Derek (More Plates More Dates)

Thanks for having me.

I really appreciate the invite.

Yeah, I think at a basic level, it is the primary anabolic hormone men rely on for the sustainment or growth of muscle tissue, bone health, bone integrity, inhibiting degradation, indirectly through some of those pathways as well, insulin sensitivity, if you have insulin.

Worse in body composition, it becomes more difficult to handle glucose adequately.

Neurological health or the aromatization in the actual tissues themselves.

There's an array of things that are supported here.

critically by testosterone and its indirect metabolite activity as well through its aromatization to estrogen and I guess notably but often overlooked it's easy to forget but in adolescence the 5 alpha reduction to DHT so the conversion of testosterone to DHT is necessary for full maturation sexual differentiation to basically reach full adult male maturity and

There's a myriad of examples where FDHT is either too low via genetic predispositions or through different means than there is inhibited maturation.

And that's where you get into some of these more unique intersex cases.

But essentially, at a base level, this is the primary case.

Male, all but significantly impactful in females as well.

Hormone that is present at about 10x the concentrations in males and kind of differentiates them in terms of sexual identity and male characteristics.

Yeah, yeah.

And like, again, it's a non-exhaustive list that I just presented.

Like, the list extends beyond into erythropoiesis, the production of red blood cells, intratesticular testosterone production, absolutely critical for fertility as well.

And women...

All but not directly analogous intra-gonadally, but elsewhere in the body, the activity of testosterone is still necessary for a lot of the same things.

Cognitive health, some level of cardiovascular support, bone integrity, anabolic activity in muscle tissue, all of the same stuff is still the case in women, just to a...

much lower magnitude so but similar as you would expect there's less of a concentration required to sustain a female musculature than a male so the concentration differential is about 10x but in women the main function of testosterone still overlaps with males but intragonadally it is more to facilitate as a substrate of estrogen production so getting that sufficient amount of aromatization into

estradiol, but also the conversion into estrone, which then turns into estradiol as well to facilitate all of the female fertility facilitated processes.

I think it would be highly speculative because obviously I would love to just point to some clear-cut literature that says based on these studies on, you know, inhibiting IGF-1 or having really low androgen levels equals lower body weights equals longer lifespan or something to that effect that could be a common kind of denominator, but it's not as cut and dry.

I do think there is some level of metabolic activity

resource demand that is needed to actually support the infrastructure of a male that is more intensive than a female.

So I would, in general, like larger humans are going to die quicker than smaller ones, at least from what I've seen trend wise.

And

in supporting that it is something that requires more hormone production in general, which is also more intensive on all organ systems accordingly to actually facilitate and get that hormone production to the level it needs to sustain that larger human.

So that's a highly speculative take on it, but that would be part of the reason.

But at a high level, if you want to extrapolate to

You know, at higher levels, androgens will be neurotoxic in a dose dependent manner past supra levels.

It will cause cardiac remodeling in a negative manner, like all of the dyslipidemia, all of the negatives that you would hear about when it comes to anabolic steroid use.

to some extent at supra levels are going to be present from testosterone all but to a more muted extent because it's not a synthetic drug that is manipulated in a lab to create you know something that is not a substrate for aromatization and some of the other stuff that is protective but that's a high level speculative take

The like the male castrati, like so the men that are like, yeah, they castrate like they are osteoporotic as a consequence of a lack of sufficient aromatization into estrogen.

and their growth plates, the epiphyseal growth plates don't close fully because of that lack of aromatization in adolescence, which is facilitated essentially entirely by testosterone as a substrate, similar to what it is in women.

But if you castrate a male in adolescence and he no longer has intratesticular testosterone production, he is now functioning off of solely adrenal production, which is like a drop in the bucket to what you actually need to function at a high level.

Like you're not going to have

sufficient bone development and you are going to suffer from osteoporosis inevitably.

And if those those who don't know what the castrati are, it's really interesting.

So it's individuals who were had angelic singing voices.

And I'm not sure where the last who the last documented one was, but it was actually more recent than many would probably think.

It's like within the last 100 to 200 years.

But anyways, you can listen to them on YouTube singing and some of these old audios that were recorded.

And it's, you know, a youthful, angelic singing voice that comes across as somewhat and like androgynous to some extent.

And obviously going through male puberty and being subjected to male amounts of testosterone and DHT.

Would you know like quote unquote wreck that voice because it's going to be masculinized and get like fully you know the deepening that would happen that's irreversible so the castrati were individuals that were castrated in order to prevent them literally from going through puberty adequately so they would actually grow into.

men without the full maturation that would come from androgen exposure in adolescence.

And as a result, you know, they would have a lack of adequate sexual differentiation maturation and their bones would reflect that as well via the osteoporotic outcomes they underwent.

Notably, though, their estrogen levels are in the ground.

So you saying a second ago about the estrogen.

Well, it's definitely a lower capacity to build muscle and bone, which is less resource intensive.

And you're a smaller human.

So maybe as a result, you are literally a walking human.

I don't know, like shell of a man, essentially.

So you don't require as much to sustain, but your quality of life is dramatically hindered.

So total testosterone is the number that most people are familiar with, which reflects the total production that can be detected in your sample of blood that was taken.

So floating around how much testosterone is there inclusive of the testosterone bound to binding proteins.

So just because it's in your blood though, it doesn't mean it's biologically active.

If it's bound to these binding proteins produced by the liver, it could be either, uh,

entirely inactive or like readily available to be dissociated but not yet fully active as well so you have you know shbg is the primary one sex hormone binding globulin produced by the liver this acts as a regulator of androgenicity in the body which is like how much androgen exposure systemically you would be exposed to and the body has this kind of regulating mechanism

to partly to make sure that you know females stay feminine males stay male and regulate which tissues get which hormones when and transport it around the body because these are hydrophobic like they're fat soluble and would not go through the blood to where you want them without some sort of carrier so they have a hydrophilic

similar to like how cholesterol will get moved around through its, you know, ApoB particles and whatnot.

And these binding proteins, SHBG and albumin, comprise the vast majority of testosterone.

I think SHBG is about 60% of your total T will be bound by SHBG.

And then like 38% is albumin.

And then 2% to 3% roughly, depending on how much

shbg produce and some other factors is actually free testosterone so the free testosterone number is just like freely circulating not bound to binding proteins and it's like ready and readily available to be used by target tissues should it bind to the androgen receptor and cause the transcriptional activity but

In general, the two numbers you care about the most are going to be the total testosterone, which is like total production reflection.

So like how much are you actually capable of making, which is important.

A lot of people will just say, look, you're free because that's like the number of the matters.

That's what's actually available to use.

And that's true.

But it still doesn't reflect total production capacity, which is important to assess the viability of the organ, response to the pituitary output, a myriad of things.

So total testosterone, total production, including that bound to binding proteins influenced by liver health, diet, a bunch of different factors, free testosterone, about 2% to 3% in an optimally healthy male typically.

That is just freely available to be used.

And then as far as measurement, kind of like best practices, typically in the morning is the best.

Testosterone is kind of it's like a pulsatile hormone.

secretion fashion so you would see in a diurnal rhythm chart showing the secretions of testosterone throughout the day it kind of pulses out in waves so you would have like the biggest pulse early in the morning and then it kind of like goes across ebbs and flows throughout the day until it reaches its low point later at night and then as you sleep it starts to ramp back up again so typically the best way to assess peak levels would be early in the morning

and ideally you would have um not taken certain confounding variable supplements like biotin that can cross detect as you know estrogens and whatnot and typically labs will provide kind of like a guideline of what not to do but in general the rule of thumb is you know go and fasted early in the morning avoid uh your multivitamin probably if it has biotin in our biotin containing supplements

and be hydrated to reflect your actual hematology profile correctly because some people incorrectly think they have a elevated you know hematocrit level when in reality they're just super dehydrated when they go in because they just got up rolled out of bed and are you know dehydrated from hours of sleeping and you know not hydrating properly when they wake up and they just roll in and think that oh I'm gonna have a heart attack and then I gotta donate blood now which might not be the case so I know that's a mouthful but early in the morning

And ideally, you would get a repeat measurement before you make any sort of especially before you make any sort of choices on path forward, because you definitely want to get confirmation if you have a low rating or even one that's like mildly concerning, because, again, these things can be so variable depending on so many factors that you might have.

a blip where it's a snapshot in time of your blood.

You see, you know, a 495 total T and you think, well, that's not great.

It should be closer to a thousand.

That's what I hear is good.

And, you know, all these podcasts and whatnot.

That's what my friends are at.

They're at 900.

Like I only have 495.

I should have way more than that.

And some people haphazardly get on testosterone, shockingly, but it happens.

And there are a lot of clinics that will tell you like, oh yeah, you can get that up.

Let's get this up to, you know, 900.

that's all they need to give you know to justify it to themselves um so yeah you definitely don't want to go off of one reading you want to go off of symptoms and repeat measurement to confirm your findings before you even decide what the path forward is for natural interventions and assessment of what is happening at the organ level and at the hypothalamic pituitary level

Um, in general, I think, um, it does get convoluted because people will see a reference range and assume, and understandably so, like there's a lot of things that people will just say, oh, target the top of the reference range.

This is where you should be.

And in general, it's not a bad recommendation often for things that modulate things.

quality of life related outcomes you know like even when we talk about vitamin D it's like you know you should probably be at like 60 even though the low end is like 30 typically if you were at 40 people would be like you know try and bump that up to 50 or 60 with testosterone people think similarly and justifiably so sometimes but often what is overlooked is the fact that

The actual androgen receptor content, which is like how many androgen receptors you have in like a concentrated area, or also the sensitivity of it, like what kind of transcriptional activity do you get subsequent to binding?

Those things all factor into how much of an impact the androgen has after binding to the receptor.

So just because you have less testosterone than the next guy, it doesn't necessarily even mean that you have less muscle growth potential or less bone support capacity or less neurological support.

It's not guaranteed any of these things based on absolute values.

It should be a combination of symptoms as well as blood values.

But oftentimes, too, the blood values should be superseded by symptoms in some cases, too, because you'll have some individuals who have insensitivity at the AR.

So it's not just about how sensitive are you and can you get away with lower testosterone.

Some guys need higher testosterone to be able to actually function well, and they might otherwise be told, oh, you know.

You don't need testosterone.

Your total testosterone is 900, but they might have a super high sex hormone binding globulin that's gobbing it all up and they have a low free testosterone or their actual receptor activity after binding is like subpar or they have a gene mutation that inhibits the actual activity of it.

And that's where you get into some of these convoluted cases with like the Olympic boxer and like we're not going to go down that road, but some of these individuals who like

You know, there's a spectrum of androgenic activity that is influenced not just by the total levels on paper, but it is very much dictated by your actual response to the hormone too.

In general, it's very crude the way they assess if you are one of...

the individuals on this like spectrum of androgen insensitivity it's literally like manual assessment essentially of like your gonadal development which is like kind of uh you know demeaning potentially if you're somebody who is like already obviously insecure about what's happening and then you're just subjected to some sort of like subjective analysis of like an expert who determines if you've had sufficient enough like male sexual secondary characteristic development

But in general, there are proxies for activity.

And, you know, if you're somebody who has...

Like if you looked at blood work, for example, some individuals think, oh, the guy with a natural like 1300 total T, that's probably great.

That guy is like an outlier genetic phenom.

Oftentimes it's a reflection of some sort of problem.

Like they need to produce more to reach adequate activity.

So like sometimes the body is screaming at the testes because it's not getting adequate production to do what it needs to do.

And it's resulting in you shooting out more gonadotropins to make more testosterone.

Typically, you will see this reflected in some sort of symptom, either through actual development in adolescence being not adequate or through biomarkers.

It becomes pretty clear because there will be other factors that are clearly outlier oddities in blood work when you see somebody who is not responding adequately.

Like these are very outlier scenarios that I'd be deviating into where people are like, you know, overshooting to try and meet some sort of physiologic activity.

Like most guys are going to be falling into the bucket of they have low gonadotropins or low response to it from age-related decline.

That's more of like, you know, what most people will find relevant.

So I'll start there.

In general, the thing you would be looking to first is, okay, like what are your levels, your total and your free levels?

Do they look good?

Do you have any symptoms?

And let's just say you do have symptoms and you're looking at these numbers and they look okay.

At that point, you would be looking, the actual output from the pituitary is going to be dictating what the signal to your testes is to actually produce testosterone.

So the LH from the pituitary signals to the lytic cells to make the intratesticular testosterone.

So is that signal adequate is one thing to assess, and that has a clinical reference range.

um but also individuals who are primary hypogonadal uh similar to what we talked about when it comes to assessing you know when women are hitting menopause like what kind of would you look to in men if you are not responding and producing adequate testosterone at in the testes like you will be trying to make more luteinizing hormone typically to try and push that signal so it's your body's going to recognize

I'm not getting enough testosterone out of this LH that I'm making.

So the signal isn't sufficient.

I'm not getting enough testosterone and or enough estrogen from that to provide the negative feedback that tells me to stop making GnRH and the other, the pituitary hormones.

So I would just, it would just keep shooting and trying to like probably overshoot you into adequate territory.

So you would, if you're a primary hypergonadal, you would see the reflection typically of high gonadotropins.

Or you would also see some sort of like structural defects.

And that's where you would get into like, you know, ultrasounding for, I think the prevalence in males is like 15% of males have a varicocele.

I don't know if you know what that is, but it's like varicose veins in your testes essentially.

And it looks like, like twisted kind of like,

The same thing you would see in varicose veins in your legs.

It's like in the side of like the testes and it inhibits thermoregulation and significantly impedes testosterone production locally and fertility.

So that is,

Often time well 15% of men from what I recall is the number for prevalence pretty significant though for something a lot of people don't know exists and if you are, you know doing all the lifestyle stuff and it's not working and You think you're doing everything correctly and you must need testosterone Sometimes it can be overlooked that there are structural defects.

So like typically the first thing you would look to is like

am I capable at the organ of responding to the signal?

And like, is the signal adequate to begin with?

Because if there's like a primary hypogonadal outcome, it would be some sort of like structural response problem in the testes themselves.

if that's not an issue and you've ruled out all structural problems, you know, age-related decline is not a factor and you're, you know, otherwise, you know, everything's all accounted for from that angle, you would look upstream to the pituitary and say, okay, well, at that point, am I producing enough LH and FSH?

And this is typically the outcome you would see in men, uh,

not always but like a lot of men who are kind of like not sure if they need testosterone they'll have like a relative proportional inadequate signaling driven through a myriad of factors including but not limited to lifestyle some age-related decline toxins exposures a myriad of things and that's kind of like where people have this uh

opportunity to try and incrementally maximize all the areas in their life to try and improve the output.

Because if you have sufficient functioning organs and your output is just insufficient, you might be able to get that up to snuff to where you need it just by getting leaner, losing body fat, fixing your diet, addressing micronutrient deficiencies, quitting smoking, not drinking anymore, fixing your sleep, you know, all the smorgasbord of things.

SHBG, sex hormone-binding globulin.

Yeah, and it gets really complicated in this regard because what a lot of people don't address is, so DHT, dihydrotestosterone, mentioned earlier how it's like the primary hormone that will determine if you reach full maturity in adolescence.

It will still be markedly male probably if you have adequate testosterone production, but you won't get full maturation if you have zero DHT from a defect in the enzyme that encodes for 5-alpha reductase or something.

But that hormone, the most androgenic hormone in the body that essentially determines if you fully masculinize or not, where you end up with a micropenis, that has a much higher binding affinity for SHBG than testosterone does.

And then testosterone has a much higher binding affinity for SHBG than estrogen does.

So even though on paper, we're talking about the importance of free test versus total test, which is very important.

Also very important, which most people aren't going to test in their blood, is the DHT level that males will rely on through adolescence and to some extent in adulthood, potentially, depending on their test levels.

That is going to get gobbed up even more proportionally by SHBG.

So if you have high SHBG, not only is your free test potentially inadequate, despite adequate testosterone production, proportionally your free DHT, which is like the main androgenic hormone, is like way more gobbed up.

And this gets really rough in females because they, a lot of them, are using things like combined oral contraceptives, which crank SHBG through the roof, through the liver interaction with the oral, combined oral contraceptive pills, depending on which drug they're using.

In general, ethanol estradiol plus some progestin, depending on how androgenic the progestin is, it'll depend on how much the SHBG goes up.

But

You'll see in adolescent women or women who are, you know, in full adulthood that are taking combined oral contraceptives, their total testosterone will suppress upwards of 50 to 60 percent and free testosterone upwards of like 70 to 80 percent.

So they're walking around like borderline asexual castrated by a pill, essentially.

That's with oral, but like any sort of progestin that is synthetic will have negative feedback to some degree, all but much lesser so via a localized IUD releasing a levonorgestrel or something.

And you're not having to take that supporting estradiol that comes compounded into it.

So it depends on the format, but a lot of girls are still using the combined pill.

So it's just worth noting nonetheless that...

when these SHBG levels are skyrocketed or even like high on a clinical reference range,

If you are somebody who is like moderate, you know, tea production or low normal or whatever, like the proportional hit to your DHT getting gobbed up could be like the differential between you being symptomatic versus not, as well as your free tea.

Even though it's proportionally less gobbed up, the DHT could be like nuked entirely essentially via the SHBG levels being high.

Yeah.

So like a common thing that people hear is when you get 30 years old, your total testosterone will decline by 1% per year.

But the reality of what makes this even worse is your SHBG levels will increase year over year proportionally faster, thus making the velocity of free testosterone decreases dramatically more so proportionally.

So even though total test decreases by 1% a year, your free test will decrease by up to 2% per year.

And that's the one that you need to like do stuff in the body through like freely circulating activity.

So...

it's very important and very relevant for dictating what activity you have in different tissues in the body because it's ultimately the only one that can actually bind to the receptor and do what it's supposed to do so the shpg levels will be dictated by age will be dictated by liver health to some extent will be dictated by other medications especially oral formulations um

Insulogenic signaling as well, hugely implicated.

If you're on a ketogenic diet, you can absolutely expect your SHBG levels to be through the roof and your free test to be much lower.

So carnivore diet guys, there's a reason they eat fruit now.

It's because their free test levels were all shit and their total test levels were high and they thought it was fine.

But in reality, they had like borderline hypogonadal free test levels often because they were overlooking the fact that insulogenic signaling is needed to actually get SHBG to a meaningfully reasonable level for a male.

Yeah.

And these binding proteins also exist for other hormones in the body because they all function in similar ways through cargo systems and transport mechanisms in the body.

Like you will have binding proteins for IGF-1.

You'll have binding proteins for thyroid hormones.

Like it's not uncommon to see people with like normal on paper levels for certain hormones.

But then when you dig deeper, all the free hormones are like normal.

proportionally horrible because they're all about like the the total production looks okay but it's because it's factoring in all these like bound up hormones that are in use like unusable essentially

Like, I mean, would you say that's... It depends on the person and lifestyle.

So, but yeah, probably, especially among women, because, you know, a lot of them are... You only have so much androgens to work with to begin with.

Like, your production is, you know, a tenth of males, typically.

And then if you are occupying...

all of your androgens because you know essentially the shbg is going to with a much higher binding affinity mop up all your dht and testosterone not all of it but like a significant amount of it if it's high in any like higher than it should be

Like it will impact your like free androgenic signaling so significantly that might put you into like the, you know, female hypogonadal equivalent territory essentially.

So you could be like, it's not uncommon for girls to walk around borderline asexual or like literally no drive throughout their entire adolescence, 20s, 30s and think it's normal.

And it's just not what they're supposed to be walking around like.

Bone integrity.

So that sounds like a bit lesser.

So depending on if they're on like, obviously, you know, if you're on a combined role contraceptive pill that has estrogen in it, you know, however much it does that to what dose, you know, you get into the nuance.

But ultimately, like you're inhibiting natural hormone production quite dramatically.

through a myriad of means, like think about guys who are just like natural having to deal with what they deal with as is, the sleep impact, the cortisol impacts, the fat impact of being obese.

And then if you have women who deal with all those same problems, you're gonna have all the suppressive results of all of those lifestyle things, the diet, the nutrition, the whatever,

And then you also factor in medications on top of that, too, that maybe men don't typically have to take to, you know, achieve contraception.

Like, you know, that's typically often I think the final blow that will like push women into like, you know, closer to low drive territory often and almost certainly lower quality of life for a lot of them.

now that's not to say because i think this gets misconstrued often is it's not to say don't use contraceptives at all like there are absolutely better ways to go about it i'm just giving examples that i see as commonplace

It does get tough because as you would imagine, a lot of the lifestyle related things that lead to low testosterone will come with the decrement to quality of life just via, you know, if you have poor sleep, like you're not going to feel great because you didn't rest enough.

And then you add that on top of the inhibition of stress.

you know, your output of gonadotropins, pituitary hormones, and response to them as well.

Like it's like a one-two punch off in a lot of this stuff.

So in general, I would look to things like libido, erection quality.

Obviously that's more, you know, circulatory often, but still notable nonetheless.

If you suddenly, you know, if you don't have morning wood anymore, like you got to look into it regardless if it's circulatory or hormone mediated, might be a combination of both.

Um, you no longer are able to hold muscle as easily or build muscle as easily.

You're losing strength in the gym.

Your recovery capacity is inhibited relative to what it was when you were younger.

Um,

Mood dysregulation, irritability, and these are all like really general vague symptoms.

And I would love to just say, oh, look at, you know, this exact thing will happen.

But in reality, it's often a constellation of things that comes as a vicious circle effect of the, you know, factors that led to that deterioration of testosterone to begin with.

Or if you were just, you know, never had reasonable testosterone to begin with, you would have probably not gone through puberty adequately to begin with.

So like the genetic factors, like some of these like more outlier cases become a bit more obvious because it's like you just never really like fully masculinized in adolescence.

You may have a higher voice, you know, a lot of those things are less relevant for the average person.

For the average person, it's going to be more of these general symptoms and it's warranted to get a test at that point and just see what's up.

So then that in combination with the test and things that we just talked about is kind of like where, you know, like pre-diabetic, you know, progressing towards, you know, pre-diabetes, insulin resistance.

A lot of this stuff is going to be ultimately determined by blood work, though, because a lot of people aren't going to be able to identify this autonomously, reliably.

So that's kind of where I'd point to the more vague stuff, like the quality of life.

Like, do you notice a blatant deterioration with no other factors changed?

Erection quality, you know, libido, vigor, muscle mass, strength, fat, body composition, stuff like that.

I have absolutely seen seven-year-olds with, you know, 900 total T's.

I would love to bang out an exhaustive list, but forgive me, I guarantee we'll miss something.

But like alcohol, you know, the direct toxicity effects of that does inhibit actual steroidogenesis

in the testicles themselves it will also impact sleep dramatically which has the vicious backhand effect of you know inhibited uh output of signaling hormones which indirectly will also impact body composition which you know the whole downstream cascade of that um smoking obviously not helpful um how much alcohol is it is it like

I think like obviously the safe answer for me is to say no drinking.

I think it would be more like a dose dependent toxicity effect.

And what is your capacity to handle it?

Because ultimately the testes are very high.

affected by oxidative stress and if you're not capable of handling that adequately like it will reflect in your inadequate output of hormones locally so i would love to give like hard and fast numbers but there are a lot of people who will be able to get away with like murder and probably be okay there are some guys who like you might be low normal uh function to begin with and like that you know couple drinks a week like you know throws off your sleep a bit and kind of pushes you over the edge like it all depends

um it is very much a spectrum so like going from like optimal to like blatantly hypogonadal from a symptom perspective it's not like it's just on verse off like your way there is a you know it's a transition of you know shittiness as you arrive to that like worst case scenario um so uh other things i could point to um if you have a totally fat deficient diet i think that's

you know, of a macro distribution that would be reflective of something that's almost certainly going to hinder your capacity to produce hormones.

Also, if you have a void of carbohydrate intake diet, it would also be something that would inhibit freely circulating hormones from liberating themselves.

And lack of protein, like you would not be able to produce, you know, get as robust of a response recovering from workouts and be able to build muscle, which indirectly is going to improve body composition and improve your hormones as well.

So it's all kind of like balanced diet.

Don't eat bad.

Micronutrient intake.

I could definitely point to if you're deficient in protein.

Not every mineral or vitamin is going to be, you know, game changing, dramatic impact on your test levels.

But things like zinc, magnesium, vitamin D, like these all have a marked impact on your testosterone, either response to it or capacity to produce it.

Or even like you mentioned in our podcast, a conversion of vitamin D into active vitamin D. You might think you have adequate vitamin D status via your dose you're taking that's super high, but you're not actually utilizing it.

But you think you are, and that's impacting your testosterone production and your response to it at the androgen receptor itself as well.

So I think from a minerals and vitamins standpoint, the low-hanging fruits are typically going to be like...

B vitamins, but in particular, like, from a mineral side, you know, you have, you know, magnesium, zinc, and the vitamin D3 are going to be three things that...

specifically on top of the minerals and vitamins that everyone's familiar with from multivitamins and whatnot are more difficult to get in adequate doses.

All but zinc is typically adequately in many multivitamins, but magnesium in particular almost never is because of the weight of it.

You would be having to take a multivitamin that's like eight to 10 capsules otherwise, which just nobody does.

And then the vitamin D, it's fat soluble.

Typically, you're going to have it in like a soft gel or something, and it's not always going to be at the dose you need.

in the multivitamins, it's just worth noting.

So those are just some low-hanging fruits that are, if you don't look to those as part of your micronutrient optimization strategy, like you could be overlooking low-hanging fruit that dead, like,

is a deterioration of you know 100 plus nanograms per deciliter per deficient uh micro potentially depending on how severe the deficiency um other things i could point to being obese like the worst one probably that i probably should have mentioned first but is like so dramatically impactful on your uh negative feedback to the hypothalamic pituitary axis so by that i mean

Men who are obese and women, if you have a significant amount of fat, it is going to elevate your aromatization, which is your conversion of testosterone to estrogen.

And this is more impactful in males because of how the brain gets signaled from estrogen, not testosterone.

directly as significantly there's a bit of a nuance there but in general like you need adequate estrogen to tell your brain okay we're good you don't need to make enough to sauce more testosterone because i have enough estrogen like that's kind of like the downstream cascade of these metabolite conversions is you produce testosterone

in order to produce other things too and the estrogen is a very potent mediator of telling your brain we're good and if you have a significantly elevated amount of estrogen being converted from your testosterone that you make because of how much fat you have you are basically achieving the proportional increase in estrogen that is much higher than the amount of testosterone substrate

that led to that conversion so you have that signal telling your brain okay we're good but the amount of testosterone you actually had to begin with was not good so that's problematic people who are obese have you know upwards of i would love to give hard and fast numbers but it could be like significant like half of a reference range maybe you know it could be the differential between you being you know

the quality of life of you're fine versus you're blatantly in, you know, severe deficiency.

And what else could I point to?

Um,

Yeah, as long as you are losing ideally like visceral fat and like overall fat loss is going to be very supporting of getting that ratio back into balance of your estrogen and the amount that's converted to estrogen, estradiol in particular.

And once that balance is favorable because you are leaner, you will have a balanced amount of feedback to the brain that then regulates like the perfect homeostasis between, okay, now we have adequate testosterone and estrogen.

So you will actually notice more testosterone being produced because it realizes that

To get this signal that we deem adequate, we had to produce more testosterone to get that amount of estrogen.

So there's a Goldilocks zone.

Of course, you can't just, you know, become, you know, a malnourished, you know, low like bodybuilder shredded person and just continue to get this elevation and proportion.

It's at some point you will end up.

essentially starving your body of the nutrients needed to actually support hormone production but in general you know guys who are you know like 12 like 12 to 15 body fat ish will find that they have a increase in testosterone dramatically relative to when they were obese and it's like

super significant in how much it will improve hormone status.

And then the sleep, I think I might have already mentioned that.

I think it is pretty dramatic pending and exceeds your capacity to recover.

So that sounds like a weird way to answer the question, but like some people have a higher tolerance for stress and that's, you know, reliant on a bunch of different factors.

But if you are somebody who is not fueling yourself correctly to handle that amount of endurance training, like you were, let's just say you're in a calorie deficit and

and you're trying to be, like, I don't know, six-pack shredded for the summer and, like, look as good as possible, but also fuel your, like, endurance event efforts, like, you're probably, like, not doing two... You're not doing two birds with one stone.

Like, you're doing two things, like, inadequately, almost certainly, and malnourishing yourself and ending up in a state of hormone deficiency as a result, probably.

Like, you see in studies all... There are cases that you can point to of...

what happened to natural bodybuilders as they diet for a show.

And you can see in like, as they start to get closer to stage ready, which is like the most shredded, basically any documented human gets essentially.

The requirement to get there is a state of malnourishment, essentially.

And at some point, typically, once you start to cross into that single-digit body fat threshold, you start to become so malnourished that you are inhibiting your actual capacity to produce hormones adequately.

You almost enter into like...

you know, preservation mode slash like hibernation or something.

And it's kind of just like save yourself.

We're starving to death.

Like, how do I stop everything metabolically taxing from happening?

Let's shut down all systems.

Nor do we have the substrate to actually produce these hormones to begin with.

That's kind of what happens when you get like really, really malnourished.

And with endurance running, like I've seen guys out eat, you know, 5000 plus calorie per day diets when they're doing like really intensive endurance activity.

So if you are not fueling adequately and with the right fuel, micronutrient density, macro allotment, the how much of it is like carbs versus fat versus protein.

Yeah, you could absolutely exercise yourself into a state of hypogonadism easily.

I would caveat not easily.

It's hard to train that hard.

Kudos to the people mentally strong enough to do that, I guess.

And like some people might not even realize how significant of a deterioration hormone production I'm talking about.

Like to give context, men who are dieting for bodybuilding shows naturally, it is not uncommon to see the end result of a hormone profile on like the last week.

Them to look more female on paper than like their girlfriend.

Like that's how low their testosterone levels are.

Not always, but sometimes.

yeah i think we're pretty convinced that there is an effect it's just the magnitude at which you often see hyped up i think maybe over exaggerated there are low-hanging fruit things to absolutely avoid like don't use you know plastic tupperware and like heat it up and stuff like that try and use glass when you can um

Try and ensure you have like high quality air, if possible, like pollution, I think is a big factor for like your body's capacity to deal with stress and like the allocation of resources to be chronically dealing with a toxic environment will inhibit systemic like broad systems.

Yeah.

Water quality like you can make sure you have like decent water I think I'd be solid but as far as like the actual magnitude of impact of those things for most people I think is gonna be relatively negligible in contrast till like the obesity the diet the exercise the sleep quality the Potential

Carcinogens that might be exposing themselves to, you know, some of the lifestyle stuff is like way more important to be addressing as like the base infrastructure before you start thinking about like, oh, it must be my like shower that is like shooting chlorine on me.

Like it must be that or it sure gets a shower filter, but like it's not going to be the game changer.

I do think avoiding like the basics.

So like, you know, switch to glass where you can don't use plastic water bottles, stuff like that.

And there is.

blatant evidence showing interactions with estrogen receptors with some of these compounds as well as androgen receptors which in turn will impede the ability of the actual hormones you produce to bind to those receptors and do what it needs to do so you're like essentially competing with yourself for

activity in the body like you're you know competing with these like uh even if they're like moot activity compounds they still act as like anti-androgens or anti-estrogens via their occupying of receptors so to whatever degree they are doing it at all is not ideal because it's inhibiting like space that could be occupied by actual endogenous hormones that you need to produce and need to work properly and you don't want to be competing with like environmental toxins to like do things in the body

Mm-hmm.

i did a video a while ago on like the earliest finding i could find of recorded testosterone levels in i think it was like military soldiers or something one thing i think is notable is the actual detection sensitivity of testing is absolutely much different now than it was you know 60 years ago so to contrast like

Oh, the total test of some guy 60 years ago versus now is equivalent even on like a testing methodology basis is like flawed to begin with because it's probably not an accurate comparison.

But is there a trend downwards?

I would say yes.

And I think it is mostly dictated by the obesity, the diet, the lifestyle stuff.

So yeah.

You know, like there's obviously things to deal with in the environment that are less favorable and are not supportive and probably not benign.

But like in general, I think most people that worry about this stuff, they would be put their mind at ease by dialing in everything else, which is not that hard to do.

It's often free or, you know, cost less money.

You're like eating less food, you know, go to the gym, et cetera.

I'm not saying that's easy to do, but like dial in your basics.

And once you do that, you have your baseline.

Let's just say you get a blood test and you see where you're at.

From there, you can start doing some of the minute changes, like putting a chlorine filter on your shower head, do this, change your water source, whatever.

Do you notice an incremental uptick in your gonadotropin output or your response to it at that point?

If yes, like, okay, maybe it was a meaningful change.

But until you do that, you're kind of just taking shots in the dark, assuming...

All of these things are, you know, occupying your mental bandwidth and concerning you that may not be worth your concern to that degree.

For example, if you ingest cholesterol, it doesn't necessarily mean you're going to have a dose-dependent elevation in your serum cholesterol, as I'm sure everyone knows here.

But there are certain baseline requirements to serve as the substrate for producing cholesterol-derived

steroids in the body and these are all ultimately derived from cholesterol and then get cleaved and manipulated through enzymatic processes to make all the hormones in your body including but not limited to testosterone estradiol etc so in general it does seem like having a sufficient amount of fat

Is worthwhile and does seem to impact how much hormones you can actually produce and the carbs for actually mediating.

And this is going to depend on, you know, activity levels, how demanding of exercise you do, if you burn through them versus not, if you're sedentary versus not.

But in general, the insulogenic signaling is somewhat necessary to facilitate a balance of free androgens, including free other hormones in the body that often go overlooked, to actually do what they're supposed to do.

Because a lot of people won't even measure the free levels of the IGF-1, the T3.

Some of this stuff gets hyper-nuanced when you get into what hormones are actually bound up that you don't realize.

Estrogens, DHT, et cetera.

So having a balanced diet and then the protein, like you mentioned, from like a mechanistic perspective, like I think in general, these things all serve as building blocks is the simplest way I can put it.

And having a deficiency entirely of one or the other, it's just like it's kind of the expected outcome.

Like it's often not going to be ideal to be missing something entirely that your body utilizes for critical, you know, structural things.

And it's not to say that it will absolutely happen.

I'm sure there are a lot of people that thrive on long-term ketogenic diets or may even clinically require them.

So I certainly don't want to come out here and suggest,

If you're on a ketogenic diet, stop doing it.

Like talk to your doctor first, obviously.

It's just like mechanistically, this is what happens if you have a lack of insulin signaling, you will have less capacity to suppress the binding proteins.

Be informed before you like freak out about anything.

Yeah, I think it's kind of like in the simplest way I could put is like descending order of intensity, essentially.

So like, you know, weightlifting at the top and then you have like some of your more like hit style workouts underneath that.

And then at the bottom of it would be like the most basic of, I don't know, barely exerting yourself, but like getting out there and moving.

that is going to have the least impact in general and at the top it's going to be you know the muscle building facilitating processes the things that build bone etc resistance training that's going to be the most directly impactful but ultimately it's also going to be what is the overall exercise regimen that you adhere to because a lot of people the problem is not even necessarily like oh what's the perfect thing like it has to be something you enjoy enough that you'll adhere to it so it's like adherence almost trumps

optimal in some capacity so like get the thing you can adhere to

The diet model that you can adhere to, like a lot of people, the diet that on paper is the best, it won't be the one that you stick to for more than like six weeks.

So like, don't do that one if that's the case, because you're not going to stick to it and then you're just going to end up where you were before.

So calories trump everything, unfortunately, you know, or fortunately, because it gives you a lot more versatility with like your choices.

I think it's not like you're stuck in a myopic kind of, you know, box of I have to be on like the Mediterranean diet or I have to be on the carnivore diet or I have to be on the vegan, you know, the whatever.

There are a lot of ways to skin a cat and ultimately it's going to come in mainly from energy balance and then also from there optimizing for, you know, having adequate protein, fat presence, carbohydrate balance to support your, you know, whatever exercise you're doing and the intensity of it and all the things underlying that.

Yeah.

Like in general, I think the most reliable things that move the needle, if you were deficient, what is, I don't know, people are familiar with the ZMA.

It was like the first like combo supplement that was sort of seen as like a testosterone booster that was available on the market.

And it's, you know, like zinc, magnesium, and I don't remember if the A was something else, but

Vitamin D is the third thing you want.

I don't remember what the H stands for.

But those are the three things that move the needle most reliably that are natural.

You, you know, otherwise would get through your diet, but likely not sufficiently.

Maybe zinc you might, but like magnesium, pretty difficult, I would say for a lot of people, they don't realize how deficient they are.

And then even like supplementing accordingly, it's like, you know, getting one that you respond to.

that you tolerate well with your digestive system, has the yield that actually produces enough magnesium from like the elemental weight of the supplement, which is not that complicated.

I don't wanna make it sound super complicated.

Like a lot of them are fine.

Miranda has great articles on magnesium formats that are bioavailable and yield more than enough magnesium.

And yeah, the vitamin D, having an adequate amount, making sure you're converting it and actually getting the activity from it.

Mechanistically, there is some level of gene transcription capacity facilitated through these, like vitamin D is a hormone, for example, and it does also affect androgen receptor activity.

and some like the capacity for androgens to do what they do, not just like the production of the amount of them.

So similar to what I talked about earlier, where you have this kind of like receptor interaction, how well can you actually utilize these hormones to do the things it needs to do in the body?

Some of this is going to be facilitated by the adequate minerals and hormones through vitamin D supporting it.

And it's not necessarily measurable as much like directly, but all you can really do is like backfill accordingly to hit your needs and then assess your kind of like proxies and your blood work and your symptoms and kind of go from there.

I think if you were on the low end of the reference range or literally hypogonadal and you were

clinically low or deficient for those depending if it's all three or not because obviously there'd be an additive effect most of them are i mean at least vitamin vitamin d magnesium pretty common yeah yeah i would say like you're looking at probably a potential incremental difference of 100 to 150 total t maybe it kind of depends on the person of course like i've seen more robust response in some studies but i also don't want to like over exaggerate the expectations

but it is meaningful.

Like it's something that happens and some of it can't be directly measured either.

Like we're talking about the total T number, but it's like, how do you know how much your deficient vitamin D is impacting your ability to like use it correctly?

And then even if you had the sufficient vitamin D, the magnesium impact on all that and the DNA interactions and whatnot, it's like, you know, you would have, you'd be speculating at best.

So, and then there are some other more like tangential supplements that are not as like,

obvious no brainers that are helpful.

They're just facilitating mechanisms that are not like this is a vitamin you need almost regardless of what your test levels were kind of thing.

Yeah.

I think one that I would be worth mentioning, all but the literature isn't super robust.

It is a boron.

So that potentially has a suppressive effect on SHBG levels.

There's some literature that looks promising, all but

I wouldn't hang my hat on and say it's a guarantee.

It's going to suppress your SHBG from like the high end of the reference range to something that's like much more, you know, much better.

But like it may, it does seem to work for some people.

And in general, it can be a supporting adjunct that, um,

some people are, it's not something you typically get through your diet and like significant quantities anyways.

Like often people will, it'll come into multivitamin typically, but the quantity that moves the needle for SHBG, I believe it was like six to 12 milligrams and can be meaningful for actually liberating free testosterone, not for actually producing more total T. Um, the other one that's probably worth mentioning ashwagandha specifically, uh,

extract that is standardized to a sufficient quantity of with analyze not just your standard run-of-the-mill generic ashwagandha you want to look for ideally a patented you know uh sensoril or a ksm-66 these are patented formats of ashwagandha that are standardized to a um target yield so you know that what you're getting is what you're supposed to be getting rather than relying on you know

certificates of analysis from China of a generic extract.

So I would.

With analytes.

It's like the, it'll show right on the label.

It'll be like ashwagandha bracket standardized to X percentage with anilides.

And depending on if you have KSM 66, that's 5%.

Sensoryl is 10%.

The difference between why you would pick one or the other is the actual total dose you could get away with using less milligrams of the Sensoryl because it has more with anilides per milligram inclusion in your product.

But they're both like impactful.

Yeah, it seems to be.

And when I say testosterone, it's like the indirect effect via suppressing cortisol seemingly and kind of like the stress response manipulations that it can induce, which are favorable for people who are obese.

Anxious who have very stressful lifestyles who could benefit from it, but it is not a catch all supplement that will benefit everyone.

And some people will push them into anhedonia territory, which is like a numbing of emotion.

So you don't want to really.

Yeah.

If you overdo it, it will like literally suppress your stress response so significantly that everything's just like black and white.

I would go with the clinically supported dose for something that's efficacious.

I wouldn't necessarily suggest somebody...

you know, take something that's lower than what I've seen to actually work.

But in general, it seems to be a cumulative effect over time.

Maybe there are some people who might push you over the edge sooner and like certainly something to be cautious of and be aware of as a disclaimer before you jump on

Any testosterone augmenting supplements, just be aware of the mechanism of how it works based on your own individual biochemistry, because this is not something like a vitamin D that you can just sequester into sub Q fat and just like get rid of at some point.

It's like it could impact your mood regulation quite significantly for a bit, depending on like your.

what your neurotransmitter balance is at baseline.

Like if you are already borderline, like emotionally numb as a person and you take ashwagandha, like you might literally like cease to care about anything for all I know.

600 milligrams.

I think is the dose, but double check on that because I might be misremembering.

Right.

I'm pretty sure.

And that is impactful to the tune of upwards of another 100 points seemingly.

I could be misremembering exactly, but it's like I think it's triple digits pretty reliably for those who can benefit from it.

And for some people, it's like a game changer supplement that really improves their quality of life outside of just the testosterone enhancing capacity of it.

Because some people deal with a lot of stress in their life and need that extra resilience or suppression of how much it's affecting their mental state.

Like some people, they can't even get to sleep because they're ruminating and they're constantly anxious.

And having that kind of suppressed stress response can be very, very net beneficial for

And then on top of that, improves their sleep and also improves their testosterone through the reduction of the kind of like glucocorticoid responses.

And yeah, so it works for sure.

The literature seems sound on it.

Some of it is funded by some of these companies that do have the patented extracts.

So just be aware of that.

But at least from what I've seen in blood work anecdotally too, it seems to work.

Tonkat Ali, another very notable one.

This is one that works for a different mechanism.

It seems to be...

A bit more speculative how it works, but it seems to do a few things potentially.

One being minor CIRM activity potentially, and this is more speculative.

CIRM is like a selective estrogen receptor modulator, so something that...

binds to estrogen receptors and either like positively or negatively modulates them in selective tissues.

So there are certain tissues where it would be more favorable to have a selective inhibition of certain hormones versus others that would be detrimental.

Like you wouldn't want to inhibit estrogens activity in bone, for example, because that would cause bone degradation.

Having an inhibition at the hypothalamus level may, depending on the person, help increase testosterone via the inhibition of that feedback loop.

Now, I don't necessarily think it is a CIRM.

That's just like the tertiary potential mechanism, and it is speculative.

The main mechanism that people seem to agree on that it does do, suppression of SHBG to some extent, as well as the upregulation of steroidogenesis

intratesticularly, so like locally upregulating, I believe it's steroidogenic acute regulatory protein that basically incorporates cholesterol into the mitochondria to actually undergo these enzymatic cleaving sequences that result in the production of testosterone locally.

So it seems to like help upregulate the process that actually

uh, enzymatically spits out testosterone essentially, uh, locally.

So that one seems to work well for individuals who have high SHBG levels or, um, potentially higher estrogen levels than they, you know, as otherwise fixable via basic lifestyle changes and whatnot.

Um, cause everyone has their own proportion of metabolism at the end of the day.

And it's not always going to be optimal, even if you have what is otherwise like a great diet and lifestyle.

Um,

But also it's just like, I think it's for people who have adequate, everything looks on paper to be sufficient, but their SHBG might be a bit high or they could use a little bit of a boost.

And it seems to work to the tune of 100 to 200 nanograms per deciliter for some people.

And it depends on how potent of a standardized extract you get.

You want to look for one that is HPLC tested for uricominone.

That's the active ingredient in Tonkat Ali that actually has the bioactive effect that you're looking for.

There are a lot of Tonkat Ali supplements that just say Tonkat Ali or it'll say Tonkat Ali like...

100 to 1 or like 10 to 1 or whatever like these are kind of meaningless numbers from what I understand like you're not going to get a 200 to 1 version of a tongue cat and even if you did there's no indication there's any yuriko minon in it so similar to the ashwagandha you want something that actually says this is how much of the literal ingredient that does what you're looking to get out of it in it and here's a third party test to verify it so

Eurycomanone.

Got it.

E-U-R-Y-A-C-O-M-A-N-O-N-E, I think.

Yeah, that's a good question.

Boron is a mineral that is, seems to be something that is mechanistically, I wouldn't be able to say for certain what the differential is and how they affect the SHBG binding complex.

Like I would be trying to, I might misremember and I don't want to misspeak.

Yeah.

I feel like that's almost like a lower hanging fruit thing because it's just typically part of a multivitamin that may just not be dosed high enough.

And you can just like stack on top and see if it has an incremental decrease to SHBG.

And then the Tonkat is like more of a speculative one that you don't want to just like take until you've exhausted some of the other options.

But it's like the more exotic kind of like.

hammer that you might want to take to the situation if it's like your last resort before you know i've tried everything my lifestyle is perfect my diet's dialed my micronutrients are accounted for my sleep is good i don't drink i don't smoke and my total t is still inadequate and i don't feel that great should i try some of this like one of these exotic things that seems to have a reasonable safety profile and like an efficacious you know um

you know, impact in men and young healthy men at that.

Like there are literature showing the effects in young healthy men, not just like age related, like declined men.

So notable.

Now, as far as its impact on women, I would think mechanistically it would do a similar thing, but like, I don't have a study I could point to that says it's the same.

So I would think, but I don't know.

I think a lot of those have been disproven, like tribulus, diasporic acid, fenugreek.

One that is notable that might do something is shilajit.

If you get a high quality shilajit, it may provide enough.

Like the actual capacity of your organ to respond to hormones is partly conditional on its ability to tolerate stress and reactive oxygen species locally too.

So if you have shilajit,

more than you can deal with and you introduce a potent antioxidant to the equation, you may be able to like attenuate and neutralize the kind of like decrement to performance and kind of like net out more local hormone yield.

So Shilajit seems to be impactful on intratesticular antioxidant activity, but I wouldn't, it's another one that requires like careful sourcing.

And it's also one that's like,

more speculative and indirect because like there are probably better ways to manage your oxidant like your antioxidant profile i would think so so your top four supplements for testosterone would be

Zinc, magnesium, vitamin D, not in order, just the top three, I would say.

And then I guess for impact, I would probably say like Tonkat Ali, but probably Boron would be my safer next choice just for like safety profile.

Yeah, ashwagandha and just be like cognizant of how it works because you may be able to get the benefit at a lower dose.

You may be able to cycle it depending on how you respond to it, like similar to you with caffeine.

Like there's no hard and fast rules on all this stuff.

Like there are studies you could adhere to like the protocols designed, but they're ultimately just designed by, you know, scientists who thought this was the way to do it.

And like for you and your individual biochemistry, it may not be the ideal way.

Because once you get that blood test, you're going to be like, fuck, I shouldn't have taken ashwagandha because now I have no idea what this means.

If you do assess your cortisol stress response, I would highly recommend a Dutch test over a blood test.

Why is that?

salivary cortisol levels are far more indicative of what's happening from a stress response standpoint than your like transient serum cortisol levels will be.

Oh, really?

Yeah.

And because it's just like the snapshot in time and in the serum is just like not an accurate reflective measure.

The salivary levels will fluctuate and they get like multiple readings.

They create like an average curve for you and they should map out your day as opposed to with blood.

You like one big draw and

The cortisol is measured one time and it's like, okay, you're like high end of normal.

Like what do we do with that information?

The salivary one's a little bit more indicative of like, here are multiple time points of the day.

And like, here's where we'd expect you to be at these points.

And like, this is how you're responding to your day stressors kind of thing.

And it's like less intrusive to like spit in a tube, you know, or whatever.

I've actually not done a Dutch test personally, but I'm pretty sure it's just you spit in a tube.

Um, like there are definitely scenarios in which it's more obvious because there is a structural issue that cannot be rectified via any sort of lifestyle change or like sleep hygiene manipulation or whatever.

Like if you have primary hypogonadism and you've ruled out the ultrasound, like varicose, yeah, there's no issues.

You're not like cooking your testes in like a hot tub every night.

You're not, uh,

I don't know, like your sleep is dialed, your micronutrient intake is on point.

Also, satisfactory amounts of calories, like I think I might have probably indirectly touched on this, but like via the getting to a good body fat, like you still need to have an adequate amount of energy to actually meet the needs to produce hormones too.

So like adequate amount of calories, not overdoing it, not underdoing it.

If you've done all the stuff that we kind of like talked about,

And you've ruled out pituitary adenoma, you've ruled out any sort of like, I don't know, like structural defects, and signaling is adequate, or even supra physiologic, and you're just not responding, like at that point, it's kind of like, okay, you're

We could try hammering you with some HCG and see if we can stimulate a satisfactory response with like a manual, like extra push at the lighting cell or use some, you know, some of these other like augmenting, you know, steroidogenic supporting things like Tomcat or whatever.

But if that's not working either, like your testes are cooked and you got to be on test at that point because you're just not responding to any natural stimulation whatsoever.

That is not typically the outcome of a lot of guys who end up on testosterone.

A lot of guys end up on it through like secondary, like hypogonadal symptoms through like the pituitary, either inadequate output or insufficient response to that output plus an insufficient amount coupled with it coming out of the pituitary.

There's not a lot of people that are literally showing up with like, your testes don't respond whatsoever.

In those individuals, it's kind of like, if you've exhausted all resources, you've tried the whole manual stimulation directly, because HCG is the way you would actually test that out, is you would actually look at, okay, if we actually hit your lighting cells directly with a signal, and we escalate that to the maximum degree,

And we use FSH too.

Exogenous.

It's like, if you're still not responding to that, like there's no saving it at that point, unless you have like such a significant amount of oxidative stress that you're just like not dealing with, but that would have been taken care of with the lifestyle stuff we mentioned.

So.

Primary hypergenital, like you're going to probably be on exogenous testosterone.

And it's literally like testosterone.

You can't fix it with N-clomiphene.

You can't fix it with HCG.

You can't fix it with HMG.

There's no other way around it.

Like you're taking the literal hormone because it's the only thing that will get you testosterone.

Like you can't produce it.

So there's that.

And there's different ways you can take it, of course, which we could get into later.

But the next situation that's a bit more relevant is like the secondary hormone.

hypogonadism situation where somebody has pro like testes that function just potentially to like a suboptimal capacity

And there might be some level of like low gonadotropin output facilitated through some level of like lifestyle or diet or whatever.

Like Peter, for example, like he's pretty dialed.

And like he did a lot of stuff to try and like fix it before he went to any sort of replacement.

Sleep hygiene is on point.

Like the guy, like what else could you do when you're him, right?

He's, I think, 50 years old.

So what he did was he used HCG, which was assessing, okay, like,

are the testes responding to like a manual signal?

And they were.

And he's like replaced his hormones entirely by using a manual LH mimic, essentially.

Why his pituitary wasn't shooting out enough LH to hit the amount, like the enough stimulation he would need to produce the same amount of tests that would hit his like optimal?

Variety of factors, age related decline, who knows, but probably a combination of multiple things.

And at that point, it's kind of like, do you want to manually backfill with signal or do you want to take hormones pending?

You've done all the exhaustive, you know, things to try and like check the boxes because, you know, some people don't care as much and don't want to check the boxes, but like

In general, I would say it would be worthwhile to learn why you have the problem, even if your intention is to just end up on testosterone anyway.

I wouldn't delay treatment if you're symptomatic and it's hurting your quality of life.

But I also would do some due diligence to just assess what's happening.

And I think HCG for people who are secondary hypogonadal is...

sometimes a good middle ground of assessing like is this a testicle functionality problem or is it like my pituitary output is not sufficient because at that point you can kind of tell like which organ is it that's failing me here so there's that and then like upstream to that there's the actual hypothalamus and the GNRH output which is the thing that stimulates the pituitary to make the LH and the FSH and throughout that whole cascade you could have

insufficient signal from that insufficient response to that signal and then insufficient pituitary output from that weakened signal and the response to it like it's a deteriorating thing that by the end of it when it actually hits your testes may just be like suboptimal for your response to be adequate through often age-related decline but

It's a culmination of things.

So certainly back to the original question, like how do you make sense of all this and decide when is the appropriate time to be on hormones versus not?

That's where you have to work with like a really highly educated medical professional in general.

Like I would not try and cowboy this yourself.

Even trying to like learn it from...

you know, online content, whatever.

Like, I think it's good to learn how this stuff works mechanistically.

So you go in informed and don't end up putting on a haphazard regimen by a doctor who actually just wanted you on medications.

Because if you know this stuff, it's pretty easy to identify who's like,

a shitty clinic who just wants to like get you committed and stuck on lifelong hormone support and you can like weed it out really quick even if the doctor seems well intentioned he wants to help you he wants to you know support your quality of life says all the right things seems professional seems knowledgeable if you don't know this stuff it's kind of like you would be going in blind and assuming that's what you need to do and a lot of people just end up on hormones and

That's it.

And sometimes there's nothing wrong with that.

Sometimes that might be what you need, but sometimes people want to know what were the natural avenues I could have taken.

Could I have, you know, done something else?

Could I have maintained the signal from my brain to my testes this whole time and I'm just missing something?

Um, yeah, it would be in general, if you are satisfactory in your replacement of these hormones to a physiologic replacement level, like you should notice a amelioration of all symptoms.

That's the best way I could put it.

Now, again, it's obviously you should not expect that you're going to feel exactly the same as you did when you were like 20 years old.

Like I think some people think when they're 50, oh, I'm going to get on TRT and it's going to be, you know, like being 20 again.

And like to some extent it could be because like on paper, like your test levels might be the equivalent, but...

It doesn't mean the way you metabolize the hormones into estrogen is going to be the same.

It doesn't mean that the way you respond is going to be exactly the same.

In general, though, the target is to ameliorate the symptoms and then dial in from there kind of thing.

So I think what people should expect is the intention of it is get rid of your symptoms, similar to menopausal therapy.

You want to get rid of your hot flashes.

You want to ensure that you are not...

your bone integrity is like actually supported.

Like all these things are like your baseline requirements of why you're doing it is just to like get rid of the negative and get to a baseline.

Indirectly, you will feel much better.

So it's like you will feel better from the result of it.

But like, don't expect to be Superman unless you're

You might feel like Superman relative to your stage.

It just depends how deficient you were to begin with.

And it's all contingent on multiple things.

So it's hard to put hard and fast generalities on this stuff.

But like your target should ideally be symptom relief.

Yeah, I definitely wouldn't make any rash decisions based on numbers on a piece of paper because I know a lot of guys who like the best physiques in natural bodybuilding are like guys with 500 total testosterone.

So I know guys with three times the amount of testosterone production, much worse physiques.

Like it's not always the number on a piece of paper.

It's your genetics, your response to it.

literally how many muscle fibers you have at birth.

Like there are a lot of factors that determine what you're going to look like, how you're going to respond, the shape of your muscle bellies and how they appear to people.

Your body fat level, especially like if you are leaner, you will just appear more muscular, you know, stuff like that.

I think the only issue is, like, defining what restoration of physiological testosterone production equates to is, like, when we were talking about, like, coffee and, like, how much caffeine is in a cup of coffee.

Like, it could vary so much.

Like, some guy's replacement, adequate physiologic replacement, what he was when he was younger, highly variable.

And in that traverse trial, using androgel to bump your total T from, like,

hypogonadal to like 400 is not necessarily indicative of what I would say a lot of people are looking to the data to see what the results were of testosterone therapy.

Because a lot of guys are on injectable test, boosting to 1000 total T with a disproportionately high free testosterone.

Because when you inject infrequently too, you drive your SHBG down proportionally.

That is not the same as a guy who's using an androgel to get to like 430 total T. So taking that outcome and running with it as like no cardiovascular risk, I think that's a bit haphazard personally.

Now, it's obviously promising data and like it's great that it came out.

Like it's very, very promising.

The only problem is like how many guys are actually using that medium of therapy like...

I don't know, none.

Like, I don't know a single guy using Androgel.

And that's fine.

Like, it's still data, and it's still worthwhile, and it's still good.

It's just, like, not... Don't take that as, like, the sign-off that, like, you're, you know, 200 milligrams of testosterone and enanthate per week, that you're, like...

more aggressive protocol has been designed to do is going to be the same outcome.

It's not.

You're going to have the erythropoiesis increase that might not be reflected in the traverse trial.

You're going to have the disproportionately high androgenic signaling.

You're going to have a lot of things that you were looking to get the reassurance that won't happen, but you absolutely need to be cognizant of because it will probably happen still.

To the opposite side of the coin on that androgel, you know, like it's not necessarily physiologic replacement.

The thing to note is it should be expected that if you use more testosterone, you're going to have more of the erythropoiesis.

Like that's literally what it does.

So to think that it would be a net negative because you have a 25% increase in that via your testosterone administration is,

you were hypogonadal to begin with which presumably is the reason you're getting on trt you know depends on the person but like going from hypogonadal where you might be like borderline like anemic for all we know and then having the 25 bump like maybe you need that to actually like have adequate oxygen carrying capacity and like actually sufficiently fuel your body

So it's not to say it's like net bad, net good.

It's all about where do you achieve?

Like the problem is, is like the definition of symptom relief too is so vague because you could achieve symptom relief at, you know, 450 total T maybe depending on the person or it might be at like 800.

Or it might have been, like, even if it was 450, like, if you got up to 800, you're still in normal on paper.

So, like, is that bad?

You know?

Like, who's to say?

I think most people would say it's the high of normal because that's literally what it is on a reference range.

So, it all is going to be just being cognizant of the fact that androgens will do what androgens do, which is they will, in a dose-dependent manner, derive erythropoiesis.

They will...

induce cardiac remodeling if you push it too hard not necessarily within physiologic limits but like these are things to be aware of dyslipidemia will become more of a concern at a higher level especially depending on the medium of administration if you're dosing infrequently like once a week with a shot it's going to be a different outcome than if you're doing like daily you know little pulsatile uh cream administrations or like micro injections like subcutaneously where you're bleeding out the effect more

it will all be impactful.

So I think it's more about, there is a risk, all but there's not gonna be data that says directly, if you replace to 800 total T, it's going to be dangerous, nor is there data that says it's safe either.