Welcome to Hubberman Lab Essentials,

where we revisit past episodes for the

most potent and actionable science-based

tools for mental health, physical

health, and performance.

I'm Andrew Huberman, and I'm a professor

of neurobiology and opthalmology at

Stamford School of Medicine. And now for

my discussion with Dr. Kyle Gillette.

Dr. Gillette, great to have you back.

>> Great to be back. Thank you. I'd like to

begin with a question about what all

males ought to do in order to optimize

their hormones. What should they be

doing? What should they avoid doing if

the goal is to have a long arc of

healthy hormone optimization throughout

the lifespan? There's many things that

you should do. An analogy that I often

make is when there's a brand new car

that comes off the assembly line, you do

a full scope of diagnostic workup, hook

it up to the computer. And I think we

should do the same thing with humans as

well. during puberty, you know,

obviously you're a functioning human,

but uh I would say there's still

development and I think that the the

human always develops. I don't think

development ever ends, but you want to

monitor that progress across a person's

lifespan.

>> What do you think are the key things to

look for in blood work? I mean,

testosterone is always the topic that

comes up in the context of male hormone

optimization, but certainly there are a

lot of other hormones that are important

as well. Mhm. And with testosterone, you

want to get either testosterone and SHBG

or a free testosterone.

>> Could you define SHBG for our listeners,

please?

>> It is sex hormone binding globbulin. It

is the protein that binds up all

androgens and estrogens in the body. So

the stronger the androgen, the stronger

it binds. During puberty, strong

androgens, especially DHT, which is the

strongest bio identical androgen, has a

huge role, a prominent role in secondary

sexual characteristics. And if your SHBG

is very high, then your DHT can run

higher because it's not metabolized, but

there's not quite as much free DHT. So,

you want to balance between um a high

enough free DHT and a high enough total

DHT. So assuming that there's no major

intervention, how often do you recommend

that people get their blood work done

>> using shared decision-m with their

physician, usually a good follow-up is

about 6 months.

>> So on a daily basis, uh maybe you could

just take us through the arc of a day

and um and push out some of the

protocols that you use or the things

that you like to see your male patients

use in order to try and optimize their

hormone status.

>> I'll briefly touch on some of the

lifestyle pillars to start. Diet and

exercise are the first two. Um, in

puberty, sleep is particularly

important, of course. Um, but with diet

and exercise, um, throughout a lifespan,

you want to not exclude things that are

helping you. For example, during

puberty, if you're consuming dairy and

then all of a sudden you cut out all

dairy, dairy can help increase IGF-1 and

free IGF-1. And and just uh again for

our audience maybe you just mentioned

what IG what having enough IGF-1 can do

for us that's beneficial is

>> it helps you grow it helps with u

genital development secondary sexual

characteristics and long bone growth um

skin growth hair growth a host of things

>> so getting an array of nutrients that

include dairy what other sorts of

nutrients are important during

development

>> you want to have adequate vitamin D

vitamin D helps with testosterone

production helps again with bone

mineraliz ization and stature. Um, after

an age of about 25, and there's not a

strict cut off, but up to about an age

of 25, optimizing your growth hormone

and IGF-1 helps with bone density and

bone growth. So, uh, from the dietary

standpoint, you want to have enough free

estrogen. Not too much when you're

growing, but you want to help, um,

basically stockpile bone to prevent a

risk of osteoporosis or thin bones,

fractures when you're older. I realize

that some of this relates to ethics and

food allergies and things of that sort,

but would you say that on balance that

most people would benefit from eating a

combination of, you know, quality

proteins from animal sources and

non-animal sources, fruits, vegetables,

and starches? I mean, what do you think

for instance about people following a

pure carnivore or a very uh pure vegan

diet in their 20s and 30s?

>> In their late 20s, it might be a

reasonable option. In early 20s and

certainly teens, it is a horrible idea

because it is likely to significantly

decrease your free androgens. So, you

will have less testosterone acting on

receptors through the body.

>> Are there any other micronutrients or

macronutrients that people in their 20s

and 30s should emphasize?

>> Fiber is going to be paramount in kind

of like setting your set point of your

gut microbiome the rest of your life.

There is prebiotic fiber, which you can

think of as fish food for your good gut

microbiome. Your gut microbiome is kind

of like an aquarium or a fish tank. Any

fiber or food that you're putting in

your gut, it's either going to it's

going to skew your gut microbiome

towards something that is more

beneficial or or more detrimental.

>> And would you say that the prebiotic

fiber and the getting essential fatty

acids that would be important to do

throughout the lifespan or just for

people in their 20s and 30s? throughout

the lifespan. Um, particularly important

in the teenage, 20s, 30s because it

helps with brain development. Um, you're

certainly more of an expert than me when

it comes to um, brain development, but

it does continue to de develop through

really throughout the lifespan, but

certainly through the 20s and 30s as

well. In a previous discussion of ours,

I asked you about um, caloric

restriction and testosterone. And if I

recall correctly, the idea was that if

somebody is overweight, they have excess

fat atapost tissue, then getting rid of

some of that atapost tissue by through

caloric restriction and exercise,

provided it's done not too fast in a

healthy way, is going to be beneficial

for testosterone in the long run. But

that for individuals who are not

carrying an excess of body fat, caloric

restriction is actually going to lower

testosterone.

First of all, do I have that correct?

And second, are there any um addendums

to that that you'd like to to give us

now?

>> That's correct. Um if you look at an

individual in a caloric deficit, several

changes will happen. One is that they'll

have less building blocks for hormones.

Another is that they will be in a

catabolic state more often. So that

balance of anabolism and cat catabolism

will be different. They'll likely have

less signaling from growth hormone and

IGF-1. And they'll also have the high

SHBG that we defined earlier as the

binding protein. So their free androgens

and free estrogens will go down.

>> Now what are some of the other pillars

of creating the proper environment for

hormone optimization?

>> Uh stress is probably the next one. um

during uh both puberty but also the 20s

and 30s individuals are figuring out how

they want to cope with stress and also

figuring out what they want to choose to

put their effort into.

So if someone is overstressed then it

can have uh it can put all the other

lifestyle pillars and then they stop

dieting well um they stop exercising and

everything else can go a skew. What

would the be some of the additional

things that everybody should do?

>> Another one is finding what your purpose

is in life. So, I call this spirit, but

it's really just the self-actualization

component of Maslo's hierarchy of needs,

which is basically your physical needs,

your mental needs, and then your purpose

in life, what you really like to do. The

idea is not to pick the end goal, is to

pick a goal, and then once you reach

that goal to assess and then pick

another goal and so on. I think

sometimes when people hear about picking

a purpose, they're like, "Oh my

goodness, I have to define sort of like

naming oneself that you you you actually

can change your your your goals and

purpose over time." I'd like to return

to the key things that people should do

or I should say the key things that men

should do to optimize their hormones.

What do you think is a healthy

sustainable exercise regimen that anyone

can follow that will also support their

hormone status?

>> For really vigorous exercise around 3 to

four times a week is very sustainable

over a long period of time. On top of

that, you could add in three or four

more instances of less vigorous

exercise. when they study the effect of

exercise, specifically vigorous

exercise. Um, one area that's been

studied is uh vigorous exercise episodes

lasting longer than an hour. And they

usually track it by a rating of

perceived exertion, which isn't perfect

and it's not extremely actionable, but

it's helpful for clinical science. But

the takeaway from that is basically do

not it is not hormonally helpful to

train especially regularly train uh

vigorously for longer than an hour.

These days for better or for worse I

think for worse younger guys are asking

about and using testosterone replacement

therapy so-called TRT. Why in the world

would any male in his teens or 20s or

even 30s whose blood levels of

testosterone and estrogen are at the

appropriate levels, I mean within the

normal reference range? Why would they

you take exogenous testosterone

given all the negative effects on

fertility um some of the challenges that

it can present if the dosages aren't

quite right etc. Why would they do that?

Certainly, if they are not being paid

for a particular endeavor, like they're

not making money. If they are playing a

sport, chances are they're not allowed

to do that anyway. It's it's on the

bannes list. So, to me, it just seems

like a crazy idea. Um, but then again,

I'm of a generation that really hasn't

thought about doing that stuff until

people were in their 40s and 50s or even

never. So is there ever a case for

somebody in their 20s or 30s to take

testosterone espe if their blood levels

are within the 300 to 900 nanogs per

deciliter reference range. You know

everyone has their different reason uh

as far as like when does the benefit

outweigh the detriment. Not very often

if you're um in your 20s and certainly u

probably almost hardly never. There's

always, you know, rare cases like

Coleman syndrome and whatnot, but um

almost never if you're very young.

>> Okay. So, for people in their 20s, 30s

and beyond, 40s, etc. whose testosterone

and estrogen levels are at the

appropriate ratios and in the within the

normal reference range, uh libido,

energy, recovery, etc. are feeling, you

know, at least um workable for for their

lifestyle. For those people, what can

they do besides get great sleep, train,

but not too hard or too often, etc.,

etc. What are some of the things in the

realm of supplementation that can help

them optimize their testosterone and

estrogen without suppressing their own

endogenous production of testosterone

and estrogen? Let's mention creatine as

the first one. Creatine is interesting

because it has multiple different

effects. It helps with amino acid

synthesis. It also helps with oxidative

stress. It can also serve as the backup

fuel tank for your mitochondria. So,

kind of holding backup ATP and it does

slightly increase total testosterone.

And it also increases the conversion of

testosterone to dihydrotestosterone.

So, potentially it's especially useful

in um men in their even their teenage

years and their 20s. You mentioned the

conversion of testosterone to

dihydrotestosterone and there is

mythology out there that creatine can

increase hair loss. I'm guessing because

there's at least one study showing that

creatine can increase DHT.

Dihydrotestosterone and DHT is one of

the primary hormones that can promote

male pattern baldness. Uh so the

question therefore is does cre creatine

supplementation

increase the rate of hair loss

>> in each individual?

Uh preventing hair loss is a very poor

reason to take creatine because it's not

going to take you to a supra physiologic

level. It's not going to uh you know

increase your androgens to an unnormal

level of binding.

So I feel like um this if that was a

reason to not take creatine for hair

loss then

>> you mean for sorry you mean hair loss is

not a reason to avoid taking creatine.

>> Correct. Hair loss is not a reason to

avoid taking creatine. Um it think of it

as just bringing you to what you are um

naturally inclined to have. If your

conversion of testosterone to DHT is

already high then often creatine does

not affect this. It just kind of resets

your balance between testosterone being

aromatized to estrogen or being five

alpha reduced DHT. So it's not going to

speed up hair loss more than um just

naturally being a male does. So in some

individuals it will have no effect. In

some individuals for whatever reason

they have almost no five alpha reductase

activity, it will return them to natural

or normal.

>> Uh so what other supplement-based tools

uh can people consider? Another one we

can loop in with creatine is betaine.

Some people are non-responders to

creatine. So you can increase that to 10

grams or you can use its cousin betaene

to help with amino acid synthesis and

shunting of energy. Along with that, I

would put Lcarnitine.

>> Betaine. Uh do you recall uh what dosage

people typically would take if they're I

creatine nonresponder?

>> One to three grams. In fact, yeah,

several versions of creatine have

betaine mixed in because it helps with

the processing of methionine and

homocyine.

>> So, if somebody is already taking

creatine and likes it in response to it,

I'll raise my hand such as myself, would

adding betaine help or is it redundant

with creatine?

>> Only if their homocyine is persistently

elevated. And homoyine is kind of like

an inflammatory marker that can build up

if you're not converting enough of it

downstream.

>> How would I know? just a blood test.

>> So, Lcarnitine, uh, what are the ways to

take Lcarnitine? I know that there's an

oral form, so capsules, and there's

injectables. The injectables, I think

you need a prescription. Is that right?

>> Correct. You need a prescription for the

injectables or you should really get a

prescription for the injectables

for when you inject it. Um, of course,

at the supervision of your doctor, it's

usually done intramuscularly. It's an

aquous solution, so it does not have

like an oil or a carrier oil in it like

TR like testosterone esters do. Um,

however, if you inject it too

superficially, it's not going to make or

break anything. Often it just burns if

you inject it subcutaneously and it does

not um disseminate throughout the body

as well. Lcarnitine potentially has

localized effects if you inject it. If

you ingest it orally then it has a very

low bioavailability maybe only 10%.

>> So what are the dosages of Lcarnitine

that one needs to ingest then if they

want to get a benefit because if only

10% is being absorbed uh it's probably a

lot of Lcarnitine. How much should

people take per day?

>> Usually I recommend uh for oral

Lcarnitine between 1,000 milligs and up

to four or 5,000 millig.

>> So one to four maybe even five grams.

>> Correct. up to 5 g a day. If you're on

that much, especially if you have a

disregulated gut microbiome, you should

be concerned with TMAO, which is a

potential carcinogen that both carnitine

and choline can convert into and your

gut microbiota determine how much that

happens.

>> Is it true that I can offset any

negative effects of alpha GPC uh choline

that is NLC carnitine um that I take by

ingesting garlic? Is that right? There's

a compound in garlic called allisonin. I

believe it's a l l i c i n. It's also

part of the scientific name, the genus

of types of garlic. And this can help

decrease the conversion to TMAO.

Bourberine actually slightly decreases

the conversion to TMAO as well. Um

probably through alteration of the gut

microbiome. And then just um optimizing

your gut microbiome can decrease

conversion. So not everyone needs

allisonin, but it's something that you

should certainly consider if you are on

a high dose.

I'm going to continue to take the 600

milligrams of garlic every time I take

my Lcarnitine, but I'm going to skip the

bourberine because bourberine gives me

brutal headaches and it makes me crave

carbohydrates because it drops my blood

sugar.

>> It has many other effects including the

dawn phenomenon where it drops your

blood sugar when you're sleeping and you

can't even realize it.

>> Okay. And what we did not talk about is

what Lcarnitine does.

>> It's a shuttle. So I think it's named

carnitine palmatil co-enzyme A.

Basically, it's it just takes nutrients

from outside your mitochondria and puts

them in. It also has a unique effect.

Well, not too unique because tedalaphil

actually has this effect as well, is

that it increases the density of the

androgen receptor in the cytoplasm of

your cells. So, even if your androgen

receptor sensitivity doesn't change and

even if your testosterone does not

change, you will have more testosterone

binding to that increased number of

receptors. Does one need to cycle

Lcarnitine, creatine, betaine?

>> No reason to cycle any of those. What

other supplements can one use to try and

improve hormone profiles? And and here I

realize we're using a very broad brush

because when we say improve hormone

profiles, what are we really talking

about? And for me at least, I I think

about the subjective um stuff. You know,

do people feel like they are going to

have more energy as a consequence of

doing these things? Are they going to

have the more optimized libido? Are they

going to have more optimized uh recovery

from exercise? Right? Because I mean,

it's not clear to me that taking one's

testosterone from 600 to 800 is always

going to be a good thing, especially if

estrogen is increasing in parallel. That

could cause issues. It could certainly

make things better. It could certainly

make things worse, right? Let's briefly

mention vitamin D, which is also a

hormone. It's actually a sterile

hormone. and have if you have deficient

vitamin D and you replace it, then you

will optimize your testosterone.

Let's also mention boron. So if you have

a very high SHBG, boron can acutely help

lower it, usually in a dose of 5 to 12

milligrams per day. It's not really a

sustained effect, but uh boron is

depleted in soils in many countries. I

believe it's very high in soils in

Greece and Turkey. So eating dates or

raisins that are from those areas

potentially have more boron. Boron also

meet might be one of the reasons why the

reference range for testosterone is much

higher in those countries than other

countries. And just to remind people,

the SHPG sex hormone binding globbulin

is attaching to the testosterone

molecule and limiting the amount of

so-called free testosterone that's

available to have its impact on cells.

Okay. So, vitamin D3, I'm guessing

you're talking about vitamin D3

specifically when you say vitamin D. And

then boron, 5 to 12 milligrams per day,

right? Um, and then what are some of the

other things to optimize uh testosterone

that are in supplement form?

>> We can talk about things that affect the

steroidenesis cascade. So, we could

touch on tonad ali. I know we've talked

about that a little bit before. It's

>> Yeah, but I'm guessing a number of

people probably haven't heard that

conversation.

>> Also known as longjack and that

upregulates several different enzymes in

the steroidenesis cascade. And by that

um what you mean if and this is another

good thing to Google. I think anybody

interested in hormone optimization

should understand where where sterile

hormones come from. They come usually

from cholesterol and they can be shunted

off to vitamin D very easily. They can

be shunted off to testosterone or

estrogens or progesterrogens quite

easily as well. But Tonat helps with the

conversion of multiple key steps where

you synthesize testosterone.

Another um think of it as like a

co-enzyme or a co-actor, an upregulator

of these steps is insulin and IGF-1.

So a good rule of thumb is if you're not

expecting as much growth hormone insulin

and IGF-1, for example, lower carb

diets, caloric deficits, you're trying

to cut body fat or body weight, then

tonat is going to be theoretically

especially powerful.

What sorts of dosages of Tongut do you

recommend to your patients?

>> Anywhere from 300 to,200 milligrams a

day. With Tongat, you need to be careful

with the standardization

because and if you're thinking about a

general Tonat supplement, which is by

far the most wellstudied, then um you're

looking at the uricomone content, which

is a plant compound that is likely the

main um active pharmacologic effect. So

that's the compound that's having the

effect on the body. And if you

standardize the uricomone very very

high, then theoretically you're having

more effect at a lower dose. My blood

work tells me that it causes an increase

in free testosterone for me and also a

slight increase in luteinizing hormone

for me. Um what are some of the other

effects on various hormones that you've

observed in the blood work of your

patients taking Tonga Ali? Tongat can

also slightly increase DHEA.

And if you have a very high SHBG, again,

that's the protein that binds up your

androgens and estrogens, an extremely

important protein. Uh the higher your

SHBG, the more it helps decrease it. So,

they've studied tonat in uh populations

with very normal SHBGs, and it does

nothing for SHBG.

>> Interesting. Does that mean it does

nothing for somebody overall? So if

somebody has SHBG that's in the normal

range, will taking Tongut benefit them

in any other way?

>> Yes, it it'll increase their total and

free testosterone.

>> What are some of the other hormones that

you uh prescribe to your patients uh who

do not want to go on testosterone

replacement therapy or take exogenous

DHEA or anything like that?

>> We could talk about Fidosia next. Uh

Fidosia is interesting because it's a

genus of plants. Fidosia is one of them.

There's many others that are very

interesting. Um, that species is likely

the most wellstied and it will increase

LH. So, um,

>> I would not consider it an LH mimetic.

So, it doesn't really mimic it, but it

increases the release of luteinizing

hormone from the pituitary. That's a

hormone that binds to the latic cell to

the LH receptor kind of like hCG does,

and it will increase the release of

testosterone.

>> What dosages uh, do you have patients

take? I've heard of uh some potential

toxicity to the testicular cells.

>> There was one study and this is a rat

study but you can equate the dose of

toxicity in rats in humans. They did not

give these rats any antioxidants but it

increases a couple different um like

pro-inflammatory markers. One is GGGT or

gamlutamal transferase comes from both

the testes and the liver and one is

alkaline phosphatase also known as alkos

again coming from both areas. There are

several different ways that you can

attenuate this increase and you can also

just check to see if you have increased

in the rat dose that equates with humans

that had no effect. So the safe dose was

an average of 300 mg a day.

>> So that would be 300 milligrams a day in

humans is the dosage that did not have

toxicity. Correct.

>> Correct. And often even if there is

toxicity in rats, there is not toxicity

in humans. So it's not directly

equitable. But to be safe, um, another

regimen that I have people take is 600

milligrams every other day or 600

milligrams three times a week, often

Monday, Wednesday, Friday. My

understanding is that nowadays a lot of

people are using testosterone. Let's not

even call it replacement therapy because

some of these people have 600, 700 or

even, you know, 800 nog per deciliter

read. So they're not replacing anything

that is diminished. They're just trying

to augment what's already there,

increase what's already there. My

understanding is that taking a low dose

more frequently is going to be more

beneficial than the kind of old school

way of giving, you know, 100 or even 200

milligrams in a single injection once

every two weeks. Is that right? And and

what do you do with your patients? So,

let me give you a hypothetical. Somebody

comes into your office, they um do their

blood work and they have um blood levels

of let's say 600 NOGS per deciliter

testosterone. Their estrogen is also in

normal range. everything else checks

out, but they're complaining of, you

know, slightly diminished libido,

slightly poor recovery from workouts,

maybe um, you know, reduced motivation

and drive, although no major depression,

and you come to the conclusion that

testosterone therapy, not replacement,

but testosterone therapy might be a good

option to explore. What's a typical

dosage uh, range and frequency of

administration range that you might

consider exploring? And

>> some of this depends on the SHBG and

free testosterone as well. So if that

same individual had a very high SHBG,

which again is the binding protein that

binds up the testosterone and all

androgens and estrogens, if it is

extremely high and they have a free

testosterone of two, then they might

need a different dose because they need

enough testosterone in order to um have

a normal yugenatal free testosterone.

But a general normal dosing range,

especially for someone starting, is

around 100 to 120 milligrams divided

over the course of a week. Usually

either every other day or three times a

week, occasionally twice a week. Many

people with SHBG a bit higher can get

away pretty easily with twice a week.

This is assuming that the esther is

cipionate or ananthate.

>> So two 60 mgram injections of

testosterone cipionate per week.

>> Yeah. very common dosing

>> to hit that 120 milligs per week as kind

of the typical average.

>> Correct.

>> And I would consider this um like a

physiologic yugenatal dose. For many

people, even 200 milligrams a week is

far above the reference range. All of

this is said with the caveat that

testosterone is normally released in a

pulsatile manner. So it's high in the

morning, low in the evening. Whereas if

you're on uh testosterone therapy, then

um you're going to have a steady state.

So your testosterone level is going to

be pretty much the same even in the

evening.

>> In your experience, when patients do

that, they I'm guessing they report the

normal constellation of positive

effects, you know, improved mood,

improved energy, improved sleep,

recovery, etc. What are some of the

hazards or things that um can crop up in

blood work or just subjectively that um

can be warning signs that even a dosage

of 120 milligrams divided into these two

or three dosages per week is too high.

So this is when you really have to be uh

at least well-versed in every organ

system, not just the gonatal um like you

know genital system. You need to have uh

you know dermatology prowess. Acne is a

very common change. Lots of different uh

skin pathologies or even bruising can be

related to hormone replacement. Hair

loss is very common to see as well. Um

mental status changes. It could in

occasionally it even induces a manic or

a bipolar episode because testosterone

is also dopamineergic.

And then cardiovascularly not just in

the heart but also concerns for like

microvascular eskeemic disease, feritin

buildup because the estrogen also

increases and then uh fertility concerns

as well and lipid concerns too. So you

really have to be you know hematologist,

dermatologist, cardiologist, um

lipidologist, the whole nine yards. So,

another reason or set of reasons rather

to uh if one is considering using

testosterone therapy to really do this

in close communication with a really

good physician because that's a lot to

monitor. Knowing whether or not you have

acne or not is one thing, but knowing

whether or not your LDL is going up,

your APOB is going up, that's a whole

other biz and that needs to be done

through blood work is what I'm hearing.

>> Correct. And if your physician that is

managing or prescribing your uh

testosterone therapy or your HRT is not

well verssed in these systems, you would

want him or her to be part of an

interdisciplinary team where they have

other experts that can monitor those

systems. There are males out there who

want to increase their testosterone and

other hormones, maybe growth hormone,

etc. who opt to not take exogenous

testosterone. So, no cream, no pellet,

no no um pill, no injectable cpionate,

but decide to take Clomophin a couple

times a week.

My understanding, I've never done this,

I would say if I had. My understanding

is that taking Clomophin maybe 2 50

milligram tablets a week is what I hear

people are doing, will increase what

luteinizing hormone,

the various estrogen receptor subunits.

Could you explain how Clomophin would

benefit anyone and is this a good

strategy? I'm I'm hearing that it's

being done quite a lot now.

>> It will increase testosterone in a dose

dependent manner, but it has many other

pharmacodnamic effects which is the

effect of the drug on the body other

than its effect on the hypothalamus and

the pituitary. So in the hypothalamus

and the pituitary, it uh does what's

called negative feedback inhibition um

or it it blocks the oxygen of estrogen.

So it crowds out estrogen from the

estrogen receptor on the hypothalamus

and the pituitary.

>> Why would I want to take something that

would increase the activity of an

estrogen receptor? I just can't find the

rationale for that.

>> The main rationale behind taking a ser

is as a very temporary measure that is

not going to suppress pituitary or

hypothalammic function. if your

testosterone is just so drastically low

that it is unlikely to recover anyway.

So most of the time it is not clinically

useful and um serum should not be

prescribed very often. Certainly not as

long-term testosterone replacement um or

testosterone optimization in most

individuals. There's always exceptions

to everything, but um there's five

different estrogen and estrogen related

receptors. There's two main estrogen

receptors in Clomid and every serm has a

very unique profile because they

selectively inhibit some receptors in

some tissues but not other receptors in

other tissues. For example, um Clomid

can inhibit receptors that are in the

eye and it can cause um visual changes,

blurry vision um especially at higher

doses and it also acts in every other

tissue of the body. So side effects from

Clomid and other selective estrogen

receptor modifiers are very common.

>> Alcohol, does it increase aromatase, the

enzyme that converts testosterone into

estrogen or not? And um is there a dose

dependence there?

>> It significantly does. There is a dose

dependence. In general, I would not

recommend more than uh three to four,

you know, standard drinks. uh one huge

glass of wine is probably five standard

drinks every two weeks. The other thing

to keep in mind with alcohol is it has a

lot of calories, 7 kilo calories per

gram, almost as much as fat, which is

nine. And then it's also very gabaurgic.

So it it can activate inhibitory

neurotransmission. Um and that can also

affect how many how much uh LH and FSH

is released. So that can also decrease

testosterone almost kind of uh similar

to how opiates can decrease

testosterone. I want to go back to the

prostate and talk to you about something

that's kind of a newer emerging trend. I

know that um you've talked a little bit

about this in uh previous podcasts that

a number of men or I should say a number

of physicians are prescribing lowdosese

talopil also known as seialis to their

male patients. So in dosage ranges of

like 2.5 milligrams to 5 milligrams per

day, but not for erectile dysfunction,

but rather for improving prostate health

and presumably they get sort of a boost

in terms of blood flow um to the

genitalia as well. But again, not

specifically to deal with uh erectile

dysfunction, but to deal with prostate

health and blood flow to the prostate.

Is that something that you sometimes

often prescribe to your patients? And of

what age?

>> Tedal is a very underrated medication.

Um the age would kind of depend on the

indication.

So tadalaphil is also a blood pressure

medication. It can very slightly

decrease blood pressure especially at

higher doses. At higher doses it theor a

high dose would be 20 milligrams not 2.5

milligrams but consistently it can

somewhat affect with the cones in the

eye that have to do with red and green

sight. Although if you remove it that

effect is reversed. So basically if you

don't need really really good red green

discrimination you can take higher doses

but in general I recommend no higher

than 10 milligs a day usually just two

or 5 milligs.

One uh other benefit or other use of

tadalapil is that it increases the

density of the androgen receptor

similarly to lcarnitine.

So that's an interesting benefit.

Another benefit is that if you give it

to people with nocturia, which is

urinating at night in general, it will

cut the episodes in half. So it could go

from two to one, which can make a big

difference for your sleep, which will

secondarily make a big difference for

your growth hormone and testosterone

optimization.

>> Interesting. So you said 2.5 to 5

milligrams per day is kind of typical

for these prostate enhancing effects.

>> Yes. I get a lot of questions about

drugs to offset hair loss. Most of those

drugs are going to operate through the

DHT system, the dihydrotestosterone

system, for the reasons we talked about

before, DHT receptors being on the scalp

and causing beard growth on the face. Is

it the case that a number of people

taking um things like Propecia and other

things to block the DHT or disrupt the

DHT pathway are going to experience

diminished um sex drive, diminished um

you know, kind of motivation and general

vigor? And if so, are there alternatives

like topical DHT antagonists that they

might use um if they want to keep their

hair but not have those negative

effects?

>> Many people that have just a bit of

predisposition, they can use things that

are topical anti-androgens.

Uh ketoconazol is one of them. Caffeine

is actually another one.

>> Wait, you have to explain how this

works. How do people get caffeine into

the hair follicle? Topically, the

caffeine enters the scalp and crowds out

like somewhat crowds out the androgen.

It is a weak effect. It's likely just

strong enough to be clinically

significant. Usually, caffeine is put

into formulations with other things like

ketoconol that are also weak

anti-androgens. Of notes, spironolactone

can be prescribed topically, but is it

is absorbed systemically because the

size of the molecule. So unless your

doctor specifically prescribes that for

you, especially as a male, do not use

topical spironolactone.

Topical finasteride is also a smaller

molecule. So it is also systemically

absorbed, but it is not extremely well

systemically absorbed. If you take

topical finasteride, then usually your

systemic DHT will decrease by about 30%.

Topical dutasteride is likely a tiny bit

systemically absorbed, but it's unique

because its half-life is much faster at

a lower dose. So topical dutasteride

will not affect your systemic DHT at

all. And I've seen this anecdotally on

many people on topical dutasteride

therapy. On behalf of the audience and

and just for myself, thank you so much.

You have an immense amount of knowledge

and you're exquisitly good at sharing it

with people in an actionable way. So

thank you.

>> My pleasure.