true that the

neoortex is more plastic than the

hypothalamus, but it's a matter of

relativity. And so as you say, the one

thing we know is that there's plenty

plasticity there. The the other thing I

noticed, so I I' I've gone to society

for neuroscience meetings pretty

regularly every year since 1977. And

after a while, I noticed something.

Every year when I went to the

neuroscience meeting, the brain was more

plastic than it was the year before,

right? I mean, because there more and

more of these demonstrations and it's

like um I I you know, I think synapses

can come and go just about anywhere. Um

and so hardwired let let's let's say

there's might be less plasticity in the

hypothalamus surely. So um but that

doesn't mean there's none.

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subscription. What are some of the other

effects in human studies of behavior

impacting hormones that come to mind for

you? I mean, it's been a while since

we've touched into this and we haven't

done it much on this podcast. I mean,

obviously competition, winners, losers.

You explained the data there. Um, what

are some other scenarios, just studies

that that have been striking to you or

that have stood out over the years?

>> No, I think for testosterone, I think

the big ones have been have have been

competition, you know, between males.

Um, and no, I don't, you know, I mean,

there there's a stress response, but

that's a whole other thing.

>> What about sex behavior itself?

>> In animals, at least, we know that that

there's a relationship there that that

in in males, in males of most species,

let's take rats, uh, if you take away

the testosterone, within a few weeks,

they'll they'll stop mounting

altogether. And if you give them

testosterone, after a few weeks, they

they start mounting again, right? So, we

know that that um plasticity is is there

and we know that it's driven by

testosterone. But, uh in in animals

where they're in charge of their own

testosterone, we've known for a long

time that if a male is exposed to the

odors of a receptive female, that causes

a spike in their testosterone. And so,

uh that's kind of preparing them for

maybe maybe some maybe I'll be lucky.

Maybe there's something coming down the

pike. Uh and so we know that that's a

reciprocal relationship uh when the

animal's in charge of the of the

hormone.

>> For the longest time, thanks to your

textbooks, and by the way, folks, uh

Mark has um authored some of the most

important textbooks on hormones and

behavior, developmental neurobiology.

He's a he's a true scholar of the whole

field. And so immensely grateful to him

that those textbooks have formed the

backbone of a lot of uh solo episodes of

the podcast. So um you know the textbook

version of male versus female sexual

behavior has been a story about females

having a circuit that goes from brain to

body to control this thing they call

lordosis the arching of the lower back

the receptivity the willingness to mate

and the males having a circuit that goes

from brain to spinal cord to body um

involving uh arousal erection mount

counting, um, insertion, ejaculation. I

mean, your lab and others has really

parsed this, uh, right down to the the

details. And yet, of course, people have

sex that way, but also other ways. And

so, for a lot of people who aren't

familiar with hormones and neural

circuits and behavior, the sort of

strict context kind of is is still forms

the framework, you know. I mean, I I've

learned and I'm now fortunate that this

podcast has been around more than five

years, so I no longer have to tap dance

around things, right? So, people will

say, "Oh, well, you know, there's this

lordosis behavior in the female. She's

she's receptive um or not. Um he mounts,

etc." And then there's gay men who have

to have sex a certain way that mimics

the female sex pattern of behavior. And

so, people do this onetoone, right? And

I think that it's understandable why

they do that if they're not

>> educated. But how should we make sense

of these biological circuits that are in

the textbooks that define stereotyped

literally motor behavior? It's almost

like saying like like females have sex

this way with males, males have sex this

way with females. But then the caveat is

always like, oh, but in humans all that

goes away and there's these like bonabos

that are a little bit more like humans.

So did we waste all our time um studying

that stuff? I mean really

>> and you're getting at exactly what every

textbook author has to deal with, right?

which is, you know, uh, as the old joke

go, you you you you look where the light

is, right? So, we know so much more

about the circuits that are involved in

the motor behaviors because they're

relatively easy to trace and relatively

easy to manipulate and relatively easy

to to study. We know lots about the

motor patterns in animals. We know a lot

less about the motivational

patterns in animals which in human

sexual behavior is I mean in many ways

that's the whole show you know that's

that's really what's uh and and we don't

really have good animal models of of

libido right and this was brought home

to me many years ago now I I was on a

session of 60 Minutes the CBS news

program and uh Leslie Stall was there in

our lab. I mean, the producers had

called me up and said, you know, can you

show us a way that that early

testosterone exposure changes behavior

permanently. And I said, "Sure, I can do

that. Give me some time." So, I went to

the lab and castrated a bunch of rats on

the day of birth. I know how to do that.

I'm not proud of it, but I I know how to

do that. Um, and they came three months

later, and uh, so I I showed them those

motor patterns you talk about. So,

here's a typical female. I've given her

hormones, estrogen, progesterone, so I

know she's going to be receptive. And

here's a male rat that I know has had

lots of experience copulating. And uh

Leslie immediately dubbed him Romeo.

Okay. Well, this is Romeo. And she hates

rats, by the way. So, she she was she

was very brave. And so, I I drop a

female on top of Romeo and he starts

mounting and she shows the Lordosis

posture. And it's all beautiful and

easy. And we do that several. I said,

"Now I'm I'm going to drop a male, a

control male in." And Romeo, of course,

you know, you don't know unless you try.

He mounts several times and the male rat

acts like nothing's going on. I mean,

it's just a bored thing on Earth. And

Romeo eventually gives up. Now I drop

into the cage a a male rat who I

castrated on the day of birth 90 days

before and I've given him the same

hormones I gave the female to make her

receptive. Romeo hops on and sure enough

a beautiful lordosis right that of the

sort that the that the control male

never showed. So here this pre this this

neonataly castrated male is showing very

female-like patterns

and Miss Stall kept asking me would you

say this is a gay rat

and it's you know I'm sitting there and

I'm definitely in a tough spot because I

don't think my rats have an orientation.

I mean we we just saw Romeo happily

mount any rat I he threw in the cage

because what do you know? You know try

your luck. Um, and so, uh, you know, she

asked me several and I I knew she wanted

me to say that, but I said, "What I

would say, I don't remember exactly what

ended up in the final." What I would say

is that this is a rat whose sexual

behavior has been permanently changed

because of something that happened to

him a long time ago at the very

beginning of development. And, and

really, that's the best I can do in

terms of any rat model of sexual

orientation. I don't think my rats have

a sexual orientation. If I give the

female those hormones, she's going to

show ordosis to whoever mounts her. And

my male rat, he he will mount any rat he

comes across just in case he gets a word

ordosis out of them.

>> Well, good on you for not um getting uh

coralled into giving a particular

answer. Uh I've recently joined CBS as a

correspondent. If we have this

conversation on 60 Minutes, I promise to

not try and force an answer. Romeo is an

interesting um case because I think for

most people, including myself, um I

thought that you were going to say that

Romeo was willing to um try to mount a

female

>> if she was receptive, he would mate. If

not, he wouldn't. Um but I was surprised

that he would try to mount a male as

well. That doesn't align, at least with

my experience, of of male human

behavior.

>> Well, certainly not. That's right. This

is the thing that's distinctive about

humans is we're not actually that

particular about what particular

behaviors we engage in, what motor

behaviors, and we're overwhelmingly

interested in who our partner is. Right?

That is an overriding concern that that

I don't think my rats have. I think I

think few animals do. Here's the you're

the anthropologist from Mars and um and

I tell you here's a person that 50%

here's whoever's the sexiest man alive

this year. People magazine or I don't

know who that happens to be. Well, this

is an interesting discussion alto

together because there's this people

have been lining up the images of these

people and claiming that they're sort of

like this eff like effeminite drift that

takes us back to a time in the early 90s

when there was this sort of revision

about male male facial. We can get back

to that. But yeah, yeah, it's not the

point being that it's not fixed.

>> Who?

>> Yes. Yeah. Well, well, whoever, let's

say it's George Clooney. So, uh, so

here's someone that half the planet

believes is an ideal sexual partner,

right? But the other half of the planet

finds him totally unacceptable,

even if the behaviors they engaged in

would be pretty much the same. And so,

you know, in terms of positions and

who's doing what to whose genitalia,

etc. I mean for for for most people

it it isn't that there has to be one

particular act. I suppose there's some

but for most people there maybe a

variety of acts that they that they want

to be engaged in with that other person

and their overwhelming concern is the

the gender of that other person or the

sex of that other person. Um you know

it's it's hard to have an animal model

of that. I I actually do know of one

example in sheep if you want to talk

about this

>> of all things.

>> Yes. Oh, I I I I noticed it. So, um so,

uh Chuck Rosselli out at Oregon, he's

the one that studied this very

carefully. I guess shepherds have known

for ages, um that in any herd, there are

some rams who will not mount a female

ever and keep mounting other males. And

of course, to maintain a shepherd,

to maintain a herd, you don't need every

male to reproduce. So, but in the old

days, they got those males got sent off

to solder, right? Well, um, hearing

these rumors, uh, Chuck did these tests

where he would put a bunch of females

that are in stocks, so they can't move

and they're all ready for mating. And he

put a ram in with them. And most rams,

of course, will mount the females. He he

puts in these rams that that prefer

males. If there's a variety of sheep's

butts sticking at him out at him, uh

he'll mount males, including sometimes,

you know, having intermission through

the anus and all the way to ejaculation

and and he never mounts a female. In

some cases, they'll have one of these

I'm going to call them gay rams. I think

I think they have an orientation. He'll

put the gay ram where there's a dozen

females and he might be in that paddic

for 12 hours and never mount a single

female.

>> Highly unusual for male rams.

>> And these are not typical ram there.

It's like a small percentage of the

population. And um and I don't know how

to explain that. I mean, you would think

that the that these gay rams that well,

you know, an ejaculation is an

ejaculation, right? An orgasm is an

orgasm. I presume they have or you you

would think that at some point that well

there's nothing else to do in here. I'll

mount one of these and they never do.

And I don't know how you can explain

that except that there's some aversive

component that that that that rams do

care about the sex of their partner and

that and that for these gay rams um

there's some aversive component to that.

By the way, Chuck told me uh not too

long ago, there's a company that has

identified these gay rams and decided

that instead of sending them off to

slaughter, they're going to harvest

their wool and sell them as and and make

them into clothing. So, you you can buy

you can buy um wool clothing that came

from gay rams and and know that you

saved them from the slaughterhouse.

>> There's no response that's appropriate

to to that statement. And apparently

they apparently they they you know they

they're out of stock. So it's it's been

a big success.

>> Actually I can think of about 50

different responses to that. None none

of which are are appropriate or have any

real conceptual uh importance. So I I I

won't I won't say fascinating because

rams while of course they have

sociodnamics

um presumably there isn't pressure uh

independent of reproductive pressure to

um to be a gay ram or a straight ram.

And I I guess I I left off the kicker,

which is uh Chuck eventually dissected

the preoptic areas of these various

rams. And he found a difference between

the preoptic area of gay rams and and

straight rams, a difference in how they

process testosterone in in exactly that

part of the brain, the preoptic area

where Simon saw a difference between gay

and straight men. So there may be

something about the hypothalamus, the

preoptic area, uh that has something to

do with orientation if if we're talking

about an organism as complicated enough

to have an orientation, including sheep.

This is a particularly um nice moment uh

not just for this episode but for the

entire podcast arc uh because there are

these moments that come up every once in

a while where a larger principle shows

up in a new way that I think um is

really important for people to

understand. Across neuroscience we see

this pushpull right a flexor muscle like

the bicep when it flexes the tricep

relaxes. When the tricep flexes, the the

bicep relaxes these antagonistic

relationships. You see this in the

hunger circuit. I mentioned one earlier.

Like hunger and feeling full are they're

like a pushpull. They're like a seessaw.

And um uh and you see this over and over

and over again. It's it's a it's a very

consistent theme of of brain function.

And you said something that I was not

aware of, but makes perfect sense. I

just wasn't aware that there were, you

know, data um at the level you

described, which is clearly there's an a

pettitive aspect to sex behavior.

Heterosexual males wanting to have sex

with females, heterosexual females

wanting to have sex with males, and and

so on. Every derivation there, there's a

desire. In species where there's strong

pheromone and odor determination and and

receptivity stuff gets played out that

way, it looks one way. In humans, it may

have some of that, but it plays out

different way. Receptivity is

communicated differently, although odor

may be very important in ways we don't

quite fully understand. But this idea

that there's an aversive aspect to it,

right? I think this is important and

it's something that I have not heard

discussed before. And I think that

sociologically it has relevance because

I think that um there's so many

different aspects to the notion that our

species, humans, um come in gay and

straight and perhaps bisexual varieties.

We know that's true

>> clearly.

>> But there is this um not uncommon

theme whereby

many people I I'm only you know say many

people, right? not all um that the

concept of mating with same sex is

aversive to them and that has shaped a

lot of the the landscape around this and

I'm I'm not trying to get political

here. It's just I think it's it's worth

acknowledging that that may be a real

phenomenon, too. I'm not trying to

justify mistreatment of anybody, but I

think that we're never going to get

where we want to go as a as a species um

society until we really at least

understand the biology and how to work

with it. And so the idea that same-sex

sex, right, um would be aversive as an

idea to people, some people like, oh,

they haven't been educated. Okay,

perhaps, you know, but there may be a

biological basis for that. I think the

data is still out and I but I think it's

to me at least it's pretty clear that

for men at least for there's an

asymmetry here that that that experiment

where I said you know who wants to have

sex with George Clooney half the

population says sure the other half

population never. If we reverse the

experiment, what percentage want to have

sex with Margot Roby? And yeah, half the

population, the men would see her as a

very desirable sexual um partner, but

you know,

the women too would many women would

also would at least consider the idea of

having sex with her. And and we know

there are plenty of women who are

straight in one part of their lives and

later they fall in love with a woman and

now they feel like they're they're gay.

Right? So females, women are more

plastic in terms of their sexual

longings and sexual orientation

than men are. I'll be a little more

specific. I I think it's among males

where sometimes for many males, not all,

uh there's an aversive idea that that

the idea of having sex with the same-sex

partner is aversive. Now, of course,

context matters, right? There's same sex

happening in prisons all the time when,

you know, if the conditions are are

enough and and I don't know where that

aversive component came from. It could

be that our society maybe it's all

socially inculcated, you know, again

before we're aware of it at all. Um, but

I I think there's also at least the

possibility that there's a biological

component to it. And I think that's what

uh Chuck was getting at in that here's

this difference in the brain. He he

doesn't know when the difference

happened uh in their pre-optic areas.

Um, but it seems to correlate with this

idea that maybe these gay rams um, no,

they they they're not interested in

having sex with her. They're, you know,

only

>> it's aversive to them.

>> It's aversive. Yeah. There's no other

way to I can't I don't know any other

way to explain uh how they choose never

to never once mount a female.

>> Yeah. I feel like that the

acknowledgement of a of an aversive

pathway for sexual partner choice is as

important as the acknowledgement of

biological uh coralates of

homosexuality.

>> Yeah.

>> Because if this sort of conversation is

ever to advance past the sort of like

okay what's okay to say now that we're

willing to say now trust in science

disappears. I really believe that. Now,

of course, the problem is that people

leverage

fragments of what they hear in order to

make arguments in in favor of whatever

stance they have. And that that's the

complication. That's why I like long

form because no matter what gets pulled

out, we can go back to the full

conversation.

>> And this makes you old-fashioned because

this that's not the world. I mean, our

world seems to be hurtling towards this.

>> Yeah.

>> Yeah. I mean,

>> world of snippets.

>> People will notice that we have not used

the word gender. We're talking about

biological sex and sex, the act. And

we're talking about male versus female

partner choice. And we're talking about

a desire for one or the other. And an

aversion to one or the other. And I

think the aversion piece is an important

theme. So here's a hypothesis

>> if I can come to a sbatical. I'm due for

a sbatical at some point. It may be that

in male humans that there's a pathway or

a molecule that serves as an aversive to

sex with other men circuit, peptides,

neurons, etc. that suppresses um sexual

desire and activates some level of

disgust. Let me just say it bluntly.

Might not be the same disgust that they

would experience to something more

aversive, but okay. And that in women

there is no such pathway. There's either

desire for women or desire for men. But

as you said, you know, stati stat

statistically women are more open on

average to samesex

a interactions. And it may be because

there's no aversive signal or the

aversive signal has a less robust

circuit. to me that that would explain

these differences that these sex

differences and who people are willing

to have sex with. Your hypothesis fits

the data.

>> I mean, it is true that in the like the

early 90s, for instance, when the first

gay characters were on television, like

the real first real world, I'm really

dating myself here, and subsequent

characters started to dismantle some of

the stereotypes that had been seen in

like comedies in the 80s and things like

that of the affeminite gay man, right?

What you saw was indeed that

heterosexual women, as far as we know,

seem to be more like generally accepting

of gay men before heterosexual men

embrace that as as typical.

>> That's my impression, too. I think I

think it's pretty clear.

>> Yeah. And then and then there's a

societal shift and then it sort of

becomes like, you know, uh like if you

like I spend some time on X, formerly

known as Twitter, right? And there's

some um gay political uh accounts and um

and you just kind of notice like it's

just people are like comfortable with

it. Men and women seem to be comfortable

with that, right? I mean, of course, you

don't see a lot of attacks now. That's

very different than what you would have

observe would have observed for instance

in like the late 80s, early 90s, right?

Anyway, I think these are important

biological uh phenomenon. this notion of

an aversive pathway. You could imagine

where societal standards or community

standards or household standards might,

you know, amplify or reduce like the the

the sort of expression of these things.

>> I'm I'm sure they do.

>> Yeah.

>> And and I'm sure, you know, cultures,

you know, can amplify or uh reduce that

component. Um the question is, you know,

to what extent? I mean, and and I don't

I don't think we know. One thing that we

haven't talked about and it is a small

percentage of people but it's something

that um people think about um is this

notion of sort of um neither here nor

there kind of mixed sex right is there a

biological coralate of that um a

graduate student my year when you were

my professor um Nikki Oipka Nola Oipka

>> um who was already famous for dog

training dogs for the beast master show.

She's amazing. Um, and had very well-

behaved dogs uh that she would bring

everywhere with her. Studied a species

of mole in Tilden Park that could

transiate its testes into ovaries and

back again. And I thought, well, that's

like alien weird levels of stuff. But

she would occasionally go over to UCSF

when babies were born that were sort of

back then they called them, no one uses

this language now, pseudo hermaphrodite.

Yes.

>> What is the deal with exposure to

prenatal androgens and neither clearly

here nor there a genitalia?

>> Yeah. So in most of those cases we're

talking about congenital adrenal

hyperplasia also known as cah. And the

congenital means it's present at birth.

And the adrenal hyperplasia is referring

to the fact that the adrenal glands are

slightly larger. And the reason they're

slightly larger in this case is because

these are individuals where the the the

fetus itself is not able to make some of

the adrenal steroids that are important

for staying healthy. And so the brain

detecting, hey, where's the where are

the adrenal steroids that we need here?

Drives the pituitary to tell the the

adrenal gland, hey, we need more

steroids. The adrenal gland gets the

message. It hypertrophies, but the

machinery isn't there to make those

steroids. And so instead, the adrenal

gland makes testosterone and other

androgens.

And actually, this can happen in either

XX or XY individuals. And in XY

individuals, u people might not notice,

but in XX individuals, what that means

is that prenatally her genitalia being

exposed to more testosterone than is

typical. And so uh under the influence

of this extra testosterone the clitoris

may grow to be bigger than the typical

clitoris. In some cases in extreme cases

um the the phalus looks like a penis and

the skin around that area that would

normally form the labia again there

might be enough testosterone that it

starts to look like a scrotum except of

course there are no there are no testes

inside there because this is an XX

individual. So these individuals are

identified at birth typically especially

in XX uh individuals and there's a

there's an easy treatment which is oh

they can't make you you know you do the

test and you oh they can't make adrenal

steroids so we'll give them some and so

for the rest of their lives they take

adrenal steroids orally and get the

benefits of that and that shuts off the

hyperactive adrenal gland so that it

shuts off the the role of the output of

testosterone. So this is an what's known

as an interex phenotype. And yes, you're

right. And in the older literature, they

were sometimes known as pseudoh

hermaphrodite. Huh? With the idea being

well that a hermaphrodite is some is an

individual that can that can function

and reproduce either as a male or

female. And so supposedly they were

pseudo because they can't do that

because they have only ovaries. Well,

uh, you can imagine, uh, first of all,

um, being called hermaphrodite,

nobody liked that. And if you ask them,

well, does it better if I put this

pseudo at the beginning? Does that that

make you feel like you're being less

stigmatized? No. But a much more

accurate uh description is to say that

it's intersects. They have a a fallus

that's somewhere between a clitoris and

a penis. And the skin around there is

sort of like a scrotum and sort of like

a sort of like labia. So uh in the old

days once this got recognized it was

standard procedure to tell the parents

oh uh this is an emergency. We need to

do cosmetic surgery. We need to do

surgery to make this little girl look

like all the other little girls. You

know sometimes the surgery was you know

there could sometimes be successful or

not. And indeed, they knew how to make

her look like

other girls. Um, but many of those

interex folks when they grew up were

pretty angry that someone had done this

surgery on them that wasn't needed

medically, right? They were already

taking care of the problem with the

exogenous adrenal steroids. And so, who

asked you to to deal with my, you know,

to do surgery on my clitoris? In some

cases, uh, the tip of the clitoris was

missing and so these women grew up and

were an orgasmic because they couldn't

get the stimulation that they normally

would have had. These days, um, there's

much more thanks to the activists like

Cheryl Chase and others who started

getting the pediatricians attention.

Hey, you you need to think about that.

You're you're doing elective surgery on

an infant who cannot possibly have

informed consent. And so these days

they're more of a wait and see attitude

which which I think is absolutely that.

So wait till they're grown up and ask

them then if they want to have surgery

and my guess is most will will say no. I

think that's been the pattern so far. So

these are females who were exposed to

more testosterone than other females. So

does that mean that they're going to be

attracted to women when they grow up?

And and the answer is well interestingly

uh if you look at groups of women with

CA they are more likely to be same-sex

attracted to be lesbians than the than

the population at large but most of them

are straight. But what's interesting

about that is the older they get as you

keep surveying them the higher the

percentage of them that report having a

lesbian orientation.

M

>> so it's possible first of all that

indicates that yeah maybe prenatal

testosterone increases the the odds of

them uh being lesbians when they grow

up. Uh, and and you also wonder, well,

how many of them always had that

same-sex attraction, but, you know, were

following the pathway society laid out

for them, and then as they get older,

they said, well, no, screw this. I, you

know, I I know who I'm attracted to. I

don't have to fit the heterosexual mold.

And so, it it's, you know, that's

entirely consistent with the idea that

prenatal testosterone makes you more

likely to be attracted to women when you

grow up. There's another syndrome that I

know you've talked about um which is

androgen insensitivity syndrome

sometimes abbreviated AIS and it turns

out the gene for the androen receptor

that responds to testosterone and other

androgens is on the X chromosome and it

may sometimes be that a woman will have

an X chromosome that has a copy of the

androceptor gene that doesn't work

and if she passes that X chromosome onto

a daughter then she's sort of duplicated

herself. What's interesting is when that

X chromosome is given to a son, in other

words, that egg with an X chromosome

that has a dysfunctional copy of the

Andraceptor gene, if it gets fertilized

by a Y-bearing sperm, now we have an XY

individual.

And as you've explained clearly in your

in your basics podcast, uh we know

what'll happen in development. The Y

chromosome will mean that the

indifferent gonad will develop his

testes. The testes will secrete two

hormones that are going to guide sexual

differentiation in the periphery. One of

them being antimmalarian hormone which

is going to suppress the development of

the malarian ducts and therefore no

ovduct no uterus will form and the

testus will also release testosterone

which normally would masculinize the

body. But in this case, because there's

no functional androceptor to respond to

it, the testosterone goes round and

round, but the body doesn't respond. And

so the wolfie and ducks don't develop.

The periphery looks like a typical

female. And these individuals when

they're born often are not identified

because the baby's born. The doctor does

that very careful analysis by looking