Huberman Lab - Dr. Kyle Gillett: How to Optimize Your Hormones for Health & Vitality

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.

Today, my guest is Dr. Kyle Gillette.

Dr. Gillette is dual board certified

in family medicine and obesity medicine,

and practices out of a clinic in Kansas

and via telemedicine.

He provides full spectrum medicine,

including hormone health, preventative medicine,

obstetrics, which is the branch of medicine and surgery

concerned with childbirth

and the care of women giving birth, and pediatrics.

I first learned about Dr. Gillette

from a podcast of all things,

and was immediately struck by the breadth and depth

of his knowledge on all things,

hormones and hormone optimization.

As you’ll see very soon today,

Dr. Gillette can teach you how to optimize your hormones

using behavioral tools, nutrition, exercise-based tools,

supplementation, and hormone therapies,

if those are appropriate for you.

There are many professionals out there,

including many medical doctors, of course,

talking about hormone health.

What really sets Dr. Gillette apart from the pack

is his ability to understand how the different factors

that I described before, nutrition, supplementation,

exercise, and hormone therapies,

how those interact with one another,

and the safest and most rational ways

to approach hormone optimization.

During today’s episode,

you will learn how to optimize your hormones,

not just testosterone and estrogen,

but also prolactin and other hormone pathways

that impact your mood, mental health, and physical health.

Dr. Gillette is also an avid educator

about hormones and other aspects of health.

He does this on zero cost to consumer platforms,

such as Instagram and other social media.

On Instagram, he is Kyle Gillette, M.D.

That’s K-Y-L-E-G-I-L-L-E-T-T, no E at the end, M.D.

So Kyle Gillette, M.D. on Instagram,

and he is Gillette Health on all other platforms,

including LinkedIn, Twitter, YouTube, TikTok, and Facebook.

If you go to his Instagram or his other social media,

you will learn a lot about hormone health,

about the latest science impacting obesity

and metabolic health.

He is a wealth of knowledge,

and again, he’s providing all that information

at zero cost to you, the consumer.

What you are soon to hear is a conversation

between me and Dr. Gillette about all things hormones

and hormone health and hormone optimization.

We dive deep into mechanisms,

but we are clear to establish what each word

or set of concepts mean.

So if you have no background in biology, or even if you do,

I’m sure that you’ll come away

with a wealth of valuable knowledge.

We also talk about specific protocols related, again,

to lifestyle factors, nutrition, supplementation,

and where appropriate hormone replacement therapy.

I know there’s a lot of interest about these topics.

Dr. Gillette is very thorough about addressing

both male and female issues and addressing hormone health

for people at all stages of life.

I’m sure that you will come away from this episode

with the same impression that I did,

which is that Dr. Gillette

is an extraordinarily clear communicator,

and that he has tremendous compassion for his patients,

and that he has a deep love of understanding biology

and medicine in ways that can benefit you.

Before we begin with today’s episode,

I want to emphasize that this podcast is separate

from my teaching and research roles at Stanford.

It is, however, part of my desire and effort

to bring zero cost to consumer information about science

and science-related tools to the general public.

In keeping with that theme,

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.

Today’s episode is also brought to us by Element.

Element is an electrolyte drink

that has everything you need and nothing you don’t.

That means the exact ratios of electrolytes are an element,

and those are sodium, magnesium, and potassium,

but it has no sugar.

I’ve talked many times before on this podcast

about the key role of hydration and electrolytes

for nerve cell function, neuron function,

as well as the function of all the cells

and all the tissues and organ systems of the body.

If we have sodium, magnesium, and potassium

present in the proper ratios,

all of those cells function properly

and all our bodily systems can be optimized.

If the electrolytes are not present

and if hydration is low,

we simply can’t think as well as we would otherwise,

our mood is off, hormone systems go off,

our ability to get into physical action,

to engage in endurance and strength

and all sorts of other things is diminished.

So with Element, you can make sure

that you’re staying on top of your hydration

and that you’re getting the proper ratios of electrolytes.

If you’d like to try Element,

you can go to drinkelement, that’s lmnt.com slash Huberman

and you’ll get a free Element sample pack

with your purchase.

They’re all delicious.

So again, if you want to try Element,

you can go to elementlmnt.com slash Huberman.

Today’s episode is also brought to us by Thesis.

Thesis makes what are called nootropics,

which means smart drugs.

Now, to be honest, I am not a fan of the term nootropics.

I don’t believe in smart drugs in the sense that

I don’t believe that there’s any one substance

or collection of substances that can make us smarter.

I do believe based on science, however,

that there are particular neural circuits

and brain functions that allow us to be more focused,

more alert, access creativity, be more motivated, et cetera.

That’s just the way that the brain works.

Different neural circuits for different brain states.

Thesis understands this.

And as far as I know, they’re the first nootropics company

to create targeted nootropics for specific outcomes.

I’ve been using Thesis for more than six months now

and I can confidently say that their nootropics

have been a total game changer.

My go-to formula is the clarity formula,

or sometimes I’ll use their energy formula before training.

To get your own personalized nootropic starter kit,

go online to takethesis.com slash Huberman,

take a three minute quiz,

and Thesis will send you four different formulas

to try in your first month.

That’s takethesis.com slash Huberman

and use the code Huberman at checkout

for 10% off your first order.

I’m pleased to announce that the Huberman Lab Podcast

is now partnered with Momentus Supplements.

We partnered with Momentus for several important reasons.

First of all, they ship internationally

because we know that many of you

are located outside of the United States.

Second of all, and perhaps most important,

the quality of their supplements is second to none,

both in terms of purity and precision

of the amounts of the ingredients.

Third, we’ve really emphasized supplements

that are single ingredient supplements

and that are supplied in dosages

that allow you to build a supplementation protocol

that’s optimized for cost,

that’s optimized for effectiveness,

and that you can add things and remove things

from your protocol in a way

that’s really systematic and scientific.

If you’d like to see the supplements

that we partner with Momentus on,

you can go to livemomentus.com slash Huberman.

There you’ll see those supplements

and just keep in mind that we are constantly expanding

the library of supplements available through Momentus

on a regular basis.

Again, that’s livemomentus.com slash Huberman.

Today’s episode is also brought to us by InsideTracker.

InsideTracker is a personalized nutrition platform

that analyzes data from your blood and DNA

to help you better understand your body

and help you reach your health goals.

I’ve long been a believer in getting regular blood work done

for the simple reason that many of the factors

that impact your immediate and long-term health

can only be analyzed from a quality blood test.

There are a lot of blood and DNA tests out there,

but a major issue with many of them

is that you get numbers back about levels of hormones,

metabolic factors, lipids, et cetera,

but you don’t know what to do with that information.

InsideTracker has solved that problem

by creating a personalized dashboard.

So you take your blood and or your DNA test,

you get the results back,

and where certain values might be too high

or too low for your preference,

you can click on that and it will direct you immediately

to lifestyle factors, nutrition, supplementation, et cetera,

that can help you bring those numbers back into the ranges

that are ideal for you.

So it not only gives you information

about where your health stands,

it gives you directives as to how to improve your health.

If you’d like to try InsideTracker,

go to insidetracker.com slash Huberman

to get 20% off any of InsideTracker’s plans.

That’s insidetracker.com slash Huberman to get 20% off.

And now for my discussion about hormone health

and optimization with Dr. Kyle Gillette.

Dr. Gillette, welcome.

Thank you for having me.

Well, I’m super excited to talk to you

because I found out about you on a podcast

and it immediately became clear

that you are an encyclopedia of knowledge

about hormone health for men and for women

across the lifespan.

So I have many, many questions,

but before we dive into those questions,

I’d love to just get a little bit of your background

in terms of your medical training

and what your particular orientation is

toward treating your patients.

And how do you think about this whole landscape

that we call hormone health?

What is a hormone?

How do you envision people managing their hormones?

If you could just kind of fill in a few of those blanks

for us, I think a lot of people would appreciate it.

Absolutely.

So I’m dual board certified in family medicine

and obesity medicine.

I’ve kind of tailored my training

in order to provide what I call a balanced approach

to total health, which includes body, mind, and soul.

I recently saw a podcast with Joe Rogan and Mr. Beast,

and Joe asks Mr. Beast,

how do you become such an amazing YouTuber

and have all these great clickbait videos?

And how did you become good at it?

And it turns out he just became obsessed

when he was a teenager.

And that’s essentially how I’ve tailored my education

as well.

I’ve become obsessed with optimal human performance,

their body, their mind, and even their spirit.

So I attended med school at the University of Kansas,

which is one of the few med schools

that still emphasizes full spectrum care.

They emphasize exercise as medicine.

They emphasize food as medicine,

of which I was active in both of those interest groups.

In residency, I was active

in a lot of mindfulness curriculum,

and then also things like walk with a doc,

where you emphasize preventative medicine.

And that’s something that we’ve kind of got away from,

and that niche led me to hormone health.

It didn’t really start as hormone health,

but it’s a very important component of health in general

that many people don’t emphasize.

Great.

Well, this idea of preventative medicine,

I think is starting to really take hold

in the general population,

especially given the events of the last few years,

people realize that they are showing up to health challenges

at a bunch of different levels,

and with some people feeling very robust,

other people feeling back on their heels.

When someone comes to you as a patient,

what are some of the first things

that you want to know about them?

I mean, obviously you want to know their blood pressure,

you want to know something about their mental health

and family history, but in terms of hormone health,

what are the sorts of probe questions that you ask

and what are you looking for?

And I ask this because I’d like people to be able to ask

some of these very same questions for themselves.

Yeah.

So when you do a physical exam and a history,

you have a lot of different parts.

You have your history of present illness.

If they have a complaint,

maybe the patient doesn’t have a complaint.

And that case, things like their social history

and their family history are extremely important

because that gives you an insight into their genetics

and an insight into their hormone health.

So patients will tell me, oh, I’m doing okay,

but it helps to ask them, well, how are you now?

Let’s say the patient is 50.

How are you now versus when you were 20

and what has changed?

So I’ve gotten the question a lot.

How do you get your doctor to order a better lab workup

or to even include your basic hormones?

And there’s no magic answer to that.

But what really helps is you tell them,

my energy is not as good as it used to be.

My focus is not as good as it used to be.

My athletic performance is not as good as it used to be.

So you don’t have to have a pathology

in order for a lab to be indicated.

You just need to have that pertinent symptom.

I think that’s gonna be really helpful

because for many people,

the idea of getting a blood test to look at their hormones,

it just seems like such an enormous hurdle to get over.

And many doctors won’t prescribe them.

And would you say that it’s using the approach

you just described that it’s equally effective

for men and women?

Or do you find that for one reason or another

that men and women have different challenges

and advantages in trying to access their deeper hormone data?

Yeah, it’s slightly different.

With women, there’s a lot more objective data.

So if they’re having menstrual irregularities

or if they’re not having a period,

if they’re having too heavy of periods,

then those are things that they talk about

very frequently with their doctor.

Men are more hesitant.

So men really wanna know what their testosterone is,

but at the same time,

they really don’t wanna tell their doctor

how their libido is or how their energy is,

because it’s almost like they feel less masculine

or they feel less like a guy when they say that,

even if they’re just talking to their doctor about it.

Yeah, I think that that raises a really important point,

which is that the whole discussion around hormone health

is a bit of a barbed wire topic,

because in many ways, when we hear the word hormone,

we think testosterone and estrogen,

we think notions of masculinity and femininity.

And of course, testosterone and estrogen

are present in all sexes, right?

All chromosomal backgrounds

and just to varying degrees and ratios.

But it also raises all these issues about sexual health

that it’s kind of interesting

because I’m surrounded by medical doctors

in my lab at Stanford.

And the more physicians that I surround myself with,

the more open is the discussion around sexual health

and reproductive health.

But in the general population,

I think some of these topics are a little bit taboo

or against kind of barbed wire.

And so I think that people are seeking

a lot of this information on YouTube

and through communities that may or may not

be very educated about the actual biology.

So along those lines,

we could probably assume that hormones

are changing across the lifespan, I think, right?

Certainly from childhood and puberty and onward.

If you would, I’d love to just kind of take a snapshot

of what you think everybody should be thinking about

or doing to optimize their hormone health,

male or female, let’s say in their 20s.

And then maybe we can migrate that to their 30s and 40s.

But before that, could you just tell us

what everyone should be doing for their hormone health

from puberty onward?

Yeah, the law of diminishing returns applies.

So doing a little amount

of what I call lifestyle interventions

over a long period of time

is gonna be far more helpful or efficacious

than doing a lot and then doing nothing

or doing a lot and then doing nothing.

So I talk about the big six pillars.

The two strongest ones are likely diet and exercise.

For hormone health, specifically resistance training

is particularly helpful.

For diet, caloric restriction can be particularly helpful,

especially with the epidemic of metabolic syndrome

that is continuing to ongo in this country

and in developed countries in general.

So those are the two most powerful.

So number one and number two are diet and exercise.

For the last four, I have a little bit of alliteration.

So there’s stress and stress optimization.

That has to do with cortisol.

That has to do with your mental health.

That has to do with societal health

and collective health of your family as well.

When you’re a member of a family

or even a very close friend,

trying to achieve optimal health together is very important.

It’s the same thing with nicotine cessation.

It’s the same thing with hormone optimization.

If you do it as a household unit, it’s far more helpful.

So after stress, you have sleep optimization.

Sleep is extremely important,

especially for mitochondrial health as well.

And then you have sunlight,

which encompasses anything that’s outdoors.

So you move more, you have cold exposure,

you have heat exposure, that’s sunlight.

And then last one is spirit.

So that’s kind of the body, mind, and soul.

If you have all the other five

and they’re dialed in completely,

but you don’t have your spiritual health,

whatever you believe,

then that’s going to profoundly impact your body

and your mind as well.

And we’re definitely going to touch into this notion

of spiritual health,

because I think for some people

that might draw connotations of certain things

that may or may not be accurate,

but I know a number of academic laboratories

that are focused on this and a number of,

not just functional medicine clinics,

but research clinics and hospitals throughout the country

that are achieving some really interesting data,

not just in people that are quite sick,

but in healthy people

who are trying to further optimize health.

So we will definitely touch back to that.

If you would be so kind as to maybe give us

a little bit more detail about some of these other areas.

So when people hear diet, I immediately think,

okay, now we get into the combat

around vegan, plant-based, carnivore, et cetera.

But I think that my general view of this

is that most people should probably be eating

as few highly processed foods,

highly palatable foods as possible,

which doesn’t mean eating foods

that don’t taste good, of course.

But what other sorts of things do you recommend

in the realm of diet?

And then I also want to know about caloric restriction,

because my understanding is that a caloric surplus

can actually support certain hormones like testosterone.

So how does one combine caloric restriction

and still optimize hormones?

But what would you say is a really terrific way

to think about and approach diet?

Yeah, diet should be an individualized approach.

So if you have a car, each car is made different

and requires a different sort of fuel,

whether it’s a race car, whether it’s a diesel truck,

they have different fuels

for different performance outcomes.

So if you’re trying to tow something

or you’re trying to go fast.

So it’s the same way with athletes.

It’s pretty well studied.

The more intra-workout carbs

ultra-long distance athletes take,

in general, they do better.

I think they’ve studied this in cyclists quite often.

It also depends on your genetics.

So you can have a genetic polymorphism

and you metabolize carbs and sugar better,

even when they’re unopposed by fiber.

How does one determine whether or not

they have such a polymorphism?

I mean, I’m an omnivore.

So I do eat some high quality meats, not in huge quantities,

but I also eat vegetables and starches.

I feel fine.

I’ve never done an elimination diet.

I think I did a very low carb diet once

and all it gave me was a lot of psoriasis and poor sleep.

So I backed off.

I probably didn’t do it correctly,

but I know a lot of people that do quite well

on a very low carb or zero carb diet.

Yeah.

Particularly those who are at risk of cancer

because you have less glucose

that can be easily uptaken into cells.

And then also people with auto-immune diseases.

They tend to do well on lower carb diets.

Yeah.

But yeah, as far as the, how do you know,

basically you can use your biofeedback,

how you’re feeling to guess what you tolerate well,

or you can just get genetic testing,

which can be fairly expensive,

but most of all it requires a physician

or someone who knows how to interpret the test accurately.

And if someone had the means,

or would you say that getting regular blood testing

is a good idea?

And if so, what is regular blood testing?

Is it every three months?

Is it every six months?

Of course, the backdrop of life is changing too,

stress levels, et cetera.

Yeah.

Every three to six months for preventative purposes.

At times you need blood tests at faster frequencies

than that.

And then you should also get a blood test

when you’re fasting and when you’re not fasting.

So if you’re looking for damage to the beach,

you wanna, you don’t just look at low tide,

you look at high tide and you see what’s happening

at high tide as well.

That’s a great way to put it.

And in terms of general recommendations around exercise,

I mean, I’m of the mind based on the data that I’ve seen

that almost everybody should,

or everybody should be getting 150 to 180 minutes minimum

of zone two cardio per week,

kind of could continue while having a conversation,

but if one were to exert any more effort,

it would have a hard time getting the words out,

at least that, right?

For cardiovascular health and general brain health

and musculoskeletal health, plus resistance exercise.

Is that more or less the contour of what you recommend?

Yeah, that’s more or less the contour.

The more you’re doing your zone two cardiovascular exercise,

the slightly less important a long duration

of caloric restriction is.

Interesting, and that brings us to caloric restriction.

So it’s very clear that caloric restriction

can allow one to lose weight, right?

This is the classic Kiko, C-I-C-O,

calories in, calories out.

We are not disputing calories in, calories out.

Somehow that always has to be stated 50 times in any forum

because of whatever follows,

people I think will anchor to and assume

that we don’t mean that,

but I know you and I both agree on calories in,

calories out as a fundamental law of thermodynamics.

But it’s clear to me that based on what I’ve read,

that when one is in a slight caloric surplus,

that hormones like testosterone can be optimized.

But is that true for somebody

who’s showing up with excessive body fat?

How does this all work?

Because body fat is manufacturing enzymes

that convert testosterone to estrogen.

So in other words, how does someone know

if they should use caloric restriction

or avoid caloric restriction?

Yeah, here’s how to parse that out.

So before I delve into the details a bit more,

I should say as a board-certified

obesity medicine physician,

obviously the laws of thermodynamics apply.

And then in addition to that,

there is nothing special about intermittent fasting

or caloric restriction or exercise

when it pertains to losing body weight in general.

When you do lose weight,

about 33% of that is lean body mass

and about 10% of fat cells, adipose cells,

are actually lean body mass as well,

because it has proteins and water

and things like that in it too.

So the reason for exercise

and the reason for caloric restriction in general,

including intermittent fasting, is health reasons.

That’s how you increase your health span.

It’s not necessarily gonna make the weight

on the scale change, but that doesn’t matter as much.

It’s been fairly well studied in both mice and humans.

It’s much easier to study in mice.

So that’s a precursor to our six types of people,

the ones that care about my studies

and the ones that care about human studies.

But if you calorically restrict mice by 40%,

then they can have improved testosterone parameters,

but only if they’re obese to start.

And it appears to be that same way in humans as well.

So the easy way to think about it is if you’re obese

or you have metabolic syndrome,

caloric restriction will improve your testosterone.

There has been a study,

and they talk about all these studies in a systematic review

from the Mayo Clinic proceedings in March of last year.

And they note that there is a study in young, healthy men,

and they calorically restrict them,

and their testosterone does decrease.

So if you’re young and healthy

and you don’t have metabolic syndrome,

then caloric restriction

will likely decrease your testosterone.

That clarifies a lot for me,

and I believe it will clarify a lot

for other people as well.

And I’m delighted that you pointed out

this distinction about intermittent fasting

not being the only way to achieve caloric restriction.

There are a number of young, healthy,

or older healthy people I know

who like using intermittent fasting,

even if they’re not trying to lose weight,

for a couple of reasons.

Some believe that it might extend lifespan.

I think that’s still a bit of an open question.

It’s a bit of a hard experiment to do

because the control group is,

no one wants to be in the control group, as I say.

A dozen mice, captive audience.

Exactly, and the other feature of it

that’s a little bit tricky is that

many people like intermittent fasting

because of the mental effects,

the clarity of mind that they feel during fasting,

the increased pleasure in eating when they finally do eat.

And here I’m referring to intermittent fasting of the sort

where eating windows are anywhere

from eight to 12 hours a day,

not extended fast of 24 hours or more.

So the question, therefore,

is for the healthy, lean enough person, right?

Non-obese person, is intermittent fasting a bad idea

in terms of hormone health?

Is oscillating between this period of kind of feast

and famine within a 24 hours a problem

if one is getting sufficient calories to maintain weight?

Yeah, so if they’re in a caloric maintenance,

then it’s not going to be deleterious.

It’s not gonna be bad for their hormone health.

There’s a couple of different hormones

that we can talk about.

We can talk about testosterone.

We can talk about DHEA, which you usually go hand in hand.

And then we can also talk about growth hormone,

which is not a steroid hormone, but it’s a peptide hormone.

So it’s a chain of proteins,

amino acids that are put together instead of a sterol.

Think of sterol hormones as coming from cholesterol.

So intermittent fasting,

you do get a little spike in growth hormone after you eat,

but you also get a huge spike in growth hormone,

a more significant, less negligible spike overnight.

And that is improved if you are intermittent fasting.

So it’s probably gonna help your growth hormone

and subsequently IGF-1 levels,

which will help more in older age groups

than younger age groups.

And I like to eat dinner.

So for me, that means sometime around six or seven o’clock,

sometimes eight o’clock.

I confess last night, because I was working late,

I ate pretty big.

It’s basically my only meal of the day.

At 10 o’clock, that’s a rare thing for me.

Can I still achieve a high degree of growth hormone output

if I, let’s say I avoid food in the two to three hours

before going to sleep?

Or does one have to be very deep into a fast

in order to achieve the increase in growth hormone?

There’s still pretty good growth hormone output,

even if you eat two or three hours before you sleep.

It’s just the law of diminishing returns.

The longer you go, you get slightly more and slightly more.

Great.

And I know a number of people think of growth hormone

in the context of the exogenous growth hormone

and the fact that that can, in some cases,

be associated with cancers.

I’ve been asked many times before,

can the increase in growth hormone

from things like saunas or intermittent fasting

cause levels of growth hormone that are so high

that they cause cancers?

My impulse is to say no,

that seems like it’s not likely to happen,

but I should probably verify that statement with you.

Yeah, so quite unlikely.

I think about growth hormone and especially IGF-1.

And there’s actually an IGF-1 and IGF-2,

but I think about it in terms of endocrine IGF-1,

mostly IGF-1 that’s synthesized in the liver

and released in the liver versus IGF-1 that’s released.

Classically, an example of this would be

your IGF-1 levels increase

after resistance training or exercise.

And that’s more like paracrine or autocrine

and they have more local action.

So that IGF-1, it’s pretty well studied

that if you just give people IGF-1,

it’s not going to, at physiologic levels,

it’s not gonna improve their body composition.

However, that IGF-1 that’s autocrine and paracrine

just working in those local tissues and muscles

is likely part of the reason why you get

a improved body composition response after exercise.

I see.

And just to clarify for me and for others,

what can we say are the major functions of IGF-1 and IGF-2

that are distinct from just growth hormone?

Are they just kind of the active form of growth hormone,

the kind of the pickaxe end of the assembly line?

So they have a much longer duration of action.

I believe the half-life of IGF-1 is several days,

almost a week,

whereas growth hormone has an extremely fast half-life

of only hours.

So growth hormone acts significantly on the liver

to produce IGF-1.

So it’s around in the serum, in the blood long enough

to where it’s producing an effect pretty much all the time.

Very interesting.

Well, and then your other pillars, stress,

we’ve talked a lot about stress on this podcast before

and tools for managing stress.

Sleep obviously is a big one.

I think if nothing else,

I will either put people to sleep with my podcasts,

certainly not this one, but my solo episodes,

or hopefully convince people that sleep is the foundation

of mental and physical health and performance.

Are there any aspects of hormone optimization

that can improve sleep?

I know sleep can improve hormone optimization,

but are there any aspects of hormone optimization

that can improve sleep?

And for people that are suffering

from this common syndrome of going to sleep

and then waking up at three or four in the morning,

we know that can be associated with depression,

but are there any hormonal indications

that might lead to that kind of situation?

Yeah, there’s three big ones.

The first one is not super common,

but it’s a very direct correlation.

If you have a growth hormone deficiency,

a true deficiency, whether you’re an adult or a child,

then your sleep is likely going to be affected.

And let’s say you’re a child with growth hormone deficiency.

Once that is replaced with therapy,

your sleep is gonna get significantly better.

The second one that’s a very common scenario

is if you’re having what’s called

vasomotor symptoms of menopause

or vasomotor symptoms of andropause,

which are also applicable.

And that’s where your progestogenic activity,

so your main progestogens are progesterone

and then pregnenolone,

and then 5-alpha, 3-alpha progesterone,

which is-

Where are those manufactured in the body?

So, they’re manufactured in a few places.

In men, they’re manufactured some in the testes,

in the leydig cells.

In women, they’re manufactured in the ovaries

until menopause,

and then they’re also manufactured in the adrenal glands.

So, if you’re pre-adrenopausal,

where your adrenal glands are still working fairly well,

you usually still have a decent amount

of progesterone around,

and this can be measured too.

So, after menopause,

women make progesterone from their ovaries,

or sorry, from their adrenal glands.

If that progesterone crosses the blood-brain barrier,

especially if it’s 5-alpha and 3-alpha reduced,

so it’s modified a little bit,

then it is both a GABA agonist,

which helps sleep just like GABA does,

gamma-aminobutyric acid,

the main inhibitory neurotransmitter,

of which lots of things work on.

Alcohol works on GABA as well.

GABA, pentin also works on GABA.

Migraine medicines, many of them work on GABA.

Benzodiazepines and also non-benzos.

So, an example of a benzo would be Xanax.

An example of a non-benzo would be Ambien.

So, those all work on GABA.

So, GABA is also helped

by the progestogenic activity as well.

That’s why a lot of women in menopause

feel like their sleep is much worse,

is because they have lower activity of those progestogens.

And for men in so-called andropause, low testosterone,

is that also one of the causes of poor sleep?

Low testosterone can lead to poor sleep,

but my third scenario is actually if a man begins TRT,

then they develop poor sleep because of sleep apnea.

It drastically raises the risk

that somebody is going to have sleep apnea.

And then a lot of people,

especially when they first start it

in the first month or two,

it puts them into this hypersympathetic state

because they have overactive androgen receptors,

especially after a long time of being hypogonadal.

Then they have a physiologic dose of TRT,

and that causes the sleep issue itself.

Interesting.

I have a lot of questions

about TRT, testosterone replacement therapy.

I should just mention that when you say

it increases sympathetic activity,

you don’t mean that taking testosterone

increases sympathy for others.

It may in fact do the opposite.

Although it’s very clear from my discussions

with my colleagues in the endocrinology side,

and also with the great Dr. Robert Sapolsky,

that increasing testosterone

merely exacerbates existing features of people.

So the jerks become bigger jerks,

kind of people become even more kind in general.

But I wanna get into TRT in depth,

but it’s very interesting to me to hear

that testosterone replacement therapy

increases the risk of sleep apnea.

And I wanna make sure that I ask that,

is that also the case in people

that are using TRT who are not hypogonadal?

Because in the classic situation

is somebody isn’t making enough testosterone,

they’re below 300 nanograms per deciliter on the chart,

they go and intake TRT.

But many people nowadays,

let’s be honest, are taking doses of testosterone,

even though they are in the sort of standard range

because the range is so large

because of other symptomology.

Is that right?

Yeah.

I do love the analogy that Dr. Sapolsky had

about monks taking testosterone

and making them more and more generous.

So that does appear to be what testosterone usually does

is it exacerbates, if you will,

what you’re previously like.

So it’s not gonna change you as a person.

But if you’re eugonadal before you start testosterone,

Meaning you have normal testosterone

and then you start TRT or self-administered TRT,

steroids, however you wanna look at it,

then your risk of sleep apnea still goes up

in a dose-dependent fashion.

So the higher the dose, the more risky.

With the sympathetic

and the parasympathetic nervous system,

the sympathetic is the fight or flight nervous system.

The parasympathetic is the rest and digest.

So if you have too much fight or flight

and stress can cause that too,

then you’re not gonna rest as well at night.

I wanna touch on testosterone in women

because there is testosterone in women.

I’d like to know where that testosterone comes from,

which tissues.

I’d like to know whether or not

testosterone replacement therapy makes sense in women.

I’m hearing more and more about women using testosterone.

And I’d like to know whether or not

knowing a woman’s testosterone,

for her to know her testosterone

is of equal, less than, or more value

than knowing, for instance,

progesterone and estrogen levels,

because I think there are a lot of misconceptions

about the roles of testosterone in women.

For health optimization,

testosterone is just as important to know.

For pathology prevention, for example,

breast cancer, osteoporosis,

estrogen and progesterone are more important to know.

So when you’re thinking about women,

women think that they have such a tiny amount

of testosterone because you test it.

Most people test a free testosterone,

so testosterone that’s unbound,

which is by far the smallest proportion of testosterone.

Any androgen is bound by lots of different

steroid-binding proteins,

but the ones that are most pertinent

are called SHBG or sex hormone-binding globulin,

and that binds the androgenic steroid,

for example, DHT or dihydrotestosterone.

It’s associated with prostate enlargement.

It’s associated with male pattern baldness.

It binds that the most strongly,

and then it binds testosterone next most strongly,

and then it binds things like androstenedione

or DHEA, dehydroepiandrosterone,

and then it binds the estrogens,

the weakest, like estradiol.

So if you look at the total amount of testosterone,

women actually have, almost all women, not all women,

but almost all of them have significantly more testosterone

than estradiol,

but it’s because it’s in different measurements.

So estradiol, a lot of time, is grams per mil

as opposed to nanograms per deciliter.

So women have more testosterone than estrogen

and significantly more DHEA than either.

Interesting.

Do women make dihydrotestosterone?

Yeah.

And where does this testosterone come from?

Because they don’t have testes.

Yeah, so most testosterone in women that are premenopausal

can come from theca cells, T-H-E-C-A.

So theca cells are cells in the ovaries

that can produce testosterone.

And a lot of people have actually heard about hyperthecosis,

not the term itself,

but a lot of Olympians that are,

their chromosomes are XY, they’re females,

and they’re not taking any PEDs.

Wait, they’re XY, but they’re females?

Oh, sorry, they’re XX.

Oh, okay.

Thank you.

So they’re XX, they’re not XY.

And they have never transitioned

or been on any sort of hormone replacement or testosterone,

but they naturally produce a huge amount of testosterone,

as much as many men.

And some of these women,

I believe they were from Botswana,

were banned from competing in the Olympics

in certain distances.

I believe they were banned from the 400 meter and 800 meter

because their natural testosterone was deemed to be too high.

So they mistakenly thought that they were using steroids.

They actually knew they were not using steroids.

They knew it was their theca cells

were just genetically gifted, I suppose,

and they still made them change distances.

So one or two of these athletes changed to,

I believe it was a 3K or the 5K,

and they still did quite well,

but it was not their best event.

Interesting.

Yeah, that’s turning out to be a very interesting

and controversial area of this notion of hormone therapies

and natural variation in hormones

on different chromosomal backgrounds.

Fascinating, we should probably do a whole episode

about that because it’s very much of the times.

So men and women both make DHT.

I’d like to ask about DHT in men.

So often we hear about testosterone in men

and free testosterone and being the unbound form, of course,

but dihydrotestosterone, where does it come from in men?

What is the cascade of events that takes testosterone

to dihydrotestosterone?

And what are some of the quote unquote positive

and negative effects of,

here I’m only referring to endogenous dihydrotestosterone.

And in fact, I’ll make it very clear whether or not

I’m talking about taking something

or one’s own natural production.

Here we’re just, I think up until now,

we’ve just been talking about natural production.

So tell us about DHT in men.

It’s such a powerful hormone during development, obviously,

but what is it doing?

DHT is a very androgenic hormone.

So whether you’re talking about DHEA,

which is a mild, a weak androgen,

or testosterone, which is a relatively strong androgen,

or DHT, which is a very strong androgen,

they bind to the androgen receptor

in both men and in women.

So the effect of all three of those

is mediated by the androgen receptor.

There’s a couple of different beta-estradiol receptors

and alpha-estradiol receptors,

but there’s only one androgen receptor.

Intriguingly, it is on the X chromosome.

So men get their androgen receptor gene from their mother.

Women get one androgen receptor gene from their father,

one from their mother.

Often the one that is more sensitive to androgens

and people with PCOS, that’s the one that’s active.

The other one is methylated and inactive.

Can I just pause you one second?

Sorry to interrupt, but I have to ask this question

before I forget, and I know a number of people

are probably wondering.

I’ve heard that whether or not one develops

male pattern baldness,

whether or not a male develops male pattern baldness,

just to be very precise,

you could get some information about that

by looking at your mother’s father,

and that would, in keeping with what you just described,

that the X chromosome, which of course

is handed off through the mother,

is carrying the genes that encode

for the number and distribution of these androgen receptors

that DHT will bind to.

Because of course, I think as you’ll probably tell us,

that DHT is responsible for male pattern baldness

and beard growth, is that right?

Should I look at my grandfather or my mother’s side

to determine what I’m likely to look like

in terms of my DHT-ness?

Is that a word?

Yeah, it’s the best guess that you can make

purely from phenotypes.

And you can measure your genotype

and get a better idea of that.

Assuming that it’s true male pattern baldness,

it’s related to the gene transcription

of the androgen receptor.

So I like to think of it as how much

of this androgen receptor gene

is activated by any androgen.

So if you have an extremely sensitive gene,

which usually means you have very few CAG repeats,

which is basically just a certain,

CAG encodes for a certain amino acid.

And if you have very few of the repeats,

then your androgen receptor gene works better.

Think of it as a corollary to Huntington’s disease,

where if you have very few of what we call

trinucleotide repeats,

then it’s not as severe of a disease.

But after you get more and more CAG repeats,

which by the way, in the population,

you’re getting more and more CAG repeats.

So it’s a natural selection of process

that has been ongoing for a variety of number of reasons.

But anyway, if you have more repeats,

then that gene activates in the cytoplasm

and moves to the nucleus

and causes gene transcription more often

and hair loss more often.

So does that mean that we’re seeing more hair loss now

due to elevated levels of DHT than we were 50 years ago?

Probably not.

The hair loss 50 years ago,

well, not 50 years ago,

but 500 years ago was probably more significant

because on average, 500 years ago,

people were more sensitive to androgens.

So there’s a syndrome called

androgen insensitivity syndrome, AIS.

And that syndrome was related to when men

who have the copy from their mother, who is a carrier,

their AR gene or androgen receptor gene

is completely insensitive.

So think of it, it doesn’t have a,

it’s not related to the CAG repeats,

but think of that receptor as just not working at all.

So there’s a continuum.

So everybody’s receptor works a little bit better

or a little bit worse.

And the better your receptor works,

the more likely you are to have male pattern baldness.

To zoom out from this, but still keeping an eye on DHT,

what do you like to see all women and all men do

to optimize DHT?

And here I’m talking about regardless of age.

So we’re still in this from puberty onward phase.

We haven’t yet micro dissected out decade by decade,

which we will do.

But what do you like to see people do to keep DHT in check?

But before you tell us that,

could you tell us what positive things DHT does

when it’s in the proper range?

Yeah, so DHT helps a lot for the same reason

why testosterone helps.

It activates the androgen receptor gene.

It helps effort feel good.

So it can be motivating.

So that’s how it’s active in the CNS.

It also is active in cardiovascular tissue.

So if you look at someone that has heart failure,

or if someone has cardiac hypertrophy,

the level of DHT can matter

because it’s also binding to the androgen receptor

in the myocardium or in the heart itself.

So you think of the classic bodybuilder heart.

That’s an easy example to make.

They have very thickened muscle.

Their muscle is very strong because they’re pumping blood

often with high blood pressure.

And that DHT and the testosterone and any DHT derivatives

like Masterone or Oxandrolone, Premobolin

also bind to the heart and they cause even more hypertrophy

or enlargement of that muscle tissue.

So then let’s say the person stops in their recovering

and they’re trying to have cardiac remodeling,

which is where you take a very thick heart

and cardiac remodeling is important

in a lot of different cardiac pathologies.

But if you give them finasteride or dutasteride,

which inhibit the enzyme that converts testosterone to DHT,

so making less activity at the androgen receptor gene,

they have cardiac remodeling and their heart health improves.

I see.

So for the non-bodybuilder, the typical woman or man

or younger or older, what sorts of things support DHT

and thereby heart health?

Presumably DHT is involved in some of the other things

that testosterone is famous for in both men and women.

Things like libido, as you mentioned,

making effort feel good.

So motivation drive and vitality.

I guess it’s be the general phrase.

What sorts of things support DHT?

What sorts of things create problems for DHT?

There’s lots of dietary changes and supplementation

that you’re probably doing right now

that’s affecting your DHT.

You mean me personally?

Well, everybody, all of the listeners,

because let’s say you have a diet high in plant polyphenols.

Many of those inhibit the enzyme

that converts testosterone to DHT.

Could you give us an example of one of those,

either in supplementation form or in food form?

Curcumins, certain curcuminoids,

depending on the structure,

will inhibit the enzyme called 5-alpha reductase

that converts testosterone to DHT.

Turmeric.

Yeah, turmeric, black pepper extract.

So it’s used often to increase bioavailability.

It’s also called biopurine.

It’s also a 5-alpha reductase inhibitor.

So, and on top of that, people have different genetics too.

So some people, their 5-alpha reductase enzymes,

there’s three of them.

They’re on chromosome two, three, and four, I believe.

But some of them are active in the prostate.

Some of them are active in the brain.

And so it depends on which tissue.

They’re tissue-specific enzymes

that depend on how much DHT you convert.

Do you recommend that people avoid curcumin and turmeric

for that reason?

And is there any specific recommendations

for men versus women?

If a man or a woman, by the way, in women,

a lot of times if you just ask your doctor for a DHT check,

it’s the same unit as in men.

So it’s essentially undetectable.

So you have to, you know,

especially if they’re on oral contraceptives,

which is a different topic,

their DHT is very likely undetectable,

especially if it’s free DHT.

You can measure both a DHT and a free DHT.

But if someone’s DHT is already low

or if they have somewhat insensitive androgen receptor

via genetics or via lifestyle,

then I recommend they avoid bioavailable curcuminoids

like bioavailable turmeric, black pepper extract,

and they might be a good candidate for creatine.

Creatine, like creatine monohydrate,

can significantly increase the conversion

of testosterone to DHT.

Interesting.

There’s also a lot of really interesting data

coming out now about the role of creatine

as a brain fuel

and maybe even as a cognitive enhancer over time.

The data are still ongoing,

but some of the studies in humans are pretty impressive,

at least to me.

I’m glad you mentioned this thing

about curcumin and black pepper.

I wish we’d had this conversation six years ago

because I had the experience of jumping on the bandwagon

of the excitement around turmeric,

and I took a turmeric supplement.

It was a couple of capsules of what I thought to be,

and I think was high quality turmeric.

And I’ve never felt as poor as I did

in the subsequent few days.

Flatline of, let’s just say,

everything that one would want to have in life,

energy, vitality, just, it was a cliff.

And a friend somehow knew

that curcumin could inhibit 5-alpha reductase.

It converts testosterone to DHT, as you pointed out.

I stopped taking it.

It was the only new addition to my diet and supplementation,

and things bounced back within about three, four days,

but it was remarkable.

I mean, I felt like garbage.

And it was actually kind of frightening

to experience the sharpness of that cliff.

But I know that some people like turmeric

for its anti-inflammatory properties, et cetera.

Sounds like people either need to experiment or,

and if they do, obviously, to approach that with caution.

Anytime you add or remove something,

you need to talk to your doctor.

You’re a doctor, and I’m guessing that

if one were to experiment,

would you say that most of these effects

of things like curcumin are reversible as they were in me,

or is there any potential of permanent damage

if people have been taking them for a long time?

The effects are nearly always reversible.

When you’re talking about 5-alpha reductase inhibition,

so what turmeric does, but stronger,

the most common story that we hear

is regarding a supplement known as saw palmetto,

which a lot of older men take for their prostate health,

or finasteride, which you can take for your prostate,

or your heart, or your hair, or dutasteride.

So if you’re having side effects on these,

then it’s probably because of a couple different reasons.

One can be your ratio of androgens to estrogens is off,

and that needs addressed.

Another one can be it’s inhibiting the conversion

of your progesterone to that other type of progesterone,

the 5-alpha, 3-alpha that we talked about earlier

that’s helping with your sleep,

and your brain, and your calmness,

and that’s definitely an effect.

Another one is depending on the type of supplement or med,

they inhibit different isoenzymes

of that 5-alpha reductase.

So if they’re just inhibiting one and two,

then that’s gonna be a different effect

than if they’re inhibiting two and three.

So finasteride does two and three,

saw palmetto does one and two,

and then dutasteride does all three.

The third one is active in the brain,

and dutasteride inhibits that third one

a little bit weaker in vivo, but strongly in vitro.

It’s really hard to parse out.

You can use biofeedback and experimentation.

I do think with supplements, it’s safe to experiment.

The time that it takes to set in

is usually about three months.

So the risk of, and this is anecdotally,

there’s been lots of research published

about if post-finasteride syndrome is real or fake,

and it is real, but it’s one of those things

that’s a combination of organic and inorganic disease,

almost kind of like fibromyalgia,

where it’s definitely real,

and there’s lots of things that you can do to help with it,

but it’s very unlikely to occur

if you stop taking your supplement or medication

after you have side effects.

Interesting.

Well, I certainly feel better

when I’m taking five grams of creatine monohydrate per day.

I know most people take it for muscle growth

and tissue repair and things of that sort.

Mainly, I think brings water

into the muscle tissue, et cetera.

But I take it for the brain effects,

and also because I like to think

that it gives me a little bit of a DHT bump

that I can actually see in my blood charts

when I’ve done them.

I know many people want to avoid the hair loss

that can sometimes be associated

with DHT levels going too high.

And so I’ve been asked many times,

does creatine monohydrate cause hair loss?

It would make sense that if creatine increases DHT and DHT,

binding to the androgen receptor on the scalp

can induce hair loss, that that would be the case.

Is that true, or are people just overly concerned

about something that’s trivial or non-existent?

Each male, and so yes, it can potentially add it.

I don’t like to say it causes it,

but it can be a little bit more fuel to the fire.

So just like everybody has a different sensitivity

of their androgen receptor,

they have a different amount of gene transcription

that is going to cause death of the follicle.

That’s an arbitrary threshold.

So you don’t really know until you start losing hair.

And if somebody takes a little bit of creatine

to increase their DHT,

maybe for the cognitive enhancing effects

or for whatever reason,

and they notice a little bit more hair

falling off out in the sink,

and they stop taking it,

you said death of the follicle, which sounds very dramatic.

Are those little stem cell niches

that reside in the follicle, which hairs grow from,

are those then abolished?

Like there’s no going back,

or can one rescue the hair?

It takes months.

If they’re still there,

the hair will come back.

So the loss of the hair itself

is a normal part of the hair cycle.

So you have your antigen phase,

your catagen phase, your telogen phase,

and then your hair loss,

and then a new follicle.

Of the stem cell niche in the hair follicle.

Think of it like sharks have teeth.

So a shark loses a tooth

and they have a new one that comes through,

or losing your baby tooth and you have a new one,

but your hair just always keeps coming through.

So it’s natural for it to die and lose.

That’s why when you start 5-alpha reductase inhibitors,

often you have a big shed.

So what happens during that big shed

is all of these cells that are unhealthy,

they immediately jettison that hair,

and then they start making a much healthier new follicle.

So out of the hairs

that are at the end of their telogen phase,

then they have what’s called telogen effluvium,

which also happens after pregnancy,

also happens in thyroid pathologies.

So you shed it, a new one comes in place,

and you think that you’re having a horrible hair loss

caused by your finasteride or whatever you’re doing,

and minoxidil does this too,

but you’re really just having a new, healthier follicle.

If you go a really long time, if you go a year,

then those hairs might come back and they might not.

So for simplicity’s sake,

if somebody is concerned about

or is experiencing hair loss, male or female,

what are their options of ways to offset that hair loss

that are not going to negatively impact

other tissue sensitive to DHT?

And what I’m basically saying here is,

I could imagine taking a DHT inhibitor,

a pill of some sort or an injection of some sort,

and offsetting hair loss,

maybe even stimulating more hair growth.

It’s clear that I’m not doing that,

but I know people that do,

but then experience some of the other negative effects

of blunting DHT, reduced affect, reduced libido,

reduced drive, disruptions in prostate function,

or even sexual function generally.

So what can people do if they want to maintain

or grow back hair,

but they don’t want all those other effects?

What should they avoid?

And what should they perhaps consider

talking to their doctor about?

There’s a whole host of options.

I try to separate alopecia or hair loss

into two different categories,

male pattern baldness or androgenic alopecia,

also known as androgenetic alopecia,

versus other types of alopecia,

usually telogen effluviums.

And if it’s androgenetic alopecia or male pattern baldness,

even if they’re female, perhaps say PCOS,

something like that,

then you want some sort of strategy

to decrease the activity of that androgen receptor.

So women can get male pattern baldness?

Absolutely.

Okay, I’m gonna have to wrap my head around that one,

but okay.

So there’s a lot of different things

that you can do that are topical.

The most promising is called dutasteride mesotherapy.

Essentially what it is,

is it’s very localized injections in areas

that are prone to male pattern baldness,

whether they’re a female or a male,

and it acts locally only.

And you repeat these injections from time to time.

It decreases the conversion of testosterone to DHT

just in the scalp.

So that can avoid prostate effects.

And what are some of the negative effects

of blocking DHT in females in the periphery,

meaning not on the scalp or in the brain,

but where is DHT doing its stuff?

Yeah, so it’s both DHT

and then also that 5-alpha, 3-alpha progesterone,

which is called THP or dihydroprogesterone

or tetrahydro, trihydroprogesterone.

So they’re active in the central nervous system,

but it’s also just active, again,

binding to the androgen receptor in a female as well,

causing them to have that effort feel good motivation.

A lot of women that are sensitive to DHT,

because women can be sensitive to DHT as well,

feel very different when they start an oral contraceptive,

not because it alters their DHT to a huge amount.

It does to some degree

because of the negative feedback inhibition

in the pituitary and less produced in the ovaries,

but it increases SHBG really high.

So because their SHBGs are significantly higher,

their free DHT is way lower.

Let’s see.

How does a woman know

if she has PCOS, polycystic ovarian syndrome?

What are the issues with polycystic ovarian syndrome?

What can be done about PCOS?

I confess I was naive to PCOS.

That wasn’t supposed to rhyme,

but since it does, I do confess I was completely naive to it

and I started getting a lot of questions about it

in various forums.

And I think that’s actually the reason

why I initially approached you.

I know you have treated a lot of PCOS.

What age women should be thinking about PCOS?

What’s PCOS?

Teach us about PCOS, please.

So PCOS is polycystic ovarian syndrome.

And this is one of those conditions which is underdiagnosed.

So its prevalence is much higher than we think it is.

There’s been a lot of studies

and some studies say prevalence of 10%, some say 20%.

It’s not completely clinically penetrant.

So most people don’t know they have PCOS

until they have infertility or subfertility.

And is PCOS happening at this frequency

in 20-year-old women and 30-year-old women

and 40 and onward?

Most women find out they have PCOS in their 30s,

especially it’s on a spectrum or a continuum

like a lot of things where you can have a weaker version

or a very severe version.

What are the symptoms?

There’s a criteria called the Rotterdam criteria.

And in the Rotterdam criteria,

there’s a couple of different ways that you can diagnose it.

You’re looking for androgen excess, insulin resistance,

and you can also look for polycystic ovaries.

You don’t actually have to have polycystic ovaries

or get an ultrasound of your ovaries to be diagnosed.

If you have androgen excess, for example,

androgenic acne or hormonal acne.

If you have hair growth, like a hair growth on the chin,

it’s called a hirsutism.

Or if you have, you know, like deepening of the voice,

at any symptom of too much male pattern baldness,

if you’re a female, that’s a symptom of PCOS as well.

Then you can also have insulin resistance.

So this is obesity, it’s prediabetes,

a high fasting insulin, a HOMA-IR over two,

and a fasting insulin of over six.

So if you have significant insulin resistance

and also androgen dominance, that’s a sign of it.

Androgen dominance often leads

to what’s called oligominorrhea.

So if you’re having more than 35 day intervals

in between a period, or if you have less than nine per year,

then that can be a sign that you have oligo,

which means too little, minorrhea, which means menses.

So that’s a very common sign of PCOS.

If you have infertility, so if you’re under the age of 35

and you’ve been trying for more than a year,

or if you’re over the age of 35

and you’ve been trying for more than six months,

then that can also be, it’s a very common

presenting complaint when somebody presents with PCOS.

And assuming that a woman is doing all these other things,

is paying attention to the six pillars

that you talked about earlier,

diet, exercise, caloric restriction, in some cases, right?

Not everyone needs to be caloric restricted.

Stress, sleep, and sunlight, spirit.

Assuming that they’re doing all those things,

what other things in the realm of diet or supplementation

can help them avoid PCOS if they have subclinical PCOS

or they have not developed it, but don’t want to develop it?

Because it doesn’t sound like a good thing.

Yeah, so depending on where they are,

if they’re very strong on the insulin resistance spectrum,

then optimizing their body composition,

decreasing their body fat,

and treating that metabolic syndrome can help.

So a lot of people ask, well, does everybody that’s on,

like, does everybody need to be on metformin that has PCOS?

Not necessarily, but metformin is one of the tools

that can help with insulin sensitization.

Other tools that can help are inositol.

So myoinositol is an insulin sensitizer.

It’s cousin, D-chiral inositol, is a weak antiandrogen.

A lot of types of inositol have both of those in it.

So depending on if you’re a female or a male

and you’re on inositol, the type of inositol does matter.

Yeah, this is a very important point.

Just today, I said, I’m trying this new supplement,

inositol, for its role

in perhaps enhancing sleep even further.

My sleep’s generally pretty good.

Lately, it’s been a little bit off for a number of reasons.

So I took it for the first time last night

and I said, I thought it helped, just subjectively.

And you said, what kind of inositol is it?

Because inositol is a very potent androgen inhibitor.

It turns out I was taking myoinositol,

which is not an androgen inhibitor.

The other type that you mentioned,

which is an androgen inhibitor, is D-chiral inositol.

It’s usually in a ratio of one to 25 or one to 40.

In a much lower amount compared to myoinositol.

In a supplement or in the body?

In a supplement to help induce ovulation.

But for women who have PCOS,

who might want to try and reduce androgen,

then they would perhaps want to take a form of inositol

that reduce the androgen receptor activity, correct?

They want both.

So if you’re a woman and you’ve ever talked to your doctor

about getting on the oral contraceptive or spironolactone,

which is also an anti-androgen,

but it happens to be a potassium-sparing

diuretic blood pressure medicine as well,

D-chiral inositol might be a better option.

DIM or diendomethane is another kind of weak

anti-estrogen, anti-androgen

that a lot of women should consider as well.

You mentioned oral contraception.

I’ve done a few posts on these, let’s just call them,

they really are perceptual effects

whereby it’s been demonstrated in humans several times now.

And what would appear to me to be very solid studies

where women that take oral contraceptives,

there is both a shift in their perception of men,

because these studies only looked at heterosexual,

the sort of arrangements here,

where women who are on oral contraception,

because it blunts some of the peaks and valleys

of hormone output,

no longer experience the same peaks and valleys

in their assessment of other men’s attractiveness.

So it sort of flattens their perception, so to speak.

They still find certain men attractive

and certain men unattractive,

but the degree of difference is kind of mellowed out.

And likewise, these data say that men

perceiving women’s attractiveness,

they still see women on oral contraceptives as attractive,

but a woman taking oral contraception eliminates

this kind of peak in her attractiveness

that men would otherwise perceive.

In other words, oral contraceptives are changing the way

that we perceive each other,

at least in terms of these male-female experiments.

What is going on with that?

Is that because oral contraceptives

blunt the increase in testosterone

that occurs just before ovulation?

Or is it because of a complex cascade?

What is going on?

I find this fascinating.

Yeah, so there’s differences in how your,

and I wouldn’t use the word change necessarily,

but alter the severity or alter the peak, as you said.

So it’s just like TRT is not gonna change you as a person.

An oral contraceptive will not change you as a person.

It will just change your day-to-day peaks and troughs

in libido and attractiveness.

So one of the main effects of oral contraceptives,

almost all of them have a synthetic estrogen

and a synthetic progestogen in them.

One common type of synthetic estrogen is ethanol estradiol.

There’s another new synthetic estrogen

that’s out there as well, but that anecdotally,

that seems to have even more side effects.

So this ethanol estradiol is 100 times more potent

than endogenous or bioidentical estradiol in the liver.

So it binds to the estrogen receptor in the liver,

and it’s going to increase sex hormone binding globulin,

which secondarily, as you mentioned,

decreases your free testosterone

and especially your free DHT.

So that little testosterone hump that you get

when you’re a female that’s ovulating,

that’s really flatlined.

And it’s already, it’s a pretty insignificant difference.

It’s not negligible, but it’s a little bit of a hump,

and you have significantly less of that

when you’re on an oral contraceptive.

And does that blunt the associated increase in libido

that normally would occur from that increase in androgen?

Yes. Interesting.

What about other forms of contraception, right?

Because there’s copper IUD, there’s various implants,

there’s rings, there’s a huge number

of different forms of these.

So what we’re talking about is, as I understand it,

is only the effect of oral contraception

that impacts hormone output.

Is that correct?

Yeah, there’s a lot of other effects as well.

For example, your choice of synthetic progestin

will alter how high your platelets and SHBG go.

It appears to be the higher your platelets

and the higher your SHBG, the higher risk of a blood clot.

So a lot of women know that

if they’re on an oral contraceptive

and they’re already predisposed to a blood clot

or a venous thromboembolism in their vein,

they have a blood clot in either their leg or their lung,

then it can increase that chance.

So you can choose a synthetic progestin

that is not going to have as high of a response,

but there’s various pros and cons.

Some synthetic progestins are weak antiandrogens as well.

For example, there’s one known as Slend,

which is made from spironolactone.

So some women are on spironolactone and that as well,

which is made from spironolactone,

which probably isn’t particularly necessary

unless they need it for a diuretic or hypertensive effect.

I see.

I’m just gonna intentionally interrupt and I apologize,

but specifically because I wanted to ask about,

there is this notion that oral contraception

taken over long periods of time can disrupt fertility

in ways that are independent

of just the age-related decrease in fertility.

Is that true?

It depends on what you mean by a long time.

Six to 12 months, it’s possible.

Past that, it seems very unlikely.

However, the persistently elevated SHBG

can be present for quite some time.

Wait, so if a woman takes oral contraception

for six to 12 months and then stops,

will she essentially be where she would have been anyway

in terms of her fertility at that age?

Or are you saying that it can cause permanent damage?

Her fertility would be equitable

as if she had never taken it,

if she’s certainly 12 months, but probably six months off.

And what if she,

I know of women that have taken oral contraception

for many years.

In addition to the age-related decline in fertility

that occurs, that’s inevitable.

Of course, the slope is gonna be different

depending on the individual,

but are they quickening the transition

to infertility?

Probably not.

You could make a case that

because they’ve been in an oral contraceptive,

they may have been slightly more predisposed

to insulin resistance and or lower lean body mass.

But that’s probably gonna be a negligible difference

compared to their resistance training

and also their caloric restriction or caloric maintenance.

And of course, there are also effects of having children.

Yeah.

I mean, on all these parameters, right?

Because it’s a major lifestyle shift, right?

That obviously people contend with

and have for since the beginning of human time anyway.

I wanna ask some questions about male hormone therapy

and male hormones generally.

But before I do that,

I have a couple of burning questions that I get very often

that I’m just gonna insert now.

Marijuana.

I’ve heard that it can decrease testosterone

in men and women.

I’ve heard that it can increase testosterone.

Alcohol.

I think there’s general consensus that high alcohol intake,

high barbiturate intake does in fact reduce testosterone.

What about modest increase of alcohol?

I’m not a drinker,

so I’m not asking these questions for me.

I don’t smoke pot and quite over.

I just never really liked marijuana or alcohol.

They’re not my thing.

But many people want to know the answers

to these and the data that I’ve seen

are very confused and conflicting.

So what about marijuana?

Does it reduce testosterone to a significant degree or not?

Cannabinoids itself, whether it’s THC or CBD,

are not going to reduce testosterone by themselves.

If it’s smoked marijuana,

then it’s very likely to increase your aromatase,

which increases your estrogen.

And it’s aromatizing from testosterone.

So that is going to decrease testosterone.

When you have an increased estrogen, like estradiol,

that’s gonna work on your pituitary

to make less hormones that cause the release of testosterone.

So you’re gonna have less LH and less FSH.

So it’s almost kind of like opiates

are well known to opiate agonists.

They’re going to decrease LH and FSH

and subsequently testosterone.

Smoked marijuana will as well.

As far as alcohol, high alcohol will decrease testosterone

as will any very potent GABA agonist,

whether it’s a barbiturate or a benzodiazepine

or a non-benzo or alcohol.

They’re definitely going to.

Moderate alcohol, I guess it depends

on what your definition of that is.

I guess I’m thinking like some people I know

that don’t seem to be alcoholics,

at least by my assessment,

will have a glass or two of wine four nights a week,

which to me seems like a tremendous amount

only because I don’t like alcohol.

I don’t have a problem with other people liking alcohol,

but I think for many people,

that would be considered low or moderate intake.

Yeah, I would consider that low intake.

The American Heart Association for men recommends

between one and two drinks a day on average.

They recommend it.

Yeah, so around one per week.

Wait, so I’m making my heart less healthy

by not drinking alcohol?

Yeah, they recommend a very low amount

of alcohol intake for men.

For women, they recommend zero to one.

So that’s kind of hard to interpret, the zero to one.

But the protective effect of alcohol,

especially if it’s a red wine with polyphenols in it,

outweighs the deleterious effect.

Interesting, because I’ve seen some studies

that point to the idea that even low intake of alcohol

over a prolonged period of time

might actually decrease brain volume

or at least volume of particular brain areas.

But of course, we don’t know the consequence

of decreasing the volume of a given brain area either.

I mean, one can imagine it’s decreasing

the size of one’s amygdala and making them less stressed,

although there’s no evidence to support that.

I’ve been told that I need a drink many, many times,

but I always reply that I don’t need to drink anything

in order to speak my mind.

So again, individual differences.

Very interesting.

So it sounds like smoked marijuana

may in fact reduce testosterone

or at least increase the conversion

of testosterone to estrogen, correct?

Okay.

And with alcohol and GABA agonist,

it’s important to remember that it shouldn’t be daily.

So one drink of alcohol a day

is actually very mildly immunosuppressive.

So it’s better to have two drinks of alcohol

one day of the week,

and then two more drinks of alcohol another day of the week,

and then no alcohol the rest of the time.

The same could be said even for supplements

that have GABA in them.

A lot of sleep supplements have gamma-aminobutyric acid,

which is GABA.

Yeah, I occasionally take, oh, sorry to interrupt.

I occasionally take 100 to 200 milligrams of GABA

in order to enhance sleep,

but I do it maybe every third or four nights,

no more than three or four nights a week.

Yeah. Yeah.

That’s perfect.

Okay.

So there’s a lot of sleep supplements

that should not be taken daily,

and GABA is one of them.

Another one of them is trazodone,

and melatonin is kind of arguable,

and it depends on the situation.

But in general, if you’re taking a sleep supplement,

it should not be taken every night.

The sleep supplements that I understand are okay

to take every night or nearly every night

are things like magnesium, threonate, apigenin.

If that’s not true, correct me.

I certainly take them every night

unless I forget them back home when I’m traveling.

Magnesium is one of the exceptions.

L-theanine is also another exception.

Great.

Well, then at least I haven’t put anything into the world

that’s wrong in that category yet, and hopefully I won’t.

But if I do, I’ll correct myself.

So let’s talk about testosterone in males.

You see these headlines all the times now

that testosterone levels are dropping,

sperm counts are dropping,

phenotypes of men are changing over time,

and I can’t quite follow the literature on that

because obviously those are hard-controlled experiments

to do because techniques change over time,

and sensitivity of techniques change over time.

But regardless, I’m aware that a lot of people

are considering increasing their testosterone

by taking testosterone.

A few years ago, that was considered steroid use,

and it was really extreme kind of stance.

Nowadays, it seems like there’s more discussion about it.

First off, I’d like to know,

does testosterone supplementation,

and here I’m talking about prescription from a doctor,

does it make one more prone to prostate cancer?

That seems to always be the first question that comes out.

Yeah, and there is a huge amount of misinformation

about this too.

So testosterone is not going to cause a prostate cancer.

However, normal aging causes prostate cancer,

and testosterone will grow your prostate cancer.

So if you’re a 80-year-old male and you have an autopsy,

then there’s at least a 50% chance

that you have a prostate cancer.

If you’re 90 or 100 years old,

there’s at least a 90% chance.

So for humans with a prostate,

it’s only a matter of time until you get a prostate cancer.

So that begs the question,

do you want to take something that’s going to grow it

for sure once you have it?

So it’s an individual assessment,

and it’s important to follow things like PSAs as well.

So a PSA of four or less,

I mean, ideally you wouldn’t be at four

because that’s kind of the upper threshold,

is the simplest readout of whether or not

there’s excessive prostate growth.

There’s benign prostate hyperplasia

where the prostate is growing,

but it’s non-cancerous, correct?

And then of course there are the symptomologies,

like people have challenges with urination,

they have sexual difficulties, et cetera.

I’m always struck by the correlation that people draw

between testosterone and prostate health,

and the fact that, or I should say the claim

that testosterone makes prostate health worse,

because if you think about it,

young males have high testosterone often,

if not always, certainly often,

and you don’t see a lot of prostate overgrowth

and cancer in young males.

So something’s going on here.

How should we conceptualize this?

So if you have a PSA of 3.9,

and you’re a 25-year-old male versus a 75-year-old male,

and you have a PSA of 5.9,

the 3.9 PSA is significantly more concerning.

So think of your prostate as taking cumulative damage

from not only testosterone,

but also estrogen and also growth hormone.

So that’s why obese individuals

have higher incidences of prostate cancer as well.

It’s because they don’t have those cell checkpoints

where your immune system takes a second and says,

all right, stop replicating as fast prostate cells.

Let’s see if there’s any atypical ones.

And then it finds those

and it prevents them from reproducing.

That’s why immunotherapy and cancer is so promising

is because they can target these certain things.

So the older male

is going to have that cumulative damage happen already.

And arguably, prostate cancer is a normal,

with aging, fast aging is abnormal.

Very slow aging is normal.

There’s a fine line to walk between those two,

but there’s a lot of things that can be done

to decrease the turnover, decrease the inflammation,

and decrease the congestion of the prostate over time.

There’s also a lot more than just PSAs that can be done.

There’s prostate MRIs and things like that,

that can look at the structure

and the function of the prostate.

So what should every male do

to maintain the health of their prostate?

And I realized that younger males

probably aren’t thinking about it at all,

although it seems like nowadays,

I get these kind of what I call cryptic questions.

I think women are more comfortable

talking about their hormone and sexual health

because of menstrual cycles.

They’re used to fluctuations

that sort of give them the experience

of what it’s like to have different levels

of progesterone, estrogen, testosterone, et cetera.

But I get these kind of cryptic questions

often in my direct messages

where what I think people are asking is,

is there something wrong with my prostate?

What should I do for my prostate?

These are often indirect questions

for other aspects of their life where they’re suffering.

But, and I don’t say that in jest,

I think more direct discussion would be great.

So what should all males do

to maintain prostate health throughout the lifespan?

Maintaining prostate health can be looked at similarly

how you can maintain a good, natural, optimal testosterone.

So you look for things that can hurt it.

You don’t necessarily look for one thing

that can improve it or boost it.

So for young males, those are prostatitis.

So it goes hand in hand with epididymitis.

So different infections of the prostate.

The younger the male is,

the more likely it is related to something

that could be sexually transmitted.

But another very common cause is what we call

gram negative and anaerobic bacteria.

The prostate is right by the end of the colon.

So if you have chronic constipation or if you have colitis,

or if you have, you know,

even just an E. coli overgrowth in the colon

is very likely to cause an infection

of the prostate as well.

What should males do to prevent that?

Have a diet that has good, healthy prebiotic fiber,

probiotics as well.

Make sure that they’re having regular bowel movements,

that they don’t have chronic constipation.

Have good sources of dietary fiber,

which is also known as soluble fiber,

and enough insoluble fiber.

Most people get enough insoluble or non-dietary fiber.

So that can help prevent the chance of diverticulitis,

which is another type of infection.

It can also decrease the chance of colitis

and decrease the chance of prostate infections as well.

Are there any foods and or supplements

that men should take or avoid?

What about, you hear about salt palmetto,

or supplements that support

or cause issues for the prostate?

Yeah, if there’s a strong genetic predisposition

to enlarged prostates,

or even just really early prostate cancers that grow fast,

then they can consider taking salt palmetto,

or even curcumin as an antiandrogen,

as long as they’re able to tolerate it.

It’s an individualized basis and depends on their history.

As far as making sure that their prostate is not congested,

there’s an interesting correlation

between having girls and having prostate cancer.

Having girls offspring.

So if your offspring are females,

then you’re slightly more likely to have prostate cancer.

There is some, there’s hypotheses that link estrogen

to prostate cancer rather than testosterone.

So if you have hyperestrogenism,

your prostate has more atypical cells.

In general, the higher your C-reactive protein,

which is the general marker of inflammation in your body,

we’d call it CRP,

and the test order is HSCRP or high sensitivity CRP.

If your CRP raises up very high,

if you have an autoimmune disease,

like if you have a Crohn’s flare,

or if you have a lupus or an infection,

or a sexually transmitted infection,

or even colitis, or even the flu,

your CRP is gonna raise significantly.

That you would detect in a blood test, of course.

Correct, yeah.

So you wanna get a baseline CRP

when you haven’t had any of those things recently.

And if your CRP is higher,

you also have more female offspring.

If your CRP is higher,

then your reactive oxygen species,

which are causing mutations and atypical cell turnover

in the prostate, are also likely higher.

So you wanna keep a very low CRP.

And what about blood flow and pelvic floor in general?

We should probably do a whole episode on pelvic floor.

You know, there’s so much interesting data

coming out of the fields of clinical and research urology.

I realize it’s kind of the Netherlands

of biology and medicine.

People probably aren’t thinking so much about this,

but pelvic floor is obviously a confluence

of a ton of vasculature, of nerves,

and of course the prostate resides there,

and of course the genitals reside there as well.

So I would imagine that one of the six pillars,

you know, exercise, being able to maintain

adequate blood flow to those regions is key.

What about just postural things?

People sitting too much, not hydrating well enough.

You mentioned avoiding constipation.

What are some other things, including medications,

that can serve to support the prostate over time,

and maybe even support pelvic floor in general,

both in males and females over time?

Absolutely, and this is something

that’s rightfully getting more and more attention.

The way I explain the pelvic floor

is your abdominal cavity,

which includes your peritoneum,

or where most of your organs are,

your retroperitoneum, your pelvic space.

Think of it as a box,

and your abs are the front of the box.

Your back muscles are the back.

Your diaphragm is the top of the box.

And your pelvic floor,

that’s where your port is to the outside world.

Especially important, it has muscles as well,

and you can do exercises.

Pelvic floor physical therapists

are becoming more and more utilized,

especially after childbirth,

but in other situations as well,

including by men getting care from urologists.

So you want to both strengthen that pelvic floor,

and make sure that the tubes

that are docked to the outside world

are working well enough, but they’re not too loose.

They’re not working too well.

So there’s a lot of medications

that can be positives or negatives for your pelvic floor.

We kind of talked about your gut

and colon health in general.

As far as your prostate health,

and as far as your bladder and urinary system health,

you think about a couple of different classes.

So you have your phosphodiesterases.

You have your Tadalafil.

Basically, this is gonna help decrease congestion

in the prostate.

A lot of people take it for ED,

but it can actually help you decrease your-

Could you define that?

A lot of men take Tadalafil.

It’s generic is Cialis.

Has a much longer half-life than Viagra or Levitra.

It’s half-life is almost a day.

So you can take a very low dose of it.

Instead of taking 20 milligrams,

you take two or two and a half milligrams.

So they’re taking,

you’re saying that a lot of men take it

for erectile dysfunction,

but that at lower doses,

it may have served purposes for prostate health,

independent of erection.

Correct.

The most common scenario is

if a male is waking up twice at night to pee,

on average, it’ll cut that down to once.

So if they’re waking up at four times at night,

then it can cut that down to twice at night,

just because you have easier blood flow.

We used to use other medications like Flomax,

which is Tamsulosin.

That’s an alpha antagonist.

So it basically binds to a receptor in smooth muscle,

and it helps relax that.

There’s several other alpha antagonists.

And then you also have your medications

that are hormonal like finasteride

that a lot of people take for prostate health

to decrease the enlargement of the prostate,

the periurethral area or periurethral lobe.

There are several lobes of the prostate

that tends to be especially enlarged in cases of BPH.

And BPH?

Prostate hyperplasia or an enlarged prostate.

And if you are able to shrink that area,

then at that point, it’s just a plumbing problem

and the urine is able to get by easier.

Yeah, my understanding is that now there’s a growing,

I don’t wanna say a movement,

but the idea of taking very low dose,

like 2.5 milligram or five milligram Tadalafil even daily

is becoming pretty common for many men

who do not have erectile dysfunction

simply to either maintain or enhance prostate health.

Is that correct?

Yeah, that’s correct.

Do you see any negative effects of doing that?

There can be negative effects.

It can lower blood pressure.

So theoretically, it can increase your chance

of vasovagal syncope.

A lot of people take it as an alternative to pump

because it kind of works similarly to citrulline

or a different pump products in pre-workout.

And it can certainly help with that.

But if you’re about to go do a deadlift

where you might pass out anyway,

it can certainly increase the chance that that happens

because you don’t have

that compensatory exercise hypertension response.

Could someone just take it away from exercise?

They could.

If you took Tadalafil,

then that’s gonna be, has a long half-life.

Whereas Viagra and Levitra is just a few hours,

Tadalafil is almost a day.

Some interesting studies on Viagra have been done as well.

It can potentially alter your rays and cones in your eye.

So the usual recommendation for pilots

that need to have red-green discrimination

from very long distances with very small indicator lights

is to not take Viagra.

So I usually say, if you’re a pilot and that’s your

profession, perhaps hold off from that for a while.

There’s also studies with Viagra that significantly,

which is also known as Sildenafil as the generic now,

it can increase eyebrow hair growth.

So potentially what it does is it helps vasodilate

and relax the veins, especially in older men.

And when those veins are relaxed,

you have better blood flow.

That’s one of the proposals or theories

behind why older men get the androgenetic alopecia more.

You’re having less blood flow in the scalp.

So theoretically it can also help prevent that.

So in theory increasing blood,

oh, because it increases blood flow systemically

throughout the body, not just in specific tissues.

Well, I find it incredibly interesting that,

yeah, there are these online forums building up now

around low-dose Tadalafil,

daily use of low-dose Tadalafil,

again, not for sexual or erectile dysfunction,

but for sake of long-term prostate health.

Is there any reason why women might want

to take low-dose Tadalafil?

Tadalafil is also a weak androgen receptor sensitizer,

kind of like L-carnitine,

where the density of the available androgen receptors

to bind increases slightly.

So there could potentially be a benefit from that,

but most of the time it’s used in men.

Very interesting.

We haven’t really talked about testosterone

and optimizing testosterone in males.

Assuming someone is paying attention to the six pillars,

there’s a kind of a gap, as I see it,

between doing all those things

and TRT, hormone replacement therapy.

And again, the R, the replacement in TRT

is a little bit of a, in quotes nowadays,

because a lot of people who have testosterone

in that 300 to 900 nanogram per deciliter range

opt to take low-dose testosterone anyway.

My understanding is that there’ve been some new

kind of movements in this area toward, for instance,

not doing big, large doses injected infrequently,

but rather low doses quite frequently.

Obviously prescribed by a doctor,

monitored by a doctor, et cetera.

Is that generally what you like to see in your patients

if they’re gonna take this route?

If they’re a hypogonadal patient

whose benefits outweigh risks of TRT,

then you wanna have a nice, even, steady state.

It’s not gonna be exactly the same

as producing pulsatile testosterone release endogenously

from your own body.

When you have a steady state,

you don’t have a peak or a trough.

And when you have a peak,

that’s when the androgen receptor gene is overactive.

That’s when you get more erythropoietin or EPO release.

And that leads to a lot of the side effects

of thick blood, so higher hemoglobins and hematocrits.

And then when you have a crash, you don’t feel good.

So it’s definitely not optimal.

There’s a lot of ways to get around this.

So when you’re doing testosterone replacement,

if you’re someone that needs it,

you can have different types of esters

or you could do topical testosterone.

So the ester is basically something that’s attached

to increase the biological half-life.

The most common ones are cipionate and anthate.

There’s also a very short-acting propionate,

which has almost no clinical relevance.

And there’s also very long-acting ones,

decanoate and undecanoate,

and different mixtures of all those.

So if you’re someone who has a very, very low SHBG,

you’re gonna have trouble

of regulating your serum testosterone in the long run.

If you do it topically, then the testosterone is absorbed,

hopefully bound to SHBG.

And then a lot of times you reapply twice daily

or once daily, but you have lots of variations.

So for most people,

especially for people who can’t absorb it well,

that’s not gonna be a great option.

So injections would be preferred?

Most people end up injecting

because they have either side effects from too high, too low,

or just too much of a varied dose when they do topical.

There’s also a capsule with a special lymphatic absorption.

So it’s not being absorbed through the liver.

It’s not hepatically metabolized,

but it’s absorbed through the lymph.

And it’s essentially the testosterone undecanoate

and then put into a capsule.

So, and that’s taken twice daily.

It has fairly steady half-lives,

but you have to take it at specific times of the day.

So that being said,

and it’s new enough to where there isn’t a huge amount

of data on it, but it is FTA approved.

So it is brand name now.

It’s called Jitenzo.

But the injectables in general, the lower your SHBG,

the longer of an ester you want,

because when you inject it,

whether it’s intramuscular or subcutaneous,

just talk to your doctor about the risks

and the benefits of those.

Subcutaneous has slightly longer active half-life

because the esterases take longer to reach that cipionate

or an anthe ester to cleave it.

So most men, a lot of people ask me

about like what a usual dose is.

For most people, it would be a total

of about 100 to 120 per week for an actual replacement dose.

Milligrams.

Milligrams, 120 to 100 milligrams per week,

administered two to three times per week.

And you’re not, so you’re saying dividing that

into two or three, right?

Because I’m sure there’s a bunch of people out there

thinking, oh yeah, 100 three times a week,

which is actually quite, quite high dose.

Yeah, there really does seem to be a shift

toward spreading these dosages out into,

dividing them into two or three smaller doses.

And then along those lines, five, 10 years ago,

it was common to hear about inhibiting estrogen

through aromatase inhibitors.

Nowadays you hear, and I think it’s true,

at least by my read of the literature,

that inhibiting estrogen can disrupt brain function,

can cause connective tissue issues,

and even can cause reductions in libido.

So a lot of people think that estrogen,

if you crash estrogen, that basically libido goes up,

but actually the opposite is often true.

You don’t want estrogen too high or too low.

Is that correct?

And for that reason, do you shy away

from people taking aromatase inhibitors?

Yeah, very few people truly need an aromatase inhibitor.

There’s almost always lifestyle interventions.

It can just depend on which gene,

how active your aromatase gene is.

Some people’s aromatase gene is very active.

A lot of times these individuals

have pubertal gynecomastia,

which is breast tissue growth in males,

even despite no other risk factor.

Even if they’re lean?

Some people get it if they’re lean.

I remember growing up, there were a few kids

that got mild cases of gynecomastia that were transient.

Like it’s sort of like they developed gynecomastia

and then it went away.

Often it’s unilateral on one side too.

So growth hormone a lot of times is the fuel to that fire.

Oh, interesting.

Yeah, there were a couple of kids.

I mean, they took some teasing

because back then there wasn’t online discussions

about hormones and things like that,

but then it would seem transient.

And the people I’m thinking of

were actually lean individuals.

So they weren’t overweight,

which of course can cause gynecomastia

because adipose fat tissue

can convert testosterone into estrogen.

So it sounds like, except in special cases,

that avoiding aromatase inhibitors

is probably going to be a good idea.

There’s several other ways

that you can control your estrogen

and keep it at a healthy level,

which you do have to check.

There’s a lot of patients who assure me

that their estrogen is going to be sky high

and it’s actually very low and vice versa.

But calcium deglucrate is a supplement

that can help with estrogen control.

What’s a typical dosage of calcium deglucrate?

500 to 1000 milligrams.

But is there the risk that if someone’s estrogen

is in normal range and they take the supplement

that their estrogen will go too low, is it that potent?

It’s not that potent.

It’s not near as potent as an aromatase inhibitor.

So it helps with excretion

and also the sensitivity of the estrogen receptor itself.

It kind of like helps out-compete it.

Some people also take DIM

or different cruciferous vegetable.

They get them from cruciferous vegetables like kale

or broccoli.

And that is both an anti-estrogen and an anti-androgen.

So if you’re on TRT and you’re on that,

then you’re probably just on too much TRT.

Yeah, I remember a few years ago, I had a friend

and it truly is, it’s not like I have a friend thing

because I’m very cautious about which supplements I take.

I think people might get the impression

that I’m very cavalier about this, but I’m not.

I always alter one thing at a time.

I talk to physicians, what I suggest other people do,

I actually do and have done for a long period of time.

And I recall wanting to take DIM

because I thought, well, back then you hear,

okay, reduce estrogen.

My estrogen levels weren’t out of range, so they were fine.

And I thought, well, what would the experience

be of bringing those down?

But someone I know is quite informed in this area said,

yeah, exactly what you said,

which is that DIM can reduce estrogen, but also testosterone.

So I just never opted to try and take it.

I do want, we’re sort of erring in this direction,

but we went straight from the six pillars to TRT

or to what some people now call sports TRT,

which is basically code language for saying,

taking exogenous testosterone,

even though one doesn’t need it

to get into a semi-supra-physiological range

or a high-end, like 900 to 1,000 nanogram

per deciliter range.

And people always point out, I should mention that,

oh, well, in certain countries,

the high-end range is 1,200 nanograms per deciliter.

In the U.S. it’s 900.

And so if you’re 1,200, are you really supra-physiological?

All that aside, I neglected to ask about that gap in between

where individuals could think about supplementation,

meaning non-prescription approaches

to increasing testosterone.

And here we should probably also talk about things like,

is it true that ice baths increase testosterone or not?

Lifestyle factors that go beyond the six pillars

for increasing testosterone.

If you could comment on those, that would be terrific.

Supplements that are useful.

And it’d be wonderful if you could mention

where some of these same practices and supplements

might be useful for women as well as men

to increase testosterone

for all the reasons we talked about earlier.

Yeah.

So this is where a true individualized approach comes in.

When you’re talking about what dose of TRT you should be on,

one thing to keep in mind is the law of diminishing returns.

Quality of life is a subjective thing

and it’s different for each person.

So some people are more willing to give up

a little bit of athleticism or body composition.

Some people are more willing to give up

or not willing to give up libido or sexual health.

And as we mentioned earlier,

everybody’s androgen receptor is less or more sensitive.

So you can make a case that if somebody’s androgen receptor

is half as sensitive as somebody else,

the person with the less sensitive receptor

does need a level of 1,000 or 1,200.

There’s no great way to know that.

And you can alter the sensitivity of your androgen receptor

with things like L-carnitine and Tadalafil, as mentioned.

And we’ll definitely come back to L-carnitine

because I’m really intrigued by the data on L-carnitine,

both for women and men in terms of egg quality,

sperm quality, fertility,

and a bunch of other interesting effects.

So we’ll come back to L-carnitine.

But a lot of how you feel, the biofeedback or subjective,

I feel like this comes from the ratio

of your androgens to your estrogens.

And a lot of that is lifestyle.

So if someone’s also on HCG,

that could up-regulate aromatase as well.

HCG, you might want to just,

human chorionic gonadotropin used to be found in pregnant,

it’s still found in pregnant women’s urine.

But it used to be, believe it or not,

there was a black market for pregnant women’s urine

before this stuff was developed synthetically.

So in other words, what we’re saying is,

men typically would buy pregnant women’s urine

through black markets in order to get the HCG,

in order to get the testosterone-enhancing effects of HCG.

So in other words,

men were using pregnant women’s urine for HCG.

I do not want to know how they got it into their body.

Let’s just skip to what you were going to say next

Yeah, so that’s HCG.

There’s a lot of other things that up-regulate estrogen.

Alcohol significantly increases aromatase.

So if you’re very sensitive to estrogen,

then you probably shouldn’t even consume the two glasses

three times a week.

High-fat meals also up-regulate aromatase.

So if you’re on a ketogenic diet,

but you have hyperestrogenism,

then you should take care with that as well.

All kinds of fats or just saturated fats?

I’m not sure if it’s just saturated fats,

but fat definitely increases.

Both fat in your body and consumption

of a high amount of calories increases aromatase.

So it’s the ratio of testosterone to estrogen.

I don’t want to break your flow,

but since we’re talking about fat,

I have to ask since estrogen and testosterone

are both synthesized from the cholesterol molecule,

I’ve heard that ingesting some amount of saturated fat

can be useful because of the way that cholesterol

can serve as a precursor to these molecules.

Now, I once said on a podcast that I like butter so much

I occasionally eat pats of butter.

Somehow that got misinterpreted to mean that I eat

entire many pats of butter.

I’m saying like one or two pats of butter here and there,

and I have no guilt or shame about it.

My blood lipids are in great shape also, so I feel good.

But is it possible that people who are ingesting

too little of saturated fats could directly or indirectly

reduce or somehow disrupt the proper ratio

of testosterone to estrogen in men and women?

It’s theoretically possible, but it probably doesn’t happen

in developed countries, just like it’s theoretically

possible to have not enough omega-6 fatty acids,

but that probably does not happen in developed countries.

So I don’t need the butter pats,

but I’m going to do it anyway.

I’m just curious.

Yeah.

Okay.

Grass-fed butter has good omega-3 content as well.

So grass-fed foods in general, you know,

it’s not the end all be all,

and everybody doesn’t need grass-fed foods,

but they are one of the only sources of healthy trans fat.

So a naturally occurring trans fat comes from ruminants.

So ruminants, I think of like cows,

and the rumination in the different stomachs

can change your omega-3 and omega-6 to trans linoleic

and trans linoleic fatty acids.

Which are healthy for us.

Yeah, so it’s actually omega-3s and omega-6s

that just happened to have a trans instead of a cis isomer.

So, and these healthy trans fats would be found

in ruminant cheese and milk and butter from ruminants

and the meats?

Yes.

So, and for people who are following

a purely plant-based diet or mostly plant-based diet,

are they at risk of not getting enough

of certain types of fats or other nutrients

to maintain that healthy ratio

of testosterone to estrogen or not?

If they’re a vegetarian,

they’re probably not at risk.

If they’re a vegan, they very well could be at risk.

Most vegans are aware of this very acutely

and they’ll supplement with, you know, algae

or they’ll supplement with other sources of healthy fats.

I see.

So the takeaway that I’m drawing from this

is that less so than getting saturated fat,

it’s key to get these healthy trans fats from ruminants

or the food products of those ruminants,

as well as to get proper amounts of omega-3s.

And to be clear, you don’t need any trans fats.

It just happens that those omega-3s and omega-6s

are in a trans isomer.

I see.

Okay, so that’s nutrition.

What other supplements can support healthy testosterone

to estrogen ratios?

Anything that alters aromatase

can support healthy testosterone to estrogen.

And your testosterone to estrogen ratio,

think about it as how much estrogen activity

do you have at the beta-estradiol receptor

and your alpha-estradiol receptor.

How would I know that?

So it’s hard to tell, but depending on what you’re eating,

if you have a lot of plant-based diets or polyphenols,

many of these are beta-estradiol receptors.

People know about terkesterone and also beta-ectosterone,

which are two ectosteroids

that are beta-estradiol receptor agonists.

So they activate the beta-estradiol receptor.

So if you have a very low amount of estrogen naturally,

you’re probably a better candidate for it.

For taking terkesterone or ectosterone.

I’ve never tried them,

but I know my understanding

is that they work tremendously well for some people

and not at all for others.

And so one just simply has to try.

But in promoting the activity of this estrogen receptor,

is there a risk that terkesterone or ectosterone

could cause some of the quote-unquote problems

associated with increasing estrogen activity,

like reduced libido, water retention?

Water retention, yes.

Reduced libido, probably not.

Closing growth plates in the bone, no,

because that’s the alpha-estradiol receptor.

I’ve talked before on a couple of podcasts

about tongkat ali, which is this Indonesian herb.

I guess it’s also made and found in Malaysia,

but it seems to be the Indonesian variety of tongkat ali

that’s most effective for,

potentially for reducing sex hormone in binding globulin

and thereby freeing up testosterone.

Whether or not the effects are through that pathway,

through another pathway,

a lot of people report improvements in things like libido

and maybe androgen-like phenotypes, right?

Feeling more vital, et cetera.

And of course, some of that could be placebo, correct?

But what are your thoughts on tongkat ali?

And please challenge my statements about tongkat ali

if they’re incorrect.

I’m not looking for validation here.

I just really wanna know what your thoughts are on it.

Do you ever recommend it to patients?

When?

Men, women, one or the other?

Yeah, so tongkat ali, or longjack,

it has multiple mechanisms of action,

and there have been several

placebo-controlled studies on it.

Some of them show decrease in SHBG.

At least one of them did not show any change in SHBG.

However it is, it does act on aromatase very weakly,

probably not so strongly

that you would have to be concerned of hypoestrogenism.

So it reduces aromatase and thereby can reduce estrogen.

Correct.

It’s also a weak, it’s not a CIRM,

so it’s not a selective estrogen receptor modifier,

but it’s probably a weak, it’s probably an ERM as well,

or a non-selective estrogen receptor modifier.

And that should help

with decreasing negative feedback inhibition of estradiol

in various locations and also increasing testosterone.

Interesting.

Yeah, the dosage that I’ve been using for years now is,

I think it’s 400 milligrams taken once a day,

typically early in the day

because it can kind of have a mild stimulant effect,

very mild.

And I know that some of the products out there

recommend dosages that are much higher.

Anytime I’ve taken more than 400, I don’t feel very good.

I don’t know how to describe it other than

it’s just a little overly stimulatory

in terms of it makes me kind of,

it’s like drinking too much coffee.

So that’s interesting.

And so would women ever want to take Tonga Ali

for any reason?

Yeah, absolutely.

So there’s a lot of women that have hypoestrogenism

and unlike adrenal fatigue or andropause,

there’s actually ICD-10 codes for hypoestrogenism.

ICD-10 codes?

Yeah.

That’s doctor speak, right?

Yeah, so there’s codes to where your doctor

can actually diagnose you with something.

So if you go to your doctor and you say,

I have adrenal fatigue, they can’t diagnose you with that.

Or if you say, I have andropause,

they also can’t diagnose you with that.

But if you say you have hypoestrogenism,

the most common complaint that comes with it is endometriosis

which is overgrowth of the lining of the uterus.

And those people could potentially,

I think that’s one area where we might see

Tongkat supplementation more and more

because not only does it decrease aromatase,

like we mentioned, testosterone in females

is higher than estrogen in females.

So a lot of females get estrogen

from aromatization as well.

Peripheral estrogen is sometimes what we call it

because it’s not directly produced in the ovaries,

but they could be good candidates for Tongkat

if that’s the case.

Very interesting.

My understanding is that people should be looking

for sources of Indonesian Tongkat, in particular.

Correct.

Another interesting application is essentially a,

I’ll call it a PCT, but essentially what that means is,

PCT means, I’ll define it as post-cycle therapy.

Physicians love acronyms, scientists love acronyms,

military love acronyms, but yeah, PCT, post-cycle therapy.

So this would be people coming off

hormone therapy or steroids.

This would actually be for women

that are coming off of their birth control pill

because perhaps it can help lower that SHBG

back to normal, which is sometimes persistently elevated.

And then it can help prevent

the subsequent hyperestrogenism that happens.

Does Tongkat Ali need to be cycled?

When I first started taking it, I would cycle it.

I would do a few, three, four months,

and I would take some time off.

Now I’ve just been taking it continuously for years.

And I should say, I do blood work

to check my liver enzymes and everything else.

And I don’t see any reason for me to cease taking it.

Yeah, probably not.

There’s been human studies on both Tongkat and Fidoja.

And full disclosure, I did help design

Derek’s new testosterone optimization supplement,

which has both Fidoja Erestris and also Tongkat Ali in it.

Yeah, let’s talk about Fidoja separately in a moment.

But let’s say someone is only taking Tongkat Ali

for whatever reason, do they need to cycle off?

Likely not, but I would just to be safe

because it does both affect your aromatase

and it’s an estrogen receptor modifier.

And what would be a reasonable cycle off?

So how long to take and how long to stop

before taking again?

Yeah, there’s a couple different protocols that you can do,

but 11 months on, one month off for Tongkat

is pretty reasonable.

Now, I guess this is, we’ll talk about this later too,

but if it’s combined with Fidoja,

the protocol that I would do is three weeks on,

one week off.

So that’s Tongkat Ali, but I’m curious what your thoughts

are on Fidoja Erestris, this Nigerian shrub

or this extract from Nigerian shrubs

that at least in my experience,

in my read of the literature has the potential

to increase testosterone and probably other hormones as well

by way of increasing luteinizing hormone,

something that we haven’t really talked about

much up until now.

What are your thoughts about Fidoja Erestris?

What are your ideas about the proposed mechanism

or mechanisms and where might this be useful

for people on or off hormone replacement therapy?

Yeah, Fidoja Erestris has just reached a point

where we have enough evidence to we know it probably helps

both with luteinizing hormone release,

which stimulates latex cells in the testes

to produce more testosterone,

and probably with LH receptor sensitivity as well,

which is a good combination of the two.

It does come from the Nigerian shrub,

but there is not quite enough evidence

for me to be able to say it’s safe for somebody

to take this all the time, which again, full disclosure,

that’s why I recommended that we recommended

for people to cycle this supplement.

So three weeks on, one week off, that’s likely safe.

The only toxicity studies in general are in rats

and in humans, it looks quite safe.

My understanding is that the toxicity studies in rats

showed toxicity to the testicular cells.

So that’s certainly concerning,

but that the dosages that were used

or translating the dosages used to humans

would lead to a situation where the dosages

that humans would have to take would be very, very large.

So the amount of, I no longer take Fidoja,

but I took it at 600 milligrams per day for a long time.

And I ceased taking it because I was experimenting

with other things and I didn’t want to confound those things,

not because I had any negative side effects.

In fact, I was monitoring blood work

and other biological parameters that would have told me

if there was testicular toxicity and there wasn’t,

let’s put it that way.

Yeah, I think it’s extremely safe.

And I’m just not convinced

that there’s enough overwhelming evidence

for a long-term consistent administration.

So do you recommend this to people who are not taking TRT

and do you recommend to men and women?

Yeah, so if you have a really high LH,

then there’s probably a gonadal issue,

whether it’s heat damage to the testes, a varicocele,

a history of testicular cancer,

where your LH is going to be higher.

So if your LH is already very high,

increasing it even more is probably not going to help.

However, if your LH is low,

then obviously try to find out, is it low?

Is it deficient or is it just a little bit low?

If it’s low and you don’t have an issue with prolactin,

you don’t have an issue with opioid receptor antagonism,

then naltrexone can actually potentially help antagonize

that to increase LH as well,

especially in people recovering from opiates

or likely even alcohol.

So you’re looking for a subclinical secondary hypogonadism,

which is essentially, just think of that as low LH.

So in people with that lower LH and their estrogen is fine

and their prolactin is fine,

then Fidogia is a particularly good option.

Interesting.

So three weeks on, one week off for 600 milligrams Fidogia,

400 milligrams Tonga Ali, Indonesian Tonga Ali,

could potentially be good.

And of course, everyone should always check

with their physician, clear this, do blood work, et cetera.

I always say, we don’t just say that to protect us,

we say that to protect you,

meaning that the consumer is very, very important.

You don’t wanna get,

you don’t wanna fly blind with any of this stuff.

You want to do blood work, right?

That’s the catch 22 with supplements

is most of them are safer than medications,

but the only difference between them and a medication

is one’s prescribed and one’s not.

And oftentimes with supplements,

it’s unclear whether or not what’s listed on the bottle

is actually what’s in the bottle.

But I think there are a number of reputable brands now.

The other supplement I wanna talk about

in terms of testosterone augmentation is Boron.

What is Boron thought to do?

Does it actually do that?

And do you ever recommend Boron?

Yeah, so Boron is actually an element

and you can find it on the periodic table.

It’s more plentiful in rich soils.

So frequent farming can deplete the soils of Boron.

It’s very plentiful in the Mediterranean area,

like Greece and Turkey.

So a lot of people will just eat dates

or raisins that are grown there.

I thought you were gonna tell me people eat dirt,

but there are people who eat dirt.

There are people who eat dirt.

And there’s a phenomenon called pica, right?

Where people in a, and that’s not a good thing.

They-

Often a sign of iron deficiency.

Okay, but they’re eating grapes and dates

that were grown in soil that has high amounts of Boron.

Is that right?

Yeah, so Boron can help regulate SHBG,

but its effect is mostly acute.

So it’s unlikely to have a bad effect.

So a lot of people take Boron

because it’s probably not gonna hurt

and it will lower SHBG,

even if it is for a short period of time.

So I guess you can make a case

that maybe cycling Boron can help too.

What sorts of dosages are useful for Boron supplementation?

Three to six milligrams once to twice a day.

Oh, interesting.

So that’s higher than the amounts that I’ve been taking.

I’ve long been doing this cocktail of Tonga Ali.

Again, I stopped taking Fidogia,

but for a long time with Fidogia and Boron,

I think it was two to four milligrams per day,

but maybe that could afford to go higher.

Although my blood work is where I want it, thankfully.

So circling back to Fidogia,

Fidogia was attractive to me as a supplement

because I saw increases in LH,

testosterone and free testosterone.

My estrogen stayed in check,

but I also did not see a down regulation of LH

when I would cycle off.

Whereas with HCG, human chorionic gonadotropin,

which does now arrive in forms

not from pregnant women’s urine only,

but the synthetic forms that people inject,

that as I understand it can actually suppress

endogenous hormone output

if one takes it for a long period of time.

So why would a man or woman want to take HCG

and what are the potential risks and benefits of taking HCG?

Yeah, so HCG or human chorionic gonadotropin

is actually very similar to TSH.

Thyroid stimulating hormone.

Correct.

So when a woman is pregnant,

she produces more HCG, especially in the first trimester.

When you take a pregnancy test,

whether it’s qualitative or quantitative,

you see the HCG rise

and it actually doubles every 48 hours.

So if you’re five weeks pregnant, you can get an HCG level.

And then two days later, five weeks and two days,

you can see your HCG

and maybe it went from 500 to 1,000.

So it precipitously increases.

It does a few things.

One thing is it prevents hypothyroidism

or hypothyroxemia of pregnancy,

which is one of the most common causes of miscarriage.

It’s also why if you have hypothyroidism

and you get pregnant in the first trimester,

you wanna increase your dose from 25 to 40%

to keep your free T4 high as much as possible.

And the reason why you have to do that,

as opposed to somebody who does not have hypothyroidism,

is if you have hypothyroidism,

then likely your thyroid will not respond

to either TSH or HCG.

So the increased HCG does not compensate for that.

So if you take HCG,

then it can potentially improve your thyroid function.

So that, along with selenium,

are likely the two best things

that you can do for thyroid health.

HCG and selenium?

Yeah.

I definitely make sure I get enough selenium

by eating three to five Brazil nuts per day,

which I very much enjoy the taste of also.

Who should take HCG?

And can HCG suppress

one’s normal luteinizing hormone output?

Yeah, it suppresses LH in a dose-dependent manner.

So the higher the dose of HCG you take,

the more it suppresses LH.

A common dose for fertility,

fertility is usually why HCG is prescribed.

In men or women?

In both.

Is 10,000 IUs all at one time, which is quite a bit.

That’s a tremendous dose.

Yeah.

In fact, some formulations,

some brand names of HCG come in auto-injector pins

to where you cannot even dose

lower than 5,000 units at a time.

Wow.

But I know a number of people who take HCG

to maintain testicular function

while on testosterone therapy or augmentation of some sort.

Does it work to do that?

Yeah.

Some people are on HCG monotherapy.

It can be slightly better on your lipids

than being on TRT.

Oh, so people are using HCG alone

as a kind of neither,

sort of a hormone augment, indirect hormone augmentation.

Some clinics advertise it

as a non-suppressive alternative to TRT,

but it is suppressive of LH.

But it could also increase estrogen pretty potently.

Yeah.

And is it true that increasing LH and or HCG

can improve sensitivity of the genitals?

And is that true for men and women?

I’ve heard this anecdotally.

People say HCG makes sexual activity

more pleasurable for people because of some,

is it a direct effect on some of the nerve cells

in the genitals?

Yeah, so LH is also an agonist in the prostate

and in genital tissue in general.

So it’s a very common treatment

for post-finasteride syndrome or post-5-alpha reductase.

When you’ve blocked the conversion of DHT for a long time,

it helps re-upregulate DHT.

So someone who’s been taking finasteride

to prevent hair loss comes off,

maybe because they felt lousy,

but then feels even lousier

for reasons you talked about earlier.

And then they might use HCG as a transition treatment

to transition back to normal hormone health.

Is that right?

It’s extremely helpful in many cases.

Now, when you come off the HCG,

then you need to have a strategy of how to return

to your normal as fast as possible as well.

But it will upregulate those 5-alpha reductase enzymes

you have in your genital skin,

both scrotal skin and penile skin,

and perineum in general.

You have, I believe it’s called stratum lucidum.

It’s a skin layer that is very, very thin,

but it has the highest concentration of 5-alpha reductase.

So you have a lot of activity.

And after you’ve been on something that inhibits

the enzyme, the 5-AR enzyme in those tissues,

then you do something else to upregulate those enzymes.

Whether it’s waiting and taking time,

whether it’s trying Tadalafil,

whether it’s trying creatine even,

or whether it’s trying HCG,

a lot of times those are the go-tos

for post-venastaride syndrome.

Any risks for women taking HCG

on their ability to get pregnant or risk generally?

Yeah, obviously it’ll make any pregnancy test positive.

So that’s a risk that some women don’t know.

So one could, in theory, fake a pregnancy test

by injecting HCG.

Absolutely.

Interesting.

I have no motivation to do that.

I was just curious.

Yeah.

What about prolactin?

The simple version of this that I was taught,

because I was taught mainly

from the neuroendocrine perspective,

was dopamine is a kind of close cousin of testosterone,

and also estrogen, for that matter,

drives appetitive behaviors,

including pursuit of sexual partners, sex itself,

motivated behaviors generally,

then post-copulatory, post-orgasmic states

are accompanied by a prolactin increase.

That’s the refractory period for mating in males,

and maybe even in females as well,

involved in milk letdown, et cetera.

What are sort of the general contours of syndromes

or things that people could be on the lookout for

of having too much prolactin or too little prolactin?

And I’m aware of a number of people

who take dopamine agonists, L-tyrosine, capergolin,

things like that to really boost their dopamine levels,

and that isn’t always a good thing, as it turns out.

Oftentimes, people will become kind of hyper-dopaminergic,

and so they have the drive to do all these appetitive things,

you know, fill in the blanks,

but they don’t always have the ability

because it seems just as testosterone and estrogen

need to be in the proper ratios,

dopamine and prolactin need to be in the appropriate ratios.

So how should we think about

and perhaps act on our prolactin systems?

Absolutely.

The way I describe it is the dopamine wave pool.

So if you’re increasing your dopamine too much,

you’re gonna overflow,

and then you’re gonna have that wave crash too much.

So you wanna have nice, even waves

that are not going too far above the pool of dopamine,

and prolactin will follow.

So prolactin and estrogen are quite close cousins.

Estrogen upregulates a gene called the PRL gene

or prolactin gene

that directly increases prolactin synthesis.

So prolactin is going to also inhibit

the release of testosterone from the pituitary.

So if you’re using a dopamine agonist,

then you’re going to help decrease

the prolactin-producing cells,

including if you have a prolactin-producing microadenoma

in the pituitary.

How common are those?

Because, I mean, I hear a lot about these,

you know, hypogonadism or,

and of course that can be due to an issue at the testicles,

or hypogonadism could also be, of course,

in like ovarian syndromes.

And then there’s, of course, the brain side of it,

where the signals aren’t coming from the brain.

You’re not enough gonadotropin,

not enough luteinizing hormone.

And there are ways of teasing this apart

with an endocrinologist that are quite elegant, in fact,

right, using stimulating hormones.

Too much to dive into here.

But how often does one actually have

one of these pituitary tumors?

I have heard that people that play

a lot of high-contact sports,

so boxing, football,

people that headed the soccer ball quite a lot.

Sadly, people whose jobs forced them to take head blows

for, you know, it could be military.

And so they were firing, you know, 50 caliber guns

and the kind of woodpeckering of the brain

inside of the skull.

And construction workers,

or just a concussion can cause the pituitary

to go malfunctional.

Is that really common,

or is this something that, you know,

is a rare, like 1%?

Yeah, it’s extremely common.

It’s another one of those conditions

where a lot of people never know they have it.

They just feel a little bit more fatigued.

They have that high prolactin feeling all the time.

Pituitary micro-adenomas can be non-producing as well.

So your prolactin can be totally normal.

Your growth hormone and IGF-1 can be totally normal.

That’s the second most common producing micro-adenomas,

growth hormone causing either acromegaly,

which is growth of cartilage or gigantism.

This is the big brow, yeah.

So those are fairly common causes of adenomas,

but a lot of people that have a very small adenoma,

you know, much less than one centimeter,

it’s hard to see on imaging,

even if you have a contrast

that specifically looks at the pituitary,

and many people aren’t symptomatic.

So it’s one of those things along with PCOS and prediabetes

that are much more frequent when it comes to prevalence,

which is the amount,

the percentage of people

that have it in the general population.

I’m glad you mentioned the dopamine wave pool.

I know nowadays there’s a lot of interest

in augmenting dopamine.

I know a number of people that do this

through prescription drugs, Adderall, Ritalin, Modafinil,

and those drugs, of course, hit many transmitter systems,

but dopamine is certainly involved.

People taking antidepressants like Welbutrin

tap into that system.

And of course, people are trying to inhibit prolactin

and promote serotonin or reduce serotonin.

To me, it all seems like a very delicate dance, right?

I mean, to just imagine the arousal arc

for mating behavior, for sexual reproduction,

is such an elaborate dance between sympathetic drive

and parasympathetic drive,

even across the span of minutes, right?

I mean, I’ve talked about this before on the podcast

that the arousal is kind of more parasympathetic.

Orgasm itself is a sympathetic response,

a completely different set of neurons.

And so where do you see people getting into trouble

just trying to hit the gas pedal on dopamine?

And where do you think there is a place for people

who perhaps are experiencing low drive and motivation,

not just sexual, but in general,

to increase the amount of dopamine circulating

in their brain and body?

How do you think about that, given this wave pool analogy?

Yeah, so it’s important to parse it out

and start with the least powerful interventions.

So if someone’s concerned about dopamine,

or maybe they have a slightly higher prolactin,

then they eliminate things

that could be increasing that prolactin,

such as casein or gluten,

which are mu-opioid receptor agonists,

or any mu-opioid receptor agonist in the gut.

So casein, so milk protein?

Correct.

Can increase prolactin?

Correct.

Interesting.

In addition to that, they should,

if they need a pituitary MRI,

then they should get a pituitary MRI.

If they don’t have an adenoma,

or if they don’t have a high enough prolactin level

to where they need an MRI,

if they’re having visual symptoms,

or if they’re having olfactory symptoms with the nose,

then it’s more likely that they do.

But if they don’t, a lot of times,

a prolactin under about 40 is not too big of a deal.

They can take dopamine agonists

that agonize that D2 receptor, like P5P,

which is essentially vitamin B6.

It’s pyridoxine 5-pyrophosphate,

and pyridoxine is vitamin B6.

So that can help, 50 milligrams once to twice a day.

Vitamin E can also help,

especially if it’s mixed to coferols.

A lot of people have the high levels of vitamin E,

but low levels of the gamma form of vitamin E.

So that can also help.

Fascinating.

I’m so glad you mentioned vitamin B6 and P5P.

I have heard that one can shorten the refractory period

after orgasm, essentially to be able to have sex again,

to be quite direct about it,

by way of vitamin B6 blunting of the prolactin response,

which turns out to be quite potent.

But I’ve also heard that vitamin B6 can be neurotoxic,

especially in the periphery,

that it can cause peripheral neuropathies

if it’s taken at high doses,

but that P5P is the safer form.

Is that true?

It’s pre-activated, so it does not build up.

Think of it as a allegory to how folate can build up.

It’s not methylfolate, but it builds up

and it can increase levels of homocysteine,

or if you have too much vitamin B12,

another water-soluble B vitamin,

you can have too much methylmalonic acid, or MMA.

So depending on what your enzymatic conversion is

to the active form of the enzyme,

often it’s just safer to take the active form of the enzyme.

Yeah, very interesting.

Okay, well, at risk of going down every hormonal pathway

and talking about supplementation lifestyle factors,

I think touching on, as we have,

testosterone and estrogen and now prolactin,

I’d love to chat a little bit about L-carnitine.

We talked about this earlier,

but I want to raise this discussion about L-carnitine,

not in the context of L-carnitine itself,

but in the context of fertility.

Because my read of the literature is that L-carnitine

can be very beneficial for enhancing sperm quality

and egg quality, and even rates of conception.

What forms does L-carnitine come in

that people can reasonably consider?

Again, talk to your doctor, folks.

What is it doing, and do we know how it’s doing it,

and do you often use this in your patients?

Yeah, so the way I think about L-carnitine,

and I’ll try to tie this in with creatine

and other things as well,

is if your cell is an energy factory or a car,

then L-carnitine is the shuttle that helps get the fuel

into the motor to use the motor.

The motor is mostly due to lifestyle factors,

so like your diet and your exercise.

And the type of fuel itself is NAD+.

We don’t need to get into NAD precursors

or NMN or NR or anything.

And then the accessory fuel tank is your creatine phosphate.

So creatine is your accessory fuel tank.

Your NAD status, which is largely determined

by your REM sleep and quality sleep and exercise,

along with supplementation, is the fuel.

The carnitine shuttle is carnitine palmitoyl coenzyme A,

and that takes medium-chain fatty acids.

It takes different molecules of fat.

You have two main energy sources other than ketones.

You have your glucose or carbs.

You have your fat or fatty acids.

And that takes it across the layer of the mitochondria

so that it can be utilized.

So it upregulates that.

That’s why things that have flagella in general,

the flagella are gonna work better, like sperm.

Flagella being anything,

sort of the wavy little tendrils on cell types,

of which they’re everywhere, right, in the gut too, right?

Yeah.

So those are gonna work significantly better.

And in general, your mitochondria are gonna work better.

So the worse your mitochondria are off the bat,

the better they’re going to be helped

by the shuttle that shuttles them across.

It also slightly increases the density

of the androgen receptor as well.

Is that a local effect?

So if L-carnitine is injected into a particular muscle,

will it increase the density of androgen receptors

in that muscle?

Likely so.

So how are people taking L-carnitine?

They’re capsule forms and they’re injectable forms.

Most people are gonna be taking the capsule forms

because that’s all they’re gonna have access to.

And then we should also ask,

can you get L-carnitine from food?

Yeah.

So L-carnitine is just a combination of,

it’s actually a very small peptide.

So glutathione is just three amino acids.

L-carnitine is the smallest peptide, two.

So peptide is just a protein that has amino acids

between two and about 200.

And L-carnitine is just two amino acids.

Amazing.

So it’s like a micro peptide.

Yeah, so your body synthesizes enough.

It likes to absorb the amino acids by themselves.

And then if it puts them together,

there it makes L-carnitine.

It’s not very bioavailable if you take it.

A lot of people will take L-carnitine L-tartrate

or acyl L-carnitine.

And that’s about 10% bioavailable.

So if you want one gram or a thousand milligrams

of L-carnitine, you can take 10 grams of oral L-carnitine.

Is the one gram the typical dose you recommend,

one gram per day?

For fertility and androgen receptor upregulation.

So that means taking 10 grams of the capsule form.

Yeah, so it’s about 15 to 20 capsules, which is a lot.

That is a lot.

It can also potentially increase TMAO.

Yeah, I wanted to ask about that because TMAO

on your blood chart, when that’s elevated,

that’s going to cause some concern.

You taught me a trick, however,

that one can take 600 milligrams of garlic capsule

for the allicin, is that what it’s called?

Allicin is in it, yeah.

It’s like the name allicin, but with two L’s?

Yeah. Okay.

And that had a remarkable effect in reducing TMAO.

So that’s quite potent.

And also, was it just coincidence

that it really brought my LDL down as well?

I’m not sure if the LDL is a coincidence,

but depending on your gut microbiome or your microbiota,

some microbiome beneficial bacteria

will convert carnitine and also choline.

So any choline precursor like alpha-GPC

or phosphatidylserine,

it will convert them more or less to TMAO.

So TMAO is something that you can get measured

in a blood test and see if it’s high or low.

Some people might not even need allicin.

Interesting.

Some people do benefit from it.

Interesting.

Although, I think it was you that also told me

that allicin and garlic can have positive effects

on cardiovascular tone and blood flow generally.

Is that right?

Yeah.

Okay, so maybe, so is 600 milligrams garlic

an excessive amount, or can I just eat garlic?

You can just eat-

I mean, I like eating garlic.

Yeah.

Yeah, so, okay, so one could also just eat garlic.

If one were gonna take L-carnitine in injectable form,

how much of that is bioavailable?

100%, if you inject it.

It is in an aqueous solution.

So it’s a bacteriostatic water, essentially.

So it’s not in a carrier oil.

So it’s gonna burn a lot if you inject it subcutaneously.

So it’s gonna be absorbed faster and more evenly,

and also just hurt a lot less

if you inject it into a muscle.

But one could then just take one gram per day injected,

or divide it up into a couple doses.

Yeah, or 500.

The minimally efficacious dose for injectables,

probably around 200 when it comes to sperm motility

and androgen receptor upregulation.

So it really depends on why you’re taking it.

In terms of fertility and in terms of blood tests generally,

I always say that if possible,

either by way of insurance

or by way of some other way affording it,

it would be great for people to have blood tests

to know what their hormone levels

and other levels of other things

like metabolic markers and lipids were in their 20s,

also in their 30s, also in their 40s.

I think there’s this idea that you only take a blood test

when you have a problem.

But then of course, one can’t actually do the comparison

that you mentioned earlier,

or state the comparison to one’s physician,

that things are changing over time.

And it seems to me that basically everyone should get

at least a once a year blood test.

Is there the hope that insurance

will someday just cover it for everybody?

This will be standard care.

I would think that everybody should know

what sorts of things are floating around

in their bloodstream and what they need more of

and less of in life.

I doubt it will ever be covered by insurance.

In many cases, you could make an argument

that it’s indicated.

As insurance begins to cover more of the population

for pathologies, the things like FSAs or HSAs

or care credit will likely cover this advanced testing,

which it continues to come down and down in price.

So it’ll be affordable, but it won’t be free.

Got it. Yeah.

I’d like to shift gears slightly and talk

about social interactions and relational effects

on hormones, something that I just find fascinating.

We touched on this a little bit earlier

with in terms of oral contraception,

but now that we have the backdrop

of what these various hormones do,

some involvement in neurotransmitter systems

like dopamine and prolactin and associated pathways,

prolactin, of course, being a hormone,

not a neurotransmitter.

But there’s a phenomenon in human beings

where people get very excited about a new partner.

And that excitement, no doubt,

is related to the dopamine system among other systems.

And that excitement can be maintained

or it can wane over time.

And here I’m talking about attraction,

but I’m also talking about just general excitement

in the sense of novelty,

because that’s what dopamine’s associated with.

Given that you work with human beings

and they have lives and relationships and lifestyles,

and they have hormones and all these things interact,

what are some of the ways that we could think

about adjusting our relationships

in order to optimize hormones,

as opposed to just thinking about how to optimize hormones

for sake of our relationship?

Because it’s bi-directional, of course.

And this assumes, I should say,

that one is already paying attention

to the six pillars talked about earlier,

that people are doing most things right.

How should we think about relationships and hormones?

Friendships, romantic relationships,

new partners, long-term partners?

How do you think about this kind of stuff?

Yeah, so if you have a new partner,

then it is largely regulated by the dopaminergic system,

which changes over time.

So people may have heard the saying

that you have to go through a full calendar year

with someone that you’re in a relationship,

so that you- Very good advice,

by the way. So that you really know

what to do and what not to do,

but because you experience both of your families

and the holidays and all the different situations.

But I would argue until you have moved in together,

had a baby, and then raised that baby,

preferably breastfeeding,

because that’s when you get the prolactin spikes,

you haven’t really gone through every stage in life yet.

Now, you can’t really do that

with every person that you’re considering.

Well, some people do, but it can be quite costly

in terms of time and finances and emotionally costly.

And then here, I’m definitely not referring

to any personal experience

of having done all that many times over.

But what would you suggest people do or think about

as they enter a relationship

or for people that are in long-term relationships

where they feel like something has shifted?

And indeed, those shifts may reflect the output

of different hormone systems and neurotransmitter systems.

It almost certainly has to be the case, right?

Yeah, so just like women who spend a lot of time together,

whether they’re coworkers or whatever,

a lot of times their menstrual cycles will align.

There is a lot of pheromonal and hormonal crosstalk,

including prolactin between men and women.

So spending 100% of the time together,

this is why people think it’s so hard to work together

and live together, they’re around each other 24-7.

You don’t have the reprieve

where you let that dopamine settle down

and then you’re excited when you see them again.

A lot of guys know that if they’ve gone on a hunting trip

or if they’ve gone on a trip for a long time,

they come back and they see their partner

and it’s like a new, not quite like a new relationship,

but almost like a new relationship.

And then they have that excitement again.

And purposely building that into every relationship

can help significantly,

especially if you choose to have a child or get pregnant

or be breastfeeding, because you just plan ahead

for both of your prolactins to be high

and both of your dopamines to be low

and both of your testosterone’s to be low.

So there’s a lot of planning that you can do.

Essentially, every relationship goes through a crisis.

And that crisis is personal between the two of you

and you can plan ahead and figure out a way.

Maybe it’s not supplementation.

Maybe it’s not even the amount of time

you spend away from each other,

but plan ahead to have good times

if you know you’re about to go into a crisis.

Got it.

And so it sounds like time apart and time together,

which is actually built into a number of cultures

where men and women will purposefully avoid each other

for some period of time, avoid physical touch

and maybe in proximity, and then we’ll reconvene.

And yet those are very stable relationships over time often.

Is the inverse also true?

For instance, for people that are

in long-distance relationships

where they’re only seeing each other

three or four days a week or two days a week,

does this explain the fact that some of those relationships

can go on for a very long period of time

without ever actually entering the,

let’s call it the hyper-prolactin phase

of actually moving in together and et cetera, et cetera.

Like in other words, is that a way in which people

are spiking and troughing dopamine that keeps them attached?

This kind of elusive, this sort of, what is it called?

I think it’s called like a cat string.

Like if you play with a cat and you move the string away,

they’ll keep reaching,

but you throw the string on the ground

and they’re like, they’re totally uninterested in it.

Is that what’s going on?

Because that’s a dopaminergic phenomenon,

the cat string example.

We know this experimentally.

In those cases, the relationship hasn’t really progressed,

in many of those cases, past the dopamine spike,

the fun initial stage, honeymoon stage,

whatever you wanna call it.

So it’s almost kind of like a roommate.

If you’re looking for a roommate,

if it was for college or after college or whatever,

you can fill out forms and look for common interests,

but until you’re actually together

a significant proportion of the time,

you’re not really gonna know

if you’re gonna be compatible or not.

And is there evidence

that the appearance of an infant changes?

Obviously, there are gonna be hormonal shifts.

We know actually that in both women and in men,

there’s a prolactin increase

when couples are expecting a child.

It’s almost like a brooding phenomenon.

You see this in birds where it’s actually called brooding

and it’s caused by prolactin increase,

but it turns out this also occurs in humans.

And some people would argue

this causes the dad bod phenomenon

because it actually,

prolactin’s involved in laying down a body fat,

preparing for sleepless nights.

And presumably that spike in prolactin

is there also to suppress sexual activity

because there are periods of time immediately

near childbirth where sexual activity is not advantageous.

Yeah, you see a prolactin spike right after breastfeeding.

So if you think about it,

often when you have an infant,

you’ll breastfeed, put the infant to bed,

and then immediately go to bed with your partner,

which is not particularly conducive.

It’s almost like trying to have intercourse back to back.

And it’s very difficult.

Because of the, in the prolactin sense.

Yeah, low dopamine, high prolactin.

Oxytocin is also increased significantly

to help with milk let down as well.

So yeah, as far as brooding,

there’s definitely a human equivalent of brooding.

Some humans call it nesting instinct,

which is both helpful,

but it’s not necessarily a bad change in relationship.

It’s just a change.

And as long as you know that it’s coming,

you’re gonna do better with it.

Just like any medication.

If you are aware of the side effect

and that it might happen,

then when it happens, it’s not only less severe,

it also happens less often.

Very interesting.

You tell the patient.

Well, as a neuroscientist,

I come from the framework that,

of course, hormones impact perception and behavior,

but perception and behavior also impact hormones.

I find this fascinating.

I also really like the example you gave

of people taking time apart,

but also these affiliative bonds

that are non-romantic bonds

can serve as kind of a reservoir to replenish dopamine

that is then released upon experience,

going back to one’s partner

or some sort of regular feature of home.

Very interesting.

And of course, this should exist on both sides.

I’m guessing that from both the male side and female side,

there’s an interest in kind of separation

and reunion as the theme.

And I guess the frequency will vary

for different couples in different situations.

Yeah.

And I don’t wanna make it seem like prolactin is all bad.

So prolactin does help with the nesting instinct.

It helps with breastfeeding as well.

A lot of women are diagnosed with luteal phase defects,

which is basically the phase after ovulation,

but before a period or giving birth.

The pregnancy is kind of a prolonged luteal phase.

And a lot of them will go on progesterone for this.

Progesterone can also decrease prolactin.

And prolactin is also helpful

for the maturity of lungs in infants.

So it helps the sphingomyelin to lecithin ratio.

So it can decrease.

If your prolactin is too low through pregnancy,

it spikes up very high during pregnancy.

Then it can lead to increased risk

of respiratory distress of the newborn.

Really interesting.

Yeah, so we certainly don’t wanna paint a picture

where prolactin is the bad, bad hormone to avoid.

Without prolactin, none of us would be here, of course.

It’s so vital.

I realized that earlier I raised the question

about whether or not cold exposure

could modify hormone output,

in particular, whether or not ice baths

or ice applied to specific tissues of the body,

as people are doing one way or the other,

can change testosterone levels, estrogen levels.

In other words, taking ice baths and cold showers

can increase testosterone and or estrogen.

Yeah, so taking an ice bath or a cold shower

or a cold exposure in general,

it’s not gonna correct a vitamin D deficiency

or a metabolic syndrome.

So there’s a lot of things that it will not correct

that are causes of hypogonadism or low testosterone,

but it will help acutely, specifically,

the application of cold to testes that are too warm.

So if you have a varicocele

or if you have a little bit of a primary hypogonadism,

which is where testosterone is not released by the testes,

but your LH and FSH signals are sufficiently high,

then you’ll likely respond to cold exposure better.

And there’s actually undergarments

that are designed specifically to help with fertility.

And there’s probably gonna be more and more of that

in the future.

You just need to be careful not to get frostbite

because it’s a particularly bad spot to get frostbite.

Noted.

Could you define varicocele?

You’ve mentioned it a few times.

That’s a varicose vein?

Yeah, so it’s essentially a varicose vein.

It brings warm blood and the venous flow

or the flow back to the heart is not as good.

Just like in the legs, it can happen in the scrotum.

Usually about 20 to 25% of people

have one grade of varicocele.

There’s grades one through four, one through five.

And most people just have a very mild one,

usually on the left side,

because the blood has to go through further

to get back to the heart.

And it raises the temperature of the testes.

Temperature is the enemy of testes.

So they like to be five to 10 degrees cooler

than the rest of the body.

So are saunas particularly bad for sperm production?

They can be, yeah.

When you say can be,

how long could one safely be in the sauna?

Or would you want to go back and forth

between the cold and sauna?

Is there any, are there any data?

If someone is having infertility,

then I tell them to avoid all saunas empirically.

If someone has, if they’re not infertile,

but they have a low sperm count,

I also tell them to avoid.

However, it’s mostly warmed water

that can raise the temperature of the testes

faster than the sauna.

So hot tubs and things of that sort.

Yeah, so a hot tub and a jacuzzi,

those are enemies, number one and number two, of sperm.

What about ice baths and cold showers for women?

Any evidence that it can shift hormone output in women?

Yeah, it can.

It increases the activity of the beta-adrenergic receptors,

even in the central nervous system

and the astrocytes as well.

So it can do a few things.

It can slightly decrease the drive for food,

which astrocytes and beta-adrenergic receptors

have some medications that are weight loss medicines

that also do similar things.

But it can be beneficial in women, too.

But no evidence that it changes estrogen output in women,

correct?

Not that I know of.

Me either.

Peptides, a lot of discussion these days about peptides.

Peptides, of course, just being strings of amino acids,

as you mentioned, very small ones,

like two amino acids, like L-carnitine,

all the way up to polypeptides,

which just mean many, many amino acids.

There are so many peptides that there’s,

we should probably just do an entire episode about peptides.

But I think one of the reasons I’m hearing so much

about peptides these days is that

they are not called steroids.

You know, the name steroids, I think,

has come to be associated with anabolic steroids

in the context of acne, testosterone rage, et cetera.

But of course, testosterone, excuse me,

estrogen is a steroid hormone, right?

There are other steroid hormones, as we both know.

But peptides are gaining increasing popularity.

I am willing to go on record saying that you can be sure

that many of the incredible transformations

that you see in Hollywood are the consequence

of peptide use.

And I’d put my name behind that

because I’m well aware of people

that use these to prepare for roles,

but athletes use them.

And then everyday people are using them too.

For instance, sermoralin, tesamoralin, ipamoralin

to stimulate the release of growth hormone

rather than taking growth hormone.

BPC-157, which is essentially a synthetic gastric juice

that normally repairs the gut,

is being used to treat injuries.

And there are other ones as well.

What can we say generally about peptides?

Are they safe?

Are they not safe?

What about sourcing?

And are there any peptides that you think

could be of particular use for people?

And we should probably also touch on peptides

that people shouldn’t go anywhere near with a 10-foot pole.

Yeah, definitely.

So peptides are very heterogeneous.

There’s very dangerous ones and very safe ones.

My favorite peptide is the original peptide,

which is insulin.

So insulin is a peptide.

And less than 100 years ago,

there was a scientist studying insulin.

And at some point, they saw that an animal

had its diabetes cured by insulin injection.

Less than a year later,

they were injecting insulin into every type one diabetic

because it was saving their lives.

And yet insulin can kill you

if you take it at the incorrect dose, right?

Yeah, so just like insulin should be prescribed by a doctor,

there is over-the-counter insulin, rely on or NPH.

But ideally, your insulin is prescribed by your doctor

for your diabetes as it’s life-saving.

Peptides should be prescribed by doctors as well.

And there’s several that are FDA approved.

So you mentioned a lot of different ones.

Let’s start with tesamoralin.

So tesamoralin was recently FDA approved

for something called lipodystrophy.

It happens where body fat is displaced into abnormal areas,

often as part of AIDS or severe burns, things like that.

And it helps redistribute this body fat

and give people their quality of life back.

Tesamoralin is a GHRH,

which I kind of loop into the category of GHRPs,

so growth hormone releasing peptides.

So it’s only a couple amino acids different

from endogenously produced growth hormone releasing hormone.

So growth hormone itself is also a peptide.

It’s a peptide hormone, not a steroid hormone.

So you have different somatotrophs,

which are very similar to growth hormone.

Another fun fact is that HPL,

which is human placental lactogen,

we love acronyms, right?

Human placental lactogen is nearly identical

to growth hormone.

The growth hormone in pregnancy

is not what causes the sugar spike and gestational diabetes.

It’s the human placental lactogen.

So if you look at twin pregnancies,

if they have two placentas or more placental tissue,

making more human placental lactogen,

the risk of gestational diabetes is exponentially higher.

So this HPL is only a couple molecules

different from growth hormone.

It is interesting that these different GHRHs and GHRPs

actually have pretty different mechanisms of action.

Ghrelin is also a hormone that’s released

when you’re hungry.

This is probably one of the reasons

why you have more growth hormone release overnight.

And there’s a lot of peptides

that are very similar to ghrelin.

So these peptides are not bio-identical peptides,

but they just have a couple different amino acids change.

So they’re almost identical

and they’re probably gonna be used in the future

for growth hormone deficiencies,

including in kids they’ve been studied.

So if somebody wants to increase their growth hormone output

in addition to not eating within two hours of sleep,

getting good deep sleep,

doing all the other things in the six pillars

that you mentioned earlier,

especially resistance exercise

at some point earlier in the day,

what are the risks and benefits

of taking a growth hormone-releasing hormone peptide

like cermoralin prescribed by a doctor, of course?

What should one be concerned about?

How long could one take these?

I’ve even heard that they can modify gene expression

so that they really are changing your hypothalamus

in very long lasting ways.

Yeah, there’s definitely a lot of risk,

tumor growth and cancer.

So you look at a type one diabetic,

they have very high incidencies of various types of cancer.

They have very high growth hormone,

but low IGF-1 paradoxically.

So they would likely give you a similar cancer risk

to a type one diabetic that has very high growth hormone.

However, there are the benefits of it.

You think of lipolysis, decreased body fat,

increased lean body mass.

A lot of those, you can use other things

to get those benefits.

So then you don’t need growth hormone for those benefits.

It just leaves cosmetic benefit

to which you can usually use topicals

to get your hair and your skin and your nails.

There’s a lot of other things

that you can do other than growth hormone.

So a lot of people just don’t need these GHRPs

if they don’t have lipodystrophy

or if they don’t have growth hormone deficiency.

There is other uses of them specifically in injuries.

So I know that they’ve been studied.

I’m not sure if it’s in the military.

We mentioned the woodpecker or the coup,

contrecoup injury.

So that can obviously-

Head resulting back and forth

and the brain basically slamming up

against the front of the skull.

Yeah, football, heading the ball in soccer.

Definitely people who use the 50 caliber

in military, although that’s a fairly small population.

And I think anyone that’s hit their head hard

more than once.

Yeah, we can talk about BPC-157 for a bit,

GHK copper peptide for a bit,

TB-500 or a thymosin beta-4 analog.

And then we can also talk about brin-melanotide,

which is melanotan-3.

They have melanotan-1 and 2,

and then they also have melanotan-3 and 4.

Let’s talk about BPC-157 and melanotan,

because I think those are the ones

that most people are eyeing, so to speak.

So BPC-157 is body protective compound.

157, it’s identical or bio-identical

to gastric protective compound, 157,

that’s produced in the stomach.

So as you age, you get atrophic gastritis very often.

That’s why you have less intrinsic factor,

which is kind of another peptide that binds to vitamin B12.

That’s why you can get age-related B12 deficiencies.

So that’s one reason why you have more colitis,

more diverticulitis as you age.

You don’t have that gastric protective compound.

It increases VEGF, vascular endothelial growth factor,

which basically makes your blood vessels grow more.

So that’s what causes your body to form a blood vessel.

So another medication known as Avastin,

it’s on the WHO’s list of essential medications for cancer.

So many different types of cancer, including colon cancer,

you treat it with Avastin, which is a VEGF inhibitor.

So if you have cancer or a high cancer risk,

you probably don’t wanna be taking a medication

that’s the exact opposite mechanism of action

as your essential anti-cancer med.

In other words, if you have cancer,

you’re at risk of cancer, avoid BPC-157.

Correct.

A lot of people prescribe it for six weeks.

And BPC-157, so brimelanotide,

that is FDA approved for a hypoactive sexual disorder.

Tesamoralin, that’s also approved for lipodystrophy.

Interestingly, another one of the melanotans

is also approved for lipodystrophy

and also deficiency in the melanocorticoid receptor.

So the receptor that receives

the alpha-melanocyte stimulating hormone,

it’s a very rare condition.

It’s also approved for that,

because if you don’t take it, then you get obesity.

But BPC-157 is not FDA approved,

but it is essentially standard of care at this point.

I would say it’s, you know,

if you’re not counting insulin

or growth hormone as peptides,

it’s one of the most commonly used peptides.

And anecdotally and in some clinical literature,

it’s fairly well tolerated for short periods of time.

I’m not in the camp that everybody needs to do it

two to three times a week,

or even daily for six weeks, no matter what.

The major benefit is when you’re gonna take it early on,

because it’s gonna allow your body

to increase blood flow to the injured area.

And the less blood flow it has,

for example, cartilage ligaments have horrible blood flow,

especially as people age,

it’s gonna make a significant difference.

So I would wager that that Russian gymnast

that Achilles healed in one month

and completely from a full rupture

was likely taking BPC-157 or something very similar.

Yeah, I’m willing to wager on that as well.

A remarkable recovery.

And so because it is prescription,

there are non-prescription forms.

My understanding of the non-prescription forms

and the danger of going after non-prescription forms

is that oftentimes they will contain

what they claim they contain, BPC-157 in this case,

but they are not adequately cleaning out the LPS,

the lipopolysaccharide, which can cause inflammation.

In fact, in the laboratory,

we use LPS to deliberately induce fever and inflammation

to study systemic inflammation.

So this is a warning to people,

if you’re interested in peptides,

you absolutely need to work with a physician, in my opinion,

get it from a really good compounding pharmacy

who will clean out, that cleans out the LPS.

Because if you’re buying it through a source

that a lot of people, I don’t wanna name sources,

but there are these common sources on the internet

that everyone knows about, they’re buying these sources,

they’ll ship it to anyone essentially,

but then the LPS is really causing inflammation.

And many people experience a kind of mild fever

or tingling from that when they inject it.

And they’re like, oh, I can feel it working.

That’s probably LPS action, which is not good for the brain.

I don’t know about on other peripheral tissues.

I haven’t heard of people dropping dead from this stuff yet,

but I certainly wouldn’t wanna be ingesting

any LPS unnecessarily.

So would you agree that you should work with a doctor?

After all, you are a doctor.

Yeah, definitely talk to your doctor about this

and talk to them about the dosing regimen as well.

So if they have you doing it for six weeks,

ask them, why am I doing it for six weeks?

Why not two weeks or why not as soon as I feel better?

Can I just stop it?

Yeah, there’s a lot of good questions like that

that you should ask your doctor.

And if somebody is trying to prescribe you

a bunch of different things,

then see, is this what they prescribe everybody

or is this individualized for me?

There are peptides like GHK copper peptide,

which is produced endogenously in the liver

more at younger ages.

That’s why the liver can regenerate fully

and GHK copper peptide helps.

And if you’re copper deficient,

which not a whole lot of people are,

but a lot of people that have had bariatric surgery

are copper deficient.

GHK copper peptide can help significantly

with your nervous system.

And it’s also synergistic.

So any growth agonist like thymus and beta-4

made in kids in the thymus, which shrinks,

that’s another reason why kids heal really well.

That and GHK is somewhat synergistic with BPC.

But if you don’t need all three, you don’t want them.

And if you don’t need it for more than a week,

you don’t want it for more than a week.

I really appreciate you saying that.

I often say that sometimes the best dose

of something to take is zero.

It’s often the case that the best dosage is zero.

You mentioned melanotan.

There are several kinds of melanotan.

I find it a little bit of a funny conversation

because I first learned about melanotan

from reading about peptides and discovering

that people were taking, injecting melanotan to get tan,

because it’s in the melanin synthesis pathway.

They also discovered, this isn’t an individual,

this is reading about this in various manuscripts

and peer-reviewed papers,

that it could cause things like pre-epism,

like a sustained erection that might be the last one

that anyone would ever have

because of damage to the vasculature.

Also women taking melanotan as a way to get tan

and lose body fat.

So this sounds all very recreational.

Are there any clinical usage of melanotan?

So separate from the kind of extreme biohacking

cosmetic world, which is really not the main focus

of this podcast ever,

more in terms of pursuing health optimization.

Yeah.

There’s actually three FDA-approved indications,

believe it or not.

Not many people know about this,

but there’s three well-accepted indications.

One of them is the hypoactive sexual disorder

and more in women.

That’s for brimelanotide, which is also-

Those are women that have essentially no libido whatsoever,

but other hormones are in check.

Yeah.

Classically, it’s before menopause.

So those hormonal issues are not contributing.

And when you give them this peptide,

it’s also known as PT-141.

It helps significantly.

A lot of times you use it in nasal spray.

It goes straight into the central nervous system

and acts centrally.

You can also inject it

and you can also take it via DROKI.

Men and women take it?

Correct.

It’s approved for women, but it can also help men.

And it’s relatively safe.

The only relative contraindication that I tell people,

and a lot of people say,

oh, there’s no side effects that I know of,

but if you have a family history of melanoma

or potentially have a melanoma and don’t know about it,

that’s why I’m a big advocate of dermoscopy as well

and regular skin checks,

then theoretically it’s gonna increase

that alpha-melanocyte-stimulating hormone

and it can grow that.

So that’s definitely not a good thing.

So be very careful about long-term administration of it.

It’s also approved for lipodystrophy,

which is the same exact thing as tesamoralin,

which I believe is also known as Evista or Agrifta.

And then it’s also approved for the rare genetic condition

where your receptors or your melanocytes

don’t proliferate as well.

So you usually have hypopigmentation.

It’s not true albinism,

but it’s associated with morbid, morbid obesity

and very poor outcomes from that in childhood.

So it’s used in kids actually.

Interesting.

Well, peptides are a fascinating landscape,

but thank you for that deep dive into several of them.

We will probably return to you to talk about peptides again

in the near future,

because I know there’s a lot more there

and a lot of interest.

I wanna talk about the sixth pillar, all right?

So just to remind people, you said diet, exercise,

where appropriate caloric restriction,

managing stress, sleep, and sunlight are critical

for everyone at all ages to manage

and optimize hormone health.

Then you have this sixth category,

which is a really intriguing one, which is spirit,

which is a kind of unusual thing to hear

coming from a medical doctor, except that I have

many colleagues and indeed our former director

of the National Institutes of Health, Francis Collins,

has talked about this notion of spirit.

We’ve talked about belief effects on this podcast before

with Ali Crum, how one’s understanding of the things

that they do and their world in general

really creates an important effect on everything

at the level of physiology, not just psychology.

So as a physician, how do you conceptualize

the spiritual aspect and how do you talk to patients

about this, given that people walking into your clinic

presumably have a bunch of different religious

and not a-religious backgrounds?

I’m sure some are atheists,

some are probably strong believers.

How do you deal with that?

And how should people think about this?

Yeah, I believe it is surprisingly well-received.

You wouldn’t think at first glance that a patient

really wants to talk about their spiritual health

with their doctor, but the way I think about it

and the way that it really is, is it’s like a Venn diagram

and you have a body and a mind and a soul

and you can’t have one healthy without the other healthy,

even if your mental health is phenomenal

and even if your physical health is phenomenal.

The mental aspect of spirituality,

if that piece is not there,

then that’s gonna affect your body physiologically as well.

And Ali Crum’s done some excellent work.

There’s also been a lot of other studies regarding prayer.

And I’m a Christian, I believe in God.

And that gives me a lot of that resilience and motivation.

It gives me the cornerstone or the groundwork,

how I can interact with life.

And regardless of someone’s an atheist

or regardless of what someone believes

as far as religion or the origin of the species,

they can know that their spirituality

is going to have a profound effect

on their mental and physical health as well.

People like to compartmentalize it.

So they like to talk to their doctor

only about the physical health

because it’s comfortable to do that.

They only talk to their pastor or a mom

or a reiki healer for their spiritual health.

And they just talk to their therapist or psychiatrist

about their mental health.

But you need to bring all three of those things together.

It’s well known that interdisciplinary clinics

lead to improved patient outcomes.

And that’s just disciplines within medicine.

So that’s just doctors that are specializing

in this or this.

So this takes a step back in the upper part of that tree

before you’ve reached those dichotomies or the split offs.

You have your body and your mind and your soul.

So your spiritual health and your mental health

and your physical health.

So if you’re in line in all three of those things,

that builds the cornerstone for the rest of your health

and the rest of your life.

So if someone comes into your clinic

and they say they’re feeling one way in their body,

they’re feeling one way in their emotional life,

you run their charts, you get their blood work,

and they’re an atheist or they’re agnostic,

what are some of the six pillar practices

that they can consider that are in keeping

with their atheism or agnosticism?

Because I have to assume that people who participate

or feel that they belong to a particular religious sect

will have particular prescriptives from those religious sects

that will direct them towards particular types of prayer.

But how would somebody who doesn’t have a prescriptive

coming to them from some other source,

what could they do or would they do?

Yeah, so I certainly don’t force prayer on anybody

or anything like that.

But it’s my belief that being, especially being an agnostic,

it’s almost the hardest thing because if you’re an atheist,

then you have some groundwork

and you have some spirituality,

even if it has to do with the human spirit’s interaction

with the environment,

things that can’t be physically explained well,

phenomenon like the work that Alikram does.

But if you’re agnostic, you’re still trying to find that.

So I hope that everybody does find

what they truly believe in as far as their own spirituality.

But yeah, that’s a personal journey.

From a physician standpoint,

and even if I’m friends with him as well,

from a friend standpoint,

I don’t like to push anybody in any specific direction.

So I don’t think that everybody should believe what I believe

and I don’t feel like there should be any pressure

for them to believe something different.

So I think that there can be excellent physician,

patient rapport, regardless of what we believe

and what our backgrounds are.

Yeah, that’s wonderful to hear.

I can say without revealing any names

that I have close colleagues

that in every bin of this spectrum,

but like hardcore atheists, hardcore religious

in different domains, different religions.

I don’t know if I know many,

I’m agnostic as to whether or not I know any agnostics,

I should say.

It’s not something that people commonly discuss,

but in the context of science and medicine,

but it’s starting to happen more and more.

And certainly this issue of spirituality

is one of the areas in which neuroscience

is asking a lot of questions,

like what spiritual experiences really are

in terms of how they’re grounded in the brain

or not grounded in the brain.

I think it’s a really interesting area for discovery.

And I appreciate that you bring it up

and you bring it up in the non-pressured way that you do.

I think that it will stimulate a lot of thinking,

which is ultimately the goal of this podcast.

Well, I have one final question

that a listener insisted I ask,

and it’s a very straightforward one.

It’s not at all a curve ball

and not at all related to what we were just talking about,

but it was the most common question

when I told people that I was gonna be talking to you,

which is, is caffeine problematic for hormones?

It’s amazing.

I’ve received hundreds of the same question about caffeine.

And since it’s probably the most commonly used drug

on the planet, I know it’s taking us back

into the very practical, but in closing,

we’re not quite there yet,

but in closing, is caffeine having an effect

one way or the other on testosterone, estrogen,

or other hormones that is positive, negative, or neutral?

Only if it affects your sleep.

So it works on adenosine

and it can actually slightly improve allergies as well,

but negligible effect otherwise.

Great.

Well, sorry to end on such a practical brass tacks

type of question, but I did promise to the listeners

that I would ask that question.

Listen, I want to sincerely thank you.

We covered basically an endocrinology textbook,

a neuroendocrinology textbook’s worth of information,

a ton of practical tips in there.

Where can people find out more about you?

We will certainly provide links.

And I guess the other question is, are you taking patients?

I’m sure you’ll hear that in the various venues

where people can contact you,

but where are you active in terms of public facing work?

I’m active on Instagram, Kyle Gillette, MD.

I’m also active on the social medias of my brand new clinic,

which is Gillette Health.

That’s at Gillette Health on Instagram or gillettehealth.com.

Great, we’ll provide links to those.

And I should say that the content you’ve been putting out

on Instagram is terrific

because you actually point to specific studies

and you put things into actionable context,

which is very meaningful for me.

Kyle, Dr. Gillette, I should say,

thanks so much for your time.

I really appreciate it.

I know the listeners will too.

Thank you, my pleasure.

Thank you for joining me for my discussion

about hormone health and optimization

with Dr. Kyle Gillette.

As you just heard,

he is a treasure trove of actionable, clear information.

And again, you can find him teaching more about hormones

and other aspects of health on Instagram at Kyle Gillette.

That’s Gillette with two T’s and two L’s, but no E.

Kyle Gillette, MD on Instagram

and Gillette Health on all other platforms.

And if you would like more information about his practice,

you can find that at gillettehealth.com.

If you’re learning from and or enjoying this podcast,

please subscribe to us on YouTube.

That’s a terrific zero cost way to support the podcast.

In addition, please subscribe to the podcast

on Spotify and Apple.

And on Apple, you have the opportunity

to leave us up to a five-star review.

If you have questions or comments about this

or any episode of the Huberman Lab Podcast,

or if you’d like to suggest topics

that you’d like us to cover

or guests that you would like me to talk to,

please put that in the comment section on YouTube.

In addition, please check out the sponsors

mentioned at the beginning of today’s episode.

That is the best way to support the podcast.

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.

If you’re not already following us on Instagram and Twitter,

please do so.

It’s Huberman Lab on both Instagram and Twitter.

And there I cover science and science-based tools,

some of which overlap with the contents

of the Huberman Lab Podcast,

but much of which is distinct

from the contents of the Huberman Lab Podcast.

Thank you once again for joining me

for today’s discussion with Dr. Kyle Gillette.

And as always, thank you for your interest in science.

♪♪

comments powered by Disqus