Is Your Testosterone Actually Low? Why Higher Testosterone Doesn't Do What You Think | Signal Ep 2

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21:12Dr. Jordan Feigenbaum:It feels good to worry less. It feels good to GEICO. If you've been dealing with a nagging injury, if you just came out of surgery, or you work with people who have, I want to tell you about our upcoming pain and rehab seminar in Bozeman, Montana, June 20th and 21st. This is a two-day deep dive into how we actually think about pain, rehab, and getting people back to exercise. We've updated the curriculum this year to reflect where the evidence is right now, with training lectures covering the current recommendations for exercise during injury and rehab, and breakout sessions on exercise modifications and technique tailored to specific individuals.

21:43Dr. Jordan Feigenbaum:This isn't just a powerlifting focused event. The modifications content has been expanded to cover athletes across different sports. So wherever you're meeting your current patients or clients, there's going to be something you can put directly into practice. For example, the lower extremity post-op lecture and the subsequent breakout walks through the full rehab spectrum after surgery with a strong emphasis on the middle phase of training. This is the phase that gets the least attention and causes the most problems. We spend real time on the return to sport criteria and how to structure progressions that actually get somebody there.

22:12Dr. Jordan Feigenbaum:The pain lecture also has new cases this year and is built around helping folks make sense of what they're experiencing. Not just here's what the research says, but how to use that information in a real conversation with a real person who's frustrated and confused and wants to know what to do next. Spots are limited, so if you want to learn more and register today, head over to barbellmedicine.com and look for the Bozeman Pain and Rehab Seminar. We also have a link in the show notes below. All right, welcome back. we were asking about how to read a testosterone lab value when we left off. And the first thing to understand is that a higher number is not automatically better.

22:44Dr. Jordan Feigenbaum:And the reason has to do with a cellular mechanism that most of the online testosterone discourse ignores. For decades, the prevailing belief was that testosterone fueled prostate cancer. Doctors were trained to never give a man with prostate cancer testosterone. The fear made sense. Prostate cells are androgen dependent, more testosterone, more prostate signaling, more cancer growth. But when researchers measured what happens at the prostate as serum testosterone goes up, they found something that nobody had predicted. Above a certain concentration, raising serum testosterone levels further produced no additional rise in PSA and no detectable increase in prostate cancer incidents over decades of follow-up.

23:26Dr. Jordan Feigenbaum:The cellular machinery had a ceiling, and that ceiling has a name. We call it the saturation model, and the threshold sits at roughly 250 nanograms per deciliter. Below that level, raising testosterone moves the downstream signal. Once you cross it, the receptor is already occupied, and adding more testosterone to the bloodstream produces no additional cellular response. Now, the prostate is one androgen-dependent tissue, and the question worth asking is, which other tissues behave the same way? The answer is what most of the wellness clinic industry is built on getting wrong. So libido was the next tissue that researchers asked about.

24:00Dr. Jordan Feigenbaum:Now the Framingham and HIM data sets show that it follows the same sort of plateau. Libido rises with testosterone up until around the bottom of the reference range, and then it flattens. That means a guy with a testosterone level of 600 is not more libidinous than a guy at 400. I did everything in my power to avoid saying the word horny on air, but I just did it so people know what libidinous means. but a guy at 800 does not get better erections than a guy at 500. In dose response trials going back to the late 1990s, researchers gave young men graded doses of testosterone up to 600 milligrams per week.

24:35Dr. Jordan Feigenbaum:This has to do with muscle. Lean mass and strength climbed across the entire range tested. Higher dose, more muscle. But there's a catch here. Those are super physiological doses that cannot be achieved naturally. 600 milligrams per week of testosterone is roughly three to six times of what a standard TRT prescription delivers. But within the normal physiological range, which is the target that a good clinician tries to achieve when treating testosterone deficiency, the additive effect of testosterone on muscle is small to non-existent. A 12-week trial that we'll cover in the next segment tested exactly this.

25:10Dr. Jordan Feigenbaum:They did a standard transdermal dose of testosterone in men who were in the low to normal, low to low normal testosterone range. adding testosterone to a structured exercise program didn't produce more lean mass or more strength gain than exercise alone. And there's a reason at the level of the tissues for this finding. Direct measurements of intramuscular androgen exposure don't scale with blood levels of testosterone the way that most people assume. Muscle fiber sort of regulates its own local androgen environment, which is one of the reasons that men and women see the same relative improvement in strength and muscle mass in response to exercise.

25:47Dr. Jordan Feigenbaum:And it's one of the reasons that acute post-exercise testosterone spikes don't correlate with long-term hypertrophy. And within the physiological range, baseline testosterone levels also don't predict the training response that somebody's going to get. So despite a roughly 10 to 20 fold difference in circulating testosterone levels between men and women, intramuscular androgen exposure is much closer between the sexes than serum levels would suggest. The muscle fiber sort of regulates its own androgen biology, including the capacity to produce androgens locally from precursors like DHEA. Now, a 2025 NHANES analysis of adult men found that serum testosterone didn't correlate with measured strength.

26:27Dr. Jordan Feigenbaum:There was a cross-sectional association with muscle mass, but that runs both directions in observational data sets like this. Men with more muscle tend to have less fat, and they tend to have better metabolic health, and a higher SHBG, all of which raise the testosterone reading independent of any causal effect of testosterone on muscle. The finding that holds up is the strength dissociation. Pushing the testosterone number higher does not push the strength number higher. So Austin, here's the patient this whole segment is aimed at. A guy walks in, his total testosterone is 480 nanograms per deciliter, right in the middle of the reference range.

27:03Dr. Jordan Feigenbaum:But he's convinced that 900 is the target to optimize. How do you walk him through the sort of saturation model, if at all, without making him feel like you're talking down to him.

27:14Dr. Austin Baraki:Yeah, challenging situation. And I probably wouldn't get into the details or the weeds of a saturation model unless I can tell by the way the person is talking to me that they themselves are very much down in the weeds. And some people, depending on their background, their level of education, how hard they go on the nerding out on this stuff, they may actually want to converse on that level, but most people don't. And so once again, I'll begin with, hey, tell me the context here. Why was this checked in the first place? Did you have any symptoms that were concerning to you? Like, what's the goal here that we're trying to achieve?

27:46Dr. Austin Baraki:And then from there, really, I'm going through something else we've talked about on the podcast before, just like the concept of belief change. And I'm not here to like, neuralize this guy and like, inception him with different beliefs about this, but rather trying to get to the core of like, what is driving him to believe that he has a problem right now? What is driving him to believe that 900 would be better? And what is the ultimate goal of, you know, pursuing that target? And I may, you know, quote unquote, win by getting him to grasp that, hey, if he feels well, is performing well, doesn't have any signs and symptoms of disease, then this is probably like his natural equilibrium based on combinations of how much testosterone he produces, his receptor sensitivity, his SHBG levels.

28:28Dr. Austin Baraki:These things do tend to equilibrate out based on those variables in a given person. And this is maybe his settling point, so to speak. But if he does have signs or symptoms of disease, I might point out a few examples of, hey, what if this is something else entirely that is being missed here? Have we considered that there are other possible causes or contributors? And it would be foolish of me as like the physician who's here charged with, you know, your care, your health, to just myopically look at one number and potentially miss other things that could be contributing. You know, I've had patients, for example, before who had some, you know, maybe some fatigue, and maybe they were worried about their testosterone, which was definitively in the normal range, and then missed that they had, as I've talked about before, iron deficiency.

29:12Dr. Austin Baraki:And it's like, if you're a middle-aged person and you're feeling that, oh my gosh, like what if there's a colon cancer leading you to have iron deficiency and anemia? And meanwhile, we're looking at just treating a testosterone number to make it look higher because bigger number sounds better, you know? And so ultimately it's gonna be a belief change sort of conversation. And when I say belief change, again, my goal is not necessarily to change as belief, but rather to understand where these are coming from and to see as part of the conversation if we can kind of come into a little bit better alignment.

29:39Dr. Austin Baraki:If the person has no signs or symptoms whatsoever and has a testosterone level of 480, then they under no circumstance do they meet criteria for like testosterone deficiency that would merit hormone therapy. In which case, if the person is adamant and they really want to get that level of 900, then they're basically saying, I would like to use anabolic steroids basically, right? And there are ways out there that people go and get that, but that would not be a scenario where I would recommend it or be, be prescribing it for like medical therapeutic purposes.

30:10Dr. Jordan Feigenbaum:Yeah. I think, and you probably see this all the time here. We live on online chronically, you know, there are practitioners of varying levels of expertise. It is almost like an advertising hook. It's like, we've got to optimize your testosterone level. Whether they blatantly say, no, it's gotta be high, you know, 800 to 900, or they say, well, it's for you, wherever you feel the best. But I think this misses a lot of the nuance around this. Like there's no single level that's best, right? And then the experiences you're attributing to a particular level are generally speaking multifactorial, right?

30:45Dr. Jordan Feigenbaum:Especially the less specific the signs and symptoms or the experience is if we're talking about fatigue. For example, it's like, well, think of all the things that can make you tired or not, right? If we're talking about performance in the gym, think about all the things that can go into that. Same thing with sexual health, so on and so forth, right? The more multifactorial the symptoms or signs are or the experience that you're trying to achieve, the less that the single number is going to reflect that. But that's not a great advertisement for your services, particularly if it revolves around testosterone replacement therapy.

31:15Dr. Jordan Feigenbaum:They're like, we've got to optimize you. And it's like in the back of your head, you're like, what is the optimal level? After studying this for a long time, like, you know, we both know that there are no single level. So what do you think when you see an advertisement like that?

31:28Dr. Austin Baraki:yeah i mean i think about it's like a it's like this weird level that is put on a pedestal because imagine we just mad libbed this and substituted testosterone with another physiologic parameter right like glucose or blood pressure what is what is the optimal glucose level and you know when i draw my lab tests and that's the glucose that i see and i want it to be lower and you know to most folks who are listening be like obviously your glucose is going to go up and down all the time based on a variety of things you know whether you're fasted fed what you ate your levels of activity, your sleep, all sorts of other things.

31:59Dr. Austin Baraki:And it's like, yeah, turns out it's the same thing here. And so then we also see people, for example, seeking to quote unquote, optimize their glucose levels and using things like CGMs to guide their behavior to for unclear, you know, ultimate health outcomes, especially if they if they don't have a diagnosis of type two diabetes, I recognize there are some people who like to use them for because they're, you know, geeking out on the data, or they feel like it helps them make particular food choices. There's not really, you know, long term from evidence of concrete health benefits from such a thing.

32:30Dr. Austin Baraki:And so I'm not by any means suggesting that I would enjoy this or prefer it. In fact, it would probably be more of a nightmare than anything else. But I can't help but think that if we had instead of CGMs, like CTMs, continuous testosterone level monitoring, like people might recognize at least how much more variability there are in these levels throughout the day, day to day, minute to minute, hour to hour, and maybe put a little bit less stock in like a single blood, you know, a snapshot blood draw in that way, right? Because there's a lot of appropriate physiologic and yes, sometimes pathologic fluctuations that can happen in these levels.

33:05Dr. Austin Baraki:And the kind of the net exposure to it over time within a reasonable physiologic range means you're probably fine. And so not over medicalizing it is something that I think we're both in favor of.

33:17Dr. Jordan Feigenbaum:Yeah, yeah, there's a lot of just, I guess, I don't know if they're just conditioned beliefs and where those conditioning come from. Is it society? Is it the medical establishment? Is it, you know, whatever, that again, higher is better. And it's four things that people really do seem to care about, whether it's sexual health, whether it's gains in the gym. And I just think overarchingly, when you look at the normal physiological range, you know, that is captured with a laboratory test, that if you're in that normal range and and we're talking about non-specific symptoms here there's really just not a good correlation between getting towards the higher level or trying to achieve that specifically through like a medication for example where things get better rather getting to a higher level generally reflects better health and so you don't need a testosterone lab value to get you to do that stuff where it is you know reducing visceral adipose tissue being more active sleeping well, having good interpersonal relationships, having a health promoting diet, like you should have been doing that stuff already.

34:17Dr. Jordan Feigenbaum:We don't need a lab, a testosterone test to, to motivate you. But if that functions as a behavior change sort of tool, like testing testosterone is cheap. I'm just more concerned that people get a weird reading and then have to go down a further workup and maybe some inappropriate treatment. Does that make sense to you? Yeah. I mean, we see it all the time. So yeah, I agree with that. Yeah. So we're talking about the number itself. Now, look, if the receptor saturates around 250 nanograms per deciliter, specifically for the prostate, and getting a normal man from like 500 to 900 doesn't change what the tissue is actually seeing with respect to like libido, muscle mass, and so on and so forth.

34:52Dr. Jordan Feigenbaum:The reference range itself is worth a closer look. What does the endocrine society 264 nanogram per deciliter cutoff actually define? And what does within normal limits or low actually mean on a lab report? Now, as you might remember, the endocrine society lowered their lower limit of normal from 300 to 264. This is basically a result of the testing change going from immunoassays to mass spec. Basically, as we covered on last week's podcast, or the first episode of this launch series, when researchers re-ran stored samples that they previously flagged as low using immunoassay tests, and they used the a newer technology that's more accurate, mass spec testing, more men fell below 300 than the older assays had said, basically doubled.

35:38Dr. Jordan Feigenbaum:Now what the reference range actually is, is a distribution of values that are observed in an apparently healthy men on a validized test like this. It's not a target. A number inside the range doesn't rule out symptomatic testosterone deficiency. And a number below the range without symptoms and a confirmatory secondary draw, that doesn't establish a diagnosis either. So comparing a lab value to the established range is a starting point for interpretation. That's really the point we're trying to drive home here. The interpretation itself requires symptoms, a second confirmatory draw, and the rest of the workup which also requires more thinking.

36:14Dr. Jordan Feigenbaum:So Austin, here's a scenario you probably see very often. The total testosterone of a guy comes back at 285 nanograms per deciliter, technically above the endocrine society's cutoff. Now a lot of clinicians would read that number right within normal limits in the chart and move on. What are you doing differently there outside of asking them, hey, why did you get this drawn and what are the symptoms? Yeah, you preempted me there.

36:37Dr. Austin Baraki:Yeah, I like to think that I'm firing some more neurons again in this type of situation. I think it is poor practice, insufficient to just look at the number, compare it to that reference range, say normal and move on abruptly. And the main reason is that that number alone does not exclude the possibility that this person may benefit from some intervention, be it related to their health in general or to their testosterone level in particular. And ultimately, what is the point of a lab test in general? Like we'll get in big picture philosophy here. What is the point of testing? It is to give us information that may plausibly lead to differences in management strategies, how we might do something, might lead us to do something differently than we may have otherwise done by giving us that additional piece of information that we did not have before.

37:29Dr. Austin Baraki:And so here's a situation where if I have a symptomatic person and I have a lab level at 285 and perhaps they have other risk factors for testosterone deficiency, maybe they have obesity, maybe they have some metabolic syndrome, maybe they have, you know, sleep apnea or they are at high risk of sleep apnea. And so this is a scenario where I could potentially pair it with checking a SHBG level and getting a sense of, is this just a low total with a normal free or bioavailable? Is this somebody who has definitively low free testosterone levels, which is the thing that tends to actually correlate a bit more closely with symptoms, and which symptoms in particular are they concerned about?

38:07Dr. Austin Baraki:Because the picture has to be coherent. It has to make sense what symptoms they're worried about, what signs they're worried are those even related to blood testosterone levels at all? And then other options that I might have would be just rechecking things. That's something I do pretty often when I have a lab test that is kind of in a vague range or in a gray area, and I'm wanting to try to kind of adjudicate or get higher quality data overall to make my clinical decision. So I have a few options of next steps there, but the reason why I might not automatically say in range normal and move on is because of the concept of pretest probability.

38:43Dr. Austin Baraki:If I checked this test for a, what I would deem to be a valid reason, meaning I had suspicion that it might be low and it comes in at this type of range, then my suspicion is kind of justified here to an extent, right? If I had no reason to check it, then, and I get this value, it's harder to interpret there, right? But if my suspicion was high and it's in this range, then I'm not just going to dismiss it and move on because ultimately what I care about is not the number, but is this patient somebody who may plausibly benefit from intervention and i have an array of interventions that i might offer and that includes the potential of testosterone therapy because when even when it comes to offering somebody the treatment the question is like what are you most afraid of like what catastrophic risk are we being faced with if i were to offer a particular trial of therapy to this person and the risks as we'll get to later on are like not insanely high right so if the person plausibly may benefit and i have enough supporting evidence, it may be worth a shot if I have, you know, sufficiently thought about this underlying causes address those things.

39:45Dr. Austin Baraki:So that's why I would think a lot harder about this value, especially in somebody where what I call my like pre-test probability, where I had a high suspicion of like, oh, this person's certainly at risk of having testosterone deficiency. I'll think about it harder before just saying app in range, move on, because then you lose people, they feel dismissed, my doctor didn't listen to me. And then they end up seeking care from other, you know, practitioners who may also not do very much thinking, but in a way that just leads them to write a script.

40:10Dr. Jordan Feigenbaum:Yeah, that makes sense. Yeah, I think overarchingly, again, a lab value is only the first piece of a workup. It doesn't make the diagnosis on its own. All right, so that handles the lab side of the diagnosis. The other side is symptoms. And there's a study that most men have never heard about, which symptoms actually point to low testosterone and which ones they've been told point to it, but don't. Here's what that is. We open the episode with the top line finding from the European Male Aging Study. Three of 32 commonly attributed symptoms actually correlate with low testosterone, and all three are sexual.

40:43Dr. Jordan Feigenbaum:Let's walk through what that study actually tested because the finding only lands once you see what was being asked. More than 3 ,000 men across eight European centers, they were aged 40 to 79. The researchers cataloged 32 different complaints commonly attributed to low testosterone and correlated each one against total testosterone, free testosterone, and LH. Three correlated at a statistically significant and reproducible level. Decreased frequency of morning erections, decreased frequency of sexual thoughts, and erectile dysfunction. The other 29 symptoms did not survive the analysis. They either didn't reach statistical significance or they disappeared when adjusting for age and medical comorbidities.

41:24Dr. Jordan Feigenbaum:Now this isn't the same as saying those symptoms aren't real. They certainly are and men experiencing fatigue, low mood, brain fog, etc. They're experiencing something and it deserves attention. What this data does tell us is that those symptoms have many other possible causes besides low testosterone. A man who walks in saying, I'm tired, I can't focus, I don't feel like myself, has symptoms that can be produced by at least a dozen other things before it even gets to testosterone. The usual suspects here are things we've talked about all the time. Poor sleep, untreated metabolic disease, depression, chronic stress, alcohol use, medication side effects, and so on.

41:58Dr. Jordan Feigenbaum:The wellness clinic funnel runs on that mismatch though. The symptom profile that drives men through the door of one of these clinics is the profile least specific to the condition that they're being treated for. Now the guidelines are stricter than that and they're what we should probably follow. The guideline standard requires two different diagnostic elements. Thing one, symptoms that are consistent with testosterone deficiency weighted towards the sexual symptoms because those tend to carry the highest or most robust diagnostic signal. The second is biochemical evidence on a correctly drawn morning sample with a confirmatory second draw on a different day.

42:34Dr. Jordan Feigenbaum:This is because the Massachusetts male aging study data that we covered last week shows that roughly half of initially low values will normalize on repeat testing without any sort of treatment. So Austin, you've got a patient that shows up with a list of 10 symptoms that he's already convinced are due to low testosterone. How do you walk him through any of this without sounding dismissive of what he's actually experiencing?

42:56Dr. Austin Baraki:Yeah, totally validate what the person's experiencing first because these symptoms are extremely common. And it's not that the person is making up what they're feeling. and based on the homework that they have done prior to their clinic visit, perhaps they have been funneled down certain algorithmic routes on the internet that led them to kind of suffer a common cognitive error that we see in medical trainees called premature closure. And that cognitive bias leads you to just fixate on one possible cause to the exclusion of other possible causes. And it leads to commonly diagnostic error. And in like my world, in like say hospital medicine and then things like that, a lot of harm can come from that.

43:38Dr. Austin Baraki:If somebody's like, oh, it has to be this, it can't be anything else, and then they just pursue that route, and then only on the back end when something goes really wrong do you realize, oh, I missed this alternative possibility all along. The stakes here in the short term are not nearly as high in terms of risk of death as I might see from something like this in the hospital setting, but the long-term stakes remain relatively high. If, again, somebody misses symptoms of an underlying malignancy, for example, and attributes the general nonspecific symptoms to testosterone as an example. And so I'm not wading through the nuances of clinical research studies like this with the patient, but rather pointing out that, hey, totally valid what you're feeling and certainly we'll work together to try to get to the bottom of it.

44:22Dr. Austin Baraki:I would suggest that we kind of cast a wider net. It is possible that testosterone could be related to your symptoms, whether directly or indirectly, because something else is causing both testosterone impacts and these other symptoms. So, you know, my job is to, you know, think about this really hard and try not to miss anything that could be going on, to think comprehensively about this. And if there is some underlying kind of cause that we can identify to target that, while also, you know, addressing the person's concerns along the way. So that would be kind of how I would go about it. And most people are really readily on board with something like that.

44:54Dr. Austin Baraki:Very few of them are like, no, I don't want you to look at anything else just look at this but sometimes it takes a little bit of explaining of like look the list you know my uh my job my specialty is coming up with long differential diagnoses which i'm very good at and so i'm happy to do that for the person and point out that like there's a lot of things that could be going on here and if it were me and if it were my health i would want a more thorough look at those different possibilities rather than just fixating on one thing but you're right that the the emphasis i don't know if emphasis is the right word, but the specificity in terms of symptoms.

45:25Dr. Austin Baraki:If somebody who has previously experienced a normal libido subsequently reports a loss of libido, that is one of the more suggestive and even more arguably specific symptoms that people can have outside of like extremely early testosterone deficiency where somebody like never goes through puberty or something, but that's more of a pediatric world type thing.

45:43Dr. Jordan Feigenbaum:Yeah. Yeah. I imagine, you know, as you get more information on the, the person's, you know, history of present illness, and you go through your review of systems and everything else, it's tending to lead you in a particular direction as far as how wide the net needs to be, right? And I assume, you know, things might pop up that would flag you to really, really broaden it and versus narrow it. But yeah, it would be very unusual. You got a person who says, look, I'm tired every day, I feel irritable. And then you find out their blood pressure is elevated, and they do have some, some obesity, for example, and they're experiencing some of these, what we would call like non-specific symptoms that could be attributed to testosterone deficiency, but not necessarily only attributed to testosterone deficiency.

46:25Dr. Jordan Feigenbaum:And you're like, look, it could be testosterone deficiency, but I'm leaning a little bit more strongly towards obstructive sleep apnea. And I think we need to evaluate you for that as well. And they say, no, I don't want any evaluation for that. That would be unusual. I suspect that hasn't happened to you personally that often because your clinical, your bedside manner is better, but I imagine it has happened before.

46:49Dr. Austin Baraki:Yeah, it just depends on how you frame it. If the person feels dismissed and not listened to, then it's going to immediately set up an adversarial relationship, which I go out of my way to not establish with patients. I kind of am, I'm the person who asks an open-ended question at the beginning of the encounter and shuts up and lets them speak. And I'm reading a lot of what they're saying and how they're saying it to get a sense of, has this person already come in with a bunch of prior negative experiences with other doctors, for example? And am I going to have to tread a little bit more carefully?

47:16Dr. Austin Baraki:Are they coming in mistrusting right off the bat? Are they coming in motivated to a particular end right off the bat? Or are they very open and wanting a collaborative relationship? You know, do they already know anything about me and have expectations from that standpoint? So there's all sorts of things that I'm trying to like, you know, listen to the words they choose, the way they say things and see if I can glean that additional information from them. And if not, then sometimes I might just ask outright, like, what have your prior experiences been with this working with other folks or have you worked with other folks about this?

47:43Dr. Austin Baraki:Because that can all be valuable information to me to determine like, what are this person's expectations and how can I best meet them to lead to, you know, benefit and not cause them harm?

47:53Dr. Jordan Feigenbaum:Yeah, it's hard to get good clinical outcomes when you have no therapeutic alliance because you just violated that immediately. Right. But let's say, yeah, you work with the patient and you've come to the conclusion it's reasonable to draw their testosterone because it is part of your broad net. So how do you go about doing that? Well, the first lab, when you're measuring testosterone, first thing, it needs to be done in the morning. Ideally, between 7 to 10 a.m., testosterone peaks in the early morning and falls across the day. The reference ranges are built off morning data, so you don't measure it in the afternoon.

48:24Dr. Jordan Feigenbaum:Now, that said, testosterone levels do go up a little bit, not quite as high as they normally do in the morning, about eight hours after waking. There's some thoughts with body temperature rhythms and things like that, but this is kind of the basis for why some individuals have said, you should work out at this time in the afternoon to maximize results because your testosterone levels are a little higher interestingly they tend to not recommend waking up working out first thing in the morning when the testosterone levels are even higher all right but based on what you know about testosterone levels intramuscular testosterone levels and then ultimately how the differences large differences again between like men and women and how they affect exercise outcomes you already know this is bogus so part two it doesn't need to just be in the morning you also need to be fasting because eating a meal tends to raise your blood glucose transiently for a short period of time, which can lower total testosterone.

49:13Dr. Jordan Feigenbaum:It also should not be drawn while somebody is presently ill, some sort of, you know, what is a respiratory virus, other sort of illness generally that will lower testosterone levels should not be coming off a run of bad sleep. If that can be avoided, let's imagine a scenario where a person's very motivated to get a TRT prescription and so they come in they went on all night bender uh you know didn't sleep drank a bunch they might even be sick on top of that and they're like i'm ready for this lab and they eat right beforehand um that'd be a way to artificially suppress your testosterone level and i suppose if you did that twice you know on the repeat draw and it would be some you'd have some interesting like lh and fsh data alongside of that but you could have two low testosterone levels but if the first one is low, then you've sort of bought yourself in some cases, depending on the clinical context, a more expansive sort of hormonal workup related to that low level of testosterone.

50:09Dr. Jordan Feigenbaum:So you repeat the test on a separate morning under the same conditions. So between 7 to 10am, fasted, not sick, not underslept, etc. And then you add on LH, FSH, SHBG, and potentially some other things like prolactin or whatever, depending on the clinical context. So you get a second trip to the lab with this more expansive diagnostic panel. Now again, we know that roughly half of initially low total testosterone levels will normalize on repeat testing without any sort of treatment. That's why this sort of confirmatory draw matters. Now, if the repeat draw confirms the first, LH and FSH can localize the problem.

50:44Dr. Jordan Feigenbaum:So is it located at the level of the testes? Or is it somewhere in the brain? Is it somewhere else? And if you get an SHBG, that can tell you whether the total testosterone value may be misleading because of the binding protein being abnormal. So you may also choose to get a free or bioavailable testosterone as a follow-up sort of step. This is usually reserved for cases where the SHBG comes back abnormal or the total doesn't really match the clinical picture and you need that extra bit of information to make a decision. Although again, as you mentioned, this sort of trial of testosterone replacement therapy is not really high stakes in the short term, but longer term it certainly can be.

51:24Dr. Jordan Feigenbaum:So why does this matter? Well, many wellness clinics default to prescribing TRT off a single afternoon total testosterone. People will go in the labs, 3 p.m., get a lab draw. Oh, testosterone's low, boom, earned yourself a prescription. That's one draw the wrong time of day, no ancillary labs, no symptom workup, no confirmatory repeat. The prescription comes out of the printer before the patient had a real evaluation, which is obviously part of the business model. I mean, we said this, less than a quarter of people actually had a testosterone level drawn before they received a TRT prescription.

51:55Dr. Jordan Feigenbaum:And it gets worse, half of people after they've been prescribed TRT don't have a level within the next year to confirm they're at the right level. And with that in mind, let's ask a different question. When standard TRT is prescribed properly to a man in this exact demographic at the right dose with the correct workup behind it, does it actually deliver what the wellness clinic is promising. There's one trial that tested this directly with respect to muscle mass and strength outcomes. So in this 12-week study out of Australia, 80 men in their 50s and 60s, the exact demographic a wellness clinic is marketing to, they all had low normal testosterone, which admittedly is arbitrary.

52:34Dr. Jordan Feigenbaum:There is no like specific cutoff for low normal. But in this particular study, the average testosterone level was 320 nanograms per deciliter. They all had a decent amount of visceral fat, right? That's the fat that surrounds your internal organs. They all had waist circumferences of 37 inches or more, signifying they did have some visceral adiposity. And they were split into four groups. One group got testosterone alone. Another group did exercise alone. A third group, this is the smiley face group, got both. And then the fourth group, this is the frowny face group, they got neither. The testosterone was the standard prescription dose, so not a higher PED level dose.

53:10Dr. Jordan Feigenbaum:Now, after 12 weeks, the exercise groups improves significantly. roughly a 10 to 13 percent improvement in aerobic capacity the testosterone alone group there was no improvement in aerobic fitness so adding testosterone on top of exercise added nothing beyond what exercise was already doing with respect to muscle mass both testosterone and exercise produced gains independently and combining them looked directionally better than exercise alone but it didn't achieve clear statistical significance at 12 weeks for strength, exercise was the driver across every measure tested. Testosterone alone did not move the strength needle and the combination didn't beat exercise alone.

53:53Dr. Jordan Feigenbaum:Now the author's direct conclusion, exercise should be evaluated as an anti-aging intervention in preference to testosterone in middle-aged men with low normal testosterone levels. Now there are a few caveats here and this is the last point. I really wanna get your take on this, Dr. Baraki. so this is one relatively well-designed trial but the broader testosterone plus exercise literature is kind of a mess not a mess because people aren't doing these studies well but they use different doses different populations different durations and so the results are not quite as clean this particular population was low normal not testosterone deficient but for a man with truly hypogonadal or testosterone deficient levels the calculus is clearly different here Next, 12 weeks is short.

54:35Dr. Jordan Feigenbaum:It may take longer for a significant difference between combined therapy, testosterone exercise to show up compared to exercise alone. Also, they were using a standard prescription dose, not a super physiologic dose where there is a dose response relationship between muscle and testosterone exposure. And testosterone alone did beat placebo for lean mass in men who could not exercise. And so for that population, testosterone may have a real, if not modest role. But for the man who can train, the trial says that the training's doing most of the heavy lifting, pun intended. Now, here's the final point.

55:09Dr. Jordan Feigenbaum:I wanna get your take on this. Hard training itself can suppress testosterone levels. This flies in the face of people saying, oh, you gotta exercise to boost your testosterone levels. Now, to the extent exercise reduces somebody's visceral adipose tissue, sure, you can see an indirect increase in testosterone, but lifting weights itself or doing high intensity interval training, sprints, whatever, does not raise baseline testosterone levels on average. The exercise hypogonadal male condition, EHMC, is a well-documented sort of example of this, particularly in endurance athletes, although there's similar adaptive suppression that likely shows up in people lifting weights for high volumes, and specifically if they're not eating enough.

55:51Dr. Jordan Feigenbaum:Now, a man who's low normal reading is an adaptation to their training load. Rather than just a sort of baseline deficit, it. That's a different patient than the men in the study we just discussed. And if they were to receive a standard prescription dose of testosterone replacement therapy, well, that might be like a PED for them rather than just replacement because it overrides the sort of trained down set point that the person is experiencing. We don't have a trial that tests any of this, but it is plausible. How do you think about that, Dr. Baraki?

56:23Dr. Austin Baraki:Yeah, I think you've made a good case for why this is so messy and further supports the need to think instead of just to look at look at the number and draw conclusions based on that number alone because to your point taking people who are quote-unquote low normal who may or may not have had clear you know associated signs or symptoms meaning that if they were not you know confidently or clearly testosterone deficient they may well have been on like the the flatter part of the curve in terms of the interaction between their testosterone levels and their physiology. And bumping them a little bit further up along the flat part of the curve is unlikely to have a substantial difference in their outcomes, which is kind of what was observed here.

57:05Dr. Austin Baraki:And this is not even to say anything about other caveats about like, you know, how strength testing is done in research and all sorts of things like that, right? But I think that the lower the testosterone level goes all the way down to levels of undetectable, which I've mentioned a few times before, I've seen in practice, but usually in patients with like, you know, advanced HIV, AIDS infection or something like that, the lower that level goes, the more suggestive and specific of symptoms the person has, the more likely they are to benefit from therapy. And that's about as far as I can go with this.

57:37Dr. Austin Baraki:It is a spectrum of likelihood of benefit. And it is, that is, I know, frustratingly hedgy or like vague in a sense, but that's the clinical reality is we cannot always with 100 % confidence predict who is or isn't likely to benefit based on a single blood level, right? That's why there has always been such controversy around like, where should we set the cutoff? Is some guidelines say 350? Some say 300, some say 264. It's like, if there was a single cutoff that reliably differentiated somebody who is likely to benefit from somebody who isn't, that would be the cutoff. But that doesn't exist because not only are these cutoffs, it's a single point on a spectrum, a continuous spectrum, but also different people arrive at their blood level in different ways.

58:22Dr. Austin Baraki:And as we have also mentioned, the blood testing itself is fraught of time of day and interfering factors and things like that. So that's why this is so messy. That's why this, you know, if you throw a bunch of people in a study and you give them, you know, a method of testosterone administration, I believe you said it was transdermal here, which can be a little bit, you know, less reliable in terms of its effectiveness, then yeah, you're going to come out with a messy and mostly unhelpful result outside of reinforcing what we already knew, training is good for you, right? So I think that if you want to answer a very clear, concrete question, you need to have very rigid criteria for who you're going to put into a study, but then the downside of that is on the back end, your results can only be applied to that exact population and it should not be extrapolated kind of beyond that, right?

59:09Dr. Austin Baraki:So those are my thoughts here is it's just super messy And again, reinforces the need to like think about these things beyond just a single blood test alone.

59:18Dr. Jordan Feigenbaum:Yeah. Yeah. I think if you had like a hard training person and they were quote low, low normal, wherever you wanted to arbitrarily make that cutoff. Right. And they didn't have any other symptoms outside of just this, you know, biochemical evidence of their testosterone level being maybe lower than you thought it was. Like, for example, if you had your testosterone level drawn and it came back at 300, right? You have no other symptoms. It just has this low number, low normal number, right? And then we put a person like you on TRT. It's like, well, you didn't need the replacement. So is this actually like a PED for you?

59:50Dr. Jordan Feigenbaum:Because you were previously like, again, turned down and now it's a little higher. I mean, that's plausible. We'd have to test it, right? To say it with confidence, but it does seem plausible to me.

59:59Dr. Austin Baraki:Yeah, I think that's part of why. Because I see patients for this sort of thing all the time and do these consultations with folks who have either are either, you know, testosterone therapy curious or who have been on it and wanted to get my my input on things. And I have lost count of the number of times I have a guy who maybe has followed, you know, in the in the lifting space who maybe got inundated probably again, algorithmically at this point with messages around this and decided to give it a shot. Maybe he is in his 30s or 40s and he got his level checked and it was, yeah, like 380 or 400.

1:00:30Dr. Austin Baraki:And he's like, I'm under the impression that my levels at this age are supposed to be 800. So I actually tried and went and got on some testosterone therapy because it's not terribly difficult to find. And then, and then they end up, I can think of many cases off the top of my head. They're like, I had this like debilitating anxiety. I had severe, you know, acne outbreaks. I disrupted my sleep. I felt way worse. And it's like, well, you were probably on like very super physiological levels because you may not have actually needed it in the first place, which makes much more sense compared with people who are clinically deficient, truly testosterone deficient, who feel substantially better when they're replaced to appropriate levels compared with feeling like way, way worse, which I've seen many times enough to where they would discontinue therapy.

1:01:11Dr. Austin Baraki:And those are the people who kind of get disillusioned with things, but it can certainly go in that direction. And that is a plausible explanation for me of like they were at their kind of natural equilibration standpoint based on their life, their training, their sleep, their receptor sensitivity, their intramuscular levels, all those sorts of things that are play a role in the ultimate feedback cascade. And so getting on therapy for them was just like straight up going on anabolics instead of, you know, replacing to a physiological level that they didn't actually need.

1:01:39Dr. Jordan Feigenbaum:Yeah, yeah, I think we're both coming, you know, at this and arriving at the same point where if a person is overtly low and we're talking, whatever outcome we're talking about, whether it's libido, whether it's muscle mass, strength, etc., replacing the testosterone to get it to what would be the normal physiological range is going to, they're going to see improvements there. Then there's a big flat spot within this sort of normal physiological range with the, where, where the reference range of the lab, there's a big overlap there. It's not a perfect circle, right? But the Venn diagram, there's a lot of overlap there in that range, adding more testosterone to shift you to the high normal versus in right in the middle versus low normal, probably is not going to have a big effect.

1:02:22Dr. Jordan Feigenbaum:But when you go above that range, now you're frankly, super physiological levels, the calculus changes. Yes, there is now a dose dependent relationship between testosterone exposure and muscle mass and strength. But it incurs a whole nother set of risks. And you know, that also come along with that. So it's sort of like a three different levels, if you if you will here. But overall, I think we're saying the same thing. A real diagnosis takes the symptoms weighted towards the sexual complaints, a correctly drawn morning testosterone level confirmed on repeat and a workup for reversible drivers, not a list of nonspecific symptoms and a single afternoon draw that the wellness clinics seem to thrive on.

1:03:02Dr. Jordan Feigenbaum:Austin, anything else you want to add before we wrap this up?

1:03:05Dr. Austin Baraki:Yeah, just to reiterate that final point that you made of it being kind of like a Venn diagram. Again, that there is not a single isolated blood level that can reliably distinguish the person who stands to benefit from someone who doesn't. That's why I retain kind of an open-mindedness around those sort of borderline levels, depending on my pretest probability and what the person's symptoms are. So if their level is above that, you know, say it's slightly above that 264 threshold, but they have like very suggestive symptoms, then yeah, maybe a trial is perfectly reasonable sort of thing. Maybe there's somebody who, if you, you know, bump them up a bit and they end up reporting that they feel dramatically better, it's like, okay, then we're probably on the right track.

1:03:45Dr. Austin Baraki:But I've also, again, seen people who were, you know, in similar ranges, say in like, you know, low to mid 300s or something like that, who thought it was lower than they wanted to be who tried treatment, and they actually felt substantially worse. And it stands to reason that that person probably was not clinically low beforehand. And they ended up super physiologic and dealing with some negative consequences of that. And so, you know, I'm not overly rigid about this in practice, but I definitely, you know, I think the take home point here is like, understand why you're testing. And then if you do get testing, you have to be able to think really hard about it to try to interpret it and then rule out other possibilities or incorporate other possibilities in your management plan at the very least.

1:04:24Dr. Jordan Feigenbaum:Here's what a man worried about his testosterone should take away from the episode. One, testosterone is produced by a signaling loop with at least three places it can fail. A single total testosterone value tells you almost nothing about where in the loop the problem is. Without LH and FSH to localize it, low total testosterone is a symptom with an unknown cause. Two, the number on your lab report, well, it's mostly measuring the fraction of testosterone that your tissues can't use. About 2 % of circulating testosterone is free. The rest is bound to proteins. And your interpretation of total testosterone versus free testosterone depends on SHBG.

1:04:56Dr. Jordan Feigenbaum:And SHBG is the binding protein routinely ignored by the wellness clinic workup. Three, the antigen receptor has a ceiling on what serum testosterone can do for it. For prostate function, libido, and erectile function, the gains plateau within the lower end of the reference range. Pushing a man's total testosterone from 500 to 900 doesn't produce more effect on the things he's chasing. The chase a higher number framing sells treatment without delivering at the receptor. Four, of the 32 symptoms commonly attributed to low testosterone in the largest prospective study we have, only three reliably correlate with it.

1:05:29Dr. Jordan Feigenbaum:All three are sexual. Fatigue, brain fog, irritability, and low meat are real and they deserve attention, but they're not reliably produced by low testosterone specifically, which means that treating them as if they are produces the wrong decision most of the time. Five, a real diagnosis takes symptoms weighted towards sexual complaints, a correctly drawn morning total testosterone that's confirmed on repeat, and a workup for reversible causes. The current system often stops at non-specific symptom list and a single afternoon draw. If the single number is not the diagnosis, and most of the symptoms men blame on their testosterone are not actually produced by it, The next obvious question is, what is producing them?

1:06:06Dr. Jordan Feigenbaum:And when testosterone really is low, what drove it down? Next week, we get into the causes, the specific modifiable reasons a man's testosterone ends up where it is. And we come back to Mark, because the thing that produced his 240 nanogram per deciliter level is not a testosterone problem at all. It is a condition his wife has been complaining about every night for years. His wellness clinic probably never asked. You probably know someone who has it. Episode three of four in our Signal Book launch series. We'll see you next week. Everything we covered today, the HPG axis, the saturation model, the EMAS data, the Chaslin trial, the evaluation standard, comes from our upcoming book, Signal.

1:06:41Dr. Jordan Feigenbaum:The podcast gives you the conclusions and the key evidence. The book is where the complete diagnostic approach, the case studies, and the decision trees live. If you have a lab report on your kitchen counter right now, and you're trying to figure out what it means, this book is the thing we wrote for you. Coming soon. Link in the show notes and at barbellmedicine.com. Before you go anywhere, please leave us a five-star rating and a review. it's the single best thing you can do so we can keep bringing you all the way to this nuance in health and fitness. I'm Dr. Jordan Feigenbaum. That's Dr. Austin Baraki.

1:07:07Dr. Jordan Feigenbaum:We'll catch you next week and every week right here on the Barbell Medicine Podcast.