FoundMyFitness - #106 How To Increase Your Testosterone Levels Naturally | Derek from MPMD

Starting point is 00:00:00 Welcome back to the podcast. Today we're exploring one of the most influential hormones in human health and performance, testosterone. Joining me for this comprehensive conversation is Derek, founder of the popular YouTube channel, More Plates, More Dates, and co-founder of Merrick Health, a company focused on personalized preventative health care. Derek and I recently spent an intensive eight-hour session together in Vancouver recording back-to-back podcasts where I joined him as a guest and he joined me. Today, you'll hear a deep dive into testosterone addressing critical topics like testosterone's fundamental roles in men, including muscle mass, bone density, mood regulation, libido, cognitive function, and aging.

Starting point is 00:00:39 How testosterone is accurately measured, interpreted, and optimized, including distinctions between total and free testosterone and why these nuances matter, identifying symptoms and underlying causes of low testosterone, and understanding why two individuals with similar hormone levels may experience vastly different health outcomes. Lifestyle factors that significantly lower testosterone from chronic stress and poor sleep to environmental endocrine disruptors. Practical evidence-based strategies to naturally boost testosterone levels, emphasizing diet, exercise protocols, sleep optimization, and stress management.

Starting point is 00:01:15 We also discuss an evidence-driven evaluation of popular testosterone boosting supplements, vitamin D, zinc, magnesium, aschwaganda, phenogreek, Tonga, Al-A, Al-A, Ali and more, we highlight what truly works and what's hype. We also discuss the intricacies of testosterone replacement therapy. Who should consider it? The expected benefits, potential risks, safe dosing practices, and responsible monitoring protocols. We also discussed testosterone's increasingly recognized importance for women's health, including impacts on libido, body composition, cognitive function, and athletic performance, alongside crucial considerations for therapeutic use and risk management. And finally, we have a focused exploration of testosterone's role in hair loss,

Starting point is 00:01:59 the interplay with D.HT, genetic predisposition, and also we discussed Derek's personal hair loss journey and proven strategies for mitigation. By the end of this episode, you will have a nuanced, scientifically robust understanding of testosterone and practical guidance on how to assess, optimize, and manage your levels effectively. Before we get started, I just want to briefly mention if you haven't already signed up for my free weekly email newsletter, you are missing out on fascinating health, fitness, and science topics with immediately applicable insights. Just recently, we've explored the anti-cancer effects of strength training and high-intensity interval training, the surprising cognitive effects of creatine, the brain benefits of ketones, how indoor

Starting point is 00:02:42 exercise impacts vitamin D levels, and even intriguing links between living near golf courses and increased Parkinson's disease risk. Sign up for my free weekly email news. now at foundmyfitness.com forward slash newsletter. Once again, that's foundmyfitness.com forward slash N-E-W-S-L-E-T-T-E-R newsletter. And as always, my commitment is to deliver high-quality, evidence-based information free from advertising to support our continued work and to have access to exclusive content, including our members-only podcast called the Alawquot, monthly Q&A's that are live with me, and also curated science digest that we'd send out twice a month, please consider becoming a

Starting point is 00:03:27 Found My Fitness Premium member. You can learn more about that at foundmyfitness.com forward slash premium. Once again, that's foundmyfitness.com forward slash premium, P-R-E-M-I-U-M. And now onto my discussion with Derek on all things testosterone. I'm sitting here with Derek from more plates, more dates. You may know him from his very large YouTube channel where he talks about all sorts of things, hormones, exercise, training. I became sort of aware of your work because you were on our mutual friends podcast, Peter Atia, a couple of times, super interested in, you know, your own personal experience, but you also run a company that's a preventative health company that helps people optimize their hormones,

Starting point is 00:04:19 among other things. And so, I mean, I'm excited to have a conversation with you. You've got a lot of this experience, you know, personal experience, but also experience just running this company where people are coming to your company to help optimize their hormones. And so it's a little bit of a different episode here. As you guys know, I cite everything on the podcast. And so I'm excited to kind of dive in and talk about all things, hormones with you, Derek.

Starting point is 00:04:46 So thanks for coming on the show. Thanks for having me. I really appreciate it. I'd love to kind of start. I want to talk about testosterone, as you know, you know, kind of discussed this earlier. You're very knowledgeable in this area. In fact, we had a conversation, and I was asking you some questions, and your knowledge was very impressive in terms of the scope and depth.

Starting point is 00:05:09 Oh, thank you. All things, testosterone, kind of just wanted to start with the role of testosterone and men. I mean, it's obviously fundamental for male health. But I'd love if you could kind of just outline some of the primary functions of testosterone in men. Yeah, I think at a basic level, it is the primary anabolic hormone men rely on for the sustainment or growth of muscle tissue, bone health, bone integrity, inhibiting degradation, indirectly through some of those pathways as well. well insulin sensitivity if you have worsened body composition it becomes more difficult to handle glucose adequately um neurological health or the aromatization um in the actual tissues themselves um there's an array of things that are supported critically by testosterone and its indirect metabolite uh activity as

Starting point is 00:06:11 well through its aromatization to estrogen and I guess notably but often overlooked it's easy to forget but in adolescence the 5 alpha reduction to dh t so the conversion of testosterone to dh t is necessary for full maturation sexual differentiation to basically reach full adult male maturity and there's a myriad of examples where if dh t is either uh two low via genetic predispositions or through different means than there is inhibited maturation and that's where you get into some of these more unique intersex cases but essentially at a base level this is the primary male all but significantly impactful in females as well hormone that is present at about 10x the concentrations in males and kind of differentiates them

Starting point is 00:07:06 in terms of sexual identity and male characteristics I do. We are going to focus a lot on the role of testosterone and males and men, but I do kind of just briefly before we will eventually talk about females and women, but what is the major role of testosterone in women? I mean, women obviously don't make as much as men, but they do make testosterone and it does play a functional role. Yeah, yeah. And like, again, it's a non-exhaustive list that I just presented. Like, the list extends beyond into erythropoesis, the production of red blood cells intratistical or testosterone production absolutely critical for fertility as well. And women, all but not directly analogous intradinatally, but elsewhere in the body, the activity of testosterone is still necessary for a lot of the same things. Cognitive health, some level of cardiovascular support, bone intake. as anabolic activity and muscle tissue all of the same stuff is still the case in women just to a much lower magnitude so but similar as you would expect there's less of a concentration required to sustain a female musculature than a male so the concentration differential is about 10x but in women the main function of testosterone still overlaps with males but intergenitality is more to facilitate as a substrate of estrogen production. So getting that sufficient amount of aromatization into astrodial, but also the conversion into esterone, which then turns into esterdial as well, to facilitate all of the female fertility facilitated processes.

Starting point is 00:08:53 So given the role of testosterone in all these important physiological processes that you just described everything from muscle health, bone health, neurological health, red cell production, etc. What about the tradeoffs of testosterone? And I mentioned this because of my interest in longevity, my long interest in, you know, life expectancy and looking at, you know, life expectancy between men and women. And you really see amongst like pretty much all mammal species that the females outlive the males.

Starting point is 00:09:30 obviously there's a lot of differences going on there, but testosterone is also something that does, you know, differentiate. There's a big difference between the levels of testosterone between males and female. So I'm kind of curious. I know you think about a lot of these things since I'm curious what your thoughts are

Starting point is 00:09:48 with respect to the tradeoffs of testosterone with respect to longevity. I think it would be highly speculative because obviously I would love to just point to some clear-cut literature that says based on these studies on, you know, inhibiting IGF-1 or having really low androgen levels equals lower body weights, equals longer lifespan, or something to that effect that could be a common kind of denominator. But it's not as cut and dry.

Starting point is 00:10:21 I do think there is some level of metabolic resource demand that is needed to actually support. the infrastructure of a male that is more intensive than a female. So I would, in general, like larger humans are going to die quicker than smaller ones, at least from what I've seen, trend-wise. And in supporting that, it is something that requires more hormone production in general, which is also more intensive on all organ systems accordingly to actually facilitate and get that hormone production to the level it needs to just sustain that larger human. So that's a highly speculative take on it, but that would be part of the reason.

Starting point is 00:11:06 But at a high level, if you wanted to extrapolate to, you know, at higher levels, androgens will be neurotoxic in a dose-dependent manner past supra levels. It will cause cardiac remodeling in a negative manner, like all of the dyslipidemia, all of the negatives that you would hear about when it comes to anabolic steroid use to some extent at supra levels are going to be present from testosterone all but to a more muted extent because it's not a synthetic drug that is manipulated in a lab to create, you know, something that is not a substrate for aromatization and some of the other stuff that is protective. But that's a high-level speculative take. Yeah. I mean, it's kind of a loaded

Starting point is 00:11:50 question because there's probably a lot of factors that play here in terms of like the differences in life expectancy between males and females. And you're pointing out the size difference is one one you know maybe it's the lack of estrogen right not the presence of testosterone but not a lack of estrogen obviously men have make estrogen but not to the same degree as women um premenopausal women but have you have you looked at any of that literature are you aware of it the like the male castrati like so the men that are like yeah they castrated like they are osteoporotic as a consequence of a lack of sufficient aromatization into estrogen and their growth plates, the epiphysial growth plates,

Starting point is 00:12:32 don't close fully because of that lack of aromatization in adolescence, which is facilitated essentially entirely by testosterone as a substrate, similar to what it is in women. But if you castrate a male in adolescence and he no longer has intrasticular testosterone production, he is now functioning off of solely adrenal production, which is like a drop in the bucket to what you actually need to function at a high level. Like you're not going to have sufficient bone development, and you are going to suffer from osteoporosis inevitably.

Starting point is 00:13:02 And if those who don't know what the castratia are, it's really interesting. So it's individuals who were had angelic singing voices. And I'm not sure who the last documented one was, but it was actually more recent than many would probably think. It's like within the last 100 to 200 years. But anyways, you can listen to them on YouTube singing and some of these old audios that were recorded. And it's, you know, a youthful, angelic singing.

Starting point is 00:13:29 voice that comes across as somewhat and like androgynous to some extent and obviously going through male puberty and being subjected to male amounts of testosterone and Dhty would you know like quote unquote wreck that voice

Starting point is 00:13:45 because it's going to be masculinized and get like fully you know the deepening that would happen that's irreversible so the castroti were individuals that were castrated in order to prevent them literally from going through puberty adequately So they would actually grow into men without the full maturation that would come from androgen exposure and adolescents. And as a result, you know, they would have a lack of adequate sexual differentiation maturation.

Starting point is 00:14:13 And their bones would reflect that as well via the osteoporotic outcomes they underwent. Did you happen to see that their life expectancy was increased, though? Yeah. I mean, so, I mean, it's like you're living longer, but not necessarily the quality of life is. Notably, though, their estrogen levels are in the ground. So you saying a second ago about the estrogen. Right. So maybe I don't know.

Starting point is 00:14:35 It's interesting. Like what is it? Well, it's definitely a lower capacity to build muscle and bone, which is less resource intensive and you're a smaller human. So maybe as a result, you are literally a walking, I don't know, like shell of a man, essentially. So you don't require as much to sustain. But your quality of life is dramatically hindered.

Starting point is 00:14:58 Right. Yeah. So you live longer, but you don't necessarily want to. Right. Yeah. So it's kind of interesting. I just kind of want to get your perspective on that. So I'd love to kind of dive into an area that I know you have a lot of knowledge, you know, just based off of your company, Merrick Health, where you guys are really helping people optimize their hormone levels. And so I kind of want to talk a little bit about some of the best practices for measuring testosterone, interpreting the results. Could you kind of outline some of the optimal best practices for actually measuring testosterone level? So, you know, optimal timing, repeated measures, like free testosterone versus bound testosterone or total testosterone, right? Like, what's the difference here? What do people, what should they like consider? So total testosterone is the number that most people are familiar with, which reflects the total. production that can be detected in your sample of blood that was taken. So floating around how much testosterone is there inclusive of the testosterone bound to binding

Starting point is 00:16:10 proteins. So just because it's in your blood though, it doesn't mean it's biologically active. If it's bound to these binding proteins produced by the liver, it could be either entirely inactive or like readily. available to be dissociated, but not yet fully active as well. So you have, you know, SHBG is the primary one, sex hormone binding globulin produced by the liver. This acts as a regulator of androgenicity in the body, which is like how much androgen exposure systemically you would be exposed to.

Starting point is 00:16:47 And the body has this kind of regulating mechanism to partly to make sure that, you know, females stay feminine, male stay male and regulate which tissues get, which hormone when and transport it around the body because these are hydrophobic like they're fat soluble and would not go through the blood to where you want them without some sort of carrier so they have a hydrophilic vehicle similar to like how cholesterol will get moved around through its you know apob particles and whatnot and these binding proteins shhbg and albumin comprise the vast majority of testosterone, I think SHBG is about 60% of your total T will be bound by SHBG, and then like 38% is albumin, and then 2% to 3% roughly, depending on how much

Starting point is 00:17:41 SHBG produce and some other factors is actually free testosterone. So the free testosterone number is just like freely circulating, not bound to binding proteins, and it's like ready and readily available to be used by target tissues should it bind into the androgen receptor and cause the transcriptional activity. But in general, the two numbers you care about the most are going to be the total testosterone, which is like total production reflection. So like how much are you actually capable of making, which is important. A lot of people will just say, should look at you're free because that's like the number of the

Starting point is 00:18:14 matters because that's what's actually available to use. And that's true. But it still doesn't reflect total production capacity, which is important to assess the viability of the organ, response to the pituitary output. myriad of things. So total testosterone, total production, including that bound to binding proteins influenced by liver health, diet, a bunch of different factors, free testosterone, about two to three percent in an optimally healthy male typically. That is just freely available to be used. And then as far as measurement, kind of like best practices, typically in the morning

Starting point is 00:18:50 is the best. Testosterone is kind of, it's like a pulsatile secretion. fashion so you would see in a diurnal rhythm chart showing the secretions of testosterone throughout the day it kind of pulses out in waves so you would have like the biggest pulse early in the morning and then it kind of like goes across ebbs and flows throughout the day until it reaches its low point later at night and then as you sleep it starts to ramp back up again so typically the best way to assess peak levels would be early in the morning and ideally you would have um not taken certain confounding variable supplements like biotin that can cross-detect is, you know, estrogens and whatnot. And typically labs will provide kind of like a guideline of what not to do. But in general, the rule of thumb is, you know, go in fasted early in the morning, avoid your multivitamin probably fes biotin in or biotin-containing supplements and be hydrated to

Starting point is 00:19:51 reflect your actual hematology profile correctly because some people incorrectly think they have a elevated, you know, hematocrit level when in reality they're just super dehydrated when they go in because they just got up, rolled out of bed and are, you know, dehydrated from hours of sleeping and, you know, not hydrating properly when they wake up and they just roll in and think that, oh, I'm going to have a heart attack and then I've got to donate blood now, which might not be the case. So I know that's a mouthful, but early in the morning and ideally you would get a repeat measurement before you make any sort of, especially before you make any sort of choices on a path forward because you definitely want to get confirmation if you have a low

Starting point is 00:20:29 rating or even one that's like mildly concerning because again these things can be so variable depending on so many factors that you might have a blip where it's a snapshot in time of your blood you see you know a 495 total t and you think well that's not great it should be close to a thousand that's what i hear is good and you know all these podcasts and whatnot that's what my friends are at, they're at 900. Like, I only have 495, I should have way more than that. And some people have haphazer really get on testosterone, shockingly, but it

Starting point is 00:21:01 happens. There are a lot of clinics that will tell you like, oh yeah, you can get that up. Let's get this up to, you know, 900. And that's all they need to give, you know, to justify it to themselves. So yeah, you definitely don't want to go off of one reading. You want to go off of symptoms and repeat measurement to

Starting point is 00:21:16 confirm your findings before you even decide what the path forward is for natural intervention. and assessment of what is happening at the organ level and at the hypothalamic pituitary level. So you sort of alluded to this, like, talking about reference ranges, and I kind of want to get into that because, like, you know, there are these, like, reference ranges that you see.

Starting point is 00:21:39 And I'm just kind of, like, curious, like, how does a man navigate where their testosterone should be, what the reference ranges mean? How do you look at this, you, how does, like, you know, How does your company look at this with respect to age with respect to like symptoms? Let's say someone's on the lower end of the reference range, but they have no symptoms. Or someone's at the higher end of the range, but they have symptoms. Like how does one sort of interpret what their testosterone data shows?

Starting point is 00:22:16 And how does the potential for someone who's actually hypogonadal, so people that are actually not making testosterone, right? How does that sort of complicate it? In general, I think it does get convoluted because people will see a reference range and assume, and understandably so, like there's a lot of things that people will just say, oh, target the top of the reference range. This is where you should be. And in general, that's not a bad recommendation often for things that modulate quality

Starting point is 00:22:48 of life related outcomes, you know, like even when we talk about vitamin it's like, you know, you should probably be at like 60, even though the low end is like 30. Typically, if you were at 40, people would be like, you know, try and bump that up to 50 or 60. With testosterone, people think similarly. And justifiably so sometimes. But often what is overlooked is the fact that the actual androgen receptor content, which is like how many endrogen receptors you have in like a concentrated area, or also the sensitivity of it, like, what kind of transcriptional activity do you get subsequent?

Starting point is 00:23:23 to binding, those things all factor into like how much of an impact the endergen has after binding to the receptor. So just because you have less testosterone than the next guy, it doesn't necessarily even mean that you have less muscle growth potential or less, you know, bone support capacity or less neurological support. Like it's not guaranteed any of these things based on absolute values. It should be a combination of symptoms as well as, uh, blood values. But oftentimes, too, the blood values should be superseded by symptoms in some cases

Starting point is 00:23:59 too, because you'll have some individuals who have insensitivity at the AR. So it's not just about how sensitive are you and can you get away with lower testosterone. Some guys need higher testosterone to be able to actually function well. And they might otherwise be told, oh, you know, you don't need testosterone. Your total testosterone is 900, but they might have a, you know, super high sex hormone binding globular and that's gobbing it all up. And they have a low free testosterone. or their actual receptor activity after binding is subpar or they have a, you know, gene mutation that inhibits the actual activity of it. And that's where you get into some of these convoluted cases with like, you know, the Olympic

Starting point is 00:24:35 boxer and like, we're not going to go down that road. But some of these individuals who like, you know, there's a spectrum of androgenic activity that is influenced not just by the total levels on paper, but it is very much dictated by your actual response to the hormone too. Is that something that's measured readily? Can you measure your response to your androgen receptor activity? Is that or is that something that's not really known and you kind of have to do some? There are like proxies for it.

Starting point is 00:25:04 In general, it's very crude. The way they assess if you are one of the individuals on this like spectrum of androgen insensitivity, it's literally like manual assessments essentially of like your genital development, which is like kind of, you know, demeaning potentially. if you're somebody who is like already obviously insecure about what's happening and then you're just subjected to some sort of like subjective analysis of like an expert who determines if you've had sufficient enough like male sexual secondary characteristic development but in general there are proxies for activity and you know if you're somebody who has like if you if you looked at blood work for example some individuals think oh the guy with a natural like 1300 total t that's probably great that guy is is like an outlier genetic phenom, oftentimes it's a reflection of some sort of problem. Like they need to produce more to reach adequate activity.

Starting point is 00:26:00 So like sometimes the body is screaming at the testes because it's not getting adequate production to do what it needs to do. And it's resulting in you shooting out more genital trouble as to make more testosterone. So typically you will see this reflected in some sort of symptom, either through actual development and adolescents being not adequate it or through biomarkers, it becomes pretty clear because there will be other factors that

Starting point is 00:26:24 are clearly outlier oddities in blood work when you see somebody who is not responding adequately. What will, you mentioned the gonotototropins, like what would like the lutenine, looting hormone or follicle stimulating hormone FSH? What would those kind of look like in the cases where it's kind of like a red flag? I mean, it's like, these are very outlier scenarios that I'd be deviating into where people are like, you know, overshooting to try and meet some sort of physiologic activity. Like most guys are going to be falling into the bucket of they have low gonadotropins or low response to it from age-related decline. That's more of like, you know, what most people will find relevant. So I'll start there.

Starting point is 00:27:11 In general, the thing you would be looking to first is, okay, like, what are your levels, your total and your free? levels are they do they look good do you have any symptoms and let's just say you do have symptoms and you're looking at these numbers and they look you know okay at that point you would be looking um the actual output from the pituitary is going to be dictating what the signal to your testes is to actually produce testosterone so the l8s from the pituitary signals to the light excels to make the intratisticular testosterone so is that signal adequate is one thing to assess and that has a clinical reference range. But also individuals who are primary hypogynatal,

Starting point is 00:27:55 similar to what we talked about when it comes to assessing, you know, when women are hitting menopause, what kind of would you look to? In men, if you are not responding and producing adequate testosterone in the testes, you will be trying to make more leutinizing hormone typically to try and push that signal. So your body's going to recognize,

Starting point is 00:28:14 I'm not getting enough testosterone out of this L.A. that I'm making. So the signal isn't sufficient. I'm not getting enough testosterone and or enough estrogen from that to provide the negative feedback that tells me to stop making GNRH and the other, the pituitary hormones. So I would just, it would just keep shooting and trying to, like,

Starting point is 00:28:33 probably overshoot you into adequate territory. So you would, if you were primary hypergonadal, you would see the reflection typically of high gonadotropins. Or you would also see some sort of, like, structural defects. And that's where you would get into, like, you know,

Starting point is 00:28:47 ultrasonic for, I think the prevalence in males is like 15% of males have a varicose seal. I don't know if you know what that is, but it's like varicose veins in your testes essentially. And it looks like like twisted kind of like, the same thing you would see in varicose veins in your legs. It's like in the side of like the testes. And it inhibits thermoregulation and significantly impede testosterone

Starting point is 00:29:11 production locally and fertility. So that oftentimes, Well, 15% of men, from what I recall is the number for prevalence. Pretty significant, though, for something a lot of people don't know exists. And if you are doing all the lifestyle stuff and it's not working and you think you're doing everything correctly and you must need testosterone, sometimes it can be overlooked that there are structural defects. So, like, typically the first thing you would look to is like, am I capable at the organ of responding to the signal? And, like, is the signal adequate to begin with?

Starting point is 00:29:45 because if there's like a primary hypogynatal outcome, it would be some sort of like structural response problem in the testes themselves. If that's not an issue, and you've ruled out all structural problems, you know, age-related decline and is not a factor and you're, you know, otherwise, you know, everything's all accounted for from that angle.

Starting point is 00:30:03 You would look upstream to the pituitary and say, okay, well, at that point, am I producing enough LH and FSA? And this is typically the outcome you would see in men, not always, but like a lot of men who are kind of like not sure if they need testosterone, they'll have like a relative proportional inadequate signaling driven through a myriad of factors including but not limited to lifestyle, some age related decline, toxins, exposures, a myriad of things.

Starting point is 00:30:34 And that's kind of like where people have this opportunity to try and incrementally maximize all the areas in their life to try and improve the output. Because if you have sufficient functioning organs and your output is just insufficient, you might be able to get that up to snuff to where you need it just by getting leaner, losing body fat, fixing your diet, addressing micronutrient deficiencies, quitting smoking, not drinking anymore, fixing your sleep, you know, all the smorgasbord of things. Yeah, we're going to get into a little bit.

Starting point is 00:31:10 but okay. What about the sex binding globulin hormone, SBG? S-H-B-G-S-H-H-B-G-S-H-H-H-H-H-H-H-H-H-H-H-H-H-H-B-B-Golmining globulin. Sex-Hormone Binding Globulin. Like, you're talking about, like, if you have a lot, if you have a high level of that and it's bound up to your testosterone, so a couple of questions here, what regulates those levels and what regulates, like, how much of that testosterone can then get away from that, you know, binding protein and then be used to, you know, obviously exert hormonal activity.

Starting point is 00:31:50 So, you know, can you, can you, like, dial in looking at just that binding protein itself to help kind of solve some issues? Yeah. And it gets really complicated in this regard because what a lot of people don't address is, so Dhthydrostostosterone mentioned earlier, how it's like the primary hormone. that will determine if you reach full maturity in adolescence. It will still be markedly male probably if you have adequate testosterone production, but you won't get full maturation if you have, you know, zero dht from a defect in the enzyme that encodes for five alpha reductase or something. But that hormone, the most androgenic hormone in the body that essentially determines if you fully masculinized or not,

Starting point is 00:32:32 where you end up, you know, with a micropenus, that has a much higher binding affinity for SHBG than testosterone does. and then testosterone has a much higher binding affinity for SHBG than estrogen does. So even though on paper we're talking about the importance of free test versus total test, which is very important, also very important, which most people aren't going to test in their blood, is the Dht level that males will rely on through adolescents and to some extent in adulthood potentially,

Starting point is 00:33:00 depending on their test levels, that is going to get gobbed up even more proportionally by SHBG. So if you have high SHBG, not only is your free test, potentially inadequate despite adequate testosterone production. Proportionally, your free DHT, which is like the main androgenic hormone is like way more gobbed up. And this gets really rough in females because they, a lot of them are using things like combined oral contraceptives which crank SHBG through the roof through the liver interaction with the oral combined oral contraceptive pills, depending on which drug they're using.

Starting point is 00:33:36 in general, ethanol estradial plus some progestin, depending on how endrogenic the progestin is, it'll depend on how much the SHBG goes up. But you'll see an adolescent women or women who are, you know, in full adulthood that are taking combined oral contraceptives. Their total testosterone will suppress upwards of 50 to 60 percent and free testosterone upwards of like 70 to 80 percent. So they're walking around like borderline, asexual, castrated by a pill essentially. And that's only with oral. That's with oral, but like any sort of progestin that is synthetic will have negative feedback to some degree, all but much lesser so via a localized IUD releasing a level

Starting point is 00:34:19 nodigrestrial or something. And you're not having to take that supporting estradiol that comes compounded into it. So it depends on the format, but a lot of girls are still using the combined pill. So it's just worth noting nonetheless that when these SHBG levels are sky, rocketed or even like high on, you know, a clinical reference range. If you are somebody who is like moderate, you know, tea production or low normal or whatever, like the proportional hit to your DHT getting gobbed up could be like the differential between you being symptomatic versus not as well as your free tea.

Starting point is 00:34:55 Even though it's proportionally less gobbed up, the DHT could be like nukeed entirely essentially via the SHBG levels being high. Since we're talking about the SBGH levels, I kind of want to like, what is there lifestyle? So does age regulate that and also like lifestyle factors? Yeah. So like a common thing that people hear is when you get 30 years old, your total testosterone will decline by 1% per year. But the reality of what makes this even worse is your SHBG levels will increase year over year proportionally faster, thus making the velocity of free time. testosterone decreases dramatically more so proportionally.

Starting point is 00:35:36 So even though total test decreases by 1% a year, your free test will decrease by up to 2% per year. And that's the one that you need to like do stuff in the body through like freely circulating activity. So it's very important and very relevant for dictating what activity you have in different tissues in the body because it's ultimately the only one that can actually bind to the receptor and do what it's supposed to do. So the SHBG levels will be dictated by age, will be. dictated by liver health to some extent will be dictated by other medications,

Starting point is 00:36:06 especially oral formulations. Insulogenic signaling as well hugely implicated. If you're on a ketogenic diet, you can absolutely expect your SHBG levels to be through the roof and your free test to be much lower. So carnivore diet guys, there's a reason they eat fruit now. It's because their free test levels were all shit and their total test levels were high and they thought it was fine. But in reality, they had like borderline hypogynatal free test levels often because they were

Starting point is 00:36:30 overlooking the fact that insulogenic signaling is need. needed to actually get SHBG to a meaningfully reasonable level for a male. And this is also something that would be relevant for females, too, right? Yeah, and these binding proteins also exist for other hormones in the body because they all function in similar ways through cargo systems and transport mechanisms in the body. Like you will have binding proteins for IGF1. You'll have binding proteins for thyroid hormones. Like, it's not uncommon to see people with like normal on paper levels for certain hormones,

Starting point is 00:37:00 but then when you dig deeper, all the free hormones are like proportionally horrible because they're all about like the the total production looks okay but it's because it's factoring and all of these like bound up hormones that are in use like unusable essentially.

Starting point is 00:37:16 Is that something that's common? Like I mean would you say that's? It depends on the person and lifestyle so but yeah probably especially among women because I you know a lot of them are you only have so much androgens to work with to begin with. Like your production is, you know, a tenth of males typically.

Starting point is 00:37:38 And then if you are occupying all of your androgens, because, you know, essentially the SHBG is going to, with a much higher binding affinity, mop up all your DHD and testosterone, not all of it, but like a significant amount of it, if it's high in any, like, higher than it should be. Like, it will impact your, like, free androgenic signaling so significantly that might put you into like the you know female hypogynatal equivalent territory

Starting point is 00:38:05 essentially so you could be like it's not uncommon for girls to walk around borderline asexual or like literally no drive throughout their entire adolescence 20s 30s and think it's normal and it's just not what they're supposed to be walking around like so in other words like if they have if their libido is like totally down perhaps like they're having a harder time losing fat gaining muscle losing fat um it might it could come down to this right bone and Bone integrity, right. Yeah, so that sounds like a bit lesser so, depending on if they're on, like, obviously, you know, if you're on a combined role contraceptive pill that has estrogen in it, you know, however much it does that, to what dose, you know, you get into the nuance.

Starting point is 00:38:43 But ultimately, like, you're inhibiting natural hormone production quite dramatically through a myriad of means. Like, think about guys who are just like natural having to deal with what they deal with as is, you know, the sleep impact, the cortisol impacts, the fat impact of being, you know, obese. and then if you have women who deal with all those same problems, you're going to have all the suppressive results of all of those lifestyle things, the diet, the nutrition, the whatever. And then you also factor in medications on top of that too that maybe men don't typically have to take to, you know, achieve contraception. Like, you know, that's typically often, I think,

Starting point is 00:39:18 the final blow that will like push women into like, you know, closer to low drive territory often. And almost certainly lower, quality of life for a lot of them. Now, that's not to say, because I think this gets misconstrued often is it's not to say don't use contraceptives at all. Like there are absolutely better ways to go about it. I'm just giving examples that I see as commonplace. No, no, it's this is great. This is great information. You know, since we're kind of talking a little bit about symptoms, let's kind of circle back to talking about like what are the symptoms of low testosterone. You know, we're talking about

Starting point is 00:39:56 men here, but like we talked about libido, muscle mass. Like what are, what are like the classic symptoms that men should be looking out for? Is it something that's hard to differentiate between, okay, this is testosterone or other things? It does get tough because as you would imagine, a lot of the lifestyle related things that lead to low testosterone will come with the decrement to quality of life just via, you know, if you have poor sleep, like you're not going feel great because you didn't rest enough and then you add that on top of the inhibition of you know your output of gonadotropins pituitary hormones and response to them as well like it's like a one-two punch off in a lot of this stuff so in general I would look to things like libido

Starting point is 00:40:46 erection quality obviously that's more you know circulatory often but still notable nonetheless if you suddenly, you know, if you know how morning would anymore, like, you got to look into it regardless if it's circulatory or hormone mediated. It might be a combination of both. You no longer are able to hold muscle as easily or build muscle as easily. You're, you know, losing strength in the gym. Your recovery capacity is inhibited relative to what it was when you were younger. Mood dysregulation, irritability.

Starting point is 00:41:20 And these are all like really general vague symptoms. and I would love to just say, oh, look at, you know, this exact thing will happen. But in reality, it's often a constellation of things that comes as a vicious circle effect of the, you know, factors that led to that deterioration of testosterone to begin with. Or if you were just, you know, never had reasonable testosterone to begin with, you would have probably not gone through puberty adequately to begin with. So, like, the genetic factors, like some of these, like more outlier cases become a bit more obvious because it's like you just never really like fully masculineized in adolescence.

Starting point is 00:41:56 You may have a higher voice. You know, a lot of those things are less relevant for the average person. For the average person, it's going to be more of these general symptoms. And it's warranted to get a test at that point and just see what's up. Right. Yeah. So then that in combination with the test and things that we just talked about is kind of like where. You know, like pre-diabetic, you know, progressing towards, you know, pre-diabetes, insulin

Starting point is 00:42:20 resistance. A lot of this stuff is going to be ultimately deterred by blood work, though, because a lot of people aren't going to be able to identify this autonomously reliably. So that's kind of where I'd point to the more vague stuff, like the quality of life. Like, do you notice a blatant deterioration with no other factors changed? Erection quality, you know, libido, vigor, muscle mass, strength, fat, body composition, stuff like that. So you mentioned the, the, by age 30, total testosterone decreases by about 1% per year. And then you mentioned even in general. In general.

Starting point is 00:42:56 Right, right. On average. Like, yeah, exactly. There's, and that's where I'm going to ask you. I have absolutely seen seven-year-olds with, you know, 900 total T's. So the question is then, like, there are lifestyle factors that really can sort of modulate that, you know, general decrease or not.

Starting point is 00:43:13 So maybe you can accelerate it or maybe can slow it, right? And I kind of want to dive into some of those lifestyle. factors like what should men avoid or try to minimize in terms of their environmental exposure or lifestyle factors that are known to accelerate the decline in testosterone and or increase the binding proteins so there's less free testosterone right anything that's going to necessarily regulate the ability of testosterone to exert its you know its function essentially. essentially. I would love to bang out an exhaustive list, but forgive me, I guarantee we'll miss something. But like alcohol, you know, the direct toxicity effects of that does

Starting point is 00:44:04 inhibit actual steroidgenesis in the testicles themselves. It will also impact sleep dramatically, which has the vicious backhand effect of, you know, inhibited output of signaling hormones, which indirectly will also impact body composition, which, you know, the whole downstream cascade of that. Smoking, obviously not helpful. How much alcohol? Is it, is it like any amount or like light drinking, moderate drinking? I think, like obviously the safe answer for me is to say no drinking. I think it would be more like a dose-dependent toxicity effect and what is your capacity to handle it because ultimately the testes are very affected by oxidative stress and if you're not capable of handling that adequately

Starting point is 00:44:56 like it will reflect in your inadequate output of hormones locally so I would love to give like hard and fast numbers but there are a lot of people who will be able to get away with like murder and probably be okay there are some guys who like you might be low normal uh function to begin with and like that you know a couple drinks a week like you know throws off your sleep a bit and kind of pushes you the edge like it all depends um it is very much a spectrum so like going from like optimal to like blatantly hypogynatal from a symptom perspective it's not like it's just on versus off like your way there is a you know it's a transition of you know shittiness as you arrive to that like worst case scenario um so uh other things i could point to um if you have a totally fat deficient

Starting point is 00:45:43 diet i think that's you know of a macro distribution that would be reflective of something that's almost certainly going to hinder your capacity to produce hormones. Also, if you have a void of carbohydrate intake diet, it would also be something that would inhibit freely circulating hormones from liberating themselves and lack of protein. Like you would not be able to produce, you know, get as robust of a response recovering from workouts and be able to build muscle,

Starting point is 00:46:11 which indirectly is going to improve body composition and improve your hormones as well. So it's all kind of like balanced diet. don't eat bad. Micronutrient intake, I could definitely point to if you're deficient and not every mineral or vitamin is going to be, you know, game-changing dramatic impact on your test levels, but things like zinc, magnesium, vitamin D, like these all have a marked impact on your testosterone, either responds to it or capacity to produce it or even like, like you

Starting point is 00:46:42 mentioned in our podcast, a conversion of vitamin D into active vitamin D. Like you might think you have adequate vitamin D status via your dose you're taking that super high, but you're not actually utilizing it, but you think you are. And that's that's impacting your testosterone production and your response to it at the androgen receptor itself as well. So I think from a minerals and vitamin standpoint, the low-hanging fruits are typically going to be like B vitamins, but in particular, like from a mineral side, you know, you have magnesium, zinc, and the vitamin D3 are going to three things that

Starting point is 00:47:17 specifically on top of the minerals and vitamins that everyone's familiar with for multivitamins and whatnot are more difficult to get in adequate doses. All but zinc is typically adequately in many multivitamins, but magnesium in particular almost never is because of the weight of it.

Starting point is 00:47:32 You would be having to take a multivitamin that's like eight to 10 capsules otherwise, which just nobody does. And then the vitamin D, it's fat soluble. Typically you're going to have it in like a soft gel or something and it's not always going to be at the dose you need in the, multivitamins is just worth noting.

Starting point is 00:47:49 So those are just some low-hanging fruits that are, if you don't look to those as part of your micronutrient optimization strategy, like you could be overlooking low-hanging fruit that debt, like is a deterioration of, you know, 100 plus nanograms per decilator per deficient micro potentially, depending on how severe the deficiency. Other things I get pointed to being obese, like the worst one probably. that I probably should have mentioned first, but is like so dramatically impactful on your negative feedback to the hypothalmic pituitary axis. So by that I mean men who are obese and women, if you have a significant amount of fat,

Starting point is 00:48:36 it is going to elevate your aromatization, which is, you know, your conversion of testosterone to estrogen. And this is more impactful in males because of how the brain gets signaled for, from estrogen, not testosterone directly, as significantly. There's a bit of a nuance there, but in general, you need adequate estrogen to tell your brain,

Starting point is 00:48:55 okay, we're good. You don't need to make enough testosterone because I have enough estrogen. That's kind of like the downstream cascade of these metabolite conversions is you produce testosterone in order to produce other things too. And the estrogen is a very potent mediator

Starting point is 00:49:12 of telling your brain, we're good. And if you have a significantly elevated amount of estrogen being converted from your testosterone that you make because of how much fat you have, you are basically achieving the proportional increase in estrogen that is much higher than the amount of testosterone substrate that led to that conversion. So you have that signal telling your brain, okay, we're good. But the amount of testosterone you actually had to begin with was not good. so that's problematic people who are obese have you know upwards of i would love to give hard and fast numbers but it could be like significant like half of a reference range maybe you know it could be the differential between you being you know the quality of life of you're fine versus you're blatantly in you know severe deficiency and what else could i point to um

Starting point is 00:50:06 What does weight loss do to those levels? Like if you are someone that's obese and then you lose weight, does that bring you back? Yeah, as long as you are losing ideally visceral fat and like overall fat loss is going to be very supporting of getting that ratio back into balance of your estrogen and the amount that's converted to estrogen, estradiol in particular. and once that balance is favorable because you are leaner, you will have a balanced amount of feedback to the brain that then regulates like the perfect homeostasis between, okay, now we have adequate testosterone and estrogen. So you'll actually notice more testosterone being produced

Starting point is 00:50:50 because it realizes to get this signal that we deem adequate, we had to produce more testosterone to get that amount of estrogen. So there's a Goldilocks zone, of course. You can't just become, you know, a melanoc. nourished, you know, low, like, bodybuilder, shredded person and just continue to get this elevation and proportion. It's at some point, you will end up essentially starving your body of the nutrients needed to actually support hormone production.

Starting point is 00:51:18 But in general, you know, guys who are, you know, like 12, like 12 to 15 percent body fat ish, will find that they have a increase in testosterone dramatically relative to when they were obese. And it's like super significant and how much it will improve. improve hormone status. So and then the sleep, I think I might have already mentioned that. Yeah. What I definitely want to dive into some of the diet things in a minute, but I wanted to

Starting point is 00:51:43 ask you about, um, a couple of things for with respect to maybe factors to avoid. Um, what effect does like excessive endurance training have on testosterone? Because I thought I came across some literature where it was a negative effect. And I wasn't sure like how robust. I think it is pretty dramatic pending and exceeds your capacity. to recover. So that sounds like a weird way to answer the question. But like some people have a higher tolerance for stress. And that's, you know, reliance on a bunch of different factors. But if you are somebody who is not fueling yourself correctly to handle that amount of endurance training,

Starting point is 00:52:20 like you were, let's just say you're in a calorie deficit and you're trying to be like, I don't know, six pack shredded for the summer and like look as good as possible, but also fuel your like endurance event efforts. Like you're probably like not doing two you're not doing two birds ones down like you're doing two things like inadequately almost certainly and malnourishing yourself and ending up in a state of hormone deficiency as a result probably like you see in studies all there are uh cases that you can point to of what happened to natural bodybuilders as they diet for a show and you can see in like as they start to get closer to stage ready which is like the most shredded basically any

Starting point is 00:53:03 documented human gets essentially. The requirement to get there is a state of malnourishment essentially. And at some point, typically, once you start to cross into that like, you know, single-digit body fat threshold, you start to become so malnourced that you are inhibiting your actual capacity to produce hormones adequately. You almost enter into like, you know, preservation mode slash like hibernation or something. And it's kind of just like save yourself. We're starving to death.

Starting point is 00:53:32 Like, how do I stuff? stop everything metabolically taxing from happening. Let's shut down all systems, nor do we have the substrate to actually produce these hormones to begin with. That's kind of what happens when you get like really, really malnourished. And with endurance running, like I've seen guys out eat,

Starting point is 00:53:46 you know, 5,000 plus calorie per day diets when they're doing like really intensive endurance activity. So if you were not fueling adequately and with the right fuel, micronutrient density, macroelotment, how much of it is like carbs or fat versus protein, Yeah, you could absolutely exercise yourself into a state of hypogynadism easily.

Starting point is 00:54:08 I kind of like... I would caveat not easily. It's hard to train that hard. Right. Yeah. No, it's definitely not easily. Like, there's not a lot of people that are... Kudos to the people mentally are strong enough to do that, I guess.

Starting point is 00:54:19 Well, I kind of think of the analogy here for women. It would be like when women are excessively endurance training and in a severe caloric deficit and they become amenoretic, right? So they're essential. not ovulating anymore. And in fact, you mentioned like wanting to get shredded for the summer. Well, I actually in my 20s was doing this very thing where I mean, I was running like 10 miles a day. And I was eating like carrots and hummus. And that's it. You know, and it was like not fueling myself. No, like hardly any fat. You know, it was very like very sort of like low protein, you know, low fat diet.

Starting point is 00:54:56 Yeah. And I definitely got shredded ish. But like I became a. anoretic for several months, you know, where I just didn't get my period. And so I wasn't ovulating. And so I had to add back the calories and the food. It was like, and it took a while before my body kind of like recalibrated. Yeah. But I feel like that's kind of like the analogy that like women. It is. It's like your body shuts down. It's like, okay, I'm not getting enough calories. Reproduction is not essential right now. Survival mode, right? Not reproductive like happy growth mode. It's like survival mode. And like some people might not even realize how significant of a deterioration hormone production I'm talking about. Like to give context, men who are dieting for bodybuilding shows naturally, it is not uncommon to see the end result of a hormone profile on like the last week, them to look more female on paper than like their girlfriend. Like that's how low their testosterone levels are.

Starting point is 00:55:54 That's wild. Yeah. That's wild. Just to kind of sum up the like factors to avoid. Not always, but sometimes. I wanted to get your opinion on endocrine disrupting chemicals. Like how have you or has your company looked or seen anything or do you have any speculation into like what the scientific literature has shown in terms of them affecting hormone levels?

Starting point is 00:56:22 Yeah, I think we're pretty convinced that there is an effect. It's just the magnitude at which you often see. hyped up, I think, maybe over exaggerated. There are low-hanging fruit things to absolutely avoid. Like, don't use, you know, plastic Tupperware and, like, heat it up and stuff like that. Try and use glass when you can. Try and ensure you have, like, high-quality air, if possible. Like, pollution, I think, is a big factor for, like, your body's capacity to deal with stress

Starting point is 00:56:53 and, like, the allocation of resources to be chronically dealing with a toxic environment will inhibit systemic, like, broad systems. Water quality, like, if you can make sure you have, like, decent water, I think that would be solid. But as far as, like, the actual magnitude of impact of those things, for most people, I think is going to be relatively negligible in contrast to, like, the obesity, the diet, the exercise, the sleep quality, the potential carcinogens that might be. exposing themselves to, you know, some of the lifestyle stuff is like way more important to be

Starting point is 00:57:34 addressing as like the base infrastructure before you start thinking about like, oh, it must be my like shower that is like shooting chlorine on me. Like it must be that or it sure get a shower filter. But like it's not going to be the game changer. I do think avoiding like the basics of like, you know, switch to glass where you can. Don't use plastic water bottles, stuff like that. And there is blatant evidence showing interactions with estrogen receptors with some of these compounds, as well as androgen receptors, which in turn will impede the ability of the actual hormones you produce to bind to those receptors and do what it needs to do. So you're like essentially competing with yourself for activity in the body.

Starting point is 00:58:13 Like you're competing with these like, even if they're like moot activity compounds, they still act as like antineogens or anti-estrogens via their occupying. of receptors. So to whatever degree they are, doing it at all is not ideal because it's inhibiting like space that could be occupied by actual endogenous hormones that you need to produce and need to work properly. And you don't want to be competing with like environmental toxins to like do things in the body. What do you hear? Like I often hear from many people popular, you know, media as well as just people I speak to or comments that I read about testosterone drone levels being lower now and men than they have ever been.

Starting point is 00:58:59 For one, like, is that true? Do you think that's true? And two, like, what are some of the major contributors? Is it obesity, since obesity's rampant? I mean, or is it just like everything that you mentioned all sort of like compounding together, not necessarily just like increase in, you know, BPA and plastic, you know, endocrine disrupting chemicals that are now a lot more prevalent than they were, you know, sick. six or 70 years ago.

Starting point is 00:59:26 I did a video a while ago on like the earliest finding I could find of recorded testosterone levels in, I think it was like military soldiers or something. One thing that I think is notable is the actual detection sensitivity of testing is absolutely much different now than it was, you know, 60 years ago. So to contrast like, oh, the total test of some guy 60 years ago versus now, is equivalent even on like a testing methodology basis is like flawed to begin with because it's probably not an accurate comparison. But is there a trend downwards?

Starting point is 01:00:06 I would say yes. And I think it is mostly dictated by the obesity, the diet, the lifestyle stuff. So, you know, like there's obviously things to deal with in the environment that are less favorable and are not supportive and probably not benign. but like in general, I think most people that worry about this stuff, they would be put their mind at ease by dialing in everything else, which is not that hard to do. It's often free or, you know, cost less money. You're eating less food, you know, go to the gym, et cetera. I'm not saying that's easy to do, but like dial in your basics.

Starting point is 01:00:41 And once you do that, you have like an increase. You have your baseline. Let's just say you get a blood test and you see where you're at. From there, you can start doing some of the minute changes like put in, you know, a chlorine filter on your shower head. Do this. Change your water source. whatever, do you notice an incremental uptick in your gonadotropin output or your response to it at that point? If yes, like, okay, maybe it was a meaningful change. But like, until you do that,

Starting point is 01:01:01 like, you're kind of just taking shots in the dark, assuming all of these things are, you know, occupying your mental bandwidth and concerning you that may not be worth your concern to that degree. Does chlorine have an effect on testosterone? I don't, I don't, like. Maybe. Okay. Yeah, I think more of like BPA, but, and consuming it, like, orally, like you said, hot, like heating up the plastic or like hot beverages, like going into like something plastic. But yeah, I agree. I think that these lifestyle factors are paramount. And I'd love to kind of get a little bit more into some of those, particularly like, so you've already mentioned the diet.

Starting point is 01:01:37 And I'm kind of, you mentioned protein, fat, carbohydrate, you know, like, so what, what, why are some of these important? So fats are important to make, you know, the backbones of hormones. Maybe we can talk just a little bit about like why low-fat diets and why people should be incorporating fat into their diet to make sure that they're... Yeah, like in general, it's not like if you have... For example, if you ingest cholesterol, it doesn't necessarily mean you're going to have like a dose-dependent elevation and you're like serum cholesterol, as I'm sure everyone knows here. But there are like certain baseline requirements to serve as the substrate for producing cholesterol-derived. steroids in the body and these are all ultimately derived from cholesterol and then get cleaved and manipulated through enzymatic processes to make all the hormones in your body including but

Starting point is 01:02:30 not limited to testosterone estradial etc so in general it does seem like having a sufficient amount of fat is worthwhile and does seem to impact um how much hormones you can actually produce um and the carbs for actually mediating, and this is going to depend on, you know, activity levels, how demanding of exercise you do, if you burn through them versus not, if you're sedentary versus not. But in general, it's going to be, the insulogenic signaling is somewhat necessary to facilitate a balance of free androgens, including free other hormones in the body that often go overlooked to actually do what they're supposed to do because a lot of people won't even measure the

Starting point is 01:03:14 free levels of, you know, like the IGF. one, the, you know, the T3, like you'll, you know, some of this stuff gets like hyper-newance when you get into what hormones are actually bound up that you don't realize. Estrogens, Dht, et cetera. So having a balanced diet and then the protein, like you mentioned, from like a mechanistic perspective, like I think in general, these things all serve as building blocks is the simplest way I can put it. And having a deficiency entirely of one or the other, it's just like, it's kind of the

Starting point is 01:03:45 expected outcome. Like, it's often not going to be ideal to be missing something entirely that your body utilizes for critical, you know, structural things. Well, it's interesting. I learned something for me because I, you know, I was aware of the importance for, you know, of fat, particularly like, you know, a certain amount of saturated fat, which is known to increase endogenous cholesterol production. But the carbohydrates and the insulin response and like having that insulin action or response like and I didn't realize that was also important and you know especially for the free you know hormones like the act or the amount of free hormones so it's it's it's interesting to think about like a ketogenic diet you know as you mentioned like some people can really be in in a

Starting point is 01:04:32 problematic state if they're on a ketogenic diet and their free testosterone just kind of tanks and it's not to say that it will absolutely happen like I'm sure there are a lot of people that thrive on long-term ketogenic diets or may even clinically require them. So like I certainly don't want to come out here and suggest if you're on a ketogenic diet, stop doing it. Like talk to your doctor first, obviously. It's just like mechanistically, this is what happens. If you have a lack of insulin signaling, you will have less capacity to suppress the binding proteins. Well, what you're saying is like, get your hormones measure. Measure them right. And make sure that you're monitoring that. Yeah, be informed before you like freak out about anything. Right. Yeah. With respect to other sort of

Starting point is 01:05:13 lifestyle factors that can maybe boost testosterone. So we're talking about dietary factors here. What about exercise? You know, resistance training is one that comes to my mind when I think about trying to boost testosterone. I mean, is there merit to that? Is that something that moves the needle? Yeah, I think it's kind of like into simplest way I could put is like descending order

Starting point is 01:05:32 of intensity essentially. So like, you know, weight lifting at the top. And then you have like some of your more like hit style workouts underneath that. And then at the bottom of it would be like the. most basic of, I don't know, barely exerting yourself, but like getting out there and moving, that is going to have the least impact in general. And at the top, it's going to be, you know, the muscle building, facilitating processes, the things that build bone, et cetera, resistance training. That's going to be the most directly impactful. But ultimately, it's also going to be

Starting point is 01:06:05 what is the overall exercise regimen that you adhere to? Because a lot of people, the problem is not even necessarily like, oh, it's the perfect thing. Like, it has to be something you enjoy enough that you'll adhere to it. So, like, adherence almost trumps optimal in some capacity. So, like, get the thing you can adhere to, the diet model that you can adhere to. Like, a lot of people, the diet that on paper is the best, it won't be the one that you stick to you for more than, like, six weeks. So, like, don't do that one if that's the case because you're not going to stick to it.

Starting point is 01:06:37 And then you're just going to end up where you were before. So calories trump everything, unfortunately. you know, or fortunately, because it gives you a lot more versatility with like your choices, I think. It's not like you're stuck in a myopic kind of, you know, box of I have to be on like the Mediterranean diet or I have to be on the carnivore diet

Starting point is 01:06:53 or I have to be on the vegan, you know, the whatever. There are a lot of ways to skin a cat and ultimately it's going to come in mainly from energy balance and then also from there optimizing for, you know, having adequate protein, fat presence, carbohydrate balance to support your, you know, whatever exercise you're doing. and the intensity of it and all the things underlying that.

Starting point is 01:07:16 With respect to some of the micronutrients, this kind of gets into the supplement area as well. But you mentioned some important ones that I've also kind of like come across in the literature and that being vitamin D, zinc, magnesium. Can we kind of just dive a little bit into their effectiveness? Like there's like, is there human data on it? Like, do you know anything about how they're working? I mean, I've read some of the human studies, particularly on the vitamin D and, like, getting, like, higher dose vitamin D supplementation, improving testosterone.

Starting point is 01:07:48 But, I mean, I'd love to kind of just take a moment to kind of talk a little bit more about that if you want. Yeah, like in general, I think the most reliable things that move the needle, if you were deficient, what is, I don't know, people are familiar with the ZMA. It was like a, the first, like, combo supplement that was sort of seen as, like, a testosterone booster that was available. in the market. And it's, you know, like zinc, magnesium. And I don't remember if the A was something else, but vitamin D is the third thing you want. I don't remember what the A's that before. But those are the three things that move the needle most reliably that are natural. You, you know, otherwise would get through your diet, but likely non-sufficiently. Maybe zinc you might, but like magnesium, pretty difficult, I would say, for a lot of people, they don't realize

Starting point is 01:08:37 how deficient they are. And then even like supplementing accordingly. it's like, you know, getting one that you respond, that you tolerate well with your digestive system, has the yield that actually produces enough magnesium from like the elemental weight of the supplement, which is not that complicated. I don't want to make it sound super complicated. Like a lot of them are fine. Miranda has great articles on magnesium formats that are bioavailable and yield more than enough magnesium.

Starting point is 01:09:04 And yeah, the vitamin D having an adequate amount, making sure you're converting it and actually getting the activity from it. mechanistically there is some level of like gene transcription capacity facilitated through these like vitamin Dase a hormone for example and it does also affect androgen receptor activity and some like the capacity for androgens to do what they do not just like the production of the amount of them

Starting point is 01:09:29 so similar to what I talked about earlier where you have this kind of like receptor interaction how well can you actually utilize these hormones to do the things it needs to do in the body some of this is going to be facilitated by the adequate minerals and hormones for vitamin D supporting it. And it's not necessarily measurable as much, like, directly. But all you can really do is like backfill accordingly to hit your needs and then assess your kind of like proxies and your blood work and your symptoms and kind of go from there. In your opinion, like let's say someone is on the deficient range of vitamin D, their inadequate magnesium.

Starting point is 01:10:07 perhaps there's zinc is, you know, maybe okay or in the inadequate range, would getting to that sufficient status really move the needle with respect to like testosterone? I think if you were on the low end of the reference range or literally hypogynatal and you were clinically low or deficient for those, depending if it's all three or not, because obviously there'd be an additive effect. Of some of them are, I mean, at least vitamin, vitamin D magnesium, pretty common. Yeah. Yeah, I would say like you're looking at probably a potential incremental difference of 100 to 150 total

Starting point is 01:10:47 T maybe. It kind of depends on the person, of course. Like, I've seen more robust response in some studies, but I also don't want to like over-exaggerate the expectations. But it is meaningful. Like, it's something that apps. And some of it can't be directly measured either. Like, we're talking about the total T number, but it's like, how do you know?

Starting point is 01:11:04 how much your deficient vitamin D is impacting your ability to use it correctly. And then even if you had the sufficient vitamin D, the magnesium impact on all that and the DNA interactions and whatnot. It's like, you know, you would be speculating at best. So. And then there are some other more like tangential supplements that are not as like obvious no brainers that are helpful. They're just facilitating mechanisms that are not like this is a vitamin you need almost

Starting point is 01:11:34 regardless of what your test levels were kind of thing. Yeah, I'd love to talk about those. I mean, you hear some of these herbal supplements and like some of the Ashwaganda Fenegrique with Tongut Ali. I mean, let's dive into that. Like, are they effective? Which ones are effective? Which ones are hype?

Starting point is 01:11:49 Yeah. I think one that I would be worth mentioning, all but the literature isn't super robust. It is boron. So that potentially has a suppressive effect on SHBG. levels. There's some literature that looks promising, all but I wouldn't

Starting point is 01:12:10 hang my hat on and say it's a guarantee. It's going to suppress your SHBG from like the high end of the reference range to something that's like much more, you know, much better. But like it may, it does seem to work for some people. And in general, it can be a supporting adjunct that some people are,

Starting point is 01:12:26 it's not something you typically get through your diet and like significant quantities anyways. Like often people will it'll come into multivitamin. typically, but the quantity that moves the needle for SHBG, I believe it was like six to 12 milligrams and can be meaningful for actually liberating free testosterone, not for actually producing more total tea. The other one that's probably worth mentioning ashwaganda, specifically extract that is standardized

Starting point is 01:12:55 to a sufficient quantity of wathanolize and not just your standard running the mill, generic ashwaganda. You want to look for ideally a patented, you know, censoril or a KSM 66. These are patented formats of Ashwaganda that are standardized to a target yield. So you know that what you're getting is what you're supposed to be getting rather than relying on, you know, certificates of analysis from China of a generic extract. So what was that compound they're standardized to again? With analytes.

Starting point is 01:13:27 Okay. It's like the, it'll show right on the label. It'll be like Aspergonda bracket standardized to X. percentage with analydes. And depending on if you have KSM 66, that's 5%, censoril is 10%. The difference between why you would pick one or the other is the actual total dose you could get away with using less

Starting point is 01:13:48 milligrams of the sensoral because it has more with analytes per milligram inclusion in your product. But they're both, like, impactful. Is that the active compound that affects testosterone? Yeah, it seems to be. And when I say testosterone, Yeah, clarify. It's like the indirect effect via suppressing cortisol seemingly and kind of like the stress response manipulations that I can induce, which are favorable for people who are anxious, who have very stressful lifestyles, who could benefit from it.

Starting point is 01:14:23 But there's not a catch-all supplement that will benefit everyone. And some people that will push them into anhedonia territory, which is like a numbing of emotion. So you don't want to. Really? Yeah. if you overdo it, it will like literally suppress your stress response so significantly that everything's just like black and white. What's what's a dose that would be considered overdoing it?

Starting point is 01:14:44 And what's a dose that would maybe be effective for suppressing the cortisol response and indirectly affecting testosterone by not having the cortisol decreasing the testosterone? Like I would go with the clinically like supported dose for something that's efficacious. I wouldn't necessarily suggest somebody, you know, take something that's lower than what I've seen to actually work. But in general, it seems to be a cumulative effect over time. Maybe there are some people who might push you over the edge sooner. And like, certainly it's something to be cautious of and be aware of as a disclaimer before you jump on any testosterone, augmenting supplements, just be aware of the mechanism of how it works based on your own individual biochemistry.

Starting point is 01:15:25 Because this is not something like a vitamin D that you can just sequester into subcue fat and just like. like get rid of at some point. It's like it could impact your mood regulation quite significantly for a bit depending on like what your neurotransmitter balances at baseline. Like if you are already borderline like emotionally numb as a person and you take ashriganda, like you might literally like cease to care about anything for all I know. That sounds awful. Yeah. But I mean for someone who is more of an anxious phenotype like 600 milligrams. 600 milligrams. I think it's a dose, but double check on that because I might be misremembering. but I'm pretty sure.

Starting point is 01:16:01 And that is impactful to the tune of upwards of another 100 points seemingly. I could be misremembering exactly, but it's like I think it's triple digits pretty reliably for those who can benefit from it. And for some people, it's like a game changer supplement that really improves their quality of life outside of just the testosterone enhancing capacity of it. Because some people deal with a lot of stress in their life and need that extra resilience or suppression of how much it's affecting their mental state. Like some people, they can't even get to sleep because they're ruminating and they're constantly anxious and having that kind of suppressed stress response can be very, very net beneficial. And then on top of that, improves their sleep and also improves their testosterone through the reduction of the kind of like glucocorticoid responses. And yeah, so it works for sure. The literature seems sound on it.

Starting point is 01:16:52 Some of it is funded by some of these companies that do have the patented extracts. So just be aware of that. but at least from what I've seen, blood work anecdotally too. It seems to work. Toncat Ali, another very notable one. This is one that works through a different mechanism. It seems to be a bit more speculative how it works,

Starting point is 01:17:09 but it seems to do a few things potentially. One being a minor serum activity potentially, and this is more speculative. CERM is like a selective estrogen receptor modulator, so something that binds to estrogen receptors and either like positively or negatively modulates them in selective tissues. So there are certain tissues where it would be more favorable to have a selective inhibition of certain hormones versus others.

Starting point is 01:17:37 It would be detrimental. Like you wouldn't want to inhibit estrogen's activity and bone, for example, because that would cause bone degradation. Having an inhibition at the hypothalamus level may, depending on the person, help increase testosterone via the inhibition of that feedback loop. Now, I don't necessarily think it is a. CERM that's just like the tertiary potential mechanism and it is speculative. The main mechanism that people seem to agree on that it does do, suppression of SHBG to some

Starting point is 01:18:07 extent, as well as the upregulation of steroidogenesis intratesticularly. So like locally upregulating, I believe it's steroidogenic acute regulatory protein that basically incorporates cholesterol into the mitochondria to actually undergo these enzymatic cleaving sequences that result in the production of testosterone locally. So it seems to like help upregulate the process that actually enzymatically spits out

Starting point is 01:18:37 testosterone essentially locally. So that one seems to work well for individuals who have high SHBG levels or potentially higher estrogen levels than they is otherwise fixable via basic lifestyle changes and whatnot. Because everyone has their own proportion of

Starting point is 01:18:55 metabolism at the end of the day. It's not always going to be optimal even if you have what is otherwise like a great diet and lifestyle. But also it's just like I think it's for people who have adequate everything looks on paper to be sufficient, but their SHBG might be a bit high or they could use a little bit of a boost. And it seems to work to the tune of 100 to 200 nanograms per decilator for some people. And it depends on how potent of a standardized extract you get. You want to look for one that is HPLC tested for uricominoin, that's the active ingredient in Tonkat Ali that actually has the bioactive effect that you're looking for. There are a lot of Tonket Ali supplements that just say Tonket Ali or it'll say

Starting point is 01:19:38 Tonket Ali like 100 to 1 or like 10 to 1 or whatever. Like these are kind of meaningless numbers from what I understand. Like you're not going to get a 200 to 1 version of a Toncat. And even if you did, there's no indication there's any Uri Cominone in it. So similar to the Ashwagonda, you want some. something that actually says this is how much of the literal ingredient that does what you're looking to get out of it in it. And here's a third party test to verify it. So. And what was that ingredient called again?

Starting point is 01:20:06 Uri-C-O-M-A-N-O-N-E. Got it. E-U-R-Y-A-C-O-N-E, I think. Now, how does Tonkat-L-E compared to like boron? Is it, I mean, it sounds like for men, it might be like you're getting a bigger bang because it's doing, it's working in two different ways. Yeah, it's a good question. Boron is a mineral that is, seems to be something that is, mechanistically, I wouldn't be able to say for certain what the differential is and how they affect the SHBG binding complex.

Starting point is 01:20:44 Like I would be trying to, I might misremember and I don't want to miss a peek. Okay. Well, yeah, it's just kind of interesting. But would the Toncat, L.E, work in women as well, just. through the SHBG or maybe the board like I don't know which just for off like off the topic here boron has also kind of been thought to potentially be a longevity molecule as well there's some evidence that boron may be involved in like improving aging so yeah when you said boron I was like oh really that sounds interesting yeah I feel like that's almost like a lower hanging fruit thing

Starting point is 01:21:17 because it's just typically part of a multivitamin that may just not be dosed high enough and you can just like stack on top and see if it has a an incremental decrease to SHBG. And then the Tonkette is like more of a speculative one that you don't want to just like take until you've exhausted some of the other options, but it's like the more exotic kind of like hammer that you might want to take to the situation if it's like your last resort before. You know, I've tried everything.

Starting point is 01:21:42 My lifestyle's perfect. My diet's dialed. My micronutrients are accounted for. My sleep is good. I don't drink. I don't smoke. And my total tea is still inadequate and I don't feel that great. Should I try some of this like one of these exotic things that seems.

Starting point is 01:21:55 to have a reasonable safety profile and like an efficacious, you know, you know, impact in men and young healthy men at that. Like there are literature showing the effects in young healthy men not just like age-related, like declined men. So notable. Now, as far as its impact on women, I would think mechanistically would do a similar thing, but like I don't have a study I could point to that says it's the same. So I would think, but I don't know. Are there, are there any others? You know, I hear about, you know, the fenagreek and then the some of these like deasperic acid, are there any others that are notable,

Starting point is 01:22:29 or would you say more hype? I think a lot of those have been disproven, like tribulus, deaspartic acid, fenugurique. One that is notable that might do something as shilogit. If you get a high-quality shillaget, it may provide enough. Like the actual capacity of your organ to respond to hormones is partly conditional on its ability to tolerate stress

Starting point is 01:22:53 and reactive oxygen species locally. too. So if you have more than you can deal with and you introduce a potent antioxidant to the equation, you may be able to like attenuate and neutralize the kind of like decrement to performance and kind of like net out more local hormone yield. So Shilajit seems to be impactful on intratistical antioxidant activity. But I wouldn't, uh, it's another one that requires like careful sourcing. And it's also one that's like, more. more speculative and indirect because like there are probably better ways to manage your oxygen, like your antioxidant profile, I would think.

Starting point is 01:23:33 So your top four supplements for testosterone would be zinc, magnesium, vitamin D, not in order. Just the top three, I would say. And then I guess for impact, I would probably say like Tonkat Ali, but probably boron would be my safer next choice just for like, safe. profile. Okay. Great. And less, and then if you're like the anxious person at an asherganda and just be like cognizant of what it's how it works. Because you, you may be able to get the benefit at a lower dose. You may be able to cycle it, depending on how you respond to it, like similar to you with caffeine. Like there's no hard and fast rules on all this stuff. Like there are studies you could

Starting point is 01:24:16 adhere to like the protocols designed, but they're ultimately just designed by, you know, scientists who thought this was the way to do it. And like for you and your individual biochemistry, it may not be the way. Right. I mean, I've been interested in aschwaganda. I kind of experimented with it, like, half-heartedly, like, years ago, and I think I'm going to now bring it back into circulation. Okay. Because I do, I am interested in, in the stress management part of it, like, lowering some of the cortisol and stress, although I do that with exercise. But if there's, like, a side effect of, like, you know, just a little bit of testosterone boost, like, that would be great, you know, for me. So I think that's going to be another experiment to mine that I try out.

Starting point is 01:24:59 Check your blood first, though. Yeah. No, that's already told you I want to get my hormones. I've had them measured, but like I don't feel confident. I haven't had repeated measurements. Because once you get that blood test, you're going to be like, fuck, I shouldn't have taken Astrogon because now I have no idea what this means. What the baseline was. Yeah, no, definitely for sure. But let's talk about like, let's say people are, you know, tried all these. If you do assess your cortisol stress response, I would highly recommend a Dutch test over a blood test.

Starting point is 01:25:27 Why is that? Salivary cortisol levels are far more indicative of what's happening from a stress response standpoint. Then your like transient serum cortisol levels will be. Oh, really? Yeah. And because it's just like the snapshot in time and it in the serum is just like not an accurate, reflective measure. The salivary levels will fluctuate and they get like multiple readings. and they create like an average curve for you

Starting point is 01:25:53 and they actually map out your day as opposed to with blood you like one big draw the cortisol is measured one time and it's like okay you're like high end of normal like what do we do with that information the salivary one's a little bit more indicative

Starting point is 01:26:05 of like here are multiple time points of the day and like here's where we'd expect you to be at these points and like this is how you're responding to your day stressors kind of thing cool all right and it's like less intrusive to like spit in a tube

Starting point is 01:26:19 you know or whatever right and do that And you usually spit in multiple times a day to kind of get that. Yeah, I've actually not done a Dutch test personally, but I'm pretty sure it's just you spit in the tube. Yeah. Yeah. Okay. Good information.

Starting point is 01:26:33 Let's kind of transition to like people that have, let's say like, let's get back into the men category here that have like exhausted these natural ways. They've like, you know, perhaps lost weight or done all the lifestyle factors that we've talked about to improve their testosterone. They're both total and free. all that above. Who should consider hormone replacement therapy? Like how does a man identify whether or not they're a good candidate? I mean, is it really just recommended for men with clinically low testosterone and symptoms? We kind of touched on this a little bit earlier,

Starting point is 01:27:13 but I kind of want to just go into this area now of actual testosterone replacement therapy. So, like, there are definitely scenarios in which it's more obvious because there is a structural issue that cannot be rectified via any sort of lifestyle change or like sleep hygiene manipulation or whatever. Like, if you have primary hypogonadism and you've ruled out the ultrasound, like vericose, yeah, there's no issues. You're not like cooking your testes in like a hot tub every night. You're not, I don't know, like your sleep is dialed, your micronutrient.

Starting point is 01:27:49 intake is on point. Also, satisfactory amounts of calories, like I think I might probably indirectly touched on this, but like via the getting to a good body fat, like you still need to have an adequate amount of energy to actually meet the needs to produce hormones too. So like adequate amount of calories, not overdoing it and underdoing it.

Starting point is 01:28:09 If you've done all the stuff that we kind of like talked about and you've ruled out pituitary adenoma, you've ruled out any sort of, sort of like, I don't know, like structural defects and signaling is adequate or even supra physiologic and you're just not responding. Like at that point, it's kind of like, okay, we could try hammering you with some HCG and see if we can stimulate a satisfactory response with like a manual, like, extra push at the light Excel or use some, you know, some of these other like augmenting, you know,

Starting point is 01:28:46 steroidogenic supporting things like Tongat or whatever. But if that's not working either, like your testes are cooked, then you've got to be on test at that point because you're just not responding to any natural stimulation whatsoever. That is not typically the outcome of a lot of guys who end up on testosterone. A lot of guys end up on it through like secondary diet, like hypogynatal symptoms through like the pituitary, either inadequate output or

Starting point is 01:29:15 insufficient response to that output plus an insufficient amount coupled with it coming out of the pituitary there's not a lot of people that are literally showing up with like your testes don't respond to whatsoever um in those individuals like it's app it's kind of like if you've exhausted all resources you've tried the whole manual stimulation directly because acc is the way you would actually test that out is you would actually look at okay if we actually hit your lighting cells directly with a signal and we escalate that to like the maximum degree. And we use FSAH2, exogenous. It's like, if you're still not responding to that,

Starting point is 01:29:51 like there's no saving it at that point unless you have like such a significant amount of oxidative stress that you're just like not dealing with. But that would have been taken care of with the lifestyle stuff we mentioned. So primary hypergenital, like you're going to probably be on exogenous testosterone. And it's literally like testosterone. You can't fix it with enclomaphene.

Starting point is 01:30:08 You can't fix it with HCG. You can't fix it with HMG. There's no other way around it. Like you're taking the literal hormone because it's the only thing. that will get you testosterone. Like you can't produce it. So there's that. And there's different ways you can take it, of course,

Starting point is 01:30:20 which we could, you know, get into later. But the next situation that's a bit more relevant is like the secondary hypogonadism situation where somebody has, like testes that function just potentially to like a suboptimal capacity. And there might be some level of like low gonadotropin output facilitated through some level of like, lifestyle or diet or whatever um like peter for example like he's pretty dialed and like he did a lot of

Starting point is 01:30:51 stuff to try and like fix it before he went to any sort of replacement sleep hygiene is on point like the guy like what else could you do when you're him right he's i think 50 years old so what he did was he used HCG which was assessing okay like are the test he's responding to like a manual signal and they were and he's like replaced his hormones entirely by using a manual LH mimic essentially why his pituitary wasn't shooting out enough LH to hit the amount, like the enough

Starting point is 01:31:22 stimulation he would need to produce the same amount of test that would hit his like optimal variety of factors, age related decline, who knows, but probably a combination of multiple things and at that point it's kind of like do you want to manually backfill with signal or do you want to take hormones

Starting point is 01:31:38 pending you've done all the exhaustive you know things to try and like check the boxes because you know some people don't care as much and don't want to check the boxes but like in general i would say it would be worthwhile to learn why you have the problem even if your intention is to just end up on testosterone anyway like i wouldn't i wouldn't delay treatment if you're symptomatic and it's like hurting your quality of life but i also would like do some due diligence to just like assess like what's happening and i think hcg for people who are like secondary

Starting point is 01:32:10 hypogynatal is sometimes a good middle ground of assessing like is this a testicle functionality problem or is it like my pituitary output is not sufficient because at that point you can kind of tell like which organ is it that's failing me here so there's that um and then like upstream to that there's the actual hypothalamus and the gnrh output which is the thing that stimulates the pituitary to make the lh and the fs h and throughout that whole cascade you could have insufficient signal from that, insufficient response to that signal, and then insufficient pituitary output from that weakened signal

Starting point is 01:32:47 and the response to it. Like, it's a deteriorating thing that by the end of it, when it actually hits your test, these may just be like suboptimal for your response to be adequate through often age-related decline, but it's a culmination of things.

Starting point is 01:33:02 So certainly back to the original question, like, how do you make sense of all this and decide when is the appropriate time to be on hormones versus not? that's where you'd have to work with like a really highly educated medical professional in general. Like I would not try and cowboy this yourself. Even trying to like learn it from, you know, online content, whatever. Like I think it's good to learn how this stuff works mechanistically.

Starting point is 01:33:27 So you go in and form and don't end up putting on a haphazard regimen by a doctor who actually just wanted you on medications. Because if you know this stuff, it's pretty easy to identify who's like a shitty clinic who just wants to like, get you committed and stuck on lifelong hormone support. And you can weed it out really quick. Even if the doctor seems well intention, he wants to help you, he wants to support your quality of life, says all the right things,

Starting point is 01:33:50 seems professional, seems knowledgeable. If you don't know this stuff, it's kind of like you would be going in blind and assuming that's what you need to do and a lot of people just end up on hormones and that's it. And sometimes there's nothing wrong with that.

Starting point is 01:34:02 Sometimes that might be what you need, but sometimes people want to know what were the natural avenues I could have taken. Could I have done something else? could I have maintained the signal from my brain to my testes this whole time? I'm just missing something. No, it's a really good point, you know, and also, like, talking about what any, you know, key risks and side effects are as well. So, I mean, that's, that's kind of important.

Starting point is 01:34:23 But, like, before we get to the wrist, like, what kind of benefits for can someone who is, you know, clearly, like, experiencing these symptoms of low testosterone expect from, you know, perhaps doing testosterone replacement therapy? I mean, you mentioned HCG, but I'm kind of here directing it more towards like actual testosterone placement therapy. Yeah, it would be in general if you are satisfactory in your replacement of these hormones to a physiologic replacement level. Like you should notice the amelioration of all symptoms. That's the best way I could put it. Now, again, it's obviously you should not expect that you're going to feel exactly the same as you did when you're like 20 years old. Like I think some people think when they're 50, oh, I'm going to get on TRT and it's going to be, you know, like being 20 again. And like to some extent it could be because like on paper like your test levels might be the equivalent.

Starting point is 01:35:24 But it doesn't mean the way you metabolize the hormones into estrogen is going to be the same. It doesn't mean that the way you respond is going to be exactly the same. in general though the target is to ameliorate the symptoms and then like dial in from their kind of thing so like I think what people should expect is like the intention of it is get rid of your symptoms similar to like menopausal therapy like you want to get rid of your hot flashes you want to ensure that you are not like your bone integrity is like actually supported like all these things are like your baseline requirements of why you're doing it is just to like get rid of the negative and get to a baseline. Indirectly, you will feel much better. So it's like

Starting point is 01:36:06 you will feel better from the result of it, but like don't expect to be Superman unless you're, you might feel like Superman relative to your state. It just depends how deficient you were to begin with. And it's all contingent on multiple things. So it's hard to put hard and fast generalities on this stuff. But like your target should ideally be symptom relief. Right. So you're not like necessarily going to be shredded in a couple of weeks. And yeah. I mean, I think, you know, it's important to point out, like, some guys might see that their testosterone is, like, on the lower end of the normal reference range and, like, want to do something about it, like, with respect to, like, not, skipping over the lifestyle factors and just, like,

Starting point is 01:36:45 I'm going to go straight into, like, I'm just going to take some testosterone, right? And I think that would be the case to avoid, right, if you're not, especially if you're not really having symptoms, but you're just kind of, like, freaked out by the numbers, right? Yeah, I definitely wouldn't make any rash decisions based on numbers on a piece of paper, because I know a lot of guys who like the best physiques in natural bodybuilding are like guys with 500 total testosterone. I know guys with three times the amount of testosterone production, much worse physique.

Starting point is 01:37:13 Like it's not always the number on a piece of paper. It's your genetics, your response to it, literally how many muscle fibers you have at birth. Like there are a lot of factors that determine what you're going to look like, how you're going to respond, the shape of your muscle bellies and how they appear to people, your body fat level especially, Like if you are leaner and you will just appear more muscular, you know, stuff like that.

Starting point is 01:37:33 Right. Yeah. Okay. So let's talk about some of the important risks that, you know, people should keep in mind when they're going to start testosterone replacement therapy. I know you've like talked about this, heard about it, like the cardiovascular disease risk. I mean, for a while it was a controversy, right? Like doing testosterone replacement therapy is going to increase your cardiovascular disease risk. there's the traverse trial that came that's kind of we got some pre pre public like pre pre pre data here where it seems as though this is very large trial placebo controlled where it seems as though men these are older men that were at least it seems to be hypogonadal like they were low testosterone and if they were given testosterone replacement therapy to a normal like physiological restoration range there's no really adverse effects on

Starting point is 01:38:22 on cardiovascular outcomes. What are, what's, what's the thought here with respect to cardiovascular disease risk? Um, I think the only issue is like defining what restoration of physiological testosterone production equates to is like when we were talking about like coffee and like how much caffeine is in a cup of coffee. Like it could vary so much. So like some guy's replacement to adequate physiological replacement, what he was when he was younger, highly variable.

Starting point is 01:38:53 And in that traverse trial, using AndroGel to bump your total T from like hypogynadal to like 400 is not necessarily indicative of what I would say a lot of people are looking to the data to see what the results were of testosterone therapy. Because a lot of guys are on injectable test boosting to 1,000 total T with a disproportionately high free testosterone. Because when you inject infrequently, too, you drive your. SHBG down proportionally. That is not the same as a guy who's using androgel to get to like 430 total T.

Starting point is 01:39:29 So taking that outcome and running with it as like no cardiovascular risk. I think that's a bit haphazard personally. Now it's obviously promising data and like it's great that it came out. Like it's very, very promising. The only problem is like how many guys are actually using that medium of therapy like, I don't know, none? Like I don't know a single guy using androgel. And that's fine.

Starting point is 01:39:50 Like it's still data and it's still. worthwhile and still good. It's just like not don't take that as like the the sign off that like you're you know 200 milligrams of testosterone an an ananthate per week that you're like you know more aggressive protocol has been designed to do is like going to be the same outcome like it's not you're going to have the erythropoises increase that might not be reflected in the traverse trial you're going to have the disproportionately high energetic signaling like you're going to have a lot of things that you were looking to get the reassurance that won't happen, but you have absolutely need to be cognizant of because it will probably happen still.

Starting point is 01:40:32 Yeah, this is, this is so important. And that's kind of why I was like, these are hypogonatal. And, you know, it's like, I guess their normal physiological range, that's not really accurate if it's only going to like 400. So basically you're just making a non-hypogonatal. But it is important because you mentioned your. rithroporesis. And so this is, this is another kind of concern, you know, with testosterone, which does regulate red blood cell production. It does increase, you know, the thickness of blood.

Starting point is 01:40:59 And polycythemia is a, is a, I would say, a risk factor, right? So, you know, how substantial is this? I mean, I think I've read studies where it's like almost 25% of men have thicker blood that are on testosterone replacement therapy. Now, it doesn't necessarily mean it's like to the point where it has to be treated, but it is thicker, right? It is like the hermaticra is, is thicker. So, you know, how should men weigh these risks for the cardiovascular disease risk, the polycythemia? So for people like listening or watching, that isn't a concern because it increases, you know, stroke risk. It increases the potential for, you know, cardiovascular events as well. So, like, what are your thoughts on sort of weighing those risks?

Starting point is 01:41:53 To the opposite side of the coin on that androgel, you know, like, it's not necessarily physiological replacement. The thing to note is it should be expected that if you use more testosterone, you're going to have more of the arthropoises. Like, that's literally what it does. So to think that it would be a net negative because you have a 25% increase in that via your testosterone administration, if you were hypogynal to begin with, which presumably is the reason you're getting on TRT, you know, depend on the person, but like going from hypogynatal

Starting point is 01:42:29 where you might be like borderline like anemic for all we know and then having the 25% bump, like maybe you need that to actually like have adequate oxygen carrying capacity and like actually sufficiently fuel your body. So it's not to say it's like net bad, net good. It's all about where do you achieve like the problem is like, the definition of symptom relief too is so vague because you could achieve symptom relief at you know 450 total T maybe depending on the person or it might be at like 800 or it might have been like even if it was 450 like if you got up to 800 you're still in normal on paper so like is that bad you know who's to say yeah well i think most people would say it's the high of normal because

Starting point is 01:43:11 that's literally what it is on a reference range so it all is going to be just being cognizant of the fact that androgens will do what androgens do, which is they will in a dose-dependent manner derive retropoises. They will induce cardiac remodeling if you push it too hard, not necessarily within physiological limits, but like these are things to be aware of.

Starting point is 01:43:31 Dislipidemia will become more of a concern at a higher level, especially depending on the medium of administration if you're dosing infrequently, like once a week with a shot, it's going to be a different outcome than if you're doing like daily, you know, little pulsatile cream administrations

Starting point is 01:43:46 or like micro injections like subcutaneously where you're bleeding out the effect more, it will all be impactful. So I think it's more about there is a risk all but there's not going to be data that says directly if you replace a 800 total T it's going to be dangerous, nor is there data that says it's safe either. Like you can kind of take from the diverse trial what they found and extrapolate out like what you know from graded dose response studies, which do exist and like realize, okay, like somewhere in the middle here, if you're one of those guys who like wants to hit that, you know, high normal

Starting point is 01:44:24 because I don't know, like, who's to say you're in the wrong for wanting to be like optimally vital to it all kind of depends on the person. You have to weigh the risk accordingly because it's not risk-free. You're still going to have to keep an eye on your hematology panel. Is it getting out of whack to a degree that is like unsustainable? You're like looking at phlebotomy. is just to maintain something that looks normal. Or is it like adequate slash like optimal for you now to feel like you have enough energy to not like faint when you get up?

Starting point is 01:44:53 I don't know. It depends on the person. Yeah, it's just like an understanding of all of the interplay of things and not taking the sign off, you know, the one, the traverse trial is like, you know, you get out of jail free card. Like it's just you're still going to have to keep an eye on your blood work. You're still going to have to have like a doctor who knows what they're talking about

Starting point is 01:45:10 and is like very rigorous about this stuff. You have to know how. how the different administration methods and frequency will impact things because like you're probably not going to be on androgel using a little dose that gets you to 420 nanograms per deciliter you're probably not on that protocol and if you are like yeah okay look at the traverse route and like maybe you can get like a bit more

Starting point is 01:45:29 reassurance but like you're probably not that guy and that's fine if you're not it's just like being very realistic about what to expect and you know there is uh dyslipidemia there is an increase in blood viscosity to some extent there will be a uh suppression of SHBG if you're doing injections infrequently, which will elevate your androgenic signaling beyond what is physiologic. Like most people are supra, at least transiently,

Starting point is 01:45:56 without knowing it. And by that I mean, by supra, I mean like more than you would have produced physiologically because it's not physiologic to have your hormones transiently shoot to like, I don't know, 1,500 or 1,500 total T with a disproportionately high free testosterone own from administering once or twice a week, twice a week's quite a bit better, but once a week,

Starting point is 01:46:17 for example. And then it crashing back down before you shoot again, like, that's not physiologic really at all. So you need to be aware. That's going to cause more elevations in these like problematic biomarkers than would be if you tried to maintain what is reflective of like daily normal production. So like the ideal protocol would be literally replacing your daily testicular output, which is adherence problematic for a lot of people because not everyone wants to be using like a scrotal application of cream twice a day. A lot of people don't want to be injecting

Starting point is 01:46:51 daily subcutaneously with like a micromanent testosterone. They just want to be one and done, one shot a week. Even some of the problem too is like the pharma has set it up so you might be forced to take it infrequently and at a high dose because they have these auto injector pens that are preloaded. So you like have to shoot it in one shot or you don't take it.

Starting point is 01:47:11 Yeah. So like Zyestead is like the preloaded testosterone and an anthate pharma grade that is often prescribed. And it's like, well, you either do the one shot, one kill and take the whole dose or you like don't take it. So you're touching on an important point here that superphysologic level, like the amount that you wouldn't necessarily have in like a normal physiologically. I mean, I read a study where it was like 25% of men have this. And it seems like it might be due to this, like, dosing, this injection, you know, protocol. What's wrong with the cream? Like, is that something that doesn't get your levels high enough?

Starting point is 01:47:49 Or is it just, like, annoying to have to do every day? It kind of, I mean. It depends on the person because it would be personal, subjective opinion for me to say, like, why I wouldn't want to do it. In general, the reason most people don't want to do it is adherence lifelong. Like, this is something you're going to do for. forever, typically. Somebody going to apply a cream to their scrotum twice a day, it's not that fun. Like, it's like something that you have to go out of your way to do, wherever you are,

Starting point is 01:48:21 you're traveling, whatever. Like, you will go hypogynatal with pretty quick if you don't get in the bathroom and wipe some cream on your balls. Yeah. That's not. I mean, I get that, but like, you know, like stroke risk, cardiovascular disease. Oh, yeah. If you want to be optimal, the problem is a lot of people will favor.

Starting point is 01:48:38 over adherence and sustainability, similar to diet, over optimal. And that's fine. Just you have to be accepting of the risk profile that comes along with it. Okay. What about other, like, parts of the risk profile? So, like, how does it affect the prostate? I read about fertility. I mean, being a big one, too, it's suppressing fertility.

Starting point is 01:48:58 Yeah. Sleep apnea can be exacerbated as well. I mean, these are all, like, part of the risk profile things to consider. Yeah. When it comes to prostate, that is something that, at least based on the most recent literature that I'm aware of, is, are you familiar with the androgen saturation model? Basically, if you go from hyper. Oh, yes, yes. Okay.

Starting point is 01:49:20 But go ahead. Please explain it. Yeah. So essentially, from what I understand, based on most recent literature, it shows that if you go from hypogynatal to huginatal or like the threshold of it, which is like, you know, on a reference range roughly like 300 plus nantigrants per death. decilator going from hypo to that that differential will be positively stimulating of like prostate growth you know PSA levels will go up etc but beyond that you are not necessarily in a dose dependent manner like a muscle or something going to be inducing size increases like if you took even if that were the case you'd have bodybuilders who take you know thousands of milligrams of steroids

Starting point is 01:50:02 per week they would have prostates like busting out of their bodies at that point so it's not necessarily the case, but it's not like it's still worth monitoring your PSA for trends and longitudinal patterns as you get older because like it will still have the same, you know, susceptibility to things that happen as you age. But the actual impact on prostate related issues and like growing cancer from scratch, if you don't have preexisting cancer cells, like you're not going to just like spawn cancer from taking testosterone. So I think that risk is a little bit overblown. Fortunately, we have data that seems to be pretty strongly indicating that you're not going to have to worry about that if you are somebody who is otherwise healthy, cancer-free, and you're just going

Starting point is 01:50:42 from like, you know, like you would probably have a small prostate to begin with if you were hypogonatal anyways. You're probably just going to where you would be if you had normal levels. So it's not like that growth is even bad either, getting to the eugenital state. So just keep an eye on the PSA and be aware of it, but it's not something that seems to just like dose to pendently escalate. The other stuff is worth mentioning. Um, like you in general, like when I said testosterone does testosterone things in a dose

Starting point is 01:51:10 dependent manner, even if your protocol is dialed in, if you are producing more than you would physiologically that your body can tolerate as well, like you will have the whatever backhand consequence of managing the extra estrogen, the extra DHD, you know, that could lead to extra acne, hair loss, gynaecamastia, if you have excessive aromatization locally in the tissue that is not antagonized sufficiently by the D.HT. and testosterone signaling. Hair loss in the scalp. Annoying body hair that sucks to get rid of if you care about that sort of thing. More facial hair growth, deepening of the voice, more than you already have as a male,

Starting point is 01:51:52 surprisingly. that there's like often like if you're if you were low to begin off like typically guys who get on and then like push their test levels up to high normal especially we'll notice like a little bit of a deepening um like these are all kind of like the kind of like the maximization of the male secondary sexual characteristics being like pushed to the nth degree um within physiologic parameters um sleep apnea will get exacerbated pending your neck size increases muscle increases in size, things that are contributing to the obstructive nature of your soft tissue falling into your airway will get worse pending you are dosing in a manner that pushes you there. So if you're physiologically replacing, like a lot of this stuff is probably a moot point, but a lot of people won't be. They'll be pushing to optimal, optimal, quote unquote, which is fine.

Starting point is 01:52:47 Just be aware that you will potentially increase your risk of sleep apnea and keep an eye on it. I would absolutely recommend anybody, even before they get on TRT, get their, like, a basic sleep study done. It's a lot less intensive than you might think. And there are actually, like, pretty reasonable at-home devices that measure, like, apnea episodes per hour that will, like, essentially put you on a chart of how many episodes of, like, ceasing breathing, are you having per hour?

Starting point is 01:53:14 And you could have a baseline there and see if that goes up when you get on TRT. So it's not like this is a questionable, like, what's going to happen in your sleep apnea susceptibility? like literally measure it. Like you have your baseline when you're not on it. Now you're on it. What's the difference? And like you would see in real time the literal diagnostic metric either going up or not changing

Starting point is 01:53:30 at all and then you would have your answer kind of thing. But it is a possibility for sure. Just like any of the stuff is. But if you're physiologically replacing, like the risk is relatively low. Unless we're talking about that super physiological level where it seems as though like one in four men don't even know they're in that level. They are. Even transiently.

Starting point is 01:53:50 Transient. In blood work. If you, for example, if I'm on Zayestead and I'm shooting once a week an auto-injector pen, and I'm checking on trough day, which means like typically a lot of physicians will say check your test levels on like the day where your test levels are lowest based on the pharmacokinetic profile of whatever the format of testosterone you're using. So if you're on a long astrotestrotestrone formulation, like a testosterone cypunate or an an ananthate, these are the typical prescriptions to make, allow you. to get away with dosing only like once or twice a week for adherents. But the reflection of that in blood work is you would typically see because you're bolus dosing it at once,

Starting point is 01:54:33 your bloodwork would shoot into supra range, depending on the total dose, of course, but like a lot of people, this is what happens. They shoot into like, I don't know, 1,400, 1,500, 1,500 total T with the proportional 5-alph reduction to DHT,

Starting point is 01:54:48 suppression of SHBG, disproportionate freeing of free end. signaling via more dh t being free than would otherwise be normal more free tea than is proportionally normal more aromatization than would be possible if that dose was like even spread out on an even curve throughout the week on micro injections increase in erythropoesis acutely beyond physiologic you know capacity to you know an unhealthy acute level at least for a periodic period of time and then you're in like a slow or steep depending on like the esther crash essentially into like sort of normal looking territory until your next shot.

Starting point is 01:55:26 I think that's the reality for a lot of guys. In Europe, they do testosterone, uh, undecanoi, maybe, or it's either a sustenone formulation. Maybe it's undecanoi, and they'll do like one shot every like few weeks.

Starting point is 01:55:38 It's crazy. So they'll like shoot their test into the stratosphere. And then they'll like crash into hypogynatal territory and then they pin again. Or shoot, inject. That's what I mean by pin. Yeah. Mike, I mean,

Starting point is 01:55:48 so. It's like a roller coaster of like, I can imagine it's like, like the equivalent of what females deal with times like some magnitude. I mean, it sounds, they must be like, also just like, are they get aggressive and stuff? And like, irritable, rigid regulation and be like impossible to expect. You know, like, I don't know. Like, I wouldn't want to wish that on anyone.

Starting point is 01:56:14 Like, that would suck. I mean, to me, so like, let's say adherence, like compliance, like compliance, that's a whole. that's a whole issue, right, obviously. But let's just like, if we're just talking about risk profile, right? Like you're not wanting to really get into that supra physiological level. You're not like, you know, you're not like the bodybuilder. You're not like, you know, you're the person that just really wants to keep that risk low, but you want to get the benefits.

Starting point is 01:56:42 Okay. Like that's what you want. You really don't want the risk. Like just not on the table for you. What would be the best? There's the different methods. You kind of mentioned a few. Maybe you could kind of just go through them again briefly, but like what would be the best method to get you to a more normal range?

Starting point is 01:57:01 Maybe you're not someone that's totally hypogonatal, but like, you know, low-tie symptoms, right? Lower tea and symptoms. What would, what you're aging, maybe you're an aged, you know, like a 50-year-old man or something? What would be the ideal delivery method that would really get you those benefits, but lower that risk profile? while. Yeah. And one thing just to add before we entered that sub-topic, I do want to clarify, if somebody was to take an amount of testosterone, even if it put them to like high normal of the reference

Starting point is 01:57:37 range, but it was something you tolerated in youth and like your body was capable of handling, which a lot of people are. If you do it responsibly, understand what you're taking, know how to monitor your biomarker, are lean, healthy, have a good diet, lifestyles dialed in, you're aware of the risks. All that stuff is like overseen with a level of education

Starting point is 01:58:01 and some level of rigor and like obviously decreasing need. Over time as you start to dial it in, it's not as like rigorous of an oversight process because after you're in your dialed protocol, it's just kind of like living your life and you know what to expect from your blood work at that point

Starting point is 01:58:15 and how it affects everything, you'll probably be fine. Probably. It's just being aware. it's not zero risk. Like it's just like that's the thing people need to accept if they want to be pushing, you know, to some level that is like,

Starting point is 01:58:31 just in general, like it's never going to be risk-free. But I could still also say with certainty that if you're hypogynatal, you're going to be healthier replacing to physiologic than you would staying hypogynatal for sure. Like you are a thousand percent in cardiotoxic, neurotoxic quality of life down the, you know, the toilet territory

Starting point is 01:58:53 if you're like in hypogynatal levels almost certainly. So hopefully that's like somewhat of a consolidated a raft because I don't want to like sound too it's worth being cautious and aware of all this stuff but like it's certainly not to

Starting point is 01:59:09 don't dissuade yourself out of like fixing your levels too. Like it's critical that you have adequate hormone production similar to women in menopause. Like the benefit outweighs the risk like essentially every single time essentially and you just have to be responsible

Starting point is 01:59:26 your approach to what that is. Well, especially if you're monitoring biomarkers and we'd love to like talk about some of those in a minute but I think that's the key to right like monitoring right. Yeah. Okay. So then circling back to administration

Starting point is 01:59:40 like the ideal way to go about it. I can say off the rip I would not do pellets. I would probably not do andro gel if you're a male. If you're a female, it's a bit different, which we can get into. The creams through compounding pharmacies, that's probably the only, like, tolerable way you're going to have something that you can apply scrotally to get the ideal absorption pharmacokinetic profile that would be reflective of something that's, like, more natural.

Starting point is 02:00:08 So, like, that is probably on paper, arguably the best way to go about it. It's just not necessarily something everyone wants to do, but it works well, and it will get you to the levels that are great and look pretty physiologic and like kind of reflect the pulsatile diurnal nature of normal testosterone secretion and it's also converting like locally like in the area you would actually be producing it too like there is a local effect too through like five alpha reduction in the skin and stuff like that um which can result in that's why monitoring like dht and some of this other stuff can be important but that's like a whole more nuanced discussion But in general, the cream scrotally is reliable, good, produces a very favorable outcome.

Starting point is 02:00:53 And a lot of guys will be quite happy with that method. The other method that I would say is worth considering. And like the typical one that most guys do is injection, which it's a bit more predictable, typically, in terms of like what you're going to get out of it. In terms of adherence, it's a lot easier because you don't have to shoot it daily. You can also modulate the release pattern of it through either the ester. So like you'll typically get prescribed like the longest bleed ester. So Cipionate has a half life of like, I think it's like 10 days or something,

Starting point is 02:01:24 eight to 10 days depending on how, depending on individual biochemistry and how you kind of like cleave the ester. But you can also change the way it absorbs via injecting subcontaneously into stomach fat or into any subcute fat versus intramuscularly where it's more quickly going to get absorbed and assimilated. So you can also bleed out the effect even more and make it even more stable in your blood levels. And it's pretty easy to adhere to a TRT protocol of like micro injections, even on like a relative frequent basis, like every other day is pretty damn stable. Subcutaneously is what a lot of guys do and works really, really well. And, you know, it keeps a very stable hormone concentration curve. It's pretty predictable and what's going to happen.

Starting point is 02:02:12 You just kind of like got to be aware of the, you know, how hard you're pushing it and what that will do to your risk profile accordingly. The other way that's promising that I would say is oral testosterone undecanoate lymphatic absorption patented format. So there is three, I believe, Tilando, Jiteno, Jitzo, and Keizotrix. And they've basically managed to make a lymphatically absorbed testosterone undecanoate. You can actually swallow orally, whereas back in the day they would have had to make it hepatotoxic to actually make it through the liver,

Starting point is 02:02:47 through first past metabolism, and actually, like, make it into circulation to any meaningful level. They'd have to, like, add, like, a 17 alpha-alkalated group to it and make it, like, a terrible for you oral steroid, essentially. This does not have the same level of stress. It's not stress-free, as far as I know, but it will get you a meaningfully significant, like, get you replacement of total T levels to, like,

Starting point is 02:03:12 mid to high range depending on the person likely achieve symptom relief for guys who are hypogynatal and is pretty sustainable because you're just popping something so some people prefer that pretty expensive though and kind of like a newer medium of administration but promising nonetheless typically what guys are doing those still is the injections or the cream and the other method is intranasal

Starting point is 02:03:37 which I'm sure you've probably heard of for like you know, hypoactive sexual disorder for women has a potential for that, as well as for men as like a different medium of getting like an erythro poesis stimulating free version of test because it's so acute. It's just like an unsustainable daily treatment, unfortunately. Like it's okay if you're trying to have like an on-demand libido boost as a female or something, but for a guy using it like multiple times a day in snorting something. It's like not something any guy I think would want to do for, and even if they think it's cool to begin with,

Starting point is 02:04:14 I think for once you get to like the month or a couple month mark, the novelty would probably fade. Like a lot of guys are, you know, super excited when they start testosterone injections. Like it's like this roster using like this hormone and it's, you know, I'm replacing and it's, you know, it feels like this big significant thing. And then, you know, year in, it's just like, oh, I've got to do my injection. So it's like whatever you can most sustainably adhere to that is like the safest will achieve the outcome you desire, the symptom relief is the one you should stick to. And the cream, I guess I didn't mention

Starting point is 02:04:43 the obvious, but like transference, if you have children, you have pets, like there are concerns with, you know, like what you are going to rub it off on and like how like your hygiene with it. So that's worth mentioning because like there are cases of transference issues that have been noted in media, you know, I think I did a video a while ago where some dad accidentally he was like wiping residue on his kid without even realizing it even after he like thought he cleaned it and his kid was like starting to get masculineized from the from the testosterone residue or something wow yeah crazy because it's like the levels are so low like any like significant amount will like push things in like a significant incremental direction that is like going to cause problems

Starting point is 02:05:29 so that's a thing whereas injection it's like you're in the bathroom you do it and it's clean and done totally sterile you don't have to worry about like are my hands fully clean you know is somebody going to get into it like good luck accidentally like breaking into like a multi-dose vial or something it's not going to happen so yeah there's like different like logistical advantages too to some of these administration methods that probably should not be understated but are worth mentioning so yeah i think the three most viable cream scrollel application injection intramuscular or subcue if you want to bleed out the effect or maybe the oral, all but I want to see more of the literature as it evolves.

Starting point is 02:06:15 Right. So it's kind of a newer thing. And when it comes to the injections, it sounds like more frequent subcuteinous is like, subcutaneous is like where you're going to get more, less of the probability of having that supra physiological peak versus like if you're just doing it once a week, intramuscular, not bleeding out that.

Starting point is 02:06:34 like response their effect. But again, as you mentioned, compliance is definitely going to be better if you're doing it once a week. But I mean, twice a week, three times like every other day, I mean, you know, for people that are that are really concerned about risk profile, perhaps they have already like, you know, a family history of cardiovascular disease or stroke or whatever, they probably are more incentivized to like lower that risk for any potential side effects. Yeah, like in general, I think. Or fertility.

Starting point is 02:07:03 What about men that are wanting men that? Men that are wanting to reproduce. Yeah, we got to talk about that to you. But one rule of thumb that's like to make it as easy to understand, at least for me, this was the easiest to understand, like, how I remember it is the closer something is to what would be equivalent to what you would naturally make should you have had, should you have healthy functioning testes, producing natural testosterone, that's going to be the one that has the least impact on all of the, like, intentional consequences. of like spikes in hormones. So like normally on a daily basis you would pulse out like in ebbs and flows multiple times.

Starting point is 02:07:42 So like the more you can get these like the more stable you can get it with the more micro administration spread throughout the week, the more stable everything will be. And as a consequence, less spikes into the territory that would produce things that are not representative of physiologic.

Starting point is 02:07:57 And typically daily administration is the way to go, whether it's like, Cream is going to be twice a day at least, but then for injection, it's like every day and every other day, there's diminishing returns, but you can kind of, like we said, bleed it out a bit. So, yeah. So as far as fertility goes, yeah, like you will absolutely crush your fertility pretty significantly, if not entirely, depending on some things. So intratesticular testosterone is the significant mediator of spermatogenesis. So it's not uncommon, even for bodybuilders who are on huge amounts of steroids to still accidentally get their wives, girlfriend's pregnant, thinking that they're sterile when in fact they have so much testosterone in their body that it's like actually like producing the spermatogenesis effect via the exogenous hormone.

Starting point is 02:08:54 What that does the epigenetics, all that stuff, no idea. Would freak me out of it. Well, like, it happens. And it's like on paper, these guys should be completely infertile, but still see accidental pregnancies all the time in the bodybuilding world. So I wouldn't rely on that as a means of a contraception as a guy, first of all. But you will almost certainly have like inhibited to like horrifically low, if not azuspermic level fertility if you were on even just like baseline replacement.

Starting point is 02:09:25 Because you are shutting down the signaling from your brain that other ones, dictates the intristicular activity. So by that, I mean the hypothalamus releases the GNRH, the gonadotropin releasing hormone. So it's the hormone that causes the release of genotropins, hence the name. At the pituitary gland, the pituitary response to that GNRH to then produce the gonadotropins, which are the lutinizing hormone, LH, and the FSAH follicle stimulating hormone, just like in women, goes down to the gonads. and the thing that happens is you produce intracusicular testosterone at the lighting cell

Starting point is 02:10:03 and women do too it's just thichic cells instead of you know lighting cells and that intrasticular testosterone mediates spermatogenesis in unison with the certoli cells which are also supported by follicle stimulating hormone so if you have exogenous testosterone like you're administering it yourself synthetically you have basically told your brain, I have enough estrogen and testosterone via this injection I'm doing or whatever it is. So you can not produce any more GNRH because like, why would we need you to? We have enough hormone. It's like, okay, let's turn that off. Let's turn off. As a result, we have no signal to produce pituitary hormones or the genadotropine. So we turn that off.

Starting point is 02:10:48 And now you have no signaling to your testes. And now you're just like literal organ atrophy is occurring because there's no signaling happening there. So the only thing you can really do at that point, if your HRT protocol is not built around replicating manual signal, because that is a means that some people do. If you have adequate organ function, you could theoretically do that instead of TRT. But if you're going to be on TRT, you either replicate that natural signal

Starting point is 02:11:15 or you sustain organ atrophy to the point of potentially some permanent likely deterioration, all but likely not inability to restore fertility and it's very rare that I see guys who are actually like not truly fully hypogynatal like their testes still work they just hit inadequate signaling or something via like secondary hypogonadism if those individuals maintain the signaling you can retain the structural integrity for the most part of the testes and then if you want to get pregnant or whatever you are either a currently fertile still because you're manually stimulating it or you could

Starting point is 02:11:58 like you can basically manually manipulate how fertile you are in real time essentially so you could fully retain all fertility parameters even push them to super levels if you wanted to i don't recommend it but like you can maintain everything while you're on testosterone via that manual signaling of hcg plus recombin fs h that's like the combo that basically replicates what would otherwise be the lh nephisates from your pituitary to your testes you maintain structural uh the size the functionality sperm production etc but then you also have to account for the extra testosterone you're producing that's stacked on top of your exogenous test now so now your dose might have to change and the amount of estrogen there's like local

Starting point is 02:12:44 activity in the testes for how much aromatization happens and whatnot which is different than if you're injecting it like in your butt or something so you have to account for that differential too some people get highly estrogenic from hcg in particular, which is like a female, like literally in pregnant women's urine to stimulate light cells. That's what it's like purified from. And, you know, there's some speculation as to if HCG is like healthy to be on as a guy. Like you're taking like an extract of like women's urine. It's like a light cell stimulator similar to LH and seems to mimic the effects of LH, but it's still not LH. It's HGG, which like human corinic gonadotototin isn't what comes from your pituitary

Starting point is 02:13:26 to your testes. It's just something that stimulates the lighting cells significantly. So do we see any like notable effects on like, I don't know, epigenetic modifications from HCG plus FSA-mediated babies, like not that I'm aware of, not that I've seen any literature point to, but it's worth noting nonetheless that HCG is not like a bioidentical genadotropin for men that you would otherwise be using to shoot to your testes. It's like a replacement for it.

Starting point is 02:13:54 and recombinant FSAH is like it's FSAG but it's still like grown in a lab it's not from your pituitary does that matter I don't know for sure but either way you can maintain your fertility metrics to the literal baseline if you had an adequate adjunct therapy it's just very cost prohibitive like the cost of recombin FSAH is insane and HG in itself is expensive and then you're stacking that on top of your testosterone that you're using it's not necessarily an affordable thing for everyone so a lot of guys guys just let their test these atrophy because that's what they can afford to do and they want to still get the symptom relief and then once it comes time to have a kid they have a bit of a more intensive protocol ahead of them to restore organ size and functionality which is uh more intensive of a process than if you just sustained like i'm sure like you could speak to like it's easier to keep stuff where it is than it is to try and like regain health so if you've literally atrophied an organ until like you know a fraction of its functionality it's trying to like bring it back from the it's not it's not dead but it's like very compromised um it's likely not

Starting point is 02:15:02 going to restore to like full functionality and the road to getting there will require more aggressive intervention you'll still probably get back to fertile but like it might not be as good of uh health of the sperm for all we know um it might not be the same capacity to produce the same volume. Who knows? So all that to say, yeah, you should expect your fertility to go down the toilet and you should expect that you have an adjunct protocol in place if you want to sustain it if you're on testosterone and you want to sustain the fertility.

Starting point is 02:15:34 But it's possible to sustain it. A lot of people thought until like relatively recently that if you're on testosterone, you just couldn't and you're going to be infertile for sure. And it's unfortunate because there's a lot of guys, especially bodybuilders who underwent severe atrophy and then had like real more difficult roads to recovery because of just bad information wow like imagine finding out like for 10 years you've been on like hormone therapy and you could have kept your testicles where they were the whole time and now you just have like these shriveled you know like raisins that you have to like restimulate the baseline through like

Starting point is 02:16:08 insane aggressive dosages of ac cg and fsh like not cool at what point does that atrophy start to recur. I mean, like, how long do you have to be on, you know, TRT before that really starts to happen? It's pretty quick because, like, the suppression of the gonadotropins happens, like, within days. Like, once you start to inject that hormone, like, you've introduced an amount that is going to tell your brain, we have enough. Don't make it anymore. And once the gonadotropins bottom out, you have no signal. Like, you will atrophy over, you know, the next months and get to, some level of atrophy that is variable depending on the person, but regardless, you're not stimulating activity. So even if like the structural size isn't like as significant of a drop,

Starting point is 02:16:57 like there's a lack of activity entirely. So like, you know, it's all kind of individual dependent, but like you should expect shrinkage within, you know, weeks to months. Wow. And so this is also kind of important to point out with like guys that are, you know, cowboy in it and trying to like, they want to get their tee up for like maybe some muscular effects or something, right? And they're just kind of like maybe not hypogonadal, but like lower range. Yeah, like I would treat it very seriously like it's a you know that you want to be on it. It's not something to experiment with, in my opinion. If it's like the route of hormone therapy, like treat it as such.

Starting point is 02:17:36 Like you treat it like you are on it forever probably. And biomarkers to monitor, right? let's say you are going to be on this. And so some of the biomark, you mentioned, like, lipids and we're talking about hematocrat, right? Like, some of these biomarkers are important. Like, what would be or what are some of the ones that your company measures or what you think are important to measure PSA, right? Yeah, I think hematology, you know, this kind of like covers the basics of, you know, red blood cell count, hematic credit, hemoglobin, et cetera.

Starting point is 02:18:15 Metabolic parameters. There's a lot of stuff. You want to incrementally assess how well it's working, too, how much more metabolically fit are you becoming in your blood work and insulin sensitive and whatnot? Because these are metrics of progress you can use to actually determine how well this is going for you. So it's not just about, like, where did your total tea and free tea end up on paper?

Starting point is 02:18:35 It's also about, like, the real health benefits that you're seeking, not just from a symptom relief aspect, but also from, like, like, you know, what's your fasting insulin now? Is it like way better because you have more muscle mass on your body? Like, if not, like, you know, there's things to be had that are going to be net beneficial from a health standpoint, not just like a cosmetic and like, I don't know, sexual health standpoint that should be monitored regularly. And I think one of the key things is just making sure you have a good baseline because

Starting point is 02:19:01 it's like once you, a lot of people make the mistake of like, this is kind of like mediated by default through us. Like you have to get a baseline to even like see where you're at before you would get even recommended to do anything. But a lot of people they get on hormones before they have a baseline and then they just don't know what they're looking at after they're on it. Like if you have a problem and you've shut down your system via hormones and you're trying to like retroactively figure out what happened and what went wrong, it's pretty difficult

Starting point is 02:19:29 to see what like the change was that was marked and like significant that led you to where you are that might be, you know, a problem. So if you have like a reasonably comprehensive baseline that assesses the hematol, a CMP that assesses your kidney status via C-Statin C estimated GFR or a SDMA which is like a symmetric is a symmetric dim it's another marker more progressive marker for kidney function that is a proxy for inulin clearance with relative accuracy which is like the gold standard of actual GFR for kidney for kidney filtration capacity.

Starting point is 02:20:12 I forget what it stands for, but you can just type in ADMA and STMA, and you'll see what the acronym stand for. I think you've talked about it on your show, too. I don't know what they stand for either. One of them's like asymmetric dimethylorginine. The one's, yeah. So one of them assesses vasop dilation potential and one is more of like for cardiovascular and one is more of like a kidney marker that is equivalent or slightly better than

Starting point is 02:20:34 cystatin C estimated GFR, which is not influenced by muscle mass creatantine intake or the array of things that can cause transient complete like to the point of it being unusable changes in the marker because creatinine calculated eGFR the amount of guys I've seen think that they're on borderline like death's door of kidney failure from a creatinine that's high because they're you know a muscle bound guy who takes creatine and like works out harder or whatever it's like it's startling that this isn't more widely known so either of those two kind of like strong proxies for Inulin clearance. You have your kind of like metabolic parameters to see your insulin sensitivity,

Starting point is 02:21:15 hemoglobin A1C, you know, all the kind of basics. I think the lipid panel, definitely a baseline HDL to see how much it gets lowered by the dose of testosterone you're using because you will likely see a suppression if you are elevating your testosterone beyond what you were at. It doesn't mean that it's bad or good. it's just worth noting like how much of a deterioration it has based on your dose because it's one of the proxies for kind of like androgenic activity. SHBG and your binding proteins like what's your baseline relative to after? Because if you are injecting infrequently or a dose that is significantly suppressive, like it might otherwise be a proxy for like using more than you might need.

Starting point is 02:22:03 Not necessarily the case always, but SHBG will get suppressed dramatically. by exogenous androgens in a dose-dependent manner. So it's not uncommon to see with bodybuilders who are using full-blown steroid cycles, SHBG levels, and the single digits, which is like you have essentially no regulation of androgenic signaling at that point. It's just like everything's flying around. So with guys on TRT, it's like worth knowing where you stood to begin with and then how much it decreased because it's like if you didn't know the baseline too,

Starting point is 02:22:35 any of your diet changes at that point, the carb manipulations, the exercise, size change, the calorie intake change, the sleep. You would have no idea what the impact thing was for sure that impacted the SHBG if you didn't have the baseline. So what else as far as assessing? Free tea and total tea measured through the accurate assays, which would be the gold standard for total testosterone is liquid chromatography with tandem mass spectrometry. If you use an equilibrium, if you use a immuno assay test, which is like the cheaper

Starting point is 02:23:08 version, often it will be relatively inaccurate, especially at lower, like more low levels, it is notoriously inaccurate because the very low numbers, like you need to be more specific. So like with women especially, like you don't want to be messing around with the amino assay test. You want to be using sensitive assay estradial every single time, sensitive assay testing for total T. And for free testosterone, you don't want to be using a calculation. Ideally, you would want to be measuring through equilibrium, ultra, infiltration or equilibrium dialysis, which are like actual measurements, not estimates based on calculations.

Starting point is 02:23:46 That's kind of what I recommend. I would recommend. And then estrogen is LcMS as well, the same as what you use for total testosterone. And what else? I'm probably missing some stuff. Basic liver markers would be to have like, oh. So the stuff that's going to get directly affected the most by androgens, though, is going to be like your gonadotry. opens LH and FSAH, they're going to be in the ground.

Starting point is 02:24:13 And if they're not, it kind of indicates that you don't have adequate either androgen or estrogen signaling. It would be odd if you're on testosterone replacement. Your LH nephisage weren't like at the bottom of the barrel. It would almost be questioning at that point like, am I having something inhibit the androgens from working or the estrogen? Because it's like you could theoretically blunt estrogen mediated feedback by using, you know, an aromatase inhibitor or a serum or something and like blunt that.

Starting point is 02:24:40 that response and you would see in your blood work it would be like your body still thinks it needs to make more natural testosterone and you know it's kicking up the genadotropin so if you're on like true replacement those levels should be like not like even present essentially um which is odd like seeking to have like a bottom note number as like what the target is um that would kind of indicate you've definitely kind of like satisfactory replaced to what you need to stimulate like the negative feedback um Yeah, and then I mentioned the lipids. Yeah, I'm definitely missing something. But fast insulin, some of the insulin resistance markers. And there's some stuff you should probably check, like baseline, like clotting risks, you know, predispositions. Factor 5 laden, you know, things like this. L.P. L. L.P.A.A. at baseline, especially because androgen suppress L. L.P. L. L. L.A. uniquely, which a lot of people don't realize is effective.

Starting point is 02:25:42 by androgens, which is typically not something can be manipulated through anything really that I'm aware of through like diet and lifestyle. So you might think you have like a I don't know, you might have like a think you have a better LP little A than you actually had at baseline. So like your genetics might be

Starting point is 02:25:58 like masked a bit by your androgen use. I don't know, thyroid balance. You know, thyroid levels are good to have. How much TSAH do you have? You know, T4, T3, the free balance of those hormones. IGF1. None of these are like critical necessarily, but there's worth having for basic health assessments

Starting point is 02:26:16 and to see where you land. But like, yeah, it's basically like your total test, your free test, your esterdial, the free levels, sensitive assay measurements, LHFSA, hematology, HDL, kind of like the basics, metabolic health, insulin sensitivity metrics,

Starting point is 02:26:34 I think are kind of like the critical baseline ones. It's pretty comprehensive. Yeah. I don't imagine everyone is doing that. Well, fortunately, a lot of good panels will just have it for you. It's not like you would ever be expected to remember all that stuff. And I'm probably missing it. Like, I'm sure I can't even remember it all.

Starting point is 02:26:50 I'd have to go look at our own pre-designed panels to tell you I probably should have done that at the beginning of the thing rather than rambling nonsensically. So just briefly, women, you know, this is another. I'd love to know. We've talked a lot of already about like testing methodology, timing test, you know, time of the data test and all that stuff. but, you know, how does a woman go about, like, determining whether or not she has low testosterone, needs to kind of figure out dietary lifestyle-wise, like, you know, obviously that's the first line of, you know, defense, right? You kind of dress that first. But I just would like to talk about, like, generally speaking, clinical symptoms and women, sounds like it's pretty similar to men.

Starting point is 02:27:33 We talked about that. What females are a candidate for testosterone replacement therapy? like what's the actual reference range for women? Let's say they also have symptoms. Or maybe they just want to have some of the benefits of a little bit more testosterone as they're getting into perimenopause and such. So, yeah, can we talk a little bit about like women? Yeah. So the reference range, I believe it's going to depend on the lab, of course,

Starting point is 02:27:59 but in general, I believe LabCorp is 15 to 70 nanograms per decilator. So like the rough equivalent of, you know, a bit less than maybe like one-tenth that of men. And for them, defining low-tig gets a bit more difficult because you're so close to like zero essentially that one, if you're not doing sensitive enough testing, like you're probably not going to be accurate. So that's where it's super critical that you have these levels assessed accurately through the L-CMS methodology that I mentioned.

Starting point is 02:28:34 but also like are they doing anything that is extra suppressive on top of all the stuff men already have to consider like contraceptives because it's like you could be artificially inducing a state of low tea that you otherwise wouldn't have and then maybe like self-diagnosing thinking that you have it like what you technically do maybe on paper but it's like self-mediated through something that you were also prescribed that's like a hormone too so that gets a bit tough but in general to simplify like a lot of the stuff we just mentioned is like directly analogous to like what women should look to as well like it's the same micronutrients it's the same just a different scale and proportions the same eating enough calories and not starving yourself and leading to you know amenorrhea it's making sure you have like a normal you know menstrual period all this stuff um um and then yeah like you know the the oral contraceptives is significant and worth noting if you're on that, like you almost certainly are artificially suppressing yourself

Starting point is 02:29:39 into like the equivalent of hypotorritory for women. So if you're on it, like I would probably check where you stand and, you know, decide if that's the medium you want to continue moving forward. And for some women, it works. Like it's not to say that that's something you shouldn't be on at all. Some women like that. Some women have like hyperandrogen leaning, you know, phenotypes.

Starting point is 02:30:01 And they might actually maybe benefit from some suppression it kind of depends like some women need to use like anti-andergens to maintain like a more neutral profile to not get like hercetism and whatnot which is like like hair growth that would be reflective of like masculine characteristics um so yeah like in general i'd be looking to that um basic symptom symptoms and the biomarkers while there is a reference range of 15 to 70 i don't think you're ever going to have a doctor who's not part of like i don't know like the more progressive kind of like preventive really on the cutting edge tell them for sure just because they were low or like clinically low that they should replace because there's not really like a there's no FDA approved medication for women for testosterone in the US there is in the Australia apparently which is kind of wild considering it's like the most regulated place ever that is like almost nothing is legal there but somehow like testosterone is for women shockingly but in the US everything's like off label so you're not to use that you're not to use like a male formulation andrew gel and like apply like a pea size amount to your arm or something

Starting point is 02:31:08 if you use it and even that would be done with the oversight of like a pretty rigorous doctor ideally and one of the things I can't point to is if somebody was to go on TRT as a woman one of the things that would be freaking most of them out is the side effect profile that are irreversible like for men it's not a huge deal if you had a bit of a deeper voice like it might be a benefit and you get a bit of hair growth, whatever. For women, if you get irreversible voice deepening, like that is quality of life destroying for some of them. And you can't just fix it.

Starting point is 02:31:42 So one of the things I would absolutely do, because there are a lot of doctors now that are, like, in the cutting edge that will overshoot women based on their more, like, liberal kind of like, women should be optimal and, like, they should be at, like, 200 total T. And I had one doctor, even when I was, like, first getting into this industry, who's like really respected.

Starting point is 02:32:03 I'm not going to necessarily put him on blasts because hopefully he's kind of fixed his protocols, but he had a cookie cutter protocol that was like way too aggressive. And like I could, he had my mom on the protocol. And I picked up the phone one day and like I didn't even recognize her voice.

Starting point is 02:32:18 I was like, what the hell? And fortunately, we like got her off it immediately and it's sort of like self-regulated to some extent. But it was like fast and aggressive and blatant. And I was like,

Starting point is 02:32:30 if I wasn't looking for this, like she could have been, like for sure viralized to the point of an unrecognizable voice within a matter of weeks. Yeah, yeah. So you got to be like hyper aware, even if you think you have like the most knowledgeable guy overseeing you. I would recommend downloading like a really vetted and highly reviewed app that monitors your actual like tone of your voice to assess any sort of change in inflection, tonality, deepness. Because that's the only thing that will assess in real time that change without just. some subjective assessment from your like significant other or something because eventually if you

Starting point is 02:33:06 don't when you're seeing yourself every day and it's like microchanges you don't really notice and then all of a sudden one day you notice in the mirror you have hair loss or all of a sudden you have like you know hair on your lip that you didn't have or somebody tells you like your voice sounds deeper and you didn't even realize it was happening this stuff is insidious but it will still creep up quick and you might not notice the change incrementally because you're so either the changes are still like on a daily basis you might not notice it yourself but also a lot of women are kind of with even some of them are willing to like overlook it because they feel so good with the protocol it's like my quality of life is so great now I don't want to mess with anything and they'll just stay the course and then like fuck themselves up and they don't need to they could have got the same symptom relief at like a much lower dose so wow yeah you gotta be careful if you're a woman like replacing test especially because it's uh There are a lot of doctors that like, especially the ones that have cookie cutter protocols that are like, you know, everyone should get to a total of, you know, 200 to 300. Like, it might be a bit aggressive. Maybe you should like, you know. Yeah. I mean, especially as you're mentioning, like the range is so small for us, right, for women that like, I mean, I'm concerned like even trying. I mean, I don't know if I need it right now. But so, you know, I'm not saying that I'm going to. But, you know, for women that like do go and get.

Starting point is 02:34:32 test. Again, we don't even know that they got the right test. Maybe it wasn't even sensitive enough, right? And so now they're getting on testosterone replacement therapy. And then it's like, you know, it feels like the Wild West in a way, right? Like you mentioned, there's no FDA approved TRT for women. So it's off label. You're kind of just going, I don't know, it feels like uncharted territory. So, you know. I mean like there's definitely a way to go about it that I think is net beneficial for sure. It's not like clinically. like there's not like there's a guideline that says like at this level equals you know you're the equivalent of hypogynatal and you should be on testosterone like it's always going to be an off label recommendation based on a assessment of like what kind of net benefit you would hopefully get out of it which for a lot of people with responsible use in menopause would probably be a net benefit if they needed it but your deterioration in testosterone production is not going to diminish to the same degree of velocity. is your estrogen progesterone that essentially plummet into nothingness. Like a lot of the testosterone is mediated through adrenal synthesis and like peripheral tissue conversion. It's not all ovarian.

Starting point is 02:35:41 So like you're the proportion of how much testosterone you make in each area is not going to be equivalent woman to woman. It's going to change to depend, you know, individual genetics. So like you might not have that big of a drop in testosterone

Starting point is 02:35:55 or even like the perceived impact of that drop relative to another woman. It might not be nearly a significant Like you might be totally fine and menopause just being on estrogen and progester on micronized or whatever It all depends and that's where like a nuanced assessment and like no cookie cutter protocols like there are general guidelines of kind of like where to start with things But like that's the reason you got to be like insanely educated about this stuff going in especially if you're a woman using like an off label prescription of something that is not FDA approved like there could be a huge quality of life bump but like you got to know what you're doing when you go in and like it sounds bad you almost like got to know what the ideal

Starting point is 02:36:38 protocol is for you like before the doctor tells you and you have to like find the doctor who like you know is responsible which is crazy yeah you got to do your due diligence you got to educate yourself no i mean this would podcast like this before as well and if you find that there's a a way that you could get there like for example if you found out you were like adrenal insufficient for example like there are natural things that you could do on the women's side, like DHEA, I'm sure at some point we would have ended up talking about, not meaningfully impactful for men's testosterone levels because the majority is driven through intracicular testosterone production, but for women, because you only have such

Starting point is 02:37:15 an amount, it's like, you know, 15 to 70 total, a significant chunk of that could be driven through DHA mediated conversion. And if that is the case in your low DHA, via an assessment of the biomarker DHAAS typically as a proxy, sulfated DHA, you may highly benefit from like a basic DHA oral supplement that's like, you know, easier to predict what's going to happen. It's like an actual marker you can point to as deficient based on like a validated, you know, clinical biomarker. And you know exactly what happens when like there isn't a,

Starting point is 02:37:53 it could convert technically to different metabolites, but in general, women respond favorably to an adequate DHA. dose when warranted for testosterone conversion. Like, I've seen pretty dramatic changes to the degree of women on combined oral contraceptives attenuating entirely the loss in testosterone production via the progestin and estrogen induced suppression through the DHA. So, like, by that, I mean, starting off with like a 70 total T, getting suppressed down to like, you know, 30 or something on your combined oral contraceptive, taking DHA and getting back

Starting point is 02:38:28 up to 70 while you're still on the combined oral contraceptive. What kind of dose of DHEA? 25 to 50 would be like what you see in the studies, but I would start lower for sure just to see how you respond. Because it is, again, an androgen and women, some of them respond pretty aggressively with acne flare-ups androgenic side effects. And it should still be treated with the respect that it deserves because it's an androgen. It will still mediate similar side effects. And some women don't respond favorably to it. And like, you know, testosterone could be warranted depending on the person.

Starting point is 02:38:59 You just got to know, like, the dose is like really, really. small and like it's probably like a tiny little blip of cream or gel like whatever you're using it's probably going to be uh just be like aware of you know and extremely cautious about like who you're deferring to for information on it because it's not something you want to mess with without like knowing exactly where your dose should theoretically put you on like a reference range and like what that might yield in terms of symptom relief or like benefit quality of life via an array of people that are trusted in the, like, widespread community for this kind of stuff. And you, you know, multiple opinions, not just like one guy who, you know, is a cowboy doc.

Starting point is 02:39:44 Totally. Yeah. No, this is great info. Kind of the last topic to get to, and we've already sort of touched on it, was like some of the side effects of maybe perhaps some of this androgen, you know, therapy or hormone replacement therapy hair loss. And this is something I know you've personally talked about. It's very interesting. And I sort of just want to talk about it out of my own interest. Like why does hair loss occur? Like what is the role of D.HT in that process, you know? It's kind of a crazy thing how in this day and age we have like advanced AI stuff.

Starting point is 02:40:22 We have like all these like cutting edge treatments for you can like literally completely get rid of the likelihood of ASCBD for crushing. Apo B and like different things of this nature, but like hair loss, no one has a fucking clue what happens or how to prevent it without just crushing your DHD levels essentially, which is wild that that's still a thing. But as long as I've been researching this stuff, there's been people that are like, oh, the, you know, the solutions on the horizon, like every two weeks, you'll see some viral article on Twitter's like UCLA scientists found like, Rodin regroup all his hair after shaved from like random thing.

Starting point is 02:40:57 Like, oh my God, D. Ribos is the solution. I'm going to go dump it on my head. You should see the nutty shit that people on like Reddit and whatnot dump on their heads. Bellotin, right. Yeah, I think sulfurophane was one too at one point. Oh, yeah. So farrippery. Sproats on the head.

Starting point is 02:41:09 Didn't end up working though. I'm sure it has like some like indirect benefit for like systemic health. But like at the end of the day, the unfortunate reality inherently in the name of what it is is what is causing it, which is androgenic, androgen mediated alopecia. So the miniaturization of hair follicles mediated by androgens, primarily the one that is the most potent in its endogenic activity, which is dht. And these hormones, it's not just like they convert and then have like in the blood or like at the liver or something.

Starting point is 02:41:47 There is like tissue specific concentrations of enzymes that are more prominent. And in particular in the skin, in the scalp especially too, you will have, there's way more 5 alpha reductase density in men for converting testosterone to DHT. So that like local reaction where you're converting more test osterone into DHT is resulting in like a significantly high per surface area amount of DHT than like any, almost any other area in the body with exception of like other skin areas that are hairy, you know, the prostate as well. like the scrotum when you apply the cream like you actually get a bit of a disproportionate spike in dh t i mentioned earlier but anyway and the scalp highly expressing five alpha reductase and that conversion seems to be what mediates androgenic alopecia in essentially all cases there are some fringe cases in men where okay you might have a um you know nutrient deficiency or you might have some weird genetic predisposition that was totally correct by adding in fill in the blank thing, or you had undiagnosed hypothyroidism or what have you.

Starting point is 02:43:01 Typically, not the case. Typically, it's pattern hair loss, miniaturization of the hair follicle, and if a lot of people, unfortunately, get misled by these, like, crazy, you know, wild stories, like, oh, the solution's on the horizon. Oh, just like wipe some broccoli on your head.

Starting point is 02:43:15 Oh, do this. And then they just lose their hair, and there's no recovering. Because, unfortunately, what happens is if you leave it for too long, the area starts to, undergo fibrosis. So it's not like it's something that you can necessarily recover to baseline. If you're completely slick bald,

Starting point is 02:43:32 the scalp environment is no longer habitable to like healthy hair follicles that are like, you know, your original hair, you're not going to grow it back, probably until they start like cloning hair follicles or something. So you kind of got to get in front of it similar to ASCVD as absurd as it sounds, like before it starts stacking because it's something that's cumulative and insidious and overtime eventually all of a sudden it's a problem so when you're young you know why is it this is one of the stupidest things i hear why is it that when your dhc levels are at their highest when you're

Starting point is 02:44:02 young you have no hair loss but then when you're old you have hair loss it's like the same reason that you've been stacking plaque in your artery since you're like a teenager like it's cumulative so being preventative and proactive is the name of the game when it comes to hair loss and i'm not to say that like there isn't a solution that exists in the planet that somehow addresses the downstream cascade of like, you know, TGF beta and like, you know, the WNT pathway, all this fringe stuff that is a result of the androgen induced transcriptional activity. But at the end of the day, nothing seems to be potent enough to attenuate whatever is happening downstream. So like the net result is the follicle literally like starves itself and miniaturizes.

Starting point is 02:44:49 Like the follicle becomes weaker, thinner, and over time the antigen phase, which is like the growth phase of the hair follicle, shortened, shortens, shortens, and over time, you're just like shedding weaker and weaker hair and it's growing back thinner and thinner and eventually it's so thin, sparse, and insignificant cosmetically that you can't even see it. And it's just like these follicles have essentially died

Starting point is 02:45:09 and gone, undergone literal apoptosis because each one is an organ in itself individually. And once it dies, like, it's not going to just come back from the dead. And then that area, you know, fibrosis or undergoes fibrosis and like you're screwed in that spot, essentially. essentially unless you transplant non-AGA androgenic alopecia affected hair follicles into that dead zone but like you need a lot of hair to offset like a completely bald head and it's like typically not possible if you've let yourself get too far gone so and it's really interesting too because these hair follicles

Starting point is 02:45:43 they're not prone to the same miniaturization so like even if you transplant it from here to here like it's not going to undergo the same effect, even though it's like in that area, interestingly enough. But these hair follicles are like highly prone to miniaturization if you are susceptible to hair loss. What makes you susceptible to hair loss? Genetics,

Starting point is 02:46:05 but in general, are you going to bank on you being the one guy? Like how many guys do you know who 50 years old plus have like no visible hair loss whatsoever and it looks like they did when they were 19 years old? My dad, but his hair's gray, but it's essentially the same. Is it actually, though? Yeah.

Starting point is 02:46:23 Yeah. Yeah. Yeah. Full thick, like, head of hair, but it's just white. Okay. Well, like your hair. Yeah. But it's, it's an outlier, for sure.

Starting point is 02:46:31 And you have a son, you said? I do. Oh, he must, he's going to be thrilled then. Is it, is it on the mom's side? Typically, it's thought to be the mom's dad. It doesn't always play out like that. Right. It doesn't seem like it always does.

Starting point is 02:46:42 But like, that's a good, he might not have to take, you know, the hormone-crushing drugs. He might be one in the fringe lucky ones. ones. Well, let's talk about the proactive. I mean, so, you know, what are these proactive measurements that can be done that do happen? So proactively, as unfortunate of reality as it is, you have to weigh the risks to reward on inhibiting DHD. So how far ahead you get of this kind of impacts how intensive of a protocol you have to use, as well as your like susceptibility to that androgenic stimulation, which is also going to be contingent on your hormone level. So if you're,

Starting point is 02:47:17 you know, hypogynadal, and then you correct that and bump yourself up to, you know, high normal, like you might have just doubled your endergen load

Starting point is 02:47:24 in your scalp for all you know. And the proportional increase is like magnified multiple fold because it's more 5 alpha reductase expression in the scalp than like anywhere else, essentially. So getting in front of it,

Starting point is 02:47:36 the only thing, like how they developed these drugs was they found that, um, individuals that had a mutation in the gene that encodes for 5 alpha reducts, ductase seem to not undergo full sexual maturation in adolescence and they would end up with, shockingly, the same amount of muscle mass as like, you know, they're like, for example,

Starting point is 02:47:59 siblings who weren't affected, but inhibited maturation of genitals, for example, like not full that often end up with like a micropenus. That's like where that comes from typically. But also no facial hair growth really and no temporal recession. It's like one of the hallmarks of, you know, the, they're called pseudohermaphrodites, which is like, I don't know, male pseudohermaphrodites. And maybe that's not like a correct term now, but that's what they are in the literature. And it is literally, these individuals have no inhibition in their capacity to produce testosterone. It is all the Dht.

Starting point is 02:48:35 Now, it doesn't mean that testosterone doesn't also have a similar effect on hair follicles. It's just the magnitude of effect is so much less that if you get in front of it, like, you know, day one, unless you're highly susceptible, the inhibition via inhibiting that enzyme is likely going to be sufficient to offset loss visibly for your entire life because it's a progressive thing. And you won't even notice the cosmetic difference in hair density until you've lost like 25 plus percent of your hair. So like if I pull a hair out of my head right now, visibly it would look no different. If I pull two hairs on my head, it would look visibly no different.

Starting point is 02:49:15 But once you start to get to like tens of thousands of hair follicles, so you have on average, depending on the ethnicity, but like I think it's like 70 to like 80,000, upwards of 100,000 hair follicles on your head, once you've gone to the point that you're down like 10,000, 20,000, 30,000, all of a sudden you're starting to see visibly, like in downlighting. You can see through your scalp and you couldn't before. You're starting to see yourself in pictures and you're like,

Starting point is 02:49:39 huh, that's weird. Like I don't remember seeing I have to like part my hair weird now to cover this spot. Like what the hell's going on? And then like one day, hits you and it's devastating. And you're just like, shit. I guess I am prone to hair loss. I thought I was immune this whole time.

Starting point is 02:49:51 That's not the case. Dude. Yeah. That's rough. That's depressing. Yeah. Okay. So.

Starting point is 02:49:59 No, I certainly don't want to leave a podcast saying, get on finasteroid, we're deastroid. Yeah. You're screwed. Like, there's an ROI calculation to be made similar to any sort of hormonal therapy that is not to be minimized. There are side effect profiles with these drugs, just as there is with any drugs,

Starting point is 02:50:16 but I would compel you to look at the actual literature and assess what the prevalence was among those who were subjected to DHD deprivation in finasteride users and Dutastride. And it is not much different than placebo in very, very rigorous and significant high number of subject studies that were well, well constructed studies. Like this is not something that,

Starting point is 02:50:44 a lot of it is media driven. It's not to be ignored. Some people get devastated by these drugs, but it's a minority of individuals. And it's just kind of like, do you want to be one of those individuals who takes the risk or not? There are ways to assess

Starting point is 02:50:57 if you're more likely to be one of those individuals. If you were a low androgen status individual to begin with, for example, I have low normal free testosterone with a borderline, you know, hypogynatal looking dhgely level to begin with.

Starting point is 02:51:13 And I'm still already having hair loss like and I already have symptoms will crushing my dhc to nothing be more likely to result in a side effect than somebody who's like vital no side like thriving no issues whatsoever seemingly like there is an androgen load component to assess like how significant of an impact it might have on your ability to support functions driven through androgens because it's like every person is going to have some degree of impact. It just might not be perceivable in any noticeable way whatsoever. Like you might have like a some like few percent deterioration to your nitric oxide capacity in your erection.

Starting point is 02:51:56 Will you notice that? I don't know. It depends on the person. In the studies, it doesn't seem like the prevalence is very significant. And shockingly, deastoride is a similar side effect profile to fanastriide, even in studies comparing them. where you have near full inhibition of systemic DHD versus only 60 to 70% via Finastroi, which only inhibits two of the three isoenzymes in the scalp.

Starting point is 02:52:18 So it's like, it's not, there's a side effect profile. It's just overblown by media, but it's not zero. And it's definitely worth reading the literal studies yourself before you come to an opinion because there will be people who try and plant their opinion and their subjective assessment based on their experience in your mind.

Starting point is 02:52:36 Like, oh, I had no side effects, it's fine. Just get on it, bro. don't worry about it. Or I had the worst experience ever and it ruined my life. It's gonna fuck you up. Join my lawsuit to sue Merck. That's like the kind of like disparity

Starting point is 02:52:48 in these communities. And they all have like some, it's not like they're both wrong. Like everyone has their own individual drug response and some people have like the most insane response to Tylenol. You know? Like it's not like anything is risk free in this world.

Starting point is 02:53:03 So just be aware that these are ultimately hormone therapies that you're getting on. Like it's not, It will also, not dramatically, but could suppress fertility metrics mildly because intracellular androgenic signaling does dictate spermatogenesis. That includes dh, ht. So, like, if you're reducing the dhgat a lot, that might impede your fertility to some extent, too, even if you're natural and have no testosterone therapy and you're like a eugenatal male. But yeah, the most impactful therapy for sure intervention-wise is going to be inhibiting dh-h-t. the degree to which you inhibit it will be dictated on how susceptible you are,

Starting point is 02:53:40 but if you nuke DHC into nothingness via high-dose dutasteride, it's pretty difficult, if not near impossible, to lose hair as a male. Now, the most susceptible might need to be on a topical antandrogen, or maybe their side effect profile will be superior with a lower DHC inhibition and some sort of adjunct topical anti-androgen therapy with it, or some topical 5 alpha reductase inhibition with the topical antigen. It's all kind of like a bit of a strategy approach based on your individual risk profile and what you want to take.

Starting point is 02:54:13 But if you don't attenuate miniaturization potential, like you're not going to prevent hair loss. You could take monoxid all the day. You could take all the pumpkin seed oil, sob help meadow, dumps, sulfur refing on your head, do whatever you want. Like it's not going to move the needle for inhibiting miniaturization mediated through androgens. which is ultimately what it is. And for females, PCOS females, like it doesn't take that much

Starting point is 02:54:36 of an androgen burden to start to miniaturize. Like, it's pretty quick and noticeable. And most hair loss outcomes with women come from autoimmune-related alopecia aerioda, Hashimoto's thyroiditis,

Starting point is 02:54:49 nutrient deficiencies, things of this nature. They're typically not in a pattern of like androgen-related miniaturization. But when it is, it's like often pretty obvious why. And it's just more rare. So like, you know, when people want to speculate about what caused it, what doesn't cause it,

Starting point is 02:55:06 it's like the largest anecdotal experiment plays out in real life every day with men versus women aging. And it's like, who's the ones with hair loss? Like the guys. Like, I know the most dialed of biohackers with infinite resources who are still bald as hell. Regardless of all the special stuff they tried that wasn't like the drugs that work. And it didn't work, unfortunately. I would love to have a natural therapy that moves the needle, but at least for me and what my knowledge, the extent of it, it's that DHD inhibition is almost a necessity if you're prone to hair loss. The capacity to which you do it is dictated by genetics, androgen load in the scalp, and free endogenic signaling, and your risk profile will be dictated by your own, you know, tolerance based on your interpretation of the scientific literature.

Starting point is 02:55:55 And then there's some adjunct stuff. Like once you attenuate the miniaturization potential for the androgen-related activity in the scalp, that's where you can then look to, you can have a bit of a top-up, like ketoconazol shampoo, for example, is like a mild antionerone, too, that could add some additive protection on top of, let's just say you're on fanastride instead of the more nuclear dutastoride, and you felt like that risk profile was superior, for example. Kita connozol does help. There's studies showing it's equivalent to the hair growth results of 2% monoxidil via a totally different mechanism.

Starting point is 02:56:27 which is like very significant for something that's like an over-the-counter shampoo that also you can get that attenuated dandruff to some extent suboric dermatitis um can improve the scalp environment to your your scalp environment to some extent depending on i don't know if you're prone to like i don't know fungal overgirl for example but in general it's like a mild five alpha reductase inhibitor and topical antianergen that's just like a good shampoo that doesn't require like the risk profile of a finasteride deutastriide but it's like typically for most people not going to be sufficient to offset it unless you're like mildly very lightly prone that's where you need to like layer up with the five alpha reductase inhibition pharmaceutically and then monoxidels

Starting point is 02:57:13 the growth stimulant that is FDA approved and it works reliably it's just hit or miss if it works based on your own enzymatic conversion capacity so it needs to convert into monoxidyl sulfate in the scalp to actually work. And if you have inadequate sulfo-transferase enzyme activity, it will not, you could be a total non-responder, even though you're using the full drug dose every day. Those individuals either have a issue with the scalp environment, like they're not getting it into where it needs because with topical, some of the problem often is just like your scalp either is unhealthy the environment or it's not clean enough or like you're not using a high

Starting point is 02:57:50 enough dose of the drug. It all depends on the person and the formulation that you're using. But in general, if you're using it properly and at a high enough dose, you will be limited by this enzymatic pathway and there are ways to upregulate it. One is compounding the monocidal with tretanone, which can upregulate the sulfaltransprice enzyme and allow more of that conversion to take place. And then there's microneedling, which also seems to be pretty dramatic, turning some non-responders into like significant responders or magnifying. the results like multiple fold for people who were responding, just not as well as they could be either driven through lack of adequate absorption and or lack of adequate sulfo transferase enzyme

Starting point is 02:58:31 activity that also seems to be upregulated via this like manual like micro damage essentially. There are some crazy studies with individuals who've like burned their scalps that had balding and then they ended up like a regrowing hair after which is pretty weird via like the recruitment of growth factors that like you wouldn't have gotten if it wasn't for that like dramatic event. now obviously no one's going to light their head on fire hopefully but that's the thing um so with respect to the the topical you know strategies like the mid-oxidol i mean obviously what are the side effects of that is that so it's like a very terrible blood pressure drug so it was originally prescribed for uh high blood pressure as uh loan it's in oral yeah oh i thought it was topical yeah so what they found when they prescribed it for blood pressure decades ago was that one of the side effects besides like people like fainting when they're standing up or having low blood pressure or water retention was hair growth everywhere including their scalp significantly so they're like huh maybe we can take this drug and repurpose it for a topical for hair growth because it's like essentially

Starting point is 02:59:37 a really bad blood pressure drug with a black box warning on it and they did successfully and now it's known to be like the growth stimulant for your hair and seems to avoid a lot of that systemic side effect profile that comes with the oral formulation. Some people still use the oral formulation. Dormatologists have seemingly adopted it, I would say, a little bit haphazardly, without really accepting the risk profile accordingly because it's like a pretty, it is a bit of a sketchy primitive drug, orally especially, because the liver has so much sulfo-transprice. Enzyme conversion, enzyme activity that leads to the minoxidyl sulfate conversion.

Starting point is 03:00:19 that you get systemically, it leads to some people like pericardial effusion, like water retention, dysregulation of electrolyte balance. It's a potassium channel opener. That's how it works. And systemically, it has a much more significant side effect profile than topically. And it's not uncommon to see people even microdosing it getting arrhythmias and talking about like chest pains, like freaking out and going to the hospital. And it's a lot of people just get chucked on it at like low dose. but it's still low enough,

Starting point is 03:00:50 it's still high enough that it causes like these problems and some people. Works really well though, but topically it's like the most benign, at least entry level way where you can not, you can get over the counter

Starting point is 03:01:01 like you can just buy it off Amazon or at Costco or whatever. Way more likely that you won't undergo side effects using it topically. And there are some studies, many studies that show like similar benefit profiles. It's just like a bit more of a nuisance

Starting point is 03:01:18 because it's, topical and you have to adhere to the protocol, but like, you know, black box warning drug from like, you know, pre-2000 for blood pressure versus like the topical reiteration that is like likely not to cause that. Worst case scenario, you can elevate the efficacy profile by trying the tritone with it, trying the microneedling with it. And if it doesn't work, like maybe at that point, look at the oral if you want, but like, that's kind of like the escalation risk.

Starting point is 03:01:46 Is the trininoin oral or topical? You would get like a compounding pharmacy to formulate it with a monocidal because you can't buy that over the counter. That would be like you would now have gone to the pharmaceutical route at that point because you would typically what I would do, like if it were me, is like I'd start with the monocidal topically. If no response, I would probably look at microneedling to ensure there's actual absorption occurring

Starting point is 03:02:11 and or the enzyme activity that can be manipulated via that manual because it's not an extra drug that I'm adding. It's just like manual, like, micro damage essentially that I do once a week. And newest literature reveals that you might be able to get away with only doing a 0.6 millimeter depth, as opposed to the old studies, had everyone doing 1.5,

Starting point is 03:02:31 which was, like, guaranteed to draw blood. Like, I have some of my old YouTube videos where, like, I have, like, a bloody scalp in the video because of, like, the depth that I would be going to to be, you know, using the devices. So 0.6 seems to be potentially, as efficacious with less of a cosmetic issue, quicker recovery, et cetera.

Starting point is 03:02:54 And it's not more drugs. It's something that, like, I recover from quick in my scalp seemingly. You know, there's some potential downstream issues to hitting my scalp with that once a week. I don't know. But like so far, so good from a lot of the data that I've seen and like for me using it. And then from there, I would escalate to like the pharmaceutical compounded route

Starting point is 03:03:13 at that point if you needed to with like the Tretano and no one compounded monocidal. It's funny, the microneedling, like, I'm interested in it for skin effects. And so. Yeah, people, he's on their face, too, like, all the time. Yeah. So, you know, it is something I'm going to do. And when I went to my dermatologist and saw, like, some of the brochures with their studies, like, because my dermatologist does actual research.

Starting point is 03:03:33 And it was funny in their brochure, it was like, there was, like, this whole hair loss area to the microneedling and some of the stem cell growth factors that they use. Yeah. And I was like, hmm, what's going on here? And I was like, oh, so it's like regrowing hair. and she was like, yeah, we've done like a small study and we added some, it was like a combination of growth factors that are involved in like, you know, stem cell production and the hair follicle.

Starting point is 03:03:55 And so I'm wondering if like you, but that's why I was like interested in the microneedling too with the hair. I was like, oh, so they're essentially just making it better absorbed. You're like you're getting, whereas if you were to put some, you know, stem cell factors on just your scalp, like it's just not going to get absorbed, really. Yeah, I think the majority of the benefit is likely mediated via ensuring adequate absorption of the drug because when you do microneedling on its own,

Starting point is 03:04:20 like versus monoxidyl on its own versus microneedling plus monoxide, like it's not a comparable outcome in terms of like you would expect the microneedling alone group to be very significant if it was recruiting some sort of local growth factors that were dramatic. It seems more like it's probably in ensuring you're actually getting this to where it was supposed to go to begin with, but maybe wasn't getting fully assimilated, which is fine. If that's what it does, it's just like, that's what some people need in order to get the absorption. But it could be like the difference of four X the results I've seen in some studies.

Starting point is 03:04:52 That seems like a legit pathway for some men that are like a little bit skittish about potential side effects with the oral drugs as well because like the finasteride and what is the other one? Dutasteride. You know, you mentioned the erection, but like, are there any other serious side effects? with those that are really cancer. Neurological, potentially, through the balance of like neurotransmitters, and zeolidic versus like there's a whole rabbit hole to go down of like inhibition of alopregnolone, which is thought to be the main thing implicated in postpartum depression being deprived of it.

Starting point is 03:05:30 And there's a literal pharmaceutical that was developed to like manually restore that. And women that just had birth and have postpartum depression and it seems to be efficacious. And seemingly by inhibiting five alpha reductase, you may be inhibited. inhibiting that like gab aurgic signaling through that like anzeolitic kind of like calming thing molecule essentially and it results in kind of like a depends on the person like he can get pretty severe I'm sure you've seen or at least you know depending on if you've seen the podcast where people talk about it or not but I've heard of this like post dutastro or post finasteride syndrome you'll never have you you'll never hear about post dutastoride syndrome though yeah even though it's a way

Starting point is 03:06:12 more potent drug because it's largely a media driven construction. It's not to say it's not real. There's definitely side effects from these drugs. But like there's a huge Nasebo effect that comes with these drugs where, you know, I have friends who get on it and they're like, dude, I swear like, you know, my penis is not working like I used to. I'm like, dude, like you're probably fine. Like, don't worry about it.

Starting point is 03:06:35 And it's like they've read all the stuff that could happen. And they're convinced they just like killed their ability to, you know, have sex or something. And it's like, you know, the nocebo effect is absolutely real and significant. And I think is accounting for a large proportion of people who think they are affected. Because you can actually nocebo yourself into like real side effects by believing you have them. Oh, for sure. It's very real.

Starting point is 03:06:59 Yeah. And there's actually, believe it or not, there's genes that you can, there's snips that are known that you can look at. And even 23 and me does measure these snips for placebo versus nocebo. And so like some people are more like. susceptible to a plusybo effect where they like believe in something and it's going to happen. And I'm like, like, I'm taking all my creatine. I'm like, yes, I'm not getting sleepy in the afternoon. And it could be placebo, but I don't care because it's a real effect, right?

Starting point is 03:07:24 No seebo effect is the same. And again, there's snips that like some people that have those snips are more susceptible to believing that something is harming them if they're like aware of those things. And so, yeah. Well, that's interesting to know. But clarifying quick on the monocel, though, it's a growth stimulant. it does absolutely nothing that we know of to attenuate the miniaturization caused by DHD. So like the only strategy that works is attenuating androgenic activity via either like the mild he

Starting point is 03:07:56 of connozlo, which probably is not going to be sufficient, but like over the counter, pretty benign, helpful, good shampoo regardless. That's why I use it. But if an astride or deastoride or topical anti-androgen, probably going to be necessary for most people, Minoxyl is the thing you used to regrow hair. It's not the thing that prevents loss. You can cosmetically offset the visual perception of loss via the growing of hair, but it does absolutely nothing to prevent the further miniaturization.

Starting point is 03:08:23 So at some point, if you just use monocidal, you will have a net catch-up where you miniaturize to the point that you are caught up with what you've grown, and then you blast past it and you still end up losing your hair. Okay. I see. But you can still delay the visual perception of it still, If you're somebody who wants to avoid inhibiting hormones entirely, you know, that's a strategy.

Starting point is 03:08:43 It's still like biding time. Transplants, bide time, you know, it all makes a difference. Yeah. But essentially, if you want to completely bypass it, you have to get, you have to inhibit. Essentially, you have to, like, turn your scalp into a female. Okay. Wow. Interesting stuff and your...

Starting point is 03:09:03 Mild exaggeration. Well, like, you get it. And you're, and you're... You've been doing this yourself. Yeah, I've been on due task right now for years, and at least to date, I have had no perceivable detriment to my cognitive state, to my sexual function, to anything that I would point to. And I know a lot of individuals that I respect in, you know, the anti-aging longevity community who also use it and think that it's, you know, a reasonable enough risk profile for them. And that's not to say that I, that means I endorse it or I don't endorse it. I just use it and I've been okay to date, knocking wood, because maybe something will happen.

Starting point is 03:09:41 I don't know. Are there any long-term studies looking at? Yeah, because like these are drugs that are used for benign prostateic hyperplasia and even at dosages up to like 2.5 milligrams daily of due to asteroid has been used with great success, with individuals with like no, you know, like a minority of prevalence of side effects and like they're relatively minor from what I've seen. The longest study that I know of, off the top of my head,

Starting point is 03:10:12 there's definitely studies assessing follow-ups of individuals who've been on it for like a decade plus, I think. Have they looked at like all-cause mortality or any of these like outcomes? If any, okay, this is going to be a controversial one, but my speculation is that if anything, these would net would increase your longevity

Starting point is 03:10:28 because they're decreasing endogenic stimulation significantly. because dhc is literally the most androgenic hormone in your body and if you're inhibiting it and you're just left with the testosterone and the anabolic activity because dhc is entirely inactivated in muscle tissue so you get no muscle growth benefit graded dose response studies using dutastride alongside testosterone even at super dosages the dutastride getting wiped out had no impact whatsoever on strength and muscular hypertrophy so like there's no benefit muscularily to dh t in any capacity as an adult which is notable because a lot of people think their physique is going to deteriorate if they use one of these drugs. Not the case. It has no impact on it whatsoever. So I would think, especially somebody who's on TRT and like candidly I don't take enough to put me at 400 total T. Like I take enough to put me at like 800 and like my free T is like the high normal. I think that the due tastery like probably whatever like excitotoxicity or cardiotoxicity that I might otherwise be like

Starting point is 03:11:31 net net netting over into like an area I wouldn't want. I would anticipate and speculate that the DHT reduction is probably inhibiting that whatever detriment might be there to some magnitude. Could be wrong, but like I have a net increase in intratissue aromatization from the inhibition and the 5A.R enzyme. So like in, you know, all the tissues that would otherwise be like pro longevity from estrogen locally,

Starting point is 03:11:56 you're getting a benefit, you're getting the proportional increase of, 15 to 20% of intratissue estradile. And if you don't have any side effects from that, if anything, you would think, okay, well, it's probably vasodilative. It's probably like more pro-antioxidant. It's probably less exitotoxic.

Starting point is 03:12:20 It's probably less glutaminergic, like all the stuff that is going to be potentially damaging of, I don't know, killing of brain cells. This is just a speculative thing, though. I wouldn't hang my hat on that or tell anybody that that is the case. I do think if there's some sort of direct study, though, that would be interesting. That I was just going to say the same thing.

Starting point is 03:12:36 I'm pretty sure there is some anti-aging studies on Finaster and Dutastro though that might, I wish we could pull up, but we don't have the... Yeah. Well, it's something to dive into later for sure. And maybe, you know, it'd be nice to have a study to see, like, people that are on TRT and, you know, doing these androgen, you know, blockers, like how that affects life expectancy or cardiovascular related disease, right? Yeah.

Starting point is 03:13:01 And just to like wrap it up on the hair loss front, like just because I do something, like it does not mean I endorse it because it's a very controversial topic. Side effects are real, not to be ignored. Some people, they deem the risk profiles worthwhile to the benefit they get. The depression and mental anguish they endure from going bald might outweigh the risk profile. It's all an individual decision. Don't listen to a guy on a podcast who tells you he uses something. as your indicator if you should use a heavily hormone modulating drug.

Starting point is 03:13:33 Like these are like very significant drugs that should be respected accordingly. Yeah. Yeah, for real. Thank you. Well, this has been a very interesting conversation, Derek. We've been talking for, I mean, just hours. I don't even know how many hours. Eight.

Starting point is 03:13:46 Was that your first double pod back to? That was my first back to back. Oh, really? Yeah. Especially like long podcast back, too long podcast back to back. Oh, cool. So it's been, it's been a fun day. talking to you. Thank you so much for coming on the show, talking all things, hormones. Very

Starting point is 03:14:02 informative. I've learned a lot. I have a lot to look into. I've made mental notes of things that I want to look into and I'll go back and when I look at the, read the episode again, read the transcript of the episode. I'll go back and look at some of these studies. So thank you so much for coming on the show. And you obviously have a big YouTube channel podcast called More Plates, More Dates. Where else can people follow you? You have your health care company, Merrick Health. Yeah, I think Merrick Health on social media is just at Merrick Health or the website is at MerrickHealth.com if you want to check it out. And yeah, I think I'm more plates, more dates everywhere except Twitter.

Starting point is 03:14:42 I don't think that was a handle I could get. So I think I'm just Derek Fitness there. But yeah, that's me. Awesome. Well, thanks so much, Derek. Thank you for having me. Appreciate it. Thank you for listening.

Starting point is 03:14:54 And a huge thank you to Derek for joining me today. If you enjoyed this conversation, be sure not to miss out on my free weekly email newsletter. My team and I dive into cutting-edge topics each week. We translate the latest health fitness and scientific research into practical tools that you can use. Last week, we explored the anti-cancer effects of strength training and high-intensive interval training. We've covered lots of really interesting subjects, including the creatine's effects on cognition, how indoor exercise influences vitamin D levels, why the proximity to golf courses might actually impact your Parkinson's disease risk, and so much more. You can learn more about that and sign up at foundmyfitness.com forward slash newsletter.

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FoundMyFitness - #106 How To Increase Your Testosterone Levels Naturally | Derek from MPMD

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