Huberman Lab - The Science of Sexual Development
Episode Date: April 5, 2021In this episode, I discuss how hormones such as testosterone and estrogen and their derivatives impact the early development of the brain and body and their maturation. I review published data on envi...ronmental factors shown to powerfully alter hormone pathways in animals and humans and the effects of cannabis, alcohol and cell phones on testes, sperm, ovaries and hormones. I describe the predictable relationship between genes, beard growth and balding patterns, and the importance of estrogen for brain development in people of all chromosomal sexes. Finally, I discuss how the hormones we are exposed to in the womb shape the relative length of our finger digits, the sounds our ears make (yes you read that correctly), and how those correlate with people's self-reports of their sexual preferences. As always, basic information and tools are discussed. Access the full show notes, including referenced articles, resources and more at hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/huberman Waking Up: https://www.wakingup.com/huberman Momentous: https://www.livemomentous.com/huberman Timestamps (00:00:00) Introduction (00:00:30) AG1, LMNT & Waking Up (00:06:47) Announcement: Mood Meter App Works Again (00:08:00) Maximizing Learning from the Podcast (00:10:00) New Non-Sleep Deep Rest Protocol, Spanish Subtitles (00:11:35) Sexual Differentiation: Hormones, Neurons & Behavior (00:14:15) Hormones Basics (00:15:26) Sperm Meets Egg, Chromosomal Sex, Gonadal Sex, (00:17:50) Y Chromosome Inhibition of Feminization (00:19:00) Placenta Is An Endocrine (Hormone-Producing) Organ, Adrenal Testosterone (00:19:45) Hormonal Sex, Morphological Sex (00:21:04) Hormones Fast & Slow, Sex Steroids Can Turn On Genes (00:23:06) Masculinization, Feminization, Demasculinization, Defeminization (00:23:42) Primary Sexual Characteristics: DHT Drives Penis Development (00:27:03) Secondary Sexual Characteristics (00:27:43) Penis Sprouting: Guevedoces (00:31:25) Estrogen, NOT Testosterone, Masculinizes The Brain (00:33:15) Breast Development In Males: Aromatase; Puberty, & Steroids in Athletes (00:34:50) Estrogen Powerfully Controls Brain Development In All Individuals (00:35:19) Avoiding Hormonal Disruption In Children & Adults: Specific Oils, Creams, Etc. (00:39:00) Environmental Endocrine Disruptors, Sperm Count Decline, Vincloziline (00:44:20) Androgen Insensitivity Syndrome: Hormones Need Receptors, SARMS (00:48:41) Estrogen Establishes “Masculine” Brain Circuits, Testosterone (00:49:42) Cannabis, Alcohol: In Babies, Puberty & Adults (00:56:25) Cell Phone Technology: Effects On Hormones, Ovaries, & Testicles (01:02:33) Beards & Baldness Patterns Around the World, DHT, 5-alpha-reductase (01:06:39) Creatine & DHT/Hair Loss (01:08:20) Predicting Aging Rates By Pubertal Rates (01:10:04) Hyenas, Baseball, & Jumbo Clitorises: Androstenedione (01:14:26) Intersex Moles (01:15:40) Marijuana Plants, Pollens: Plant-To-Animal “Warfare” (01:20:08) Finger Length Ratios, Prenatal Hormone Exposure & Sexual Orientation (01:29:13) Brain Dimorphisms with Sexual Orientation (01:32:00) “Older Brother Effects”: Male Fetuses Might Change Mothers & Subsequent Brothers (01:35:06) The Path Forward & A Warning (01:35:55) Support & Your Questions Title Card Photo Credit: Mike Blabac Disclaimer
Transcript
Discussion (0)
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 ophthalmology
at Stanford School of Medicine.
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.
In keeping with that theme,
I'd like to thank the sponsors of today's podcast.
Our first sponsor is Athletic Greens.
Athletic Greens is an all-in-one
vitamin mineral probiotic drink.
I've been taking Athletic Greens since 2012,
so I'm delighted that they're sponsoring the podcast.
The reason I started taking Athletic Greens
and the reason I still take Athletic Greens
once or twice a day is that it helps me cover
all of my basic nutritional needs.
It makes up for any deficiencies that I might have.
In addition, it has probiotics,
which are vital for microbiome health.
I've done a couple of episodes now
on the so-called gut microbiome
and the ways in which the microbiome interacts
with your immune system, with your brain to regulate mood,
and essentially with every biological system
relevant to health throughout your brain and body.
With Athletic Greens, I get the vitamins I need,
the minerals I need,
and the probiotics to support my microbiome.
If you'd like to try Athletic Greens,
you can go to athleticgreens.com slash Huberman
and claim a special offer.
They'll give you five free travel packs,
plus a year supply of vitamin D3 K2.
There are a ton of data now showing that vitamin D3
is essential for various aspects of our brain
and body health.
Even if we're getting a lot of sunshine,
many of us are still deficient in vitamin D3.
And K2 is also important because it regulates things
like cardiovascular function, calcium in the body,
and so on.
Again, go to athleticgreens.com slash Huberman
to claim the special offer of the five free travel packs
and the year supply of vitamin D3 K2.
It's a new month, which means it's a new topic
here at the Huberman Lab Podcast.
For the next four or so episodes,
we're going to be talking all about hormone effects
on the brain and body.
So that's a huge number of different topics.
We're going to talk about sex.
We're going to talk about reproduction.
We're going to talk about puberty a little bit more.
We talked about that in the previous episode.
We're going to talk about menopause.
We're going to talk about birth control.
We are going to talk about aggression,
competition, winning, losing.
Basically, we're going to cover as much about hormones as we possibly can in this month.
And in doing so, we are going to go deep
into tools and protocols.
We are also going to talk about a lot of tools
that relate to things that you might not want to do
in order to optimize hormone health,
regardless of stage of life or your goals, et cetera.
So it's sure to be a month rich with discussion,
rich with tools,
and you're going to learn a lot of neuroscience
and endocrinology.
There's actually a field of neuroendocrinology.
It's actually where I started my graduate work.
I did a master's in it,
which is only to say that I love the topic.
I have a lot of friends that work on this topic,
many of whom I've consulted for these episodes,
and I'm really excited to share the information with you.
Before we dive into today's episode,
all about emotions and sex,
I want to just have a few announcements
that are designed to point you to some useful resources.
Last episode, talking about the science of emotions
and relationships, I mentioned the Mood Meter app.
The Mood Meter app was developed by people
out at Yale University who study the biology
and psychology of emotions.
It's a really wonderful app.
However, many of you quickly told me
that the Mood Meter app isn't available in your area.
You went to the link we posted,
and it just was saying not available in your area.
The situation was actually a lot worse than that.
The situation was that when we recorded the episode,
the mood meter app was working.
I know because I downloaded a fresh copy of it to my phone.
And then in the ensuing weekend,
they took the mood meter app down for some repairs.
The mood meter app is now up.
It is available.
I want to be really clear.
It's not an app I'm affiliated with.
I'm just mentioning it to you.
They don't know me.
I know them, but they don't know me.
So we don't have any kind of business relationship.
They do charge 99 cents for the app.
I think the free version has disappeared
in the last year or so.
So that's Mood Meter app.
We'll provide the link again,
and the link should be working.
Hopefully they won't take it down again
in between this announcement
and the release of this episode.
Also just want to take a step back for a moment
and talk a little bit about the logic
of how to make the most of the information
on the Huberman Lab podcast.
I tend to throw out a lot of information
about a given topic.
Many of you have pointed out, however,
that I don't cover certain things.
And once again, I'll just say,
the goal is always to be accurate,
but there's no way I can be exhaustive.
There's no way I can cover everything
for a particular topic.
The good news is we have time.
My goal, at least in the first year
of the Huberman Lab podcast,
is to give you a basis, a foundation
in these different topics of neuroplasticity,
focus, sleep, hormones, et cetera.
And of course, to provide tools along the way.
We are going to host guests.
I've actually started recording
with some of these guests already.
And even those episodes will include
a little what we call primer,
a little description of the basics of a given topic
so that you can get more information from those topics.
My goal really is to educate you in these topics,
give you a foundation in these topics
and allow you to start exploring them here in the episodes
with our future guests,
but also in other podcasts and books
and other sources of information.
So for those of you that are saying
it's too much information,
I just encourage you to remind yourself
that you have a pause button, you can return to it,
everything's timestamped.
For those of you who feel it's not enough information,
I'm not covering enough,
just know that this is just the beginning.
We intend to do this for a very long time
and we will be thorough over time.
So thanks for your patience
and please be patient with yourselves.
There's no reason why you have to digest
all the information in one swoop.
The other thing is that I've been told
both that I speak too fast and speak too slow.
So there's a wonderful solution to this.
If I speak too fast or too slow,
you can adjust the speed in YouTube.
If you're listening in a different format,
I think you also can adjust the speed of playback.
So that's something that wouldn't be possible
in the classroom, but you may find useful.
And then last but not least,
I want to point people again to this NSDR,
non-sleep deep rest protocol
that the folks over at MadeFor
have put out as a free resource.
It does, as many of you pointed out,
bear resemblance to things like yoga nidra,
other forms of meditation.
But what we've done is we've stripped out intentions
or any kind of the verbiage related
to what some people might perceive
as kind of related to the yoga community
or specific to kind of new agey type techniques,
not because we don't like yoga nidra.
In fact, I've done yoga nidra daily
for almost the last, goodness, eight years of my life. I love yoga nidra. In fact, I've done yoga nidra daily for almost the last, goodness, eight years of my life.
I love yoga nidra,
but sometimes the complicated language can be a separator
and can discourage people from taking on these protocols
that are extremely useful.
So NSDR is intentionally generic.
It's designed to bring you into a state of deep relaxation
through a combination of breathing and body scan.
There's the YouTube script over at MadeFor,
which is linked in the caption.
And many people find that they prefer that
to scripts like yoga nidra scripts,
where they're doing intentions
and they're hearing a lot of kind of unusual language
around the process.
This is just very basic and I hope you'll enjoy it.
And if you prefer the more typical yoga nidra scripts, then go with those. There are many of them available on the process. This is just very basic and I hope you'll enjoy it. And if you prefer the more typical Yoga Nidra scripts,
then go with those.
There are many of them available
on the internet and elsewhere.
And last but not least, I want to point out
that all our episodes now are subtitled
both in English and in Spanish.
So for those of you that prefer
to digest this information in Spanish,
that's now available to you in the subtitles.
Today, we're going to talk about the science of sex,
in particular, sexual differentiation.
Now that's a complicated topic because sex is both
a adjective, a noun, and a verb, depending on the context.
Today, we're going to talk about the hormonal effects
and the neural effects of particular events
that happen during development
and how those guide adolescent and adult behavior,
including sexual preference.
It's an area that's fascinating
and for which there are actually
very solid textbook findings.
So textbook findings means that there are many studies
that have been aggregated over decades that point to
what we now know to be absolute truths
in terms of how hormones affect brain development,
how the brain impacts hormonal development
and how those interact to control behavior, for instance.
We are also going to talk about reproduction, the verb sex.
And of course, sex, the verb,
can also be carried out independent of reproduction.
It's not always, in particular in humans,
just to produce offspring.
So that's going to be covered in the next episode,
but you absolutely need to understand the information
in this episode in order to make sense of the information
in the next episode.
So today we're going to explore hormones, what they are,
how they work, what leads to masculinization
or feminization of the brain and body.
I'll just throw out one really interesting fact
that perhaps most of you didn't realize
that hormones have direct effects on the body.
Most people know that because there are hormone differences
and sex differences in bodies
in terms of genitalia and body hair,
distribution of body hair, et cetera.
But there are also effects of hormones on the brain directly.
And believe it or not,
there are also effects on the spinal cord,
on the neurons and structures within the spinal cord
that impact in a very direct way
what sorts of behaviors are possible.
So it's a fascinating area.
You might notice I'm going to go a little bit more slowly
through this topic than I normally do.
I want to be extremely careful with my language.
Some of these topics,
some of you may be thinking are extremely sensitive, right?
And of course, any discussion about sex and reproduction
is a sensitive one,
but today we're just talking about the biology.
We're not getting into the cultural constraints
or the cultural dialogue.
What we're trying to do today is really get to the biology,
the physiology, the endocrinology, and the behavior.
So let's start by talking about what hormones are,
just to remind you, and what they do.
Hormones, by definition, are a substance,
a chemical that's released in one area of the body,
typically from something we call a gland,
although they can also be released from neurons,
but they're released often from glands
that travel and have effects both on that gland,
but also on other organs and tissues in the body. that travel and have effects both on that gland,
but also on other organs and tissues in the body.
And that differentiates hormones
from things like neurotransmitters,
which tend to act more locally.
So that's important.
A hormone is a substance secreted
at one location in the body travels
and has impact on things elsewhere in the body.
Examples of tissues that produce hormones
would be the thyroid, the testes, the ovaries, et cetera.
And then of course there are areas of the brain
like the hypothalamus and the pituitary,
which are closely related to one another
and release hormones that cause the release
of yet other hormones out in the body.
So we're going to cover all this.
If you don't know anything about endocrinology,
you're still going to be able to understand today's discussion. And we're going to cover all this. If you don't know anything about endocrinology, you're still going to be able to understand today's discussion.
And we're going to start with a discussion
about what hormones actually do to create this thing
that we call masculinization or feminization.
So let's start with development.
Sperm meets egg.
Everything that happens before that
is a topic of the next episode.
But sperm meets egg.
This is mammalian reproduction.
And that egg starts to duplicate.
It starts to make more of itself.
It makes more cells.
And eventually some of those cells become skin.
Some of those cells become brain.
Some of those cells become muscle.
Some of those cells become fingers.
All the stuff that makes up the brain and body plan.
In addition, there are hormones that come both
from the mother and from the developing baby,
the developing fetus, that impact whether or not
the brain will be what they call organized masculine
or organized feminine.
And as I say this, I want you to try and discard
with the cultural connotations
or your psychological connotations
of what masculinization and feminization are
because we're only centering on the biology.
So typically people have either two X chromosomes
and the traditional language around that
is that person is female, right?
Or an X chromosome and a Y chromosome,
and that person will become male.
Now, it's not always the case.
There are cases where it's XXY,
where there are two X chromosomes plus a Y chromosome.
There are also cases where it's XYY,
where there are two Y chromosomes.
And these have important biological
and psychological impacts.
So the first thing we need to establish
is that there is something called chromosomal sex.
Whether or not they're two X chromosomes
or an X and Y chromosome is what we call chromosomal sex.
But the next stage of separating out the sexes
is what we call gonadal sex.
Typically, not always, but typically,
if somebody has testes for their gonads,
we think of them as male.
And if somebody has ovaries, we think of them as female.
Although that's not always the case either.
But let's just explore the transition
from chromosomal sex to gonadal sex,
because it's a fascinating one
that we all went through in some form or another.
So this XY that we typically think of
as promoting masculinization of the fetus,
we say that because on the Y chromosome, there are genes,
and those genes have particular functions
that suppress female reproductive organs.
So on the Y chromosome, there's a gene
which encodes for something called
mullerian inhibiting hormone.
So there's actually a hormone
that's programmed by the Y chromosome
that inhibits the formation of mullerian ducts,
which are an important part
of the female reproductive apparatus.
That's critical because already we're seeing the transition
between chromosome, Y chromosome and gonad.
And other genes on the Y chromosome
promote the formation of testes.
So there are genes like the SRY gene
and other genes that promote the formation of testes
while they also inhibit the formation of the malaria ducts.
So the transition from chromosomal sex to gonadal sex
is a very important distinction.
It's kind of a fork in the road
that happens very early in development
while fetuses are still in the embryo.
Now, what's interesting as well
is that just because there's a Y chromosome
that can suppress malaria duct formation and there just because there's a Y chromosome that can suppress
mullerian duct formation,
and there are other genes on the Y chromosome
that promote testy development,
the placenta itself is an endocrine organ.
I think most people don't know this,
but the placenta is an endocrine organ.
As well, the mother, which of course is carrying the fetus,
has an adrenal gland, which can produce testosterone.
There are instances, for example,
where a mother has either a tumor
or for some other reason is secreting large levels
of testosterone while carrying a fetus that is XX.
And that leads to what we would call masculinization
of certain aspects of the fetus.
Typically, that would be enlarged clitoris.
There are also some examples of other phenotypes on the body
that are created,
even though it's a purely XX chromosomal baby.
So we have to distinguish between chromosomal sex,
gonadal sex, and then there's what we call hormonal sex,
which is the effects of the steroid hormones,
estrogen and testosterone and their derivatives,
on what we call morphological sex,
or the shape of the baby and the human and the genitalia
and the jaw and all these other things.
And so it actually is quite complicated.
So, you know, it's a long distance from chromosomes
to gender identity, and gender identity has a lot
of social influences and roles.
This is an area that right now is very dynamic
and in the discussion out there, as you know,
but just getting from chromosomal sex
to what we would call gonadal sex and hormonal sex
and morphological sex involves a number of steps.
So today we're going to talk about those steps.
And there's some fascinating things
that do indeed relate to tools, do indeed relate to
some important behavioral choices, important choices about things to avoid while pregnant.
And for those of you that are not pregnant, things to avoid if you're thinking about eventually
having children, and that is not to drive development in one direction or another,
but there are examples where there are some deleterious things in our environment that can actually negatively
impact what we call sexual development overall,
regardless of chromosomal background.
So let's get started with that.
Let's talk a little bit more about what hormones do.
Hormones generally have two categories of effects.
They can either be very fast or they can be very slow.
There are hormones like cortisol and adrenaline,
which act very fast.
Adrenaline can increase your heart rate very fast
when it's secreted into the body.
Cortisol can be a little bit slower,
but it also can have some very fast effects.
And then there are hormones like testosterone and estrogen,
which we refer to as the sex steroid hormones.
The sex steroid hormones can have quick effects
through signaling, meaning they can attach to cells
and make those cells do different things.
They can have actually quite quick effects on the brain.
A lot of people don't know this,
but there are some very fast effects
of estrogen and testosterone, as well as long-term effects.
These molecules, for those of you that are interested,
are what are called lipophilic,
which just means that they like fatty stuff.
They can actually pass through fatty membranes.
And because the outside of cells,
as well as what's called the nuclear envelope,
where all the DNA contents and stuff are stuffed inside,
are made of lipid, of fat,
these steroid hormones can actually travel into cells
and then get into the,
basically interact with the DNA of cells
in order to control gene expression.
So they can change the sorts of things
that cells will become,
and they can change the way that cells function
in a long-term way.
And that's actually how the presence of these genes
like SRY and mullerian inhibiting hormone
lead to reductions or elimination, I should say, of things like the mullerian ducts hormone lead to reductions or elimination, I should say,
of things like the mullerian ducts
and promote instead what's called in males,
the Wolffian ducts,
or promote the development of testes rather than ovaries.
So all you need to know is that hormones have short-term
and long-term effects,
and the long-term effects are actually related
to their effects on genes
and how those genes are expressed or repressed,
not in order to prevent them
from having particular proteins made.
So these hormones, these steroid hormones
are exceedingly powerful.
And if we're going to have a discussion
about masculinization or feminization, et cetera,
you also need to think about the counterpart.
It's not just about masculinizing the body
or feminizing the body and brain,
it's also about demasculinizing the brain in many cases
as a normal biological function of typically of XX females
and defeminization, the suppression of certain pathways
that are related to feminization of the body and brain.
But there are some really fascinating twists in this story.
So I've just thrown a lot of biology at you,
but this is where it all starts to get incredibly surprising.
You would think that it's straightforward, right?
You have a Y chromosome,
you suppress the female reproductive pathway,
like the Mullerian ducts,
you promote the development of testes
and then testes make testosterone,
and then it organizes the brain male
and it wants to do male-like things.
And then in females, you get estrogen
and it wants to do a female-like things
and air quotes here for all of this.
And it turns out that isn't how it works at all.
Here's where it's interesting.
We have to understand that there are effects
of these hormones, testosterone and estrogen,
on what are called primary sexual characteristics,
which are the ones that you're born with,
secondary sexual characteristics,
which are the ones that show up in puberty,
and these are happening in the brain
and body and spinal cord.
And so I'm going to disentangle all this for you
by giving you some examples.
First, let's talk about the development
of primary sexual characteristics,
the ones that show up at birth.
And one of the more dramatic examples of this
comes from the role of testosterone
in creating the external genitalia.
Now you might think it's just straightforward.
If there's a testes, because there's a Y chromosome,
you know, you've got a gene that codes
for the development of testes,
you get testosterone and the penis grows
and the baby is born with a penis.
You know, one of the first things that happens
when the baby comes out is they look at the genitalia
and they try and make an assessment
on whether or not it's a quote boy or it's a quote girl.
That's been done for a very, very long time
throughout human history.
It turns out that it's not testosterone
that's responsible for the development of the penis
in a baby that has an X chromosome and a Y chromosome.
It's a different androgen. in a baby that has an X chromosome and a Y chromosome.
It's a different androgen. Androgen is just a category of hormones
that includes testosterone,
but testosterone is converted in the fetus
to something called dihydrotestosterone.
And that's accomplished through an enzyme
called 5-alpha reductase.
Now dihydrotestosterone has important effects
later in life too.
We will talk about those.
In fact, if you just want to know,
dihydrotestosterone is what we would call
the dominant androgen in males.
It's responsible for aggression.
It's responsible for a lot of muscular strength.
It's involved in beard growth and male pattern baldness.
We're going to talk about all of that,
but dihydrotestosterone has powerful effects
in determining the genitalia
while the baby is still in the embryo.
So this ends, there's testosterone that's made
and that testosterone gets converted
by this enzyme 5-alpha reductase
in a little structure called the tubercle.
That tubercle will eventually become the penis.
So you say, okay, straightforward,
this testosterone is converted to dihydrotestosterone,
and then if there's dihydrotestosterone,
it controls penis growth.
And indeed that's the case.
So that's a primary sexual characteristic.
That baby will then grow up,
and later during puberty, there will be the release
of a molecule. I talked about this last episode called Kispeptin, K-I-S-S-P-E-P-T-I-N, Kispeptin,
which will cause the release of some other hormones, conantrobin releasing hormone,
luteinizing hormone will stimulate the testes to make testosterone. So in puberty, testosterone
leads to further growth and development of the penis, as well as the accumulation of, or growth of pubic hair,
deepening of the voice,
all the secondary sexual characteristics, okay?
So dihydrotestosterone creates what we would call
the typical masculine phenotype
for primary sexual characteristics
and produces,
testosterone, excuse me,
produces secondary sexual characteristics during puberty.
There's a very interesting phenomenon
that was published in the journal Science in the 1970s,
for which now there's a wealth of scientific data.
And this relates to a genetic mutation
where 5-alpha reductase,
the enzyme that converts testosterone And this relates to a genetic mutation where 5-alpha reductase,
the enzyme that converts testosterone
to dihydrotestosterone, doesn't exist.
It's mutated in a way in a genome that it doesn't exist.
And this actually was first identified
in the Dominican Republic.
It has shown up elsewhere.
It's quite rare, but where it shows up, it's robust.
What happens is baby is born.
Typically when a baby is born, they don't measure chromosomes.
They don't look at chromosomal sex, XX or XY.
That's not typically done nowadays.
Baby is born.
If you were to look at that baby, it would look female.
There would be very little or no external penis.
And so people would say, it's a girl.
And they might have the celebration, it's a girl.
And I guess now they call them gender reveal parties
or something like that.
I don't know about this, but anyway,
they would reveal that the baby would reveal
its external genitalia simply by being there
and being naked when it's born.
Has nothing to do with gender.
It has to do with genitalia and sex.
That baby would be born.
And what was observed is that from time to time,
that baby after being raised as a girl,
perfectly happy as a girl,
would around the age of 11 or 12 or 13,
would suddenly start to sprout a penis.
There's actually a name for this.
It's called huevidosis,
which the translation is more or less penis at 12.
And as strange as this might sound,
it makes sense if you understand the underlying mutation.
What happens in these children, these huevidosis,
is that the child is born,
it has testes which are not descended, so up in the body.
They're not making a lot of testosterone early on.
They weren't able to convert testosterone
to dihydrotestosterone because they lack this enzyme,
5-alpha reductase.
As a consequence, the primary sexual characteristic
of external male genitalia, penis, doesn't develop.
And then what happens is the baby grows up
as a young child, essentially is treated as a girl.
Generally, they report being pretty comfortable as girls,
although not always.
And then testosterone starts getting secreted
from the testes because cispeptin in the brain
signals through gonadotropin and luteinizing hormone
travels down to the testes.
The testes start churning out testosterone
and there's a secondary growth of the penis.
And all of a sudden there's a penis.
And this leads to some very complicated situations
in families and culturally.
And actually the outcomes in terms of whether or not
these children decide to self-identify as males or females
and how people treat them actually varies quite a lot.
There's actually been a kind of an adopting
of a third category of sex and gender in the suavidosis
for in order to just offer them the opportunity
to explore not just what would be a typical kind of girl or woman or boy or man phenotype,
but something in between,
something that some people call intersex,
although intersex and pseudohermaphroditism
is actually a separate thing altogether.
So it's fascinating.
And the point here is that dihydrotestosterone,
not testosterone, is responsible for this primary growth
of the penis and not testosterone, is responsible for this primary growth of the penis
and that testosterone later is involved
in the secondary sexual characteristics,
deepening in the voice, et cetera.
Now, this is where the information gets even more interesting
and applies to essentially everybody.
You might think that testosterone,
because it masculinizes the body
in the secondary sexual characteristic way,
and because dihydrotestosterone, another androgen,
masculinizes the primary sexual characteristics,
the growth of the penis early on,
that testosterone must masculinize the brain.
And there are in fact aspects of masculinization
of the brain and body that are independent of genitalia.
Now it might be obvious to some of you,
but some people probably don't realize that.
Yes, indeed, the brain has receptors for testosterone.
It also has receptors for estrogen.
But the fascinating thing is that It also has receptors for estrogen.
But the fascinating thing is that if you look at the brains of people that have Y chromosomes and that have testes
and that make testosterone,
and you look at the brains of people
that don't have Y chromosomes or testes
and therefore make far less testosterone in general,
what you realize is that the cells in the brain
that differ between what I'll call males and females,
but between XY and XX,
have receptors for testosterone,
but the masculinization of the brain
is not accomplished by testosterone.
I want to repeat this. The masculinization of the brain is not accomplished by testosterone. I want to repeat this.
The masculinization of the brain
is not accomplished by testosterone.
It is accomplished by estrogen.
Testosterone can be converted into estrogen
by an enzyme called aromatase.
This is vitally important to understand.
Testosterone can be converted into estrogen
by something called aromatase.
I'll give an example of where this happens later in life to just illustrate the principle
and really embed it in your mind.
During puberty in boys, XY, chromosome individuals,
it's not uncommon for there to be transient
or sometimes long-lasting breast bud development.
Testosterone goes up during puberty,
the reasons we talked about before,
and some of that testosterone gets converted into estrogen
by an enzyme called aromatase.
Aromatase is made by several sources in the body.
One of the main sources is body fat,
so it can make a lot of aromatase.
Sometimes you'll even see a fairly dramatic
breast development in males during puberty.
Sometimes it's transient, sometimes it's not.
The other place where you see this is in athletes
and bodybuilders that take a lot of anabolic steroids
that take high levels of androgens.
So they'll be taking testosterone
at super physiological doses.
Sometimes, not always, they will convert some of that testosterone into estrogen
and they'll get what's called gynecomastia,
which is the development of male breast tissue.
Sometimes they'll get it cut out surgically.
Other times they'll start trying to take estrogen blockers
in order to try and suppress it,
or they'll try and block prolactin.
It's a topic that we're going to get into in more detail,
but what's important here is to understand that testosterone can be converted into the estrogen by aromatase.
Aromatase is not just made in body fat. There are neurons in the brain that make aromatase
and convert testosterone into estrogen. And it is testosterone converted into estrogen.
In other words, it's estrogen that masculinizes the XY individual, that masculinizes the brain.
And this has profound effects on all sorts of things,
on behavior, on outlook in the world, et cetera.
But I think most people don't realize
that it's estrogen that comes from testosterone
that masculinizes the male brain, the XY brain,
not testosterone nor dihydrotestosterone.
So I just want to mention some tools.
You might be asking yourself,
how could tools possibly come up
at this stage of the conversation
where we're talking about sexual development
and we're talking about the differentiation
of tissues in the body?
Well, this is true both for children
and parents and adults.
I want to emphasize that there are things
that are environmental,
and there are things that people use
that in their homes sometimes
that actually can impact hormone levels
and can impact sexual development in fairly profound ways.
And I want to be very clear,
this is not me pulling from some rare journal
I've never heard of it.
This is pulling from textbooks in particular.
Today, I'm guiding a lot of the conversation
on work that on behavioral endocrinology.
This is a book by Randy Nelson and Lance Crickfield,
true experts in the field.
I'm going to talk about some of the work from Tyrone Hayes
from UC Berkeley about environmental toxins
and their impacts on some of these things
like testosterone and estrogen.
I'm going to touch into them.
I'm going to give some anecdotal evidence
that's grounded in studies,
which we will provide in the caption
that I'll reference here.
One of those that's actually really interesting,
but helps illustrate the principle
that we've been talking about is a few years ago,
there was a lot of excitement about evening primrose oil.
Evening primrose oil is in a lot of products
that typically are associated with skin beauty
and skin health.
And so I'm generalizing here,
but typically it was mothers or sisters that were using it.
And there were actually examples starting to crop up
of young boys getting accelerated breast bud development
from skin contact with women
who were using evening primrose oil.
So evening primrose oil is chemically a lot like estrogen
and it has a lot of estrogenic compounds.
There are a number of things out there like this.
So believe it or not, things like pine pollen
look very much like testosterone.
Structurally, they more or less are testosterone.
Their bioavailability in humans isn't as clear.
Evening primrose oil has a lot of estrogenic elements to it,
just structurally how it's built.
And so there were cases where boys were understandably,
you know, being hugged by their mom
or maybe even like showering and taking a, you know,
using the evening primrose oil solution.
Those things will actually change levels of estrogens
in boys and girls.
And so this wasn't just an issue for young boys.
This was also an issue for young girls.
So it's not that evening primrose oil is bad. It's just that many of you have probably heard about the dangers of soys and isoflavones
and things like that. The impact of soy on estrogen levels is there are some decent evidence
to support that. However, there's a lot of other factors that are more severe. And one of those
is this evening primrose oil. So regardless of age, let's just put it this way,
because people might be wanting to drive their hormones
more estrogenic or more androgenic.
How could I know what your preference is?
I don't know.
But in any case, things like evening primrose oil
can actually promote estrogenic pathways in the body,
and some of it can go transdermal.
Likewise, because testosterone replacement therapy
is fairly widespread nowadays,
and some people accomplish that through cream,
it's pretty well understood that if someone's taking that,
that they want to avoid contact with anyone,
skin contact with anyone that is trying to promote
more estrogenic activity in their body and especially in children.
So that's one.
The other is this issue of environmental factors.
Now this, again, I'm just going to highlight
when one starts talking about environmental factors
and how they're poisoning us or disrupting growth
or fertility rates, it can start to sound a little bit crazy
except when you start to actually look
at some of the real data,
data from quality research labs funded by federal government
funded not from companies or other sources
that are really aimed at understanding
what the underlying biology is.
And for that, we should all be grateful
to Tyrone Hayes at UC Berkeley.
I remember way back when I was a graduate student
in the late 90s, goodnesses at UC Berkeley. I remember way back when I was a graduate student
in the late 90s, goodness, at UC Berkeley.
And I remember him, he was studying frogs.
He was talking about developmental defects
in these frogs that live in different waters around,
it was California, but also elsewhere.
And he identified a substance which is present
in a lot of waterways throughout this country
and other countries, so US and beyond,
certainly not just restricted to California,
which is atrazine, this is A-T-R-A-Z-I-N-E.
Again, this is the stuff of textbooks
and it causes severe testicular malformations.
So again, atrazine exposure is serious.
And what's interesting is if you look at the data,
what you find is that at sites in Western
and Midwestern sections of the United States,
10 to 92% of male frogs, these were frogs, mind you,
had testicular abnormalities.
And the most severe testicular malformations
were in the testes rather than in the sperm.
So it's actually the organ itself, the gonad itself.
Now, it's very well known now that atrazine
is in many herbicides.
And so, you know, whereas I would say in the 80s and 90s,
the discussion around, you know, herbicides
and their negative effects was considered
kind of like hippy dippy stuff
or the stuff you hear about it, you know, your local community markets and these kind of like hippy dippy stuff or the stuff you hear about it,
your local community markets and these kind of new agey communities.
Now there's very solid data from federally funded labs
at major universities that have been peer reviewed
and published in excellent journals
showing that indeed many of these herbicides
can have negative effects primarily by impacting
the ratios of these hormonesicides can have negative effects primarily by impacting the ratios of these hormones
in either the mothers or in the testes,
altering the testes of the fathers
or direct effects on developing young animals
and potentially humans.
And so you ask, well, what about humans?
Frogs are wonderful, but what about humans?
So here are the data on what's happening.
And this isn't all going to be scary stuff.
We're also going to talk about tools to ameliorate
and offset some of these effects.
One would be be cautious with evening primrose
as well as testosterone creams,
depending on whether or not you want to be more androgenic
or estrogenic, depending on your needs.
But across human populations,
sperm counts are indeed declining, okay?
So in 1940, the average density of human sperm
was 113 million per milliliter of semen.
That's how it's measured.
How many sperm per milliliter of semen?
In 1990, this figure has dropped to 66.
So it went from 113 million per milliliter of semen. In 1990, this figure has dropped to 66. So it went from 113 million per milliliter
to 66 million per milliliter
in the United States and Western Europe.
So it's not just a US thing.
Researchers also estimated that the volume of semen
produced by men has dropped 20% in that time,
reduced sperm count per ejaculation even further.
So between 1981 and 1991,
the ratio of normal spermatogenesis has decreased
from 56.4% to 26.9%.
So there's a lot that's happening primarily
because of these herbicides that are in widespread use
to reduce sperm counts.
And these are going to have profound effects,
not just on sperm counts,
but on development, sexual development at the level of the gonads and the brain, because you
need testosterone to get you to a dihydrotestosterone for primary sexual characteristics.
You need estrogen that's come from testosterone to masculinize the brain. And of course,
we're not just focusing on sperm and testosterone. You of course also know that many of these herbicides
are disrupting estrogens in a similar way
or are leading to hyperestrogenic states,
which might explain why puberty is happening
so much earlier in young girls these days.
So there are a lot of things that are happening.
Now, does this mean that you have to run around so much earlier in young girls these days. So there are a lot of things that are happening.
Now, does this mean that you have to run around
and neurotically avoid anything that includes things
like atrazine and should you be avoiding
all kinds of herbicides?
I don't know, that's up to you,
but it does seem that these have pretty marked effects
in both the animal studies and in the human studies.
You know, you can open up a textbook
like the endocrinology textbook
and find things like vinclosalin.
This is V-I-N-C-L-O-Z-O-L-I-N,
which is a fungicide and it's an antiandrogen.
You give it to animals, to rats,
and instead of forming a penis, they don't form a penis.
They basically, it's not that they form a clitoris, they just don't form a penis. They basically, it's not that they form a clitoris,
they just don't form a penis.
So let's talk about female sexual development.
And as always, what we'll do is we'll talk
about the normal biology, then we'll talk a little bit
about a kind of extraordinary or unusual set of cases,
but we'll talk about them because they illustrate
an important principle about how things work
under typical circumstances.
So there is a mutation called
androgen insensitivity syndrome,
and understanding how androgen insensitivity syndrome works
can help you really understand
how hormones impact sexual development.
So here's how it works.
There are individuals who are XY,
so they have a Y chromosome,
that are born that make testosterone.
They have testes and they don't have malaria ducts because on the Y chromosome
is this malaria inhibiting hormone.
However, these individuals look completely female.
And in general, they report feeling like girls
when they're young, women when they're older.
But there's something unusual that's happening
in these individuals because they have an XY chromosomal
type and not XX.
So what's happening?
Well, what's happening is the testes are making testosterone,
but the receptor for testosterone is mutated.
And therefore the testes never descend.
They don't have ovaries, they have testes,
but the testes are internal.
And so typically these individuals find out
that they are actually XY chromosomes
so that their chromosomal sex is male, if you will,
and their gonadal sex is male,
but the gonads, the testes are inside the body.
They don't actually develop a scrotum.
They don't make ovaries.
And when they don't menstruate around the time of puberty,
that's a sign that something is different.
And so they never menstruate around puberty.
And if they look into this deeply enough,
what you find is that they are actually XY,
they make testosterone,
but their body can't make use of the testosterone because they don't have the receptors.
And the receptors are vitally important
for most all of the secondary sexual characteristics
that we talked about,
body hair, penis growth
during puberty, et cetera.
They live fairly happy lives as females,
although of course they can't conceive, right?
They don't have a uterus, they don't have ovaries.
They also in general don't produce sperm in quantities
enough that they could actually reproduce
with somebody else, although sometimes they can.
And believe it or not, and I'm not going to name names,
but there are actually reports of several people,
fairly prominent people throughout history who have had this androgen insensitivity syndrome
or people suspected they did.
And the reason to not name names
is that it gets right to the heart
of whether or not they are male or female.
How could you say, right?
They have XY chromosomes, but gonadally,
they have testes that are inside.
And yet, if you looked at their bodies,
if you looked at their faces,
you would say almost with certainty
that they appeared female.
And that naturally occurring experiment points to the fact that testosterone
that shows up in the body
and impacts the things at the levels of the receptor
has a profound effect on phenotype,
on the external or body plan.
So again, we're talking about this
in order to illustrate the principle
that in order to have its effects,
a hormone doesn't just have to be present,
that hormone actually has to be able to bind its receptor
and take action on the target cells.
And once again, I'll just throw out the example
of where people are using performance enhancing drugs,
although that's a pretty broad statement.
Nowadays, there's a lot of excitement
about the so-called SARMs,
which are more on the receptor side.
And so we'll talk about this in a future episode.
And I just say that as a teaser,
because the SARMs and what's happening right now
in augmenting sports performance,
both with testosterone directly,
but also testosterone derivatives,
and then also altering things at the level of the receptor
is exceedingly interesting and is revealing to us the many ways
in which hormones can impact brain and body
in ways that we didn't suspect.
Perhaps the simplest way to understand
how estrogen and testosterone impact masculinization
or feminization of the brain and behavior
is from a statement.
It's actually the closing sentence of an abstract
that my colleague Nirao Shah
at Stanford School of Medicine published,
which is that estrogen,
again, it's estrogen that is aromatized from testosterone
by aromatase,
sets up the masculine repertoire of sexual
and in animals and in humans, territorial behaviors.
So it sets up the circuitry in the brain.
Estrogen does that.
Estrogen sets up the masculine circuitry in the brain.
And testosterone is then what controls the display
of those behaviors later in life.
And I find that incredibly interesting.
You would think it was just testosterone did one thing
and estrogen did another, but it turns out that nature is far more interesting than that. Okay.
So what are some things that impact sexual development early in life and later in life?
Let's talk about cannabis. Let's talk about alcohol. And dare I say, let's talk about cell phones.
Something that I never thought I would ever do
either in this podcast or in the classroom,
but these days there are really interesting data
and I think you should be aware of them.
First of all, cannabis, marijuana, THC.
I realize that there are now
a lot of different variants on this. There are a lot of different variants on this.
There are a lot of different strains of cannabis.
I personally am not a pot smoker.
It's just not for me.
I'm not talking about the moral or legal implications.
You know, in some states it's decriminalized,
in other places it's really illegal,
in other places it's basically legal.
You have to check, you know,
where you live and understand the laws.
That's not what this is about.
What we do know, however, is that with the exception
of one study, there are many studies that point to the fact
that THC and other things in cannabis promote
significant increases in aromatase activity.
Now pot smokers aren't going to like this,
especially male pot smokers aren't going to like this,
but it's the reality.
Remember, what you're hearing in the background
is Costello snoring really loud.
Should we put him on screen?
He's not a cannabis smoker, but you can imagine why.
Here, come here, Costello.
Come here, buddy, come here.
He's asleep.
Come here.
You might kill him here. Come here Costello, come here buddy, come here. He's asleep, come here.
Come here buddy, there you go.
This dog definitely does not need cannabis.
This is his state for most of the time.
He is highly parent, he's asleep still.
So some of you have asked to see Costello.
If you're just listening on audio,
maybe he'll give us some.
That's a, oh, okay.
We're going to let him get back to sleep.
He's always here.
Some of you have asked to see him.
Costello's not a pot smoker either.
He did have a dog sitter that was a pot smoker years ago.
It was his favorite dog sitter, but I'm not a pot smoker.
Again, no judgment, but here's the deal.
That cannabis, and it's not clear if it's THC itself
or other elements in the marijuana plant,
promote aromatase activity.
Now, this has been observed anecdotally
where pot smokers have a higher incidence
of developing something I mentioned before,
gynecomastia, breast bud development,
or full-blown breast development in males.
There may be some women who want to increase
their estrogenic activity.
Remember, females make testosterone,
it comes from the adrenals, right?
They don't have testes, so it comes from the adrenals,
and that testosterone can also be aromatized.
Although typically most of the aromatase activity
that we're referring to in these examples is in males.
So testosterone can increase estrogenic activity.
So you might say, oh, you know,
therefore does testosterone reduce sexual behavior?
Does it create all sorts of things
that are related to low testosterone?
Not necessarily, not necessarily.
And here's why.
Estrogen itself in males and females is important
for things like libido and sexual behavior.
I'm going to repeat that.
If estrogen is too low in males,
it can actually inhibit libido and sexual behavior.
So you don't want estrogen too high or too low,
whether or not you're male or female.
Now, of course, in females,
estrogen levels tend to be higher than in males.
I'm speaking very generally here.
You just think back to the chromosomal sex.
That's what I'm referring to when I say male or female,
although there's nuance there, of course.
In females, the testosterone that comes from the adrenals has a powerful effect on libido and desire to reproduce.
And in the next episode,
we're going to talk about how that works
in its relationship to birth control,
its relationship to menopause.
We're also going to talk about how that whole thing works
in males as well.
But cannabis and other aspects of the marijuana plant
can impact levels of testosterone and estrogen
by increasing aromatase.
And so people should be aware of that.
As well, there are good data,
I was able to find several studies on PubMed
pointing to the fact that smoking marijuana
during pregnancy can shift the pattern of hormones in the developing fetus
such that it promotes more estrogenic outcomes.
Now, earlier I said that estrogen
is what masculinizes the male brain.
In utero, that's true,
but the way that cannabis seems to work,
at least from the studies I was able to identify,
is that it promotes
circulating estrogen in the body and therefore
can counteract some of the masculinizing effects
of things like testosterone and dihydrotestosterone
on primary and secondary sexual characteristics.
So I mentioned this because, you know,
I think nowadays marijuana use is far more widespread and certainly during
puberty, it can have profound effects on these hormonal systems. And so we'll do another episode
that goes really deep into this, but yes, cannabis promotes estrogenic activity by increasing
aromatase. Most everyone can appreciate that drinking during pregnancy is not good for the developing fetus.
Fetal alcohol syndrome is a well-established negative outcome of pregnancy.
And it's something that there are cognitive effects
that are really bad.
There's actually physical malformation, et cetera.
So drinking during pregnancy, not good.
Probably drinking during puberty, not good either
because alcohol in
particular, certain things like beer, but other grain alcohols can increase estrogenic activity.
Now, this isn't just about protecting young boys from estrogenic activity. It's also protecting girls from excessive
or even hypoestrogenic effects of alcohol in puberty.
Now, many teenagers drink, college students drink,
and it's important to point out
that puberty doesn't start on one day
and end on another day.
Puberty has a beginning, a middle, and an end,
but development is really our entire lifespan.
This idea that, you know, puberty, you know, has us open and close. That's just false. Okay. So we
talked about cannabis. We talked about alcohol. Let's talk about cell phones. First of all,
I use a cell phone. I use it very often and I do not think they are evil devices. I think that they require some discipline
in order to make sure that it does not become
a negative force in one's life.
So I personally restrict the number of hours
that I'm on the phone and in particular on social media.
I only answer email at particular times of day.
But what about the cell phone itself?
You know, when I was a junior professor,
I'm sorry, pre-tenure, early professor,
I taught this class on neural circuits
and health and disease.
And one of the students asked me, you know,
are cell phones safe for the brain?
And you know, all the data point to the fact that they were,
or at least there were no data showing that it wasn't.
I still don't have the answer on that, frankly.
I don't see a lot of studies about it.
I'm not personally aware of any evidence
in quality peer-reviewed studies
showing that cell phones are bad for the brain
or that holding the phone to the ear is bad
or that Bluetooth is bad or any of that.
I'm just not aware of any quality studies.
If you are aware of quality studies, peer-reviewed studies,
please reference them, put them in the comment section,
send them to me, however you like.
I'd love to see them.
I'm not aware of them.
However, I was very interested in a particular study
that was published back in 2013 on rats.
It was basically took a cell phone
and put it under a cage of rats
and looked at basically testicular
and ovarian development in rats
and saw minor but still statistically significant defects
in ovarian and testicular development.
Since then, and now returning to the literature,
I've seen a absolute explosion of studies,
some of which are in quality journals,
some of which are in what I would call
not blue ribbon journals,
identifying defects in testicular and or ovarian development
by mere exposure to cell phone emitted waves,
let's just call that.
We don't know what they are.
And this sounds almost crazy, right?
Anytime somebody starts talking about EMFs
and things like that, you kind of worry,
like, is this person okay?
But look, the literature are pointing in a direction
where chronic exposure of the gonads to cell phones
could be creating serious issues
in terms of the health at the cellular level and in terms of the output.
So the output for the testes would be sperm production,
swimming speed in sperm is an important feature
of sperm health.
In the ovaries, it would be estrogenic output,
how regular the cycles are.
So in animals, the cycles are a little bit different
than in humans.
They don't have a menstrual cycle.
They have an estrous cycle,
which is generally around four days.
I think that it's fair to say based on the literature
that there are effects of cell phone emitted waves
on gonadal development.
The question is, what is the proximity of the cell phone
to the gonads?
Now, I've taken the literature as I observe it,
and then of course we'll point you to in the captions.
And I don't like to have my cell phone on and in my pocket.
I'm well past puberty, but nonetheless,
some of these effects were seen in adult animals.
There are effects now that have been demonstrated in humans.
So let's just talk about a couple of those effects.
So a paper published in the journal,
Clinical Biochemistry from Eskander et al.
looked at hormone profiles in people based on proximity
and free proximity to their phone and frequency of phone use
where they stored their phone on their body,
as well as proximity of where they lived to, I guess they're called these radio frequency towers,
so the base stations.
And they were looking at effects of radio frequency
radiation, RFR, on human hormone profiles.
And they show significant decreases in cortisol.
You might say, well, that might be good,
but you need that morning cortisol bump
in order to wake up.
Morning cortisol is good.
But also thyroid hormones were significantly reduced.
Prolactin in young females, that's definitely concerning.
And testosterone levels in males and females.
And so there are now quite good data showing
that being close to the phone too much of the day
and how close is an interesting question showing that being close to the phone too much of the day
and how close is an interesting question
or living near one of these base stations
apparently can have effects on hormone profiles.
And when you see a study like this, one should always ask,
well, what are the other things that could also have effects
on these hormone profiles, right?
Because you could imagine that if you ran the same study
of people that live close to a waterway
or close to a highway where there's a lot of exhaust
from buses and cars, you might see similar effects.
So you have to take these sorts of studies
with a grain of salt.
But I think it's very interesting.
And given that the last time I looked into these data
were way back when I was a junior professor
and there was like one or two studies that I could find,
one of the studies pointed to increases in testosterone
in rats where they had close proximity
to these radio frequency radiation waves.
And then in the other case,
it showed decreases in testosterone.
So there really wasn't any conclusion to take away from that.
Now there's pretty impressive amount of data
pointing to the fact that there are effects
of these things on hormones.
I don't know what to do with that information.
I'm not going to stop using my phone,
but in light of the work from Tyrone Hayes and others
looking at sperm counts and looking at the decrease
in testosterone levels and sperm counts
and fertility over the last 20, 30 years,
perhaps it's not surprising.
Although there again, cell phones and smartphones
have really been in prominent use
mostly within the last 10 or 11 years.
And so it's hard to explain all of those declines
simply on the basis of cell phone use.
There's some interesting effects of hormones that actually you can observe on the basis of cell phone use. There's some interesting effects of hormones
that actually you can observe on the outside of people
that tell you something about
not just their level of hormones,
but also about their underlying genetics.
And these relate to beard growth and baldness.
And it's fascinating.
The molecule, the hormone, dihydrotestosterone,
made from testosterone, is the hormone, dihydrotestosterone, made from testosterone,
is the hormone primarily responsible for facial hair,
for beard growth.
As well, it's the molecule,
the hormone primarily responsible for lack of hair on the head, for hair loss.
So how does that work?
Well, DHT circulates in the body
and it binds to DHT
receptors in the face to promote hair growth, but it binds to DHT receptors on the scalp to promote
hair loss. Not incidentally, the drugs that are designed to prevent hair loss
are 5-alpha reductase inhibitors.
So remember 5-alpha reductase from the huevidosis?
Well, the people that discovered the huevidosis
went on to do a lot of research
on the underlying biochemistry
of this really interesting molecule dihydrotestosterone,
the identified 5-alpha reductase,
and 5-alpha reductase inhibitors
are the basis of most of the anti-hair loss treatments
that are out there.
And so there's some interesting things here.
First of all, the side effect profiles
of those treatments for hair loss
are quite severe in many individuals.
Remember, DHT is the primary androgen for libido,
for strength and connective tissue repair,
for aggression, even if that aggression,
of course, is held in check,
but just sort of ambition and aggression
is related to dopamine,
but within the testosterone pathway,
less so pure testosterone,
although pure testosterone has its effects,
but DHT is, at least in primate species, including humans,
is the dominant androgen for most of those sorts of effects.
And if you look at somebody,
everyone can predict whether or not
they're going to go bald based on looking at their,
we're always taught our mother's father.
So if your mother's father was bald,
there's a higher probability that you're going to go bald.
The pattern of DHT receptors on the scalp
will dictate whether or not you're going to go bald
everywhere or just in the front or so crown type baldness.
And the density of the beard tells you
about the density of DHT receptors.
Now this varies by background, by genetic background.
And actually around the world nowadays,
because people travel and people form couples
and have kids with so many different people
of different mixed cultures,
you're seeing this starting to disappear,
but there are areas of the world
where all the men seem to be,
have the same pattern of baldness,
like a strip of baldness down the center
with hair still on the sides and full beards.
That's because these patterns of DHT receptors
are genetically determined.
Elsewhere, testosterone levels can still be very high,
DHT levels in the blood can be very high,
and yet people will have very light beards or no beards,
and that's because they don't have
a lot of DHT receptors in the face.
And still other cultures,
you'll see people with huge beards, tons of beard,
like their beards are growing all the way up to their eyes
and they have huge heads of hair.
And that's because they have a lot of DHT receptors
on the face and not on the scalp.
So there are a lot of effects of DHT
that you can just see in male phenotypes.
And it's interesting that these hair loss drugs
that are, or to prevent hair loss drugs are directly aimed
at preventing the conversion of testosterone
into dihydrotestosterone.
And that's why they, to some extent prevent hair loss,
but also to some extent have a bunch of side effects
that are associated with low DHT.
Along these lines, there's a particular sports supplement
that a lot of people use called creatine.
Creatine now, there's a lot of research showing
that creatine can bring more water into the muscle.
It can support strength.
It does a number of other things.
Might even have some important cognitive enhancement effects
although mild.
The studies there show that it can be significant.
Some people, not all, it's more anecdotal,
report that creatine promotes hair loss.
It differs by individual.
For some people, that's true.
For others, no.
But yes, it does appear,
based on the studies I was able to find on PubMed,
that creatine does promote 5-alpha reductase activity,
and therefore the conversion of testosterone
into dihydrotestosterone.
And so it makes sense that it might promote
some degree of hair loss, as well as beard growth,
as well as the other effects of DHT.
I recall in junior high school and middle school,
going home one summer, it was seventh grade,
coming back in the eighth grade,
and a kid that I knew that I was friends with
went from being like a young kid to,
he was like a grown man, he had a full beard.
It was amazing.
It was like he would completely transform.
I mean, puberty, as I've said before,
is without a doubt the most accelerated rate of development
that we will go through at any point in our lives,
even faster than infancy,
just in terms of the huge number of different
cognitive changes and physical changes.
Not surprisingly, that same individual
was mostly or bald by his early 20s.
And that's because he must've had
just exceedingly high levels of DHT.
I also played soccer with this kid
and he was basically like dribbling past everybody.
It was like a grown man playing soccer
with a bunch of little kids.
Full beard, bald at 20.
And so the rate of maturation,
the rate of aging is very interesting.
It's hard to know rate of aging.
There's some genetic tests that now can allow you to do that.
Things like Horvath clocks and things of that sort.
Beautiful work of David Sinclair at Harvard and others
has pointed to this.
The speed of entry and exit from puberty might be,
I'm putting it out there as a hypothesis,
might be an interesting window
into how fast one is going through their aging
or developmental arc,
because development, of course,
doesn't just start at birth and end after puberty,
it continues your entire life.
So I think it's interesting.
You will often see that people, boys and girls,
I should say boys or girls,
will develop secondary sexual characteristics
at different rates.
And sometimes it's sequential.
You know, you might see a kid will,
she'll grow very tall or she'll have a big growth spurt,
but then breast development will come a little bit later.
And then other features will come a little bit later. And then other features will come a little bit later.
You can also see this in boys.
The person that I referred to earlier,
my friend that developed full beard, you know, went bald.
He was also quite muscular, he's a great athlete.
So he went through puberty exceedingly fast.
Other people go through it more slowly.
Some people will go through puberty at age 14,
but they won't start to accumulate facial hair
until much, much later.
Or their voice will change first very early,
and then they won't get the other
secondary sexual characteristics until much later.
And so we don't really know how that impacts
or relates to overall trajectory or rate of aging,
but it's an interesting thing to think about
for each and every one of us.
I'm going to offer you the opportunity to do an experiment today while listening to the podcast.
But first I want to tell you a story
about hyenas, professional baseball,
and clitorises the size of penises.
So when I was a graduate student at UC Berkeley,
we had a professor in our department,
phenomenal scientist named Steve Glickman.
Steve Glickman had a colony of hyenas,
spotted hyenas that lived within caged enclosures,
of course, in Tilden Park behind the UC Berkeley campus.
The enclosures are actually still there.
I run past there fairly often.
The hyenas are no longer there.
This was a federally funded field station.
These animals were brought over from Africa
or were bred there.
And the reason why there were hyenas in Tilden Park,
enclosed in Tilden Park,
was because hyenas exhibit an incredible feature
to their body, their hormones, and their social structure.
Hyenas, unlike many species,
have a situation with their genitalia
where the male penis is actually smaller
than the female clitoris.
And I should say that the male penis itself,
having seen a fair number of hyena penises,
is not particularly small,
which means that the hyena clitorises are extremely large.
This was well-known for some time.
It turns out that in the spotted hyenas,
the females are dominant.
So after a kill, the females will eat,
then their young will eat,
and then the male hyenas will eat.
As well, when the female hyena gives birth,
she gives birth not through the vaginal canal
that we're accustomed to seeing,
but through a very enlarged clitoris-like phallus,
although it's not a phallus, it's a clitoris,
and it literally splits open.
So many fetuses die during the course
of hyena development and birth.
These animals have this,
what could only be described as a very large
or giant clitoris, although for a hyena,
it's not giant, it's normal.
And it splits open and the baby actually comes through,
the baby hyena actually comes through the tissue
and it's a very traumatic birth.
A lot of tissue is torn away, et cetera.
And as I mentioned, a lot of baby
hyenas die. It was a mystery as to how the female hyenas have this, we'll call it masculinization,
but it's really a androgenization of the periphery of the genitalia. And it turns out
through a lot of careful research
done by Steve Glickman, Christine Dre and others,
that it's androstenedione,
what is essentially a pro-hormone to testosterone,
it's androstenedione at very high levels
that's produced in female hyenas
that creates this enlargement of their genitalia.
So if you want to read up on androstenedione,
androstenedione is made into testosterone
through this enzyme 17-beta hydroxysteroid dehydrogenase.
It's a complicated pathway to pronounce.
It's a fairly straightforward pathway biochemically.
You may recall during the 90s and 2000s,
there were a lot of performance enhancing drug scandals
in particular in major league baseball.
And it was purported,
although I don't know that it was ever verified,
but it was purported that the major performance enhancing
drug of abuse at that time in particular players whose names
we won't mention, but you can Google it
if you want to find out, was androstenedione.
And I actually recall long ago when you could buy
androstenedione in the health food stores.
And so it was sold over the counter.
So a lot's changed since then,
but it's interesting that these hyenas
with these highly androgenized genitalia
accomplish that through high levels
of androstenedione in the females.
Now, if that's unusual,
what might be even more unusual
is that a graduate student that I was working with
at the time, alongside, we didn't share research,
her name was Nicola Sipka.
She is actually a trained animal behavioral expert.
She had trained ferrets for that show, The Beastmaster,
and she trained wolves for television shows
and was a dog trainer.
She had these two large dogs that,
unlike my dog, would actually listen to her
when she would give them commands.
A remarkable scientist.
She was studying a species of mole
that also lived in Tilden Park.
People are gonna start to wonder about Tilden Park,
what's in Tilden Park?
But this particular mole that lived there
had testes for part of the year
and had the capacity to trans-differentiate its testes
into ovaries in order to balance out the ratio of males and females
in the population to keep reproduction
at appropriate levels for that certain population.
So some animals are actually able to adjust
whether or not they have androgenized or estrogenized gonads
in order to adjust the ratios of offspring
or the males and females and therefore promote offspring.
And the last little anecdote about this,
which is also published in the scientific literature,
which is weird, but I do find interesting.
Hormones are so fascinating.
They're just incredible to me,
is going back to the marijuana plant.
You know, the marijuana plant has these estrogenic properties.
And I asked a plant biologist
whether or not this was unusual.
And I asked because there's all this stuff out there
about, oh, soy does this,
and these plants are highly estrogenic, et cetera,
although we should probably point out
that a lot of factory meats are also estrogenic. So this isn't a meat versus plants thing. But this plant biologist told me, et cetera, although we should probably point out that a lot of factory meats are also estrogenic,
so this isn't a meat versus plants thing.
But this plant biologist told me, oh yeah,
there are plants that make what is essentially
the equivalent of testosterone, like pine pollen,
as it looks a lot like testosterone,
and there are other plants that make
what is essentially estrogen.
And I said, well, why would they do that?
And plants, at least as far as I know,
don't have a consciousness.
They don't have a brain.
They don't have neurons even.
But his answer was fascinating.
He said that one of the reasons
why some plants have evolved this capacity
to increase estrogen levels in animals that smoke,
not smoke it, but then animals that consume them.
I'm guessing that animals aren't smoking marijuana,
although, I don't know,
send me the paper if you've heard of this,
is that plants have figured out ways,
they've adapted ways to push back on populations of rodents
and other species of animals that eat them.
So plants are engaged in a kind of plant to animal warfare
where they increase the estrogen of the males
in that population to lower the sperm counts
to keep those populations clamped at certain levels
so that those plants can continue to flourish
even if those animals are reproducing very robustly.
And I find this just fascinating.
And hormones, therefore,
aren't just impacting tissue growth and development within the individual and between the mother.
Remember, the placenta is an endocrine organ
and the offspring,
but plants and animals are in this communication.
And today we're in this communication.
I'm telling you that there are certain herbicides
that humans are using for which there's very good data
are disrupting the endocrine pathways.
And so it's fascinating that humans and other animals
were always in this interplay with plants
and the other things in our environment.
And hormones and adjusting the hormone levels
of animals and plants is one way
in which the environment kind of pushes back
or pushes forward,
if you will, in terms of promoting their wellbeing
and longevity, as well as you trying to promote
your wellbeing and longevity.
If anyone wants to see the incredible paper
by Steve Glickman and colleagues,
it was published in the Proceedings of the National Academy
first in 1987, that's Glickman at all.
That was the hypothesis that it was androstenedione. And then if you just Google Glickman et al, that was the hypothesis that it was androstenedione.
And then if you just Google Glickman hyenas science magazine,
there's a beautiful cover article
and feature all about that important discovery.
It's a fascinating one.
And I should mention also that those discoveries,
both the moles and the hyenas,
weren't just impactful for the world of animal behavior and endocrinology.
They've also strongly impacted understanding
of conditions that show up in the clinic,
which we haven't talked about today,
which is actually pseudo hermaphroditism.
Occasionally babies will be born where it is unclear
if they are boys or girls based on the genitalia.
And this has a very important ethical and other issues.
Do you raise them as a boy or a girl?
It's not super uncommon for this to happen.
And there've been terrible cases
where people have gone against the chromosomal sex
and the person was very unhappy
with the choice that their parents had made for them.
There were also cases where they've gone with the chromosomal sex and the person was very unhappy with the choice that their parents had made for them. There were also cases where they've gone
with a chromosomal sex
and the person was very happy about the outcome.
There've been cases where they've been treated with hormones
and there've been cases
where they have not been treated with hormones.
It's a complicated literature
and it has to be sorted out on kind of a case-by-case basis,
but it is something that does happen.
And the studies on enderstein-dione in hyenas
and in these very interesting moles,
pseudo-homophroditic moles that live in Tilden Park,
have impacted not just the science,
but the therapeutics around those important issues.
So now, last but not least,
I want to discuss the effects of hormones
while you and I were separately in utero
and the effects that that had on who we are,
who we select as mates,
so mate choice, sexual preference,
and all other aspects of what you would call
sexual development.
Now, this is something that's gotten a lot of popular press all other aspects of what you would call sexual development.
Now, this is something that's gotten a lot of popular press and it has to do with how exposure to androgens
in particular, while we were in utero,
impacted whether or not people report as homosexual,
heterosexual, identify as male or female.
I'm very familiar with this work
because I was a graduate student in the department
that first published this work,
and I'm an author on the paper.
I was not the main driver of the work,
but I was involved in the work,
and I certainly know the people that did this work.
First, it starts with a story.
There was a researcher who's still going now.
His name is Dennis McFadden.
I believe he was at UT Austin back then.
And he was studying the auditory system.
And people would come into his clinic
and he would, or his laboratory,
and he would look at hearing
and he would explore different aspects
of what they call the psychophysics of hearing
and understanding hearing thresholds
and frequency thresholds.
And he made several observations.
And those observations were that young males
tended to have what are called autoacoustic emissions
more often than young females did.
Autoacoustic emissions, as the name suggests,
are the ears actually making sounds.
Now these sounds have to be picked up by a special apparatus
because they can hear into that frequency,
but it turns out that your ears don't just take sound waves
and convert them into these things that we,
this thing we call hearing,
but they also in some cases make sounds.
So your ears are making sounds.
Strange, right?
So it turns out that there's a sex difference
in autoacoustic emissions.
Turns out also that people that self-report as lesbians,
they also have autoacoustic emissions
significantly more than females
that don't self-report as lesbian.
And Dennis noticed this and published this.
And it was an important discovery because it was one of the first discoveries
that pointed to the fact that there are sex differences
in biology that are independent of sex.
I mean, this is hearing and autoacoustic emissions.
And just to really illustrate what the former problem was
and why this study was so important.
You know, a lot of people had explored, for instance,
whether or not homosexuals had lower testosterone,
for instance, in males.
And actually the result often was the opposite,
that gay men or men that self-report as gay
often had much higher testosterone.
And those studies then became controversial
because people said, well, you know,
sexual behavior can relate to testosterone, et cetera.
And so it became very controversial.
And then there were some studies that attempted
to look at the equivalent phenomenon
in people that self-report as lesbian
or self-report as heterosexual.
And so it became very complicated,
but this was an identification of a phenomenon,
autoacoustic emissions,
that was independent of anything that had to do
with sexual or even social behavior.
1998 rolls around,
and I'm a graduate student at UC Berkeley,
and a guy by the name of Mark Breedlove,
kind of an ironic name,
given that he worked and still works on sexual dimorphism in the brain
and in the spinal cord and nervous system.
And Mark, who's a phenomenal scientist,
comes running down the hall, I'll never forget this,
and he said, give me your hands.
I was like, he's like, give me your hands.
And he pulls out a ruler and he starts measuring my fingers
and he takes down a couple of measurements
and then he goes away.
And I'm like, what was that?
Well, I was in a course that Mark was teaching
at that point.
And soon after we did a study that Mark directed
exploring the finger length ratios,
and I'll explain what those are,
of males and females and people that self-reported
as homosexual or heterosexual.
So let's just get to the basic,
what we'll call sex differences first.
These are averages.
I want to point out, anytime you get into this kind of topic
people assume it's causal, but it's not causal.
These are averages that I'm about to report.
It is the case that the ratio of what's called the D2 to D4 digits.
So the D2 is your index finger.
So your thumb is D1,
then D2 would be your index finger
that you would point with.
Middle finger is D3, which you whatever with.
And then D4 is the so-called ring finger, okay?
And D5 is the pinky.
It is the case that the D2 to D4 ratio
is greater in self-reported females than it is in males.
What does that mean?
It means that digit D2 and D4 are more similar in length
in females than in males.
And the effect is particularly, excuse me,
pronounced on the right hand,, excuse me, pronounced on the
right hand, although not always. Okay. And it does not have to do with handedness. This D2 to D4
difference has to be measured correctly. You can't just look at somebody's hands and say, oh,
you know, their ring finger and index finger are very similar. And therefore they are female in,
you know,
or they were exposed to very little testosterone in utero.
You can't look at somebody and see that their index finger
is much shorter than their ring finger and say,
oh, you know, they must've been exposed
to a lot of androgen.
You have to actually measure it
and you have to measure it correctly.
You have to measure it from the base of the finger
where there's that first crease all the way to the tip past the,
you can include the fingernails.
If you're growing fingernails, it'd be logical here, folks.
So you can't normally see it from the back of the hand.
Although I don't know if this will show up here,
but if you look at the back of the hand,
sometimes you can see it, you know, my case, for instance,
let me see if I can do this.
So my D4 is a little bit longer than my D2.
In some people it's more pronounced
and that's on my right hand.
On the other hand,
the difference actually is far less pronounced.
It's a little bit pronounced there, but not so much.
So that's sort of the typical ratio that you would see.
Turns out that in mice and in humans,
the more androgen that you are exposed to in utero,
the smaller the D4, D2 ratio,
meaning that the ring finger tends to be slightly longer
than the pointer finger.
And in females, because they're exposed to less androgen
in utero typically,
then those fingers tend to be more equal in length.
And these are subtle differences and these are averages.
I invite you to look up the paper.
This was published in Nature in 2000
and it's been replicated six times.
Now here's where it gets even more interesting
and potentially precarious.
So we're going to step cautiously here.
If you look at the finger length ratios
of men that self-report as homosexual,
they have either the typical male pattern
of D2 to D4 ratio,
or a hyper-masculinized D4 to D2 ratio.
Now this can't be something that's established
or modified by behavior.
This has to be something that was established in utero.
And in fact, it's present at birth.
Okay, so it completely divorces the interactions
between hormones and behavior.
And that's an important theme that we've been talking about
and we're going to talk about even more next episode
is that hormones impact behavior,
but behavior also impact hormones.
But this is a case of hormones impacting
what really should be considered
a primary sexual characteristic
because it doesn't show up in puberty,
it shows up before puberty,
it's actually established in utero.
And in people that self-reported lesbians,
and I remember going out there and collecting these data
with the collaborators on this work.
Again, I wasn't the main driver on the work,
but I participated in some of the analysis.
People that self-report as lesbians
also tend to have a smaller D2 to D4 ratio.
So this is consistent with the autoacoustic emission study
that Dennis McFadden had published.
And it points to the fact that early exposure to androgens
may have an impact,
not just on androgenization of the body plan,
but also separately on sexual preference.
Now this raises all sorts of interesting questions
about biological basis of sexual preference.
I'll tell you about another study,
a guy named Simon LaVey, who was at UCLA,
who trained under Hubel and Wiesel.
If any of you remember early episodes on plasticity,
David Hubel and Torrance and Wiesel,
my scientific great-grandparents,
won the Nobel Prize for discovery of critical periods
for brain plasticity.
They defined some of the most important aspects
of how we see and brain plasticity.
Simon LeVay trained with them.
And then Simon went on to discover that in the brains
of people that self-report homosexual,
there is a brain difference.
And the brain difference is in an area called
the interstitial nucleus of the anterior hypothalamus.
So it's the INAH.
And so there are published reports
that was published in science.
The other work I refer to as published in nature
and then replicated no fewer than six times
and the McFadden results that point
to strong biological correlates of mate choice,
of sexual preference.
And these tie directly to things like androgenization or estrogenization, meaning we
could call it maleness or femaleness, but that's sort of tricky territory because of the way that
we described the huge range in which sex can be defined earlier. So if you want to measure D2,
D4 ratio, you're welcome to, but you also have to understand that it's not predictive of anything, right?
It's just a window into the possible androgen exposure
that you had early in life.
There are plenty of men who report themselves
as heterosexual who are out there who have similar,
or have D two, D four ratios to females.
And there are plenty of females whose index fingers
are shorter than their ring fingers
and they're perfectly happy, ring fingers and they're perfectly happy
or they say they're perfectly happy
and we are inclined to believe them being heterosexual.
So there's variation.
In fact, Mark tells a really good joke.
If you want to know whether or not somebody is homosexual
or heterosexual, simply look at their hands,
look at their D2, D4 ratio and guess heterosexual
and you'll be right 96% of the time. Because 96% of the time, look at their D2, D4 ratio and guess heterosexual.
And you'll be right 96% of the time,
because 96% of the time people report themselves as heterosexual on average, those numbers might be changing.
So the joke really is a joke on science
because that falls within the realm
of statistical significance.
And yet it really illustrates the fact
that none of this is causal,
but it's nonetheless very interesting
because it means that hormones are organizing the brain
early in development in ways that can potentially impact
same or opposite sex partner choice later in life.
Now, of course, there are other things
that can impact opposite sex
or same sex partner choice later in life.
The study did not look at people who reported bisexual.
There hasn't been a lot of studies on that yet.
One thing that's very interesting
for which there are some good scientific data,
but there's also some controversy,
is that it appears that the probability of a male human
self-reporting as homosexual increases
with the number of older brothers that he has. Now that doesn't mean if you have an older brother, even if you number of older brothers
that he has.
Now that doesn't mean if you have an older brother,
even if you have 10 older brothers,
that you are sure to self-report as homosexual,
but statistically it becomes more likely that somebody will
with each successive older brother that they have.
And the idea that's starting to emerge
in the developmental neuroendocrinology landscape
is that there's a record within the mother
of how many male fetuses she's carried
because male fetuses are secreting certain things,
dihydrotestosterone, other things,
that can feed back onto the genome.
So these could be epigenomic effects
or onto the placenta itself,
so that there's a higher probability
in subsequent pregnancies
that offspring will self-report as homosexual.
So it's a fascinating area of biology.
And as you've noticed today,
none of this deals with the current controversies
around gender and how many genders and sex, et cetera.
That's a separate conversation that is by definition
grounded in the kind of concepts
we've been talking about today
and needs to take place,
taking into consideration all of the aspects of sex
and the effects of hormones,
both on the body, on the brain.
We didn't talk a lot about spinal cord,
but we will in the next episode on,
but we can just say on the brain and the periphery,
early effects, latey, early effects,
late effects, acute effects, meaning effects that are very fast of levels of hormones going up or
down, something that absolutely happens during the, and across the menstrual cycle, as well as
long-term effects, like the effects of these hormones on gene expression. So today, as always, we weren't able to cover
all things related to sex and hormones
and sexual differentiation or development.
There's no way we could,
but we have covered a lot of material.
We talked about some effects of environmental toxins.
We talked about potential effects of cell phone radiation,
something I never thought that I would be talking about,
especially not in a podcast,
but for which there are interesting emerging data.
We talked about considerations about evening primrose oil
and its estrogenic effects,
about creatine and its pro-DHT effects,
about cannabis, alcohol,
about plants exerting warfare on animals
by increasing aromatase,
the conversion of testosterone to estrogen.
We talked about hyenas with giant clitorises, warfare on animals by increasing aromatase, the conversion of testosterone to estrogen.
We talked about hyenas with giant clitorises,
and we talked about moles that convert
from having ovaries to testicles.
And throughout this, Costello has been snoring nonstop.
He missed all of it, although he might be learning it
in his sleep, for all I know.
And I do understand it's a lot of information,
a lot of detail.
As always, I just want to remind you,
you don't have to absorb all the information at once.
Next episode, we are going to be talking about
the science of sex, the verb, actual reproduction.
We're also going to be talking about effects of hormones
on various aspects of behavior
and ways to modulate hormones
through the use of behavior, supplementation,
also we'll touch on diet and nutrition a bit.
And we're going to talk about interactions
between those things and behavior
as they relate to important themes,
like sex and reproduction, like workplace performance,
like motivation and drive, and even anxiety.
There's a very interesting relationship
between hormones and anxiety
and the desire to explore novelty.
So just remember as we go forward
that hormones affect behavior
and behavior affects hormones,
but that doesn't mean that cutting off your index finger
will increase your testosterone.
Many of you have asked how you can help support the podcast.
And we thank you for the question.
There are several ways to do that.
The first one is to subscribe on YouTube.
If you haven't subscribed to the YouTube channel already,
please do so.
As well, please hit the subscribe button
so you're sure not to miss any of the episodes.
We do release episodes every Monday,
but we also occasionally release short clips in between.
As well, if you could subscribe on Apple and or Spotify,
that's very helpful.
And on Apple, you have the opportunity
to leave us up to a five-star review
and to leave a comment.
On YouTube, please do leave us comments
and suggestions for future episodes.
We really appreciate the feedback
and we appreciate those suggestions.
Also ask us any questions you have about the material.
Those questions help guide our office hours,
this discussion about your questions
that we hold from time to time,
as well as inform future content.
Also, if you could tell people about the podcast,
please tell your family, your friends, your coworkers,
anyone that you think might benefit from the material.
That really helps us get the word out.
And as mentioned at the beginning of today's episode,
we are now partnered with Momentous Supplements
because they make single ingredient formulations
that are of the absolute highest quality
and they ship international.
If you go to livemomentous.com slash Huberman,
you will find many of the supplements
that have been discussed on various episodes
of the Huberman Lab Podcast,
and you will find various protocols
related to those supplements.
Please also check out our sponsors,
check out the sponsor links. That's perhaps the best way to support us. Please also check out our sponsors, check out the sponsor links.
That's perhaps the best way to support us.
And of course, I want to point out
that any of the ways that support us,
whether or not they are cost-free,
like subscribing and leaving comments,
or whether or not you're interested in the products
that I've referred to, those all help us.
And so we really appreciate it.
So once again, I want to thank you
for embarking on this journey through neuroscience
and today neuroendocrinology with me.
And as always, thank you for your interest in science.