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.

[lively music]

I'm Andrew Huberman.

And I'm a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today my guest is Dr. Kyle Gillett.

Dr. Gillett 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. Gillett 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. Gillett 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. Gillett 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. Gillett is also an avid educator about hormones

in other aspects of health.

He does this on zero cost to consumer platforms,

such as Instagram and other social media.

On Instagram, he is kylegillettmd,

that's K-Y-L-E-G-I-L-L-E-T-T, no E at the end, MD.

So kylegilletmd on Instagram.

And he is Gillett 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. Gillett 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. Gillett 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'll come away from this episode

with the same impression that I did,

which is that Dr. Gillett

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.

I'm pleased to announce that I'm hosting two live events

in May, 2022.

The first live event will take place

in Seattle, Washington on May 17th.

The second live event will take place

in Portland, Oregon on May 18th.

Both are part of a lecture series entitled,

"The Brain Body Contract"

during which I will talk about science

and science-based tools.

Many of which overlap with the topics covered

on the Huberman Lab Podcast,

but most of which will not and will be completely new topics

and tools never discussed publicly before.

Both live events will also include

a question and answer period during which you

the audience can ask me questions directly about any aspect

of science or science-based tools

and I will attempt to answer them.

Tickets for the two events, again,

Seattle on May 17th and Portland on May 18th,

are both available at hubermanlab.com/tour.

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.

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And now for my discussion about hormone health

and optimization with Dr. Kyle Gillett.

Dr. Gillett, 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 is medicine.

They emphasize food is 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.

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.

In 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 doin' 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 the 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 have that pertinent symptom.

- I think that's going to be really helpful,

because for many people,

the idea of getting a blood test to look

at their hormones 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 havin' 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 want to know what their testosterone is,

but at the same time,

they really don't want to 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 varying degrees in ratios.

But it also raises all these issues about sexual health that

it's kind of interesting,

'cause 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, 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, in, let's say in their 20s.

And then maybe we could 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 going to 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 on go 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 in,

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.

- Yeah, 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 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 an approached 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 autoimmune diseases.

- They tend to do well on auto-

- 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 don't just look at low tide,

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

at high tide as well.

- I think 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 2 cardio per week

that 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 2 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 CICO, C-I-C-O,

calories in calories out.

We are not disputing calories in calories out.

But 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 going to make the weight

on a 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 mice studies

and the ones that care about human studies.

But if you correctly restrict mice by 40%,

than 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 in the control group as I say.

- It does in mice.

- Right. Exactly. - 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 8 to 12 hours a day.

Not extended fasts 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,

it's not going to be deleterious.

It's not going to be bad for their hormone health.

There's a couple different hormones that we can talk about.

We can talk out testosterone.

We can talk about DHEA, which 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 sterile,

think of sterile 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 going to help your growth hormone

and subsequently IGF-1 levels,

which will help more in the 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, 'cause I was working late,

I ate pretty big,

it was 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, 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.

- Right, 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,

it seems like it's not like 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 of 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 going to 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 hormone growth hormone?

The kind of the pickaxe end

of the assembly line? - Yeah.

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. - Yep.

- 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 podcast.

Certainly not 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 hormonal optimization

that can improve sleep?

And for people that are suffering from this common syndrome

of going to sleep and then waking up at 03:00 or 04:00

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 going to 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 and 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 gland.

So if you're pre-adrenopausal

where your adrenal glands are still working fairly well,

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-amino butyric acid,

the main inhibitory neurotransmitter

of which lots of things work on,

alcohol works on GABA as well.

Gabapentin 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,

nut 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 started

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 people become even more kind in general,

but I want to 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 want to 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,

if somebody isn't making enough testosterone,

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

they go in and take 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 going to change you as a person.

But if you're eugonadal before you start testosterone-

- Meaning?

- Meaning you have normal testosterone,

and then you start TRT or

self-administered TRT,

steroids, however you want to 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 going to rest as well at night.

- I want to 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 make 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 testos,

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 a 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 picograms 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-

- Wait, they're XY,

but they're females? - Or sorry, they're XX.

- Oh, okay. - Yeah. 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.

- [Andrew] Wow.

- So one or two of these athletes changed to,

I believe it was the 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,

'cause 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 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,

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 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 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,

'cause of course,

I think as you'll probably tell us,

that DHD is a responsible

for male pattern bald and beard growth, is that right?

Should I look at my grandfather on 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 could make purely from phenotypes.

Now 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, called trinucleotide repeats,

then it's not as severe as a disease,

but after you get more and more CAG repeats,

which by the way are,

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'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 in 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,

it's the same reason why testosterone helps,

it activates the antigen 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.

It'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 Masteron or oxandrolone,

preamble and 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 and they're recovering,

and they're trying to have cardiac remodeling,

which is where you take a very thick heart,

and cardiac remodeling's important

in a lot of different cardiac pathologies,

but if you give them finasteride or dutasteride,

which inhibit the enzyme that can 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-body builder,

the typical woman or man, younger or older,

what sorts of things support DHT, and thereby heart health?

Presumably DHT she 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 is,

I guess, could 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 BioPerine.

It's also a 5-alpha-reductase inhibitor.

And on top of that, people have different genetics too.

So some people, they're 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 units as in men,

so it's essentially undetectable.

So you have to,

especially if they're on oral contraceptives,

which is a front 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 is 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 had 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 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,

flat line 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 to 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 antiinflammatory properties, et cetera.

Sounds like people either need to experiment,

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 going to 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.

So 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 that true or

are people just overly concerned about something

that's trivial or non-existent?

- Each male and fem, 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 bit more hair falling 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 at 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 follow. - Of the stem cell niche

in the hair follicle. - Yeah. Yeah.

Think of it like sharks have teeth.

So 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 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 a lot 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 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 tissues 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 stimulate 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?

- Yeah, 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 effluvium.

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?

- [Kyle] Absolutely.

- Okay, I'm going to 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 female or 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 D HT in females, in the periphery?

Meaning not on the scalp or in the brain?

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,

'cause 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 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.

- I 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 about PCOS, what's PCOS?

Teach us about PCOS, please.

- Yeah, 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 a 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, in 30-year old women,

in 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 criteria called the Rotterdam criteria.

And in the Rotterdam criteria,

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

You're looking for androgen excess, insulin resistance,

and you could also look for polycystic ovaries.

You don't actually have to have polycystic ovaries or

to 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 hirsutism.

Or if you have,

like deepening of the voice,

any symptom of too much.

And male pattern baldness, if you're female,

that's a symptom of PCOS as well.

Then you can also have insulin resistance.

So this is obesity.

It's pre-diabetes, a high fasting insulin,

a HOMA-IR over two,

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 oligomenorrhea.

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, menorrhea 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?

'Cause 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 myo-inositol is an insulin sensitizer.

Its cousin D-chiro-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,

and 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 myo-inositol,

which is not an androgen inhibitor.

The other type that you mentioned,

which is an androgen inhibitor is?

- D-chiro-inositol.

It's usually in a ratio of 1 to 25 or 1 to 40,

in a much lower amount compared to myo-inositol.

- 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? - Yeah. 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-chiro-inositol might be a better option.

DIM or diindolylmethane is another kind

of weak antiestrogen,

antiandrogen 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 appeared to me to be very solid studies

where women that take oral contraceptives,

there is both a shift in their perception of men,

'cause 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 peak 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, men,

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 just like TRT is not going to 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 is 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 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 a oral contraceptive.

- And does that blunt the associated increase in libido

that normally would occur from that increase in androgen?

- Yes. - Yeah. Interesting.

And what about other forms of contraception, right?

'Cause there are, 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 your higher risk of a blood clot.

So a lot of women know that if they're

on a 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 anti-androgens as well.

For example, there's one known as Slynd,

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 a hypertensive effect.

- I see, I'm just going to 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.

6 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 6 to 12 months and then stops,

will she essentially be aware she would've 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 an oral contraception

for many years are, in addition to the age-related decline

in fertility that occurs that's inevitable,

of course the slope is going to 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 on a oral contraceptive,

they may have been slightly more predisposed

to insulin resistance and/or lower lean body mass.

But that's probably going to be a negligible difference

compared to their resistance training

and also their caloric restriction

or caloric maintenance so-

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

- Yeah. - Yeah.

Right, I mean on all these parameters, right?

'Cause it's a major lifestyle shift, right?

That obviously people contend with

and have since the beginning of human time anyway.

I want to 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 going to 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 whatever.

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 themself.

If it's smoked marijuana,

then it's very likely to increase your aromatase,

which increases your estrogen.

And that's going to,

it's aromatizing from testosterone.

So that is going to decrease testosterone.

When you have an increased estrogen, like estradiol,

that's going to work on your pituitary

to make less hormones that cause release of testosterone.

So you're going to 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 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.

The American Heart- - 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? - So around, 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, 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, 'cause 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 to 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?

- Yeah. - Okay.

- And with alcohol and GABA agonists,

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, so- - 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's 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 3 and 8,

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's 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

and there's at least say 50% percent 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,

'cause that's kind of the upper threshold,

is the simplest read out 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, or 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,

is 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 in 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 realize 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 they cycle,

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.

And I don't say that ingest.

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 anerobic 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,

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 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 or about saw palmetto,

yeah, supplements for,

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 could consider taking saw palmetto

or even curcumin as an anti-androgen,

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 girl offspring? - Yeah.

- So if your offspring are females,

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

There's hypotheses that link estrogen to prostate cancer

rather than testosterone.

So if you have hypoestrogenism,

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 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 lupus

or an infection or a sexually transmitted infection,

or even a colitis, or even the flu,

your CRP is going to raise significantly.

- That you would detect in a blood test

of course. - Correct.

Yeah. - Yeah.

- So you want to 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 want to keep a very low CRP.

- Interesting, and what about blood flow,

and pelvic floor in general?

We should probably do a whole episode on pelvic floor.

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 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,

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 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 different classes.

So you have your phosphodiesterase.

You have your tadalafil.

Basically this is going to 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 to tadalafil, generic is Cialis,

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

Its 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 you're saying that a lot of men take it

for erectile dysfunction? - Yes.

- But that at it 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's 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 want to say a movement, [chuckles]

but the idea of taking very low dose,

like 2.5 milligram or 5 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.

- And 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 a alternative to pump,

because it kind of works similarly to citrulline,

or 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 of 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 going to be,

has a long half-life.

Whereas Viagra and Levitra is just a few hours,

tadalafil almost today.

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,

but it's not going to- - So in theory,

increasing blood, oh,

because it increases blood flow systemically

throughout the body? - Yeah.

- 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 longterm 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 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 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 have 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 going to take this route?

- If they're a hypogonadal patient

whose benefits outweigh risks of TRT,

then you want to have a nice even steady state.

It's not going to 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 antigen 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 cypionate, enanthate,

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 going to 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 going to 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 testosterone undecanoate,

and then put into a capsule.

And that's taken twice daily.

It has fairly steady half-lifes,

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 FDA approved.

So it is brand name now. it's called JATENZO.

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 supinate or an estered clavate.

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?

'Cause I'm sure a bunch of people out there are thinking,

oh yeah, 103 times a week,

which is actually quite a 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,

5, 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 they 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 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- - It's possible.

- 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.

- Yeah, there were a couple of kids.

I mean, they took some teasing 'cause back then,

there wasn't online discussions about hormones

and things like that, but then it would seem transient.

And they were,

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.

- Yeah, 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's going to be sky high

and it's actually very low and vice versa.

But calcium D-glucarate is a supplement

that can help with estrogen control.

- What's a typical dosage of calcium D-glucarate?

- 500 To 1,000 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.

And it kind of like helps outcompete it.

Some people will also take DIM

or different cruciferous vegetable,

they get 'em from cruciferous vegetables like kale but,

or broccoli and that is both an antiestrogen

and an antiandrogen.

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,

'cause I'm very cautious just 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, 'cause I thought, well,

back then you hear, okay, reduce estrogen.

My estrogen levels weren't out of range,

so they were fine, but 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 airing 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-super 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 US, it's 900.

And so if you're 1,200, are you really super 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 upregulate aromatase as well.

- hCG, you might want to just, human chorionic gonadotropin?

- [Kyle] Yeah.

Used to be found in pregnant,

is still found in pregnant women's urine.

- Still found in

pregnant women, yeah. - But 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 how they got it into their body.

Let's just skip to what you were going to say next instead.

- Yeah. So that's hCG.

There's a lot of other things that upregulate estrogen.

Alcohol significantly increases aromatase.

So if you're very sensitive to estrogen,

then you probably shouldn't even consume

two glasses three times a week.

High fat meals also upregulate 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 and your body and consumption

of a high amount of calories increases aromatase.

- So the it's the ratio of testosterone and 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

that 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.

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, think of like cows and

the rumination in the different stomachs

can change your omega-3 and omega-6

to trans-linolenic 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 cis-isomer.

- And these healthy trans fats would be found

in ruminant cheese and milk and butter

from ruminants and the meat- - And the meat.

- And the meats? - Yes.

- 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

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.

- [Kyle] Yes.

- Or the food products of those ruminants

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

- Yeah, 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 [chuckles] 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 Turkesterone and also Beta-Ecdysterone,

which are two ecdysteroids

that are beta estradiol receptor agonist.

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 Turkesterone or ecdysterone?

- Yeah, ecdysterone. - I've never tried them,

but I know my understanding

is that they work tremendously well for some people.

- Yeah. - 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 Turkesterone or ecdysterone

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 Indonesian herb, I guess,

is 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 and 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 want to 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

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 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. - Okay.

- It's also a weak, it's not SERM,

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,

it's 400 milligrams taken once a day,

typically early in the day, 'cause 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 makes me kind of,

it's like drinking too much coffee.

- [Kyle] Yeah.

- So that's interesting.

And so would women ever want to take tongkat ali

for any reason?

- Yeah, absolutely.

So there's a lot of women that have hyperestrogenism

and unlike adrenal fatigue or andropause,

there's actually ICD 10 codes for hypoestrogenism.

- ICD 10 codes? - Yeah.

- That's doctor speak, right? - Yeah.

- Okay. - 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 and my understanding

is that people should be looking for sources

of Indonesian tongkat ali in particular.

- Correct. - Right.

- Another interesting application is essentially a,

I'll call it a PCT,

but essentially- - What that means is?

- PCT means, I'll defined it as post-cycle therapy.

- Physicians love acronyms, scientists love acronyms,

military love acronym, but we, 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 hypoestrogenism 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.

- [Kyle] Yeah.

- And I should say I do blood work