[SPEAKER_01]: A man with obesity is roughly nine times more likely to be testosterone deficient than a man at a healthy weight.
[SPEAKER_01]: It's not aging, and it's not generational.
[SPEAKER_01]: Certainly isn't whatever your Instagram influencer is blaming on microplastics this week.
[SPEAKER_01]: It's a body composition story, and it's had its name in the medical literature for years.
[SPEAKER_01]: It's called male obesity-related secondary hypogonanism or mosh.
[SPEAKER_01]: Man who's overweight on average as a testosterone level that's about 66 nanograms per desoliter lower than a man in a healthy weight.
[SPEAKER_01]: A man with obesity on average, it's about 147 nanograms per desoliter lower.
[SPEAKER_01]: Large enough on its own to drop at previously normal man below the diagnostic threshold without anything else going on.
[SPEAKER_01]: The reverse also holds a 10% reduction in body weight produces an average testosterone increase of 84 nanograms per desoliter.
[SPEAKER_01]: Metabolic bariatric surgery, where the weight loss is around 20 to 30 percent, produces increases on the order of 250 nanograms per deceler on average.
[SPEAKER_01]: This week's episode, what is actually driving men's testosterone levels down, the modifiable levels that we have to bring it back up, body composition, sleep, and the opposite extreme that men in this audience will certainly recognize training too hard on too little fuel.
[SPEAKER_01]: And we come back to Mark, because the thing that produced his testosterone level of 240 is finally on the table.
[SPEAKER_00]: doing great, recovered from my recent back tweak and had some good training this morning, so ready to get after it today.
[SPEAKER_01]: Okay, yeah, I have nothing of note to add.
[SPEAKER_01]: I am persisting and recycling oxygen as planned.
[SPEAKER_01]: So I wanted to start this episode with a discussion of what actually causes low testosterone in men and we've been building towards this in the previous two episodes.
[SPEAKER_01]: So regular listeners, we already know that most of the time, the answer is body fat.
[SPEAKER_01]: Most cases of low testosterone in adults in the United States are not due to a problem located within the testes because they set downstream of the metabolic disease and respond predictably to the signal they're being given.
[SPEAKER_01]: Now a man with obesity is roughly nine times more likely to be testosterone deficient than a man at a healthy body weight.
[SPEAKER_01]: The dose response is consistent here too.
[SPEAKER_01]: An overweight man with a BMI somewhere between 25 and 30 has a testosterone level that is on average 66 nanograms per deciliter lower than a man at a healthy weight.
[SPEAKER_01]: A man with obesity or a BMI over 30 is 147 nanograms per deciliter on average lower than a
[SPEAKER_01]: Now those figures are large enough on their own to drop a previously normal man below the diagnostic threshold for testosterone deficiency without anything else going wrong.
[SPEAKER_01]: But there's also a kind of loop here where reduced testosterone levels also drive even more body fat accumulation, which subsequently lowers testosterone further, which is part of the story that most men have never been told.
[SPEAKER_01]: Now, the mechanism has a name, and it's been in the research literature for years.
[SPEAKER_01]: We tend to discover these things decades after the original researchers have something.
[SPEAKER_01]: I don't know.
[SPEAKER_01]: What do you think about this?
[SPEAKER_01]: Whenever you come across something that you're like,
[SPEAKER_01]: Man, this is new to me, but it's been in the literature for a decade.
[SPEAKER_01]: You feel bad about that, it was a more like, I'm glad we have smarter people than us doing this stuff.
[SPEAKER_00]: Yeah, no, I mean, I think that everyone's operating within their niche, and I'm glad that people have these different niches.
[SPEAKER_00]: We know, you know, we've heard all sorts of figures over the years of like, on average, it takes, you know, research findings, 17 years to make it into, you know, clinical practice and things like that.
[SPEAKER_00]: And it's like, well, I like to think myself as being, at least somewhat a little bit more up-to-date on things, through, you know,
[SPEAKER_00]: various means that we have available to us now that we're not as accessible in the past.
[SPEAKER_00]: So me staying up to date with like, you know, thought leaders in my, my practice niche on Twitter and things like that is actually helpful to me compared with, you know, 20 years ago, people would have had to stay subscribed to various journals and actively seek out all the stuff I've kind of curated my
[SPEAKER_00]: attention so that this stuff comes to me and I'm able to say a little bit more up to date, but it's never surprising to us when we talk about something or have an idea and then we look up and it's like, oh, this paper from 1995, you know, first hypothesis this thing and people have been at it for a while, but you know, those people are solidly within their niche and we have a much broader scope.
[SPEAKER_01]: Yeah, the two things of that, that that means to me like one, I do feel a little worse if it's from like the 80s or 90s and I'm like, yeah, like that bad about that, but also just the time course it takes what you have an idea, a testable hypothesis, and then enough data has been accumulated where like, yeah, this is generally accepted as the consensus right now, meaning that I probably shouldn't jump to yeah, this is probably right if there's no evidence there yet.
[SPEAKER_01]: Right.
[SPEAKER_01]: So kind of interesting.
[SPEAKER_01]: But yeah, this mechanism has been around in the research literature for years, and it's called male obesity related secondary hypogonetism or mosh.
[SPEAKER_01]: So let's walk through it.
[SPEAKER_01]: Now, if you recall from the previous episode, we talked about the hypothalamic pituitary
[SPEAKER_01]: GNR-H to the Petuitary Glamp.
[SPEAKER_01]: Petuitary Glamp picks it up and then generates LH and FSH which goes through the testicles which produce testosterone in response.
[SPEAKER_01]: Now, excess body fat suppresses that pathway at two different points, centrally which just refers to the brain.
[SPEAKER_01]: the hypothalamus stops producing as much GNRH with its normal pulse amplitude.
[SPEAKER_01]: And then peripherally outside of the brain, it's the fat tissue itself.
[SPEAKER_01]: This rural fat, so that's the fat that surrounds your internal organs, is rich in an enzyme called aromatase, which converts testosterone into estradiol, that's a type of estrogen, before the testosterone can do its job.
[SPEAKER_01]: And this aromatase sort of loop is self-reinforcing.
[SPEAKER_01]: More visceral fat means more aromatase, which means more testosterone to estradiol conversion.
[SPEAKER_01]: And estradiol itself is a more potent inhibitor of the HPG access than testosterone is.
[SPEAKER_01]: At the level of the brain, the hypothalamus senses higher estradiol levels and reduces gNRH release further.
[SPEAKER_01]: This is the same response the hypothalamus would normally have to elevated levels of testosterone, but it's even stronger in response to
[SPEAKER_01]: So, the conversion does a sort of double-duty, it depletes the testosterone, and the resulting estrogen feedback on the brain, why it's the sort of broadcast of G&H even further.
[SPEAKER_01]: Also, low testosterone promotes more visceral fat storage on its own.
[SPEAKER_01]: It makes the visceral fat cells more efficient at taking up fat and storing it, and then the expanded visceral fat generates more aromatase activity, which suppresses testosterone even further.
[SPEAKER_01]: That wasn't enough.
[SPEAKER_01]: On top of that, adipose tissue puts out inflammatory cytokines, like TNF alpha, IL-6, and more, which add their own inhibitory signal at the level of the brain.
[SPEAKER_01]: So multiple different pathways to dial the system down without anyone touching a needle.
[SPEAKER_01]: Now Austin, when a guy in his 40s or 50s shows up to see you with the complaint that ends up being testosterone deficiency or just a low testosterone level, how often is the actual driver body fat versus something happening at the testes themselves?
[SPEAKER_01]: What's your sort of calculus on how often this happens at the bedside?
[SPEAKER_00]: Yeah, I think what you're really getting at here is how often are we dealing with situations of primary, testicular failure, meaning, you know, scenarios where the testies themselves are not doing their job versus how often is the, kind of, the lesion, so to speak, the problem higher up in the system, uh, being secondary, kind of testosterone deficiency from something going on in the brain or or even higher, um, in the, in the hypothalamus.
[SPEAKER_00]: And the breakdown is overwhelmingly in the secondary category, way, way, way more often than primary testicular failure.
[SPEAKER_00]: There are, there's a long list of possible causes and diagnoses that can contribute to primary testicular failure, but fortunately at least in
[SPEAKER_00]: adults in kind of typical modern outpatient practice.
[SPEAKER_00]: The likelihood of that being what's going on is much less common compared with secondary causes.
[SPEAKER_00]: Now, among the secondary causes, you're right, that body fat, obesity, metabolic disease, insulin resistance is a predominant cause or a large fraction of those secondary hypogonetism or secondary testosterone deficiency situations.
[SPEAKER_00]: But there are also many others.
[SPEAKER_00]: relating to pituitary issues, chronic opioid use, various other things that can lead to that secondary cause as well.
[SPEAKER_00]: With that said, I think that there has been some under-recognition of scenarios where there are, you know, testicular,
[SPEAKER_00]: failures, situations that are kind of underrecognized.
[SPEAKER_00]: And so I think that because it is so much more common for us to see secondary in practice, a lot of these, I'll call them shadier clinics or places that don't do comprehensive workups, they might check the testosterone level and see it's low and then put the person on testosterone therapy.
[SPEAKER_00]: without doing the additional evaluation that's needed to include checking those gonadotropans like FSH and LH because if you check those and they are high, then that localizes the problem as we talked about in our last episode to the testies themselves.
[SPEAKER_00]: And that requires a very different strategy.
[SPEAKER_00]: for management and has a different prognosis and has different considerations depending on for example, the person's desire for fertility, lots of other things that need to be considered.
[SPEAKER_00]: And so that's why the adequate evaluation is important here because even though most of the cases that we see in adults who have symptoms like this who present and have confirmed testosterone deficiency end up being secondary,
[SPEAKER_00]: And of those most of those end up being related to body fat, obesity, and solar systems, sleep, and, et cetera, there is a significant enough fraction of primary disease still that needs to be detected and identified because it can have a variety of additional implications and consequences for the person that might impact their decision-making over the course of their life.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: And if you get it wrong, there's something else that you're missing, which can be problematic for sure.
[SPEAKER_01]: 100%.
[SPEAKER_01]: But I think it's fair to say that the majority of the cause of testosterone efficiency, particularly in modern times, has to do with obesity metabolic disease.
[SPEAKER_01]: This aromatase loop in these inflammatory cytokines, if you were thinking about a sort of population level decline in testosterone, if it were to be there, it's not due to this sort of, you know, increase in primary testicular failure.
[SPEAKER_01]: It's usually due to an increase in obesity.
[SPEAKER_00]: But there's just point out one of the things before you move on because the one of the common causes of primary testicular failure that is historically been very under-recognized that I've seen increasing calls for more aggressive kind of awareness screening diagnosis is actually a genetic condition called client-filters syndrome.
[SPEAKER_00]: It's something that we all learn about in med school and then we're like, I'm probably never going to see a case of that and it's like,
[SPEAKER_00]: Turns out to be a lot more frequent than people recognize, and so this is that that's the kind of the one that I was thinking about the most when I talk about underdiagnosis of primary testicular filler, it's that one, as well as a few others that are that are less common, but that's the one that's like not to be missed from a primary failure standpoint, but most of the rest totally up in the brain secondary is the is the source.
[SPEAKER_01]: Yeah, absolutely.
[SPEAKER_01]: There's a third piece here to this obesity sort of cause of testosterone efficiency that almost nobody talks about and it has to do with my favorite hormone leptin.
[SPEAKER_01]: This is my pet pet hormone mainly because there's a lot of
[SPEAKER_01]: misinformation around it.
[SPEAKER_01]: Now, if you don't know what left in is, it's a hormone that's made by the adipose tissue or body fat tissue itself.
[SPEAKER_01]: The more body fat that you carry, the more left in you produce, the less body fat that you carry, the less left in you produce.
[SPEAKER_01]: Now, you may have heard about this hormone in its connection to appetite and hunger and eating related behaviors.
[SPEAKER_01]: It's been thought for a long time that it is a satiety hormone meaning it promotes fullness.
[SPEAKER_01]: And so if you have low levels of body fat, you also have low levels of leptin and so you're supposed to eat more.
[SPEAKER_01]: And if you have high levels of body fat and subsequently high levels of leptin, you should eat less.
[SPEAKER_01]: This is sort of framed as the body's natural solution to prevent obesity.
[SPEAKER_01]: As body fat goes up, leptim levels would go up too.
[SPEAKER_01]: So people should eat less and body fat should go back down.
[SPEAKER_01]: While on nature has its own solution to make sure that we don't gain too much body fat.
[SPEAKER_01]: However, this does not happen.
[SPEAKER_01]: Hunger, appetite, feelings of fullness, etc.
[SPEAKER_01]: They do not correlate to leptin levels very well, especially when they're high.
[SPEAKER_01]: Giving people high doses of leptin exogenously by injecting them with metroleptin also doesn't work.
[SPEAKER_01]: Try this.
[SPEAKER_01]: And so this term leptin resistance has been coined, meaning that the brain can't hope see higher levels of leptin, which is why obesity persists, despite this hormone that should make you full being elevated.
[SPEAKER_01]: One problem with this theory, the brain does respond to high leptin levels, meaning that leptin resistance isn't really happening.
[SPEAKER_01]: It just has nothing to do with appetite when it's elevated.
[SPEAKER_01]: So, how does the brain respond to high levels of leptin?
[SPEAKER_01]: Well, in the hypothalamus, chronically high leptin levels down regulate what are known as kiss peptin neurons.
[SPEAKER_01]: Now, these are a specialized group of neurons that are upstream of what drives GNRH production in the hypothalamus.
[SPEAKER_01]: So if you have less kiss peptin signaling, you get less GNRH, and subsequently less LH and FSH from the pituitary, and then subsequently less testosterone production by the testies.
[SPEAKER_01]: Now, leptin resistance, as a concept, has very little supporting evidence, despite decades of research.
[SPEAKER_01]: As of now, we think leptins strongest evolutionarily preserved role is a sort of low fuel alarm.
[SPEAKER_01]: When leptin levels drop, due to low levels of body fat, the brain signals scarcity pretty loudly, right?
[SPEAKER_01]: And it suppresses non-essential systems and prioritizes survival.
[SPEAKER_01]: So people get rapidly hungry, they start to eat a lot, and also, as we'll talk about low levels, of leptin can also signal decreased testosterone production, particularly in adolescence.
[SPEAKER_01]: We cover that pretty thoroughly in the book.
[SPEAKER_01]: Either way, the man with chronically elevated leptin has a hypothalamus that is not producing GNRH the way it should, and as a result, the signal to the testies is less than it should be.
[SPEAKER_01]: So let's go back to a man we've already met in the previous two episodes we've discussed Mark.
[SPEAKER_01]: He's this 45-year-old guy.
[SPEAKER_01]: He's a partner at an architectural firm.
[SPEAKER_01]: He's sedentary by the nature of his work.
[SPEAKER_01]: He's got a enlarging waist that's been creeping up for years.
[SPEAKER_01]: The textbook profile that the wellness clinic markets too.
[SPEAKER_01]: get a total testosterone of 240 on a single afternoon draw and that's what triggered the prescription for TRT.
[SPEAKER_01]: Now, this guy has some element of mush.
[SPEAKER_01]: This real fat in his abdomen has been generating chronically high aromatase levels, which converts testosterone into extra dial before it can reach its targets.
[SPEAKER_01]: And that same fat has also been raising leptin, which tells the hypothalamus to stand
[SPEAKER_01]: Now on its own, that is enough to drop a man like Mark with a previously normal HPG access a normal testosterone level below the threshold that's clinic was looking for when they ran their little algorithm.
[SPEAKER_01]: There are documented cases in the public literature of men who walked into a clinic or to a doctor's office.
[SPEAKER_01]: With the testosterone level below 150 nanograms per desoliter and got back above 450 on weight loss alone, no exogenous testosterone, no TRT prescription needed.
[SPEAKER_01]: The mechanism is reversible, but Mark's clinic didn't ask for any of that.
[SPEAKER_01]: They saw a lab number below a cutoff and they treated it to buff the chart.
[SPEAKER_01]: Body composition is one driver in the story.
[SPEAKER_01]: But there's second driver, that's clinic also did not look for and we'll talk about that after the break.
[SPEAKER_01]: But before we do, Austin, this is the patient who probably see very commonly mid 40s, BMI is above 30s, waste is, you know, about 40 inches total testosterone's 280 nanograms per deciliter.
[SPEAKER_01]: He's got fatigue, low libido, and he's red enough to know that he's below the sort of cut-off and he wants the prescription for testosterone.
[SPEAKER_01]: What does that conversation actually sound like when you see a patient like this?
[SPEAKER_00]: Yeah, it's going to first involve a lot of listening and then some more expansive history taking on this person's journey to this point and what's kind of motivating them to seek out a prescription this immediately.
[SPEAKER_00]: And then the other thing is kind of taking an inventory of the other what we'll call addiposity related kind of chronic diseases.
[SPEAKER_00]: In other words, he has the waste measurement of 40 inches.
[SPEAKER_00]: the BMI, you know, well over 30 in some of these symptoms, which I agree raises concern for a likely secondary testosterone deficiency, but he may well have lots of other things that need my attention as well as a generalist, not somebody who is, you know, a script monkey for a testosterone alone.
[SPEAKER_00]: I'm going to assess his blood pressure, assess his blood lipids, assess his, you know, glycemia, his blood sugar, his insulin sensitivity, things like that.
[SPEAKER_00]: assess his sleep, do a sleep apnea screening, get a sense of his exercise habits, his dietary habits, things like that that need to be considered.
[SPEAKER_00]: And then thinking about, when we move forward, what is this person's, what are this person's primary goals and why?
[SPEAKER_00]: What are they willing to do?
[SPEAKER_00]: What are they not willing to do?
[SPEAKER_00]: And then trying to negotiate through that plan together.
[SPEAKER_00]: It may end up being the case that somebody might not have a
[SPEAKER_00]: complete understanding of what's involved in going on testosterone therapy, if he may have enough other kind of complications of his body fat that it may actually be a wiser choice to use a different treatment compared with testosterone alone.
[SPEAKER_00]: He may benefit from either using, for example, a GLP one receptor agonist.
[SPEAKER_00]: He may benefit from using both a GLP one receptor agonist and testosterone.
[SPEAKER_00]: He
[SPEAKER_00]: He may benefit from something else entirely.
[SPEAKER_00]: He may end up deciding that he doesn't want to immediately jump on any of these medicines, but once he learns how much of all of these things that he may have are likely to be related to his body fat accumulation, visceral adiposity, and its complications, maybe he might not have ever tried anything before from a lifestyle standpoint.
[SPEAKER_00]: even though it is not easy to do, I have seen patients who, you know, when they learn about this stuff for the first time, they do find themselves able to, like, kind of, we'll call it buckle down and make a pretty substantial amount of lifestyle changes, not the most common thing, but it's also possible.
[SPEAKER_00]: So, I basically see this conversation going a lot of potential different directions, but I need to spend a lot of time.
[SPEAKER_00]: listening, inventorying the other kind of complications that he may have rather than being like ultra myopically focused on just the testosterone number alone.
[SPEAKER_00]: And then even when it comes to the testosterone, I need to make sure that the evaluation has been proper and complete.
[SPEAKER_00]: Right.
[SPEAKER_00]: Now, you're telling me somebody in whom I have a will call a very high pre-test probability of testosterone deficiency, right?
[SPEAKER_00]: I'm very suspicious.
[SPEAKER_00]: So the fact that his level was drawn in the afternoon compared with the morning, it's like I could be an ultra-stickler
[SPEAKER_00]: This fits, right?
[SPEAKER_00]: But as far as that being enough on its own to drive my prescription, not quite yet, because I do, I'm, I am going to be a stickler for making sure that my evaluation is complete and then not only the testosterone and subsequent, so for example, FSH and LH and things like that for completeness sake there, but also.
[SPEAKER_00]: again, checking for his, you know, insulin resistance, diabetes screening, lipid screening, blood pressure screening, depending on his age range.
[SPEAKER_00]: You know, we'll oftentimes, especially in this situation, do like a baseline PSA, various other sorts of things to be considered before we commit to that course of treatment or some combination therapy that he might benefit from.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: I mean, obviously, preferences are look, I can't really change a lot of these lifestyle things, then, you know, perhaps medication might be the answer.
[SPEAKER_01]: There may be additional things going on that also need to be treated on top of that.
[SPEAKER_01]: But if these open to it, yeah, lifestyle could be the first move.
[SPEAKER_01]: And then the natural question there is, well, how much does the testosterone number actually move when a man does these sort of lifestyle
[SPEAKER_01]: We see that a 10% reduction in body weight produces an average testosterone increase of about 84 nanograms per desolier.
[SPEAKER_01]: So for a man who walked in at 280, that's a difference between being maybe deficient in the normal range and then definitively above that sort of cut off with lifestyle alone.
[SPEAKER_01]: Metabolic bariatric surgery, which we've covered in detail on this podcast before, which can produce an average weight loss somewhere between 20 to 30%.
[SPEAKER_01]: Pertices increase on the order of 250 nanograms per deceler on average.
[SPEAKER_01]: Obviously, individuals vary.
[SPEAKER_01]: Uh, we think though that this sort of seven to 10% weight loss threshold is roughly where leptin drops enough to produce a large increase in testosterone levels from that mechanism itself.
[SPEAKER_01]: One in one study, 11% weight loss produced a 44% drop in circulating leptin in six months, which is actually pretty impressive.
[SPEAKER_01]: which leads to the next question, does OZEMPIC raise testosterone?
[SPEAKER_01]: Do GLP1s raise testosterone levels?
[SPEAKER_01]: And this is pretty well established here.
[SPEAKER_01]: GLP1 receptor agnes like some aglutide enters epitide raised testosterone by roughly 20 to 30% in men with obesity on top of other additional benefits to the cardiometabolic systems, sexual function, et cetera.
[SPEAKER_01]: And this is directly proportional to weight loss, mostly.
[SPEAKER_01]: Plus, the parallel improvements in things like glycemic control and the metabolic milieu, as Cloud Bernard, would appreciate me saying.
[SPEAKER_01]: The HPG access just responds better.
[SPEAKER_01]: There's also some preclinical work.
[SPEAKER_01]: I don't know if you've seen this on GLP1, and their direct effects on the penal tissue itself.
[SPEAKER_01]: So, yeah, pretty interesting stuff.
[SPEAKER_01]: There might be some, again,
[SPEAKER_01]: independent benefits of GLP1 agonist on those tissues, so we can watch this space.
[SPEAKER_01]: But practically speaking, for the guy who walks in, who's already on a GLP1 agonist, and he six months into the sort of weight loss management, he's probably watching his testosterone level climb on its own.
[SPEAKER_01]: And so I think it's reasonable to recheck their labs if they were concerned about testosterone efficiency.
[SPEAKER_01]: Once they're kind of
[SPEAKER_01]: Maybe past this point of, like, you've lost a significant amount of weight already, like I wouldn't check it one month after, but maybe three months, six months or certainly twelve months, if that was a concern, maybe a different scenario, I want to get your take on this, what about a guy who's already on TRT and then he starts a GLP one, so his endogenous production of testosterone was already shut down by being on TRT, that's the nature of that medication.
[SPEAKER_01]: But what does change is how his body is sort of handling the dose.
[SPEAKER_01]: As he loses weight, he's going to have less visceral fat, which means less aromatase.
[SPEAKER_01]: So less of the prescribed testosterone is going to get converted to Astridile, that type of estrogen.
[SPEAKER_01]: His SHBG is likely going to go up as his metabolic health improves.
[SPEAKER_01]: So they may have an even higher testosterone level in addition to maybe some altered estrogen levels.
[SPEAKER_01]: So Austin, are you seeing this in practice?
[SPEAKER_01]: Is this something you've come across?
[SPEAKER_00]: Yes, and seeing it not just in the realm of testosterone, but in other endocrine-related conditions as well, a much more common one that we see and manage as, you know, hypothyroidism.
[SPEAKER_00]: And so it's actually very common for people's dose of thyroid hormone replacement to need to be adjusted while they are losing substantial amounts of weight on these medications.
[SPEAKER_00]: And the same would go for something like testosterone.
[SPEAKER_00]: It would not be at all surprising to me if somebody, you know, who's on a particular dose at one way after they have lost a substantial amount of that,
[SPEAKER_00]: They're blood levels end up becoming high and as a result they end up essentially having too much in their system Which can be evidenced by a variety of downstream consequences and so would be you know pretty common or prototypical to need to adjust that dose to stay in a The target range for that for that person, especially as they lose substantial amounts of weight.
[SPEAKER_01]: Yeah, pretty interesting stuff here One question that comes up then is well, look does adding testosterone
[SPEAKER_01]: even if you don't, maybe need it.
[SPEAKER_01]: Make this better, okay?
[SPEAKER_01]: So there was an interesting study called the testosterone for diabetes trial.
[SPEAKER_01]: Over 1,000 men with pre-diabetes or type 2 diabetes, all over weight or with obesity.
[SPEAKER_01]: They were all enrolled in the same sort of structured lifestyle program.
[SPEAKER_01]: Half got testosterone alongside the program, half.
[SPEAKER_01]: got placebo alongside the program.
[SPEAKER_01]: Now, both groups improved significantly.
[SPEAKER_01]: They both lost weight.
[SPEAKER_01]: They both reported better quality of life, better sexual function, better mental health, better psychosocial measures, et cetera, et cetera, et cetera.
[SPEAKER_01]: Now, adding testosterone produced almost no additional improvement on top of the lifestyle program for any of those sort of quality of life outcomes.
[SPEAKER_01]: The lab numbers,
[SPEAKER_01]: for testosterone.
[SPEAKER_01]: We're higher in the group that got testosterone, but the men didn't really feel any different.
[SPEAKER_01]: This is kind of the same finding from the chaslin trial we talked about last week.
[SPEAKER_01]: Different population, different stage of the disease, same answer.
[SPEAKER_01]: When the lifestyle intervention is doing most of the work adding testosterone, particularly at like a replacement dose, doesn't seem to move the patient any further.
[SPEAKER_01]: So Austin, I think there's probably a pattern you're seeing more often now than maybe what you were seeing five years ago.
[SPEAKER_01]: Patient comes in who's already on a GOP one and their weight is dropping.
[SPEAKER_01]: And then they asked to also get on testosterone.
[SPEAKER_01]: What's your sort of play if that happens?
[SPEAKER_00]: Yeah, more history, asking why.
[SPEAKER_00]: What's driving their thinking, their reasoning?
[SPEAKER_00]: What are they seeking to gain from this?
[SPEAKER_00]: And then oftentimes, if somebody is already making excellent progress, then we can oftentimes negotiate a kind of monitoring plan.
[SPEAKER_00]: I am, as I've alluded to in previous episodes, like not super rigid about this.
[SPEAKER_00]: And I think mainly this is based on the fact that testosterone therapy, when it is used reasonably, and it is at least monitored, it's actually quite safe.
[SPEAKER_00]: And so I'm not necessarily just like shutting the person down right off the bat because that's of course a way to lose your rapport and then they're just not going to be interested in, you know, you're probably never going to see them again.
[SPEAKER_00]: So I will kind of remain open to the possibility, but rather do a little bit of education understanding of their goals, maybe a monitoring plan and suggest that we kind of.
[SPEAKER_00]: maybe manipulate fewer variables at once, and then maybe we see, hey, let's get to a place of weight stability, let's see how you feel, because then you're looking at the possibility, for example, taking a second injection every week or twice a week or whatever the case long term.
[SPEAKER_00]: And if there's not too many more benefits to be gained by doing that, then maybe it's not worth it to you, because there's time and expense.
[SPEAKER_00]: And
[SPEAKER_00]: effort and all sorts of things that you need to be thinking about in that context as well.
[SPEAKER_00]: So that's typically what I would aim to negotiate is like, hey, main open to it.
[SPEAKER_00]: If there's a clear reason to expect that it might help you, then totally we can go down that path, but maybe we see what things look like, see how you feel once you've achieved a kind of more of a weight stable place, weight maintenance level territory.
[SPEAKER_00]: Now, if they push back on that, then again, I'm just going to ask why I get a sense of where they're coming from on that and potentially
[SPEAKER_01]: Yeah, it seems like the most likely person fitting this criteria would be trying to quote optimize like a number.
[SPEAKER_01]: They're like, look, my testosterone right now is 350.
[SPEAKER_01]: It should be 700.
[SPEAKER_01]: I read online, it should be 700.
[SPEAKER_01]: And you're like,
[SPEAKER_01]: That requires some unpacking, but yet to your point, if this person was dead set, I want to use testosterone, I'm gonna find a way to do it.
[SPEAKER_01]: Then at that point, you know, you're basically then assessing risk benefits.
[SPEAKER_01]: And the person, while not terribly likely to benefit from the testosterone therapy, it's also not incredibly risky.
[SPEAKER_01]: It would be more risky if they went through another channel, perhaps obtaining these, shoulder from an inappropriate source, no monitoring, so on and so forth,
[SPEAKER_01]: Yeah.
[SPEAKER_01]: I agree.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: All right.
[SPEAKER_01]: Well, that handles the largest single driver of testosterone deficiency, which would be excess at a positive body composition.
[SPEAKER_01]: The second one, nobody asks about in the one marks clinic walk past is sleep.
[SPEAKER_01]: Now, we come back from the break, how weak of bad sleep moves a man's testosterone level.
[SPEAKER_01]: And why obstructive sleep apnea is the most underdiagnosed contributor to symptomatic low testosterone in middle age men and what
[SPEAKER_01]: All right, welcome back.
[SPEAKER_01]: We were talking about the effects of body composition on testosterone and we said a second driver was sleep.
[SPEAKER_01]: Can poor sleep lower testosterone?
[SPEAKER_01]: Yes, absolutely.
[SPEAKER_01]: And faster than most men realize.
[SPEAKER_01]: Now, in 2011, Rachel Lepro and E. Van Cauder took 10 healthy young men, average age was in their 20s, and their average testosterone, where you would expect it to be for healthy young men, normal, and they restricted them to five hours of sleep per night for one week.
[SPEAKER_01]: While they were healthy at baseline, after one week, their testosterone levels dropped by about 15% on average.
[SPEAKER_01]: Now, a 15% drop in testosterone is big, and their relationship runs the other way too.
[SPEAKER_01]: Older men, morning testosterone levels is independently predicted by measured sleep duration.
[SPEAKER_01]: The men sleeping less had lower morning testosterone, controlling for age, body mass, and the rest of the state of adjustments.
[SPEAKER_01]: testosterone production depends on sleep, though this is not strictly circadian.
[SPEAKER_01]: So the hormone itself testosterone is released during sleep itself, impulses tied to REM cycles.
[SPEAKER_01]: The morning peak that everyone references, and this is just a post-sleep peak, which can vary depending on when somebody is actually sleeping.
[SPEAKER_01]: So for a man who has a standard overnight sleep schedule, that means a 7 a.m. to 10 a.m. draw catches the peak, but for a night shift worker who sleeps from 8 a.m. to 4 p.m. the peak lands in the late afternoon when they wake up.
[SPEAKER_01]: If you drew that person's labs at 8 a.m. Before they slept, that's gonna catch the low point where the trough.
[SPEAKER_01]: Now, the mechanism on chronic sleep restriction also goes through the hypothalamus, the same place that obesity hits.
[SPEAKER_01]: The specific mechanisms are still an active area of research.
[SPEAKER_01]: Is it kiss peptin or the hypothalamus more broadly?
[SPEAKER_01]: Is this mediated by cortisol to a significant degree?
[SPEAKER_01]: Where that can have direct effects on the hypothalamic, but to a trigonatal axis or kiss peptin itself.
[SPEAKER_01]: We don't really know yet, so it's still an active area of research, but reduced sleep
[SPEAKER_01]: You get a reduced G&RH pulse amplitude either way, which means reduced LH, which is a reduced signal to the testies to produce testosterone.
[SPEAKER_01]: So a few things that translate in the real world here.
[SPEAKER_01]: There are confounding effects.
[SPEAKER_01]: Now, a 15% decrease in testosterone is big.
[SPEAKER_01]: There's another study on military recruits where they also are sleep restricted and it's even bigger drop, 50%.
[SPEAKER_01]: But the longer term effects of chronic sleep restriction, which might apply to people listening to this podcast,
[SPEAKER_01]: They're harder to measure cleanly because the same lifestyle that results in sleep restriction also tends to drive the body composition that suppresses testosterone on its own.
[SPEAKER_01]: This two drivers kind of stack here.
[SPEAKER_01]: Also, the laboratory assessment.
[SPEAKER_01]: Now, night shift workers, rotating shift workers, and men with severely disrupted sleep schedules.
[SPEAKER_01]: thinking back to my intern year in medicine, they're gonna need their testosterone drawn within the first hour or two of waking.
[SPEAKER_01]: Whatever time of day that is, the phrase sort of morning, fasted lab draw is shorthand, but the actual instruction is, hey look, the first hour or two after waking also fasted.
[SPEAKER_01]: Now, Austin, how do you approach the guy who works nights and is concerned about low testosterone?
[SPEAKER_01]: Imagine there's some scheduling issues here, trying to get the lab at the right time like before the lab closes and before the person has to go to work, how do you navigate that?
[SPEAKER_00]: Yeah.
[SPEAKER_00]: On an individual basis, as best we can really, it's a matter of kind of seeing what's feasible for the person trying to get it done, you know, within the first couple hours after they wake up, sometimes if they have a day off or a night off during the week, that might be the time to get it done.
[SPEAKER_00]: So you just try to thread that needle with working with the person schedule and when their days or nights off are and trying to get it done at that preferable time, whenever possible.
[SPEAKER_01]: system does seem to be built around these nine to five patients.
[SPEAKER_00]: Yeah.
[SPEAKER_00]: I mean, so as our biology is built around, you know, and it's circadian daylight.
[SPEAKER_00]: As cycles were not kind of evolutionarily, you know, set up for nocturnal work on a long-term basis.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: So that sort of cover covers sleep duration how long people are sleeping, but there's one more category related to, quote, bad sleep that doesn't show up as fewer hours on a clock.
[SPEAKER_01]: More has to do with sleep quality.
[SPEAKER_01]: You know, the man who sleeps eight hours and wakes up tired because of sleep itself is messed up.
[SPEAKER_01]: And this is one of the most underdiagnosed contributors to symptomatic low testosterone.
[SPEAKER_01]: And certainly the features that people associate with low testosterone also happens to be what Mark has.
[SPEAKER_01]: His airway was closing while he was sleeping.
[SPEAKER_01]: He stops breathing, his oxygen level drops, and as a result, his brain pulls him back towards consciousness enough to clear the airway.
[SPEAKER_01]: He gasps, his airway reopens, and he goes back to sleep 30, 50, 100 times an hour.
[SPEAKER_01]: He has no memory of any of it, he sleeps eight hours, but he still wakes up tired.
[SPEAKER_01]: It's also extremely common, especially with obesity, with increasing age, and in people with thicker necks, both of your hosts included in this, and really anyone who snores.
[SPEAKER_01]: By some estimates around a quarter of middle-aged men haven't, I think that's an under-diagnosis.
[SPEAKER_01]: Most of them have never even talked about it with their doctor.
[SPEAKER_01]: Now, Mark's wife has been complaining about it every night for years.
[SPEAKER_01]: Snoring was loud enough that she slept in the other room, and the pauses in his breathing were long enough that she would lie there waiting for the next breath.
[SPEAKER_01]: Unfortunately, from Mark and his wife, his clinic never asked either one of them about it.
[SPEAKER_01]: And again, to clarify, this is not unusual.
[SPEAKER_01]: Let's structively tap Nia is both very common
[SPEAKER_01]: but there is some nuance here.
[SPEAKER_01]: In many, the causation runs through obesity more than the apnea itself.
[SPEAKER_01]: The most men with obstructive sleep apnea also have the metabolic and visceral fat profile that drives testosterone down on its own.
[SPEAKER_01]: And also using a C-pap, it's one of the treatments for obstructive sleep apnea, does not reliably raise testosterone on its own in many.
[SPEAKER_01]: It does improve fatigue, these symptoms of daytime tiredness, daytime function and even sexual function, but the number on the lab report doesn't always move as much as the man might want it to.
[SPEAKER_01]: So what does this really mean?
[SPEAKER_01]: For a man with sleep apnea, treating the apnea is the right call regardless of what it does to his testosterone levels.
[SPEAKER_01]: Because the symptoms that improves are the symptoms that probably drove them to the clinic in the first place, daytime sleepiness, sexual dysfunction, etc.
[SPEAKER_01]: The testosterone may then come back as the body composition improves.
[SPEAKER_01]: Alongside a lifestyle program, he can actually tolerate because he's actually sleeping now.
[SPEAKER_01]: So, for Mark, his testosterone was being attacked from multiple different angles.
[SPEAKER_01]: It's got this mosh, right, excess had a positive, he's got sleep apnea and all this was being ignored by the clinic did an inappropriate and incomplete workup which is also unfortunately very common.
[SPEAKER_01]: Importantly, we know that this is not primary testosterone deficiency of problem with the testes themselves.
[SPEAKER_01]: So, the fix is upstream and episode four is where we get into that and what the fix actually looks
[SPEAKER_01]: All right, so Austin, two questions.
[SPEAKER_01]: We'll start with the first.
[SPEAKER_01]: Patient walks in just like Mark.
[SPEAKER_01]: He's in his 40s, BMI's 31 is waste is 40 inches.
[SPEAKER_01]: His total testosterone is 240.
[SPEAKER_01]: He's got fatigue, low libido, his wife says that he snores, never had a sleep study.
[SPEAKER_01]: He's there because he wants the testosterone fixed.
[SPEAKER_01]: What is your immediate next step besides?
[SPEAKER_01]: Ask him why the lab was drawn to the first place.
[SPEAKER_00]: Well, I mean, it's apparent to me why the lab might have been drawn based on his symptomatic presentation.
[SPEAKER_00]: But definitely, completing the comprehensiveness of the evaluation, making sure we've done our due diligence with the testosterone related things.
[SPEAKER_00]: But also these other complications of his excess body fat.
[SPEAKER_00]: So again, checking his blood pressure, blood lipids, and then doing more of a sleep assessment.
[SPEAKER_00]: And so this guy just needs a sleep study.
[SPEAKER_00]: He is ultra high risk for obstructive sleep apnea.
[SPEAKER_00]: This is a situation where, you know,
[SPEAKER_00]: earlier in my practice, I might have formally gone through each of the stop being questions and been like, you know, checking off and assessing the risk.
[SPEAKER_00]: And after a certain, you know, number of hundreds or thousands of patients that you've done this with, you're just like, nah, you just need to sleep tests.
[SPEAKER_00]: I'm not going to.
[SPEAKER_00]: Now, if you need to do the scoring to justify two insurance, then, you know, so be it.
[SPEAKER_00]: But, you know, after a certain point, you just know what the person needs.
[SPEAKER_00]: And so this person does need a sleep study.
[SPEAKER_00]: There are different ways to go about that.
[SPEAKER_00]: These days, more than ever, it's super convenient because, especially when you
[SPEAKER_00]: definitely here.
[SPEAKER_00]: I have a high pre-test probability that this person has obstructive sleep apnea.
[SPEAKER_00]: We can usually catch it on a convenient home sleep test.
[SPEAKER_00]: The person gets a kit.
[SPEAKER_00]: They just wear it at home for a
[SPEAKER_00]: You know, a night, maybe two, send it back.
[SPEAKER_00]: We get a study result.
[SPEAKER_00]: And then it's even more convenient.
[SPEAKER_00]: I can, if we're going to pursue something like positive airway pressure therapy, I could just prescribe an autopap to the person with some baseline settings to get started with and then kind of troubleshoot from there.
[SPEAKER_00]: There are other ways to go about this process.
[SPEAKER_00]: There are in lab sleep studies.
[SPEAKER_00]: There are other non-positive airway pressure-related treatments for sleep apnea.
[SPEAKER_00]: And of course, managing his body weight.
[SPEAKER_00]: and his obesity will go a long way to improving it.
[SPEAKER_00]: In fact, you had mentioned the GLP one-agonist earlier, so it turns epitide itself has a specific indication for treating obstructive sleep apnea in patients, and that might be also a consideration here.
[SPEAKER_00]: And so a lot of the symptoms he has are these kind of non-specific symptoms that can emerge from a variety of different causes.
[SPEAKER_00]: Porsally poor mood can perpetuate low levels of activity, can worsen, you know,
[SPEAKER_00]: people's cognition, their depression, their energy levels, all sorts of things that can then be experienced as a loss of libido, as fatigue, things like that.
[SPEAKER_00]: And so I'm just trying to take a comprehensive of an approach, as I can, to give this guy the best shot at improving all of the symptoms, improving his overall health, his longevity, while minimizing potential harms.
[SPEAKER_00]: And so maybe testosterone has a role in his therapy, but I think that again, completing all of this work up front is the smarter strategy compared with saying, here's the situation you feel bad, and then we'll go ahead and start therapy, kind of right up front.
[SPEAKER_01]: Yeah, and I don't know how closely read the testosterone, some of the testosterone guidelines, whatever.
[SPEAKER_01]: But you're well aware, for sure, that exogenous testosterone TRT prescription in a person who has untreated sleep apnea is a constant ideal.
[SPEAKER_01]: to there be.
[SPEAKER_01]: And there's some thought based on some studies that exogenous testosterone actually relaxes some of the soft tissue of the airway on its own, which would complicate and make the sleep apnea even worse despite the number going up.
[SPEAKER_01]: So yeah, effectively if you have sleep apnea, you're going to treat it, should treat it.
[SPEAKER_01]: Guardless.
[SPEAKER_01]: The point is that the person may still also benefit from TRT or additional interventions if they have something that's causing
[SPEAKER_01]: So, look, let's say Mark comes back from the sleep study, severe obstructed sleep apnea.
[SPEAKER_01]: He could start it on CPAP six months later.
[SPEAKER_01]: He feels dramatically better, repeat testosterone comes back as 320.
[SPEAKER_01]: A little bit better than where he started, but not setting the world on fire.
[SPEAKER_01]: He wants to know why he feels great if the number didn't really move.
[SPEAKER_01]: What do you say to that?
[SPEAKER_00]: Yeah, so I'm curious about a few things, including did we do a more expansive evaluation after that initial low testosterone value, but it may be the case that more of his symptoms were coming from really poor sleep, then it was specifically from the low blood number.
[SPEAKER_00]: The other things to think about are again that this blood number is just a snapshot in that circadian rhythm.
[SPEAKER_00]: We talked about this last time when I joked around about, for example, having your.
[SPEAKER_00]: You know, continuous testosterone level monitoring and it goes up and down all the time throughout the day and so we might just be catching it at a different period of the day when really his testes are able to produce, you know, maybe physiologically sufficient testosterone for him and more of his symptoms were coming from having, you know, essentially no restful sleep because his brain was, you know, waking him up upwards of, you know, 50 plus times an hour as you alluded to, which I've seen that and much worse in these situations.
[SPEAKER_00]: And so this is a situation where if he feels great, he's performing well, he's doing well, then this is something that I would say, let's like enjoy that, lean into it and kind of move forward with the rest of our healthy lifestyle interventions that we're wanting to focus on and work on.
[SPEAKER_00]: And there may not actually be a ongoing clinical need to measure his blood testosterone levels.
[SPEAKER_00]: I would say that a fair amount of the time patients in the situation are going to want to recheck it.
[SPEAKER_00]: And so kind of like when you talked about the patient on a GLP-1 Agnes earlier and I said, why don't we plan to recheck once we've given this a little bit more time, we've achieved the state of kind of weight stability, then this might be another situation where it's like, okay, let's, you know, if you're
[SPEAKER_00]: really wanting to keep an eye on this over time, then we can recheck once we have really settled into a steady rhythm of your like healthy lifestyle behaviors in your consistent with the CPAP use and all sorts of things like that.
[SPEAKER_00]: Of course, in the back of my mind, I'm like, even then, if you come in and you tell me you're feeling phenomenal and let's say your testosterone level at that time is like 340.
[SPEAKER_00]: Are we still gonna be having a serious conversation about putting you on testosterone?
[SPEAKER_00]: It's like again, the potential gains in that situation are slim to more likely none.
[SPEAKER_00]: For your quality of life, if you're already telling me it's quite good, and it's not to say that the risks are like sky high off the charts.
[SPEAKER_00]: But rather it's like, what are we trying to accomplish here in terms of potential benefits?
[SPEAKER_00]: And then what are we most worried about in terms of potential risks in balancing those out?
[SPEAKER_00]: When you lay it out like that, a lot of people will kind of, I wouldn't say come around in the sense that I'm trying to coerce them, but they kind of understand the clinical thought process here.
[SPEAKER_01]: Yeah, yeah, so these are the patients that the wellness clinic sees most often, but there's a different reason, well, the patient might come in and it's kind of the opposite some of these folks might be sitting in the audience right now.
[SPEAKER_01]: Question is, can you lower your testosterone by training too much answers?
[SPEAKER_01]: Yes, some people listening to this podcast right now almost certainly have done it.
[SPEAKER_01]: Now, Moses episode has been about excess, excess body fat, excess sleep deprivation, excess load on the metabolic system through a very variety of mechanisms.
[SPEAKER_01]: The opposite extreme produces the same decrease in testosterone through the opposite mechanism.
[SPEAKER_01]: The body cannot distinguish between not eating enough and starving.
[SPEAKER_01]: the hypothalamus reads both as scarcity and shuts down reproduction in the same way.
[SPEAKER_01]: This is low energy availability or LEA.
[SPEAKER_01]: In the athletic world, there's a sort of more serious type of this called relative energy deficiency in sport or reds, and has been historically described in female athletes.
[SPEAKER_01]: But it's been increasingly recognized in men and the men in our audience would probably be some of the highest risk folks for this condition.
[SPEAKER_01]: So what is LEA?
[SPEAKER_01]: Energy availability just refers to the number of calories in minus the calories that you are training in lifestyle burns.
[SPEAKER_01]: This is divided by lean body mass.
[SPEAKER_01]: What's left over after exercise is what you have to run the rest of the body to keep the lights on.
[SPEAKER_01]: Now, operationally LEA is defined as eating less than about 30 calories per kilogram of lean body mass per day.
[SPEAKER_01]: Below this point, the system starts shutting down non-essential functions to protect what is essential.
[SPEAKER_01]: Reproduction is one of the first things on the chopping block.
[SPEAKER_01]: The mechanism here, low intake, low body fat, low circulating leptin, and the sort of low leptin-level signals, scarcity to the hypothalamus, the same way that elevated leptin signals abundance.
[SPEAKER_01]: You get reduced kiss peptin signaling, reduce GNRH signaling, reduced LH and FSH signaling, and suddenly reduced testosterone production.
[SPEAKER_01]: It's the shutdown with the sort of opposite trigger here.
[SPEAKER_01]: So some interesting data has emerged here some from natural bodybuilders.
[SPEAKER_01]: This particular study from Metesu took seven natural male bodybuilders.
[SPEAKER_01]: They went through 11 weeks of contest prep.
[SPEAKER_01]: These were trained athletes who knew what they were doing presumably.
[SPEAKER_01]: And they were measured against a matched group of bodybuilders who were training also, but not prepping for a show.
[SPEAKER_01]: By contest day, those who were prepping for the show had dropped from 9.6% body fat to 6.5%.
[SPEAKER_01]: During this period, their average testosterone fell about 90 nanograms per desoliter, with most of that drop happening in the first half of the cut and then remaining at that lower level.
[SPEAKER_01]: Now, in trained healthy men cutting to contest level, leanness produces a measurable suppression of the same HPG access we've been talking about for the last two episodes.
[SPEAKER_01]: It is unclear, though, do these people have symptoms of testosterone deficiency and we know based on other data that tends to recover when people regain the weight.
[SPEAKER_01]: Some people do this, they just cut because they've been told not look.
[SPEAKER_01]: If you reduce your body fat and you get real, real lean, then when you regain body weight, you're going to be, it's going to be mostly muscle.
[SPEAKER_01]: This is almost certainly not true.
[SPEAKER_01]: It's predominantly fat earlier on, which is why this signal is recovered.
[SPEAKER_01]: chasing leanness can have a real cost.
[SPEAKER_01]: There's a sort of additional related sort of a condition that probably is even more common in some of our listeners has to do with what we call EHMC.
[SPEAKER_01]: So exercise hypogonatal male condition.
[SPEAKER_01]: Um, this is basically from folks who are not necessarily cutting right or getting too lean per se, but they're exercising too much.
[SPEAKER_01]: So you imagine a person who's lifting six days a week, doing conditioning on top of that, eating around maintenance because they're trying to stay lean.
[SPEAKER_01]: And they're sleeping poorly because life is busy and sleep is challenging.
[SPEAKER_01]: Discessing on levels can often come back low normal or even frankly, below the sort of cut points that we've talked about so far.
[SPEAKER_01]: So far.
[SPEAKER_01]: And this person might think that they need testosterone replacement therapy.
[SPEAKER_01]: reality is they probably need more food and or a revised training program.
[SPEAKER_01]: So this condition EHMC is best documented in endurance athletes, but the same adaptive suppression shows up in resistance training men that are running high volume programs with not enough food on board.
[SPEAKER_01]: This low normal reading that in that type of person is a sort of downregulation of the system doing what it should do under those conditions, it's adaptive in a way not necessarily a deficit or deficiency and testosterone that needs replacement mostly the reasons why you know it doesn't need or they don't need replacement is because people tend to be asymptomatic.
[SPEAKER_01]: performance is often preserved and so deciding to treat or intervene with training or nutrition changes.
[SPEAKER_01]: That's also on a case by case basis.
[SPEAKER_01]: Effectively, if nothing's broke, we're just searching for a problem to fix here.
[SPEAKER_01]: So.
[SPEAKER_01]: This gift kind of interesting when we talked about this a little bit in episode two, theoretically, a standard prescription dose of testosterone in a man whose own production is suppressed by their training load functions could function as a performance enhancing drug writing on top of an artificially suppressed baseline, even at the sort of textbook replacement dose, the number is going to go up, perhaps to an even higher level than their adaptive sort of floor right now.
[SPEAKER_01]: Whether that is a sort of real deficiency, being corrected or a normal adaptation, being papered over is a different conversation, and it's a conversation that pretty much never happens.
[SPEAKER_01]: And any of these wellness clinic visits, you know, how much you exercise and what are you eating?
[SPEAKER_01]: Is this EHMC and do you need to treat that?
[SPEAKER_01]: That's a controversial section here.
[SPEAKER_01]: So Austin, let's think about this.
[SPEAKER_01]: You got a guy, he's in his mid 30s.
[SPEAKER_01]: He lifts five days a week.
[SPEAKER_01]: He runs 30 miles a week on top of that.
[SPEAKER_01]: His body fasts less than 12%.
[SPEAKER_01]: He's got a low normal testosterone level around 320 nanograms per desolier, but no other symptoms outside of the number.
[SPEAKER_01]: He's convinced that he is testosterone deficient and wants to start TRT.
[SPEAKER_01]: How do you talk them through this, besides asking him, again, why was his testosterone level shift?
[SPEAKER_00]: It's an interesting case, and I don't know if it's weird that I heard those stats, and I'm like, yeah, that's not that much.
[SPEAKER_00]: That's what they are.
[SPEAKER_00]: It sounds like kind of like me.
[SPEAKER_00]: I don't run quite as far as 30 a week at the moment, but I'm, you know, in this ballpark of training load with a definitely a different level on the last time I had labs check.
[SPEAKER_00]: But yeah, the fact that this person has no symptoms whatsoever.
[SPEAKER_00]: Again, I try to bring it back to like, what are we trying to accomplish with this?
[SPEAKER_00]: And, you know, when you frame it that way of like, are you you're interested in going on therapy to make this number that you didn't know was at this level look better.
[SPEAKER_00]: For what potential gain and and at some potential downside, not in terms of like catastrophic risks, but, you know, again, it's it's not a negligible thing to commit to a potentially long term therapy like this and so.
[SPEAKER_00]: Then have a little bit more of a conversation around his training, maybe do a little bit of education around it, and then maybe just if he's willing to, just get it like rechecked and recheck it maybe after a bit of a try to figure out like when this is next planned, you know, back off or reload or something like that, is that in the plan at all?
[SPEAKER_00]: Being at a body fat, you know, you said, under 12 percent, if we wanted to characterize this more, because 12 percent is not
[SPEAKER_00]: in my mind, like, you know, insanely low for this kind of thing.
[SPEAKER_00]: If he was much much leaner, if he was, you know, stage ready, then we'd be having it and yet another type of conversation.
[SPEAKER_00]: But really, it's a matter of, I would say, rechecking this under slightly different circumstances, because if we observe, for example, he backs off a little bit, he has, you know, maybe,
[SPEAKER_00]: a little bit more energy intake in the short term and things that things like pop up well into the say 400's 500's 600's something like that, then you have your answer as far as what could have been contributing to it.
[SPEAKER_00]: Not to mention that these things should generally be rechecked once anyway in most of these situations.
[SPEAKER_00]: But continuing to come back to like getting an understanding of what are the person's primary goals and figuring out like what are we trying to achieve by doing this Aside from the number the number is what it is on that initial lab we can recheck that but what are we trying to achieve for you like your health how you feel
[SPEAKER_00]: And then pointing out that to your point, this is essentially going on PEDs if you don't have a clear medical indication and are you a competitor?
[SPEAKER_00]: That might have some considerations depending on the sport that you're in or you're going to need to pursue a TUE for like asymptomatic testosterone level at 320.
[SPEAKER_00]: I wouldn't do that if it were me and I felt fine.
[SPEAKER_00]: So there's a lot of different ways this conversation can go and it's going to be guided a bit by, you know, the back and forth there.
[SPEAKER_00]: But yeah.
[SPEAKER_00]: not being terribly excited by this result in terms of wanting to jump into action right away, more so recommending some temporary if they're willing to modify bit of training, rest recovery calories, and recheck this before committing to anything else.
[SPEAKER_00]: I think would be wise.
[SPEAKER_01]: Yeah, I do, I just, I do wonder about that PED sort of.
[SPEAKER_01]: like thought, you know, a doctor call on the dole ski years ago now we did a podcast with him and kind of broached this topic.
[SPEAKER_01]: And you know, I've been just kind of wrestling with this ever since.
[SPEAKER_01]: It's like, look, if your testosterone level is suppressed,
[SPEAKER_01]: appropriately through just a high training load and maintenance level fuel.
[SPEAKER_01]: So we're not not have like a low body fat type situation, right?
[SPEAKER_01]: It's just training load is very, very high.
[SPEAKER_01]: So we kind of kind of expect that.
[SPEAKER_01]: You're going to load testosterone level, low normal maybe.
[SPEAKER_01]: And then you go on a TRT replacement dose, 100 milligrams a week, 150 something like that.
[SPEAKER_01]: And now your new testosterone level is 700, 800, whatever, yes, right?
[SPEAKER_01]: Yeah.
[SPEAKER_00]: Yeah.
[SPEAKER_01]: How could you tell if it actually was like PED level because we think that within the Yuga Nattle or normal range, there's not really a dose response relationship between testosterone levels and training outcomes, whether that's strength, whether it's hypertrophy, cardiovascular fitness, so on and so forth.
[SPEAKER_01]: But if you weren't doing that training load,
[SPEAKER_01]: and you were taking that dose.
[SPEAKER_01]: Would that actually put you into super physiological levels because it's just a tiered, you know, a replacement dose and so it's shutting down your own production.
[SPEAKER_01]: So it's not like they're stacking.
[SPEAKER_01]: So then you're back in the still this you can add a range.
[SPEAKER_01]: So I'm trying to like wrap my head around that.
[SPEAKER_01]: How do you think about that?
[SPEAKER_01]: Am I just making this too complicated or?
[SPEAKER_00]: maybe.
[SPEAKER_00]: Yeah, I'm not entirely sure either.
[SPEAKER_00]: I think that, you know, that plateau range that you're talking about a lot of that has to do with like what people's natural kind of baseline levels might tend to be that having slightly higher versus slightly lower at baseline physiologic situations is not a reliable predictor of having much higher strength or muscle master performance.
[SPEAKER_00]: I think that if your natural levels though at, you know, you would equilibrate otherwise very naturally in a healthy state to, like, let's say around, you know, 360 or 400 or something.
[SPEAKER_00]: And then you go on a dose that pushes you up to 900.
[SPEAKER_00]: Yeah, I would expect that to have more of an impact, it's not because it's not so much comparing your baseline, you know, equilibrium physiology with somebody else's.
[SPEAKER_00]: at that level, but rather like your own pre and post is now you've doubled it and I actually probably would expect a more substantial impact there.
[SPEAKER_00]: And that's kind of what I've seen in practice, not only in terms of some of the impacts say on their adaptation, but also somebody who's like is clinically you go anaddle, right?
[SPEAKER_00]: But goes on testosterone maybe because the number was lower than they wanted it to be.
[SPEAKER_00]: I've seen a higher incidence of like side effects intolerance and
[SPEAKER_00]: in those situations.
[SPEAKER_00]: I can think of many cases that I've consulted with over the years of people who, you know, were on and then they're worried about it and they want to chat with me and they found out, oh, I went on and then I suddenly had started having tons of acne and I started having anxiety and panic attacks and those other things.
[SPEAKER_00]: I'm like, yep, you probably never needed it in the first place.
[SPEAKER_00]: And the more sensitive you are to adverse effects up front, I'm to be clear.
[SPEAKER_00]: This is made up.
[SPEAKER_00]: But my hypothesis here is that the more sensitive you seem to be to those types of adverse effects from from from initiation, it feels to me that it's more likely that you didn't need it.
[SPEAKER_00]: And the first place compared with people who are, you know, truly clinically deficient, they they much more often will tend to feel way better when they get restored to physiologic levels compared with pushing from your, you know, you go nadal baseline to super physiologic levels for you, even if it's not well outside the physiologic range on the lab test.
[SPEAKER_01]: Yeah, I just think like if there are rate limiting steps in response to training and outcomes that are related to testosterone, right, taking more testosterone is going to help.
[SPEAKER_01]: I just think that that rate the level where it becomes rate limiting is far lower than what you see in EHMC.
[SPEAKER_01]: And so by adding just more testosterone to it, you're not really gonna see a benefit until now you're in the super physiological range at that point, this sort of calculus change.
[SPEAKER_01]: That's kind of my thought, that's how I'm rationalizing all of this.
[SPEAKER_01]: I don't know if this is true, I would love a study on, you know,
[SPEAKER_01]: A thousand people with the HMC, you put half of them on TRT and just see what happens.
[SPEAKER_01]: Do they suddenly become world-beaters?
[SPEAKER_01]: Or does nothing happen?
[SPEAKER_01]: My prediction?
[SPEAKER_01]: most people would see nothing happen.
[SPEAKER_01]: And then the people who actually wasn't EHMC was actually test the Austrian deficiency and it was, you know, then they're gonna see response.
[SPEAKER_00]: Yeah, that would be one of the challenges is having more of a heterogeneous mix than you'd like at the outset, because there's not like a single test that can prove to you that that's in fact that it was in fact the HMC versus something else.
[SPEAKER_00]: But anyway, yeah, maybe someday somebody will do that for us.
[SPEAKER_00]: There you go.
[SPEAKER_01]: All right.
[SPEAKER_01]: So a real diagnosis takes the work up that we covered last week.
[SPEAKER_01]: And the drivers we just walked you through tells you what you're actually treating once that work up is done.
[SPEAKER_01]: Most of the time the answer is not necessarily just more to stoster on Austin.
[SPEAKER_01]: Anything you want to add before we wrap this up?
[SPEAKER_00]: I feel like I have repeated a lot of my key messages so far in our episodes of like, you know, talk to the person, listen, get a sense of what their concerns are, their motivations are.
[SPEAKER_00]: and then make sure your evaluation is sufficiently broad and thorough before committing to one particular treatment path.
[SPEAKER_00]: That's kind of my approach to this.
[SPEAKER_01]: Okay, five things to take away from this episode about why a man's testosterone level ends up where it does.
[SPEAKER_01]: 1.
[SPEAKER_01]: Body composition is the single biggest driver, and it runs in both directions.
[SPEAKER_01]: A man with obesity is nine times more likely to be testosterone deficient than a man at a healthy weight, and if you lose weight testosterone level goes up to a 10% reduction in body weight produces an average testosterone increase of 84 nanograms per desoliter, which ELP ones that can push the number up by 20 to 30% and metabolic barrage surgery is usually even higher, it's proportional with the weight loss.
[SPEAKER_01]: 2.
[SPEAKER_01]: Adding testosterone on top of a working lifestyle program doesn't really add any benefit to how the man feels.
[SPEAKER_01]: In the T4DM trial, they put more than 1,000 men through it, half on testosterone, half on placebo, and the quality of life improvements tracked with weight loss, not the hormone levels.
[SPEAKER_01]: The man who's doing the work does not need a prescription on top.
[SPEAKER_01]: Three, sleep is another big driver, mainly because testosterone is sleep dependent.
[SPEAKER_01]: One week of restricted sleep, drop testosterone by 15% in healthy young men.
[SPEAKER_01]: Obstructive sleep apnea is the structured chronic version of the same insult and the wellness clinic almost never ask about it.
[SPEAKER_01]: Or, treatment for sleep apnea, C-PAP, or auto-PAP, fixes the symptoms that most men come in for.
[SPEAKER_01]: It doesn't reliably move the testosterone number on its own, because that number tracks body composition more than a track sleep apnea.
[SPEAKER_01]: Both get treated in the right order by the same kind of program.
[SPEAKER_01]: 5.
[SPEAKER_01]: The opposite extreme produces the same shutdown.
[SPEAKER_01]: Men running aggressive cuts, men in a chronic energy deficit, lifters running high volumes of training on insufficient food, all can suppress the same signal that obesity does.
[SPEAKER_01]: A low normal number in a chronically underfueled, or perhaps even overreached man is a set point.
[SPEAKER_01]: It's adaptive.
[SPEAKER_01]: It's not really a testosterone deficiency.
[SPEAKER_01]: The thick there is more food or adjusting the training program, perhaps both not really exogenous testosterone.
[SPEAKER_01]: If most cases of low testosterone are downstream of something else, then the obvious question is, when is TRT the right answer at all?
[SPEAKER_01]: Look, there's a real population of men for whom TRT is the right call and they're currently under treated.
[SPEAKER_01]: On the other side, there's a much larger population of men who are currently on TRT.
[SPEAKER_01]: when it's not the right call at all.
[SPEAKER_01]: In the next episode, we close the series.
[SPEAKER_01]: What's the actual evidence on TRT?
[SPEAKER_01]: Who needs it?
[SPEAKER_01]: Who doesn't?
[SPEAKER_01]: And what the cardiovascular safety data actually says?
[SPEAKER_01]: Now that we have some evidence on it.
[SPEAKER_01]: Also, what are the fertility consequences?
[SPEAKER_01]: What are those look like?
[SPEAKER_01]: And why do most men who start TRT discontinue it within a year?
[SPEAKER_01]: and the framework that we use at Barbell Medicine to put all of this together.
[SPEAKER_01]: We also come back to Mark because the question of what happens to his number and to him is the question this whole series has been building towards.
[SPEAKER_01]: Episode 404, in our Signal Book series, that'll be in the next episode.
[SPEAKER_01]: Everything we cover today, there's Mosh, the left-and-a-Roma-Tace-Loo, the dose response on weight loss, and there are effects on testosterone levels, T4DM trial, obstructive sleep apnea pathway, low-energy availability reds, it all comes from our upcoming book Signal.
[SPEAKER_01]: podcast gives you the conclusions and the key evidence.
[SPEAKER_01]: The book is where the complete approach, the case studies, the decision trees, and the practical protocols live.
[SPEAKER_01]: Got a man in your life whose numbers don't match the stories being told about them, the book is a thing that we wrote for him, possibly you.
[SPEAKER_01]: I mean, soon, link in the show notes and up ardualmedicine.com.
[SPEAKER_01]: Before you guys go anywhere, please leave us a 5 star rating and a review.
[SPEAKER_01]: It's the best thing that you can do so we can keep bringing you on the latest nuance and health and fitness.
[SPEAKER_01]: I'm Dr. Jordan Feigenbaum.
[SPEAKER_01]: That's Dr. Austin Baraki.
[SPEAKER_01]: We'll catch you next week.
[SPEAKER_01]: And every week right here on the Barbel Medicine podcast.