274 - Performance-enhancing drugs and hormones—risks, rewards, & broader implications for the public

is often framed out to be like this Fountain of Youth Elixir you know HGH so it's you know so cost prohibitive it's what all the pro athletes are using this is the thing you need to be on to prevent any age related decline in you know bone strength uh you know not your ability to burn fats as you get older is going to go down so you need to be on growth hormone etc etc and that is kind of uh like at a bird's eye view it's kind of responsible for the growth of broadspectrum growth of tissues as you grow up and then as you get into adulthood hey everyone welcome to the drive podcast I'm your host Peter [Music] AA Derek awesome to have you here thank you for swinging by Austin I know it's a little bit out of the way for you um and great to meet you in person we've had a lot of communications over email and text but uh you as well thanks for having me yeah so so um let's give people a little bit of background on you and um maybe how you've come to to know a lot about stuff that that's awfully technical actually um so I don't know much about you or I'll pretend I don't know much about you other than that we share the same nationality uh and that you're you're a fellow kanuck so uh tell me about yourself growing up yeah so I am from the west coast of Canada born and raised Vancouver British Columbia um I how do you summarize like a childhood like how far do you want me to go well first of all when did you get interested in lifting weights nutrition when did the when did the topics that you now have pretty significant expertise in start to become a a passion of yours probably in my grade 11 is uh I don't know if in the US there's like we call it 11th grade or junior year but yes continue that one I can translate between yeah so I was a rail probably 130 I think 138 lbs at my same height and basketball player a lot of my friends were getting into working out putting on muscle and I was the last one to get into it and they were heavily encouraging me almost you know I was the only one who was left out if I didn't start so I thought okay well I might as well join and I have nothing to lose by putting on some some weight cuz I was pretty damn skinny at the time so got in the gym and a lot of people can relate to being bit by the iron bug where you start to get you know the Newbie gains and the quick progress becomes quite addicting and then you know you get on a full-blown routine thereafter and I was kind of kind of skewed away from actual sports like basketball because my three-pointer and some of the muscle memory stuff really got thrown off when you start to gain you know if you gain 30 lbs and matter of months all of a sudden your mechanics don't feel exactly the same anymore so I got uh pretty into working out and lifting weights and as you get into lifting weights it's kind of hard to avoid some of the discussion around anabolic steroids drug use and bodybuilding how are these insane brontosaurus physiques you see on stage achieved and what goes into them because you often heard it was you know D dare celtech or some other supplement on the you know front of a cover and or in a supplement store sold by somebody and then as I dug into it more started to learn about hormones pharmacology I actually had hair loss caused by androgens when I was experimenting with them as a you know recreational bodybuilder and then from there I started to dig heavily into anti-androgens 5alpha reductase Inhibitors and had this weird broadspectrum Pharma knowledge on weird Niche stuff but was all overlapping with the basis of kind of like andren therapy synthetic derivatives and just just for sort of a time scale here are you in college now or are you still in high school when you're developing this level of Interest this is my initial interest peaked in 12th grade that's yeah so that that grade I developed my interest in it and started to when I get interested in something I just go hard I just completely bury myself in Reading whatever I can find and back then it was a lot of underground forums with Jim Bros going back and forth talking about their experience with filling the blank compound or this is what I did and this is what I hear person X is doing and a lot of it was just anecdotal not that there's a lot of good literature anyways but I mean just going on the forums learning digging into whatever science I could understand and kind of conceptualizing you know getting a framework of understanding about how hormones impact physiology muscle growth potential um I don't know genetic variability in response to that and as I got into University in my first second year I got pretty hardcore into the bodybuilding got up to 260 plus pounds at my biggest and that's when I actually discovered I had sleep apnea that was severely exacerbated by getting that heavy that quickly and sort of gave me my first taste of side effects and what the potential downsides are of bodybuilding because a lot of times when you're that young it's like 20 21 years old you just think you're invincible and you just think you can you know blast compounds and at 260 lbs I mean how lean were you at that stage were you relatively unlean and just relatively unlean I would say and you were using lots of anabolic steroids or just you know exogenous testosterone and calling it a day we'll go into more detail about the nuances of this but just for reference by our standards a lot but by bodybuilder standards not really that much probably at Peak exposure a combined weekly dosage of 1,500 milligram to 2 gram or something which is obviously so just for reference for The Listener when we prescribe testosterone like when a physician is prescribing testosterone to a patient for replacement we're really only using testosterone we're not using nandrolone alandon these other things which we will talk about but from a dose perspective I don't think I've ever prescribed more than 150 milligrams in a week of testosterone cypionate for physiologic trt so you're already talking 10 to 12 13 times more than that more than what we would consider a physiologic level yeah and to conceptualize that it doesn't it does not equate to 12 to 13x the results like that is something you learn pretty quick there's only so many Androgen receptors yeah and there's only so there's a severe de finishing returns as you escalate for sure and you can even see this in the you know dose response studies there is Al but it's still pretty significant there is you know slightly less each increment you go up proportionally so anyway that was uh my first foray into extreme bodybuilding I would say and also my first taste of side effects and really kind of led me down the rabbit hole of learning about oh what are the actual implications of using this stuff getting diagnosed with sleep apnea getting a CPAP machine correcting my sleep apnea but then also realizing that it's going of a bandaid to the problem too he should probably not be 260 plus pounds and taking all this so am I allowed to swear on here by the way I don't know okay yes yeah and and so um the other question I have for you at this point in time is how sophisticated is your understanding of managing the side effects of these hor hormes because obviously again we're going to talk about these in detail but I think it's a great intro to the story of you're learning this the hard way sometimes but you know for example like the estrogen effects the DHT effects you've already alluded to them a little bit with hair loss um what is your degree of sophistication around those um in in your early 20s when you're taking these doses quite minimal so back then you were told you take x amount of drug has to be a base of testosterone at this dosage relative to your other synthetic androgens that you're using alongside it based on what exactly arbitrary bro rules that are passed down the great mine essentially it's like your ratio of test to DEA must be two to one or else you get Deca dick and things like that I haven't even heard of deca dick so what's that oh it's like the progest well back then they thought it was too little test compared to Deca because if you had you decadon being a synthetic hor yeah so nandrolone is a progestin that is derived from testosterone but it is quite different than how it behaves and interestingly enough is the base for some of the synthetic progestins that women use for oral contraception but anyways that that compound is you know riddled with certain side effects for people who are prone to more the progesterone receptor interaction and it's um unique effects on I don't know cognitive Health especially too even sleep quality but back then anyway you were told you know random things that were just down the grap Vine based on no real science it was just anecdote I tried it and this is how I felt my penis worked or it didn't work now it's working so this must be the correct way to do it stuff like that and then also predetermined dosages of aromatase Inhibitors you know you have to be on you know a milligram of remedex every day or every other day because you're on 500 test or more per week you know stuff like that was seen as acceptable and smart like you were doing prevent ative you know taking preventative health measures by doing things like that is what we thought back then no minor attention is paid to blood pressure you know if you have a bloody nose in the squat rack it's probably you know a sign that you should either lower the dball or you know think about something but not much talk about you know Angiotensin receptor blockers or even how to choose a compound more intelligently it was uh often you must have estrogen side effects or something by the way what was your monthly cost of drugs at that point in time when it comes to anabolics it's actually not that expensive like a vial of test is probably you know 60 to 70 bucks V testosterone is 200 is 2,000 milligrams right it's 2 gram as a v usually underground labs dose it at 250 per milliliter I don't know why okay it's kind of interesting cuz in Pharma you're used to the 200 increment but in UGL underground lab it's almost always 200 50 if it's test e testosterone enanthate or testosterone cypionate almost always 250 and so what underground labs tell me about that this is obviously you're not walking into the pharmacy and getting branded Depot testosterone which is the FDA approved version of testosterone so does that mean these are compounding pharmacies that are doing this or how does this work no no but it's literally just some guy who orders raws from China and then makes them in what you hope to be a sterile and professional environment but you have no idea if it's his bathtub or what so there are certain Labs that would so his only motivation to do this financial well also is if I screw this up people aren't going to come back to me to buy the drug so um but wow so you know when we talk about GMP good manufacturing process uh which is what ensures sterility for injectable compounds that's not the case you know recently I did an AMA on compounding pharmacies and problems associated with them and um because you know they're not subjected to the same GMP requirements especially the community- based compounding pharmacies they've had a number of these awful incidents including one where I mean literally hundreds of people died from compounded solumedrol because it was injected right so these were being you know sent out they were being manufactured without proper sterile technique sent to hospitals this is all being done legally and then the hospitals were using these to do you know facet blocks and things like that for people with back pain and literally in one outbreak more than a hundred people died of menitis wow a fungal menitis due to this so so so the stakes are very high when you're talking about injectable compounds not being done steril so we'll we'll I guess we ought to come back to visiting the topic of what the Underground Market looks like for these compounds yeah I guess to their what they Bank on is the fact that with synthetic anabolics you don't have acute health issues it's more chronic over a span of Decades of abuse so even worst case scenario if you get a badly compounded version of whatever if you can even call it that you would have a elevated CRP from the you know carrier oils or solvent but most people weren't even checking blood work let alone yeah so and if you had a side effect you assumed it's the copious amounts of anabolics you're on not necessarily anything related to the manufacturing or anything as long as the reputation of the lab was m maintained across the forums and the Bros were happy that meant this is high quality so some people would actually send it for third party testing there was certain people who would come out with access to University labs and whatnot and they would kind of under the table you would send a you know a milliliter of your stuff in like a perfume uh you know atomizer and they would test it for you and send you hplc results and you would find out if the UGL underground lab has you know good stuff relative to what it says on the label but that that was essentially it as far as quality control how many of the guys that you were training with and yourself um understood for example the impact on fertility and long-term effects Visa gonadal function at that age very few people ever brought concern to it because we were always told as long as you when you come off you will restore fertility in due time once the you know ester's cleared Etc as long as you had good Baseline function you weren't primary hypogeal to begin with you're going to be good you just have to get the compound out of your system was what we were told back then no attention was paid to maintaining testicular volume you know Li ex Cel stimulation to maintain things nothing it was just you know come off your stuff do a and the PCT regiment's post Cycle Therapy to restore fertility were just made no sense when you look back on it back then it made sense but now in hindsight it's like oh you know the the rule of thumb was literally stop your drugs wait 2 weeks start a PCT of novedex plus Clomid for 4 weeks you recover fully is you know you just assume you don't actually check your blood work and then after that as long as you are healthy you can you know the responsible thing is wait time on equals time off and then you go time back on but often it was just you know come off 2 weeks PCT and then get back on or wait until some arbitrary amount of time is F regardless of Health markers and then get back on uh what dose of Clomid were you guys taking in the PCT it's like 50 Mig once or twice a day 25 to 50 twice a day depending and it wasn't like based on anything scientific it was just you just choose yeah amazing doses I mean those are again just so high compared to what we would use clinically in um traditional trt um and maybe if we have time we can come back and talk about some of the risks associated with Clomid use period um from a lipid perspective that is so you're in college University to be sensitive to the Canadians and uh you're you're obviously studying some are you in biology biocam what are you studying no business so okay yeah so for me I was pursuing a undergrad in like it's the business faculty at Simon Fraser University and that was to lead me to a job as an an accountant or something of that nature to be determined and I was working as a bouncer downtown while I was getting my degree and then I kind of just transitioned into posting online and then realized I could replace my income doing that on a computer rather than having to bounce which is not like a sustainable job and I don't know it was like I always felt like I should not be an accountant this isn't something I find exciting it's not really where my interest lies I'm okay with numbers but it was kind of just from high school thinking what's a good business job go downtown Vancouver get a job as an accountant at a big company and you're good and that that was the end that was the dream back then not that it was but it was you know the end goal in mind of getting your degree didn't end up doing that fortunately and started making online content on a WordPress blog it wasn't actually on YouTube for I don't know a couple months but started writing about you know dieting you know how to bulk with not getting fat um how to cut basic stuff about you know diet principles bodybuilding sort of talked about you know dating Social Circle Dynamics stuff I was super interested in at the time and then it kind of transitioned from there into discussion about my foray into anabolics side effect management I know anything I could think of that was of use that I thought I could impart on the viewer hey don't screw yourself up I've gone through this and learned the hard way way potentially you know so let's go back to kind of your journey through that so you're you're in your early 20s and you're kind of at Peak anabolic steroid use um are you using growth hormone as well I did try it periodically um I didn't notice a ton from it and it seems to be variable in how people respond I think a lot of it is conflated with the effects on like fluid dynamics so a lot of people that get a lot of Edema water retention that they perceive to be enhanced muscle and then they you know say oh my you know genetic sealing is higher now because of all the you know the satellite cell proliferation and hyperplasia that's happening so I'm going to keep using it and or it makes me never get fat which is something I would hear quite often which and which is not true but it's uh I did try it up to I think the most I use at a time is like I might have tried six I use six to eight IUS acutely but didn't notice anything more than meaning six to eight IUS daily yeah which is quite a bit that's a huge do but it was for a span of like weeks essentially and didn't really notice a lot from it so decided it wasn't worthwhile to continue because it's super cost prohibitive and like that's the thing that drives cost mostly for bodybuilders it's not the anabolics it's the the growth hormone typically um or health screening because a lot of people don't want to pay for that so they got to have their budget for the anabolics and the food but you know blood work out the window all right so I mean I think this probably for folks paints a picture of your empirical curiosity in the topic um you know whenever we have patients in our practice ask us questions about growth hormone um and we have our research team go and look at answers a lot of the times what we say both to the patients and what I have to remind the research team is look you're going to get very limited very narrow information from the literature this is not like researching the question of what are the effects of physiologic hormone replacement you know of testosterone estrogen progesterone things like that for that we can turn to the literature and we can you know get a lot of information but when you're trying to ask the question hey what happens when you take growth hormone outside of its medically intended purpose such as hypo you know hypo you know low levels of growth hor or things like that I said look it's not an appealing answer but you're going to have to kind of go into bodybuilding forms you're going to have it sounds like the most unscientific thing yeah but um a bodybuilder with a good head on his shoulders or good head on her shoulders will probably have more relevant observations about the The Good the Bad and the Ugly with with these compounds so I think what's kind of interesting what what I find so interesting about your work Derek is that you you've in my mind taken the Best of Both Worlds right so I think you've you've learned a lot through your own experience with these compounds coupled with obviously observing you're being you're surrounded by a lot of bros who maybe don't have your observational skills and and then you've coupled that with your own Obsession of going down the rabbit hole and that's why you know it's I think if anybody can extract meaning from some of this stuff it's you so maybe we'll start with going a little deeper on growth hormones since I think in many ways that's the one for which we have I believe kind of the least Insight outside of that very narrow application which is you know people who have growth hormone deficiencies where clearly replacing growth hormone is a good thing to do so let's start with one application of growth hormone now I will admit this is a question that has literally been asked of me more than once and the first time it was asked of me I was shocked uh and I don't say that to pass judgment but it never occurred to me that one would do this but it's been asked enough times that I have to believe it's a real thing so a person approached me person I know and said look um my son is 12 he's a very good athlete he's an exceptional tennis player but I'm 5'9 my wife is 5'5 he's not going to be an inch above 510 he's never going to go anywhere in tennis despite his remarkable athleticism can we give him growth hormone to get him you know to be a 61 62 kid so he really has a chance to be a pro tennis player so when you hear that do you think like I can't believe someone would ask that or are you like yeah dude welcome to the world yeah I'm not surprised somebody would ask that to be honest um I've heard much worse but it's uh not something that I believe you could look to any literature and find oh you're going to completely surpass your otherwise predetermined genetic ceiling like it seems like if you had some of the literature and idiopathic short stature is interesting because they actually have prescription protocols that are even higher than GH deficiency so you have an unexplained you know lack of height velocity as you're growing up but not necessarily you know igf1 deficiency or anything you can point to in the blood work that looks odd and they are prescribed you know uh upper end range even higher than GH deficient patients which is seems kind of odd to me um but uh for individuals who don't have you know they're not lagging behind significantly there's no indication for it it's kind of hard to justify I imagine especially as a Doctor Who's hearing that well I mean look I don't think this person was asking me to to do anything about it I think he wanted to bounce the idea off me I mean I think he clearly knew I would never have anything to do with this and I wanted to sort of not get preachy which I don't think I did but what I said was look it strikes me as a bad idea because you just don't know what the risk associated with this is and I'm not even talking about like oh what if your kid has cancer and you make the cancer worse which again at that age pretty small risk we can talk about the risks of cancer and growth hormone in terms of propagation but I said look if you were asking me to come up with a risk I would be worried about I would be worried about bone health for example and I'm making this up but I'm saying look how do we know if these new elongated bones that your son is going to develop that take him from being his natural or genetically predetermined 5' 10 to 6'2 How do we know if those bones are of the same caliber and how do we know if we're not setting him up for osteopenia when he's 50 instead of you know normal life or something like that I said I said look given all the unknowns you just have to ask yourself the question like is it worth that risk have you seen some of the recent surgeries to enhance height in adults it's crazy they like put screws in their knees and then they basically increase their height by a millimeter every day and they crank it until they've got upwards of half a foot an extra height and then that area just fills in with new bone and they have to learn to function these new mechanics both the femur and the dep apparently you pick you pick which if you want to do both or if you do one or the other but you put screws in and if you want to max out your height you can basically crank upwards of half a foot an extra height and there are people doing this and paying for surgery and going to these facilities where you basically get manually stretched and then bone forms in the space and then you have to learn to move move with those new mechanics and this is becoming a more it's not a trend I would say but there's a lot of viral content surrounding it right now and certain people that are showcasing before and afters as marketing material too it's pretty crazy what H how do how do you accommodate that from a muscle in tendon perspective that's that's the question uh proponents for it seem to assert that you eventually adjust to it with very intensive um exercise routines you know Rehabilitation stuff and you try and basically learn all your motor patterns again and eventually everything adapts and I would assume that your athletic capacity would be inhibited pretty dramatically if permanently potentially and there's huge risk there but it's just just showcases how extreme some people are willing to go all right so if that's the most extreme story I've heard about either the use of growth hormone or even surgical technique let's talk about a far more typical story sure so my patients and probably most people listening to this are not bodybuilders but I think there is sort of a a belief that growth hormone is the elixir of life and there are no shortage of longevity doctors out there which is why I I I bristle at the term when I'm looped into that group um longevity clinics out there who B basically sole intervention is giving you growth hormone it's like here's a bunch of supplements that are proprietary and whatever and growth hormone yeah um and I think the there are two responses to that so if you look at the traditional you know medicine approach to that the you know uh what I call Med 2.0 what you might call just sort of the evidence-based medicine guidelines they th that group which is the majority of medicine would look at people doing that and say that's the most dangerous careless you know unethical thing you could ever do those people are not doctors they're you know that that shame on them um at the other end of the spectrum you have the people that Embrace that point of view which is like the other people are idiots this is modern medicine this is the future we should all be on growth hormone once we reach a certain age and I find myself on neither side of that because I simply can't come up with an evidence-based point of view so my very naive point of view which I'll acknowledge is naive is given how many people are taking growth hormone and it is quite ubiquitous and especially in sports which I think we'll talk about if there are really serious consequences to its use even chronically I feel like epidemiology would give us that answer so it's possible that no one's looking it's possible that there is a signal there but it's not large it's possible that not enough people take it for long enough and there's so many explanations for why this isn't happening but there isn't a clear signal um conversely I think that there are probably a lot of reasons why growth hormone chronically given exogenously especially if it's kind of super physiological could be problematic for example if you have a tumor that is growth hormone or or you know sensitive to growth hormone um and it's already initiated are you propagating it so that would be kind of both sides of that so let's go back to tell people about what growth hormone is where it comes from you know what are the challenges of measuring it let's let's just do kind of a growth hormone 101 yeah so growth hormone is most people know it as like the primary hormone responsible for determining height as you grow in adolescence like you know androgens are more sexual differentiation maturation but um growth hormone and the subsequent growth factor production igf-1 will be a fairly sign ific determinant on if you grow to I guess like Target height whatever you could become and it's pretty like during puberty especially pretty important for the proper development of your infrastructure bone Etc connective tissue as you get into adulthood it becomes one of those things where it drops significantly for stuff as you reach adulthood and as you get older it drops precipitously as well and that kind of begs the question is this one of those things that you should be replacing to optimize you know function fat loss Vitality what have you and it's tough because a lot of the proponents that assert such things have Financial incentive and it's kind of hard to Wade through the nonsense and kind of figure out what is the truth here and it is often framed out to be like this Fountain of Youth Elixir you know HGH oh it's you know so cost prohibitive it's what all the pro athletes are using this is the thing you need to be on to prevent any age related decline in you know bone strength uh you know not your ability to burn fats as you get older is going to go down so you need to be on growth hormone etc etc and that is kind of uh like at a bird's eye view it's kind of responsible for the growth of broadspectrum growth of tissues as you grow up and then as you get into adulthood it becomes it's not irrelevant but it's far less important because you're not trying to you know push a human from you know childhood into adulthood essentially and even when you have this push of exogenous growth hormone to manually manipulate your levels after it's called epiphysial plate closure there does not seem to be any benefit to be gained from enhancing like the length of bones for example like you could still enhance um bone mineral density to some extent and it seems to be you know you could enhance connective tissue Integrity it kind of depends on what your situation is and how igf-1 deficient or lack thereof you are but it's not going to impact your height in adulthood it's not going to really do anything other than regulate um like lipolytic action um how does it do that by the way it just liberates free fatty acids into circulation so it's kind of seen as the opposing hormone to insulin so it's like when grow does it do that through lipoprotein lipase I mean what is it actually acting on substrate with on the atopa site that it seems to be driven through different like Baseline I don't know states that you're in like if you have you know gin receptor agonism from being fasted for example a lot of people point to the literature on if you're deprived of calories oh growth hormone goes up there are different situations in which it'll go up deep sleep obviously super impactful on if you're going to have release or not as well but the main actions that I'm aware of at least in a state of growth hormone pulsation is kind of the underpinnings are you were trying to liberate free fatty acids for utilization as substrate for energy or anti-catabolic action so the actual like mechanism enzymatically and whatnot it's a bit fuzzy and what's the relationship then between GH and igf in the liver how does this all work because we don't really measure GH in people right because it's pulsatile so what are we stuck with as a proxy yeah even if you inject GH like a large dose of it you will only see a spike in serum for a transient period of time and people who were trying to assess the quality of their growth hormone back in the you know with the underground stuff they would be trying to time it very specifically down to the minute to assess the quality of their stuff but the best proxy for GH production endogenously seems to be widely accepted as igf-1 which is after you produce growth hormone from the pituitary there is action in the liver but also paracrine and autocrine action on you know muscle especially if you are exercising resistance training but a lot of the serum igf1 is driven through liver production and that is has its own implications in terms of its effects that seem to be more it's like ingenic in itself to some extent and um yeah which is kind of counterintuitive right because if igf-1 has Inogen properties which are promoting a fat storage and GH is promoting lipolysis don't those act at odds with each other and how how how does how does one sort of uh become more dominant yeah it's this weird orchestrated feedback loop and these feedback loops are present in the body in multiple you know multiple different uh I don't know hormone substrates will reduce in multiple different metabolites that then have negative feedback through different systems and this seems to be no different if you have GH at a certain level and it results in a certain amount of igf-1 you will have negative feedback that will then lower your production of HGH while the igf-1 is elevated and as it declines you have this decrease in inhibitory feedback that then tells your body okay now that igf-1 is not present in significant quantities it's okay to you know release GH again so it's this like finally tuned Balancing Act in your body where your body has kind of like counteracting things it's not counteracting but it's like the balance between anabolic or anti-catabolic it's it's kind of hard to and frankly I don't even know how to elucidate in like a super clear way that is completely accurate but it's it seems to be kind of uh when one is high the other one would be low and conversely in order to kind of maintain a not necessarily at the same times but to maintain like a balancing act in the body so we have a real sense of how to dose for example testosterone or estradi in the case of HRT for women because we know what physiologic normal levels are during various periods of a person's life and so if we're replacing testosterone to the level that we think is normal either for your age or for some earlier age we can measure the hormone we administer it and we can do the calculation hey this person has a lot of sex someone binding globulin or they don't or whatever the case might be when when people are administering growth hormone and again let's just talk about this through the lens of the context you're talking about it now which is you know Rejuvenation or you know whatever longevity the the waste basket term how do they know that you know because typically they're using about one to two units per day isn't that the typical dose yeah it depends large on liver function too so some people with compromise function or type 1 diabetics for example they could have super high GH production but very low igf-1 from seemingly lack of Inogen signaling because it also has a positive relationship with igf-1 production but that is it can be difficult because you could have a person on a ketogenic calorie deprived diet model who has an igf-1 that is on the low end of the reference range be manually administering growth hormone and be using a higher dose than would otherwise be necessary to get to high normal optimal function put in quotation marks um so it that's the best proxy we have as far as I'm aware is that serum biomarker igf1 but there's not really you know uh cut and dry way to so people would use the zcore presumably of their igf1 as the dosing as the output for determining how much GH to administer yeah my understanding is that regardless of its idiopathic short stature GH deficiency they would use igf-1 as a metric to kind of dial in the dose so if your igf-1 is higher than it the target then you would dial the dose back accordingly or if it's not high enough then you would what did they target a zcore of one to two meaning one to two standard deviations above the mean is therapeutic or just being above zero for example which means you're above the 50th percentile the target for I think it's mainly just correcting but as far as what is correct I guess the reference range if it's in the middle or the highend of normal I don't recall off the top of my head but it's something in the neighborhood of middle of a standard Lab Corp reference range as far as I know could be off on that but yeah so okay so let's talk about the physiology of this so you give GH there's a feedback signal because GH comes from the pituitary but it's spoken to by the hypothalamus so we're going to talk about this again when we talk about testosterone of course because that's a really obvious issue so what happens Upstream of the pituitary I.E what happens to the signal from the hypothalamus to the pituitary to make endogenous to make your own growth hormone when you take it from the outside does that get shut off as well yeah the negative feedback that I spoke about ly when you have elevated igf-1 it will give negative feedback and there is an elevation something called somato Statin which is like a basically tells your body don't make as much GH essentially and there is different receptors which gets a bit confusing as to how you produce the growth hormone Upstream there's the Gin receptor which Super confusingly is also called like the GH receptor I believe it's also called and then you have the ghrh receptor and the reduction of ghr endogenously as well as the agonism of gin receptors can both stimulate growth hormone and the way by which they achieve your end output can be different that's why there's different drugs that Target different receptors for actual elevation typically ghr drugs are coupled with ghrps to get like a 1+ 1 equal 3 effect of sorts but this is why also when you are fasted or malnourished you could have significantly more output via the grin receptor agonism as that is the and this is the same gin hormone that plays an important role in management of hunger yeah so for people who don't know gin is like I don't know if it's the primary but I think it's probably pretty accepted that leptin and gin are kind of like the signals that you're full vers hungry so gin and grin receptor agonism is what would tell your brain you're hungry so for example if you gave somebody a really potent gin receptor Agonist like ibam Moran is a commonly orally bioavailable ghrp you use that even if you're not hungry you'll want to eat your pantry like it's insane so that compound plus a ghr will seemingly have a downward pressure on some mastaan activity and simultaneously increase the output from the pituitary to produce more GH so you can kind of like max out your endogenous production through these peptides essentially but those are the primary mechanisms involv like those three things is the Gin receptor ghr and then also samat Statin as a negative feedback so if someone is just taking exogenous growth hormone and um how long would they need to take it before they would start to compromise their own ability to make endogenous growth hormone once they came off um I think it's pretty quick like igf-1 elevations are not instant like in the serum you would see GH spikes in a matter of minutes like it's very transient in your system very short halflife but the downstream igf-1 conversion can increase over days and then stay elevated for days and this is why igf-1 as a biomarker has been asserted to be a potential way to catch people doping further out than the HGH isop form differential amuno assay which is the current accepted gold standard test that they use um cuz igf1 will stay elevated for a relatively long period of time but let's just say a person's on GH for two years M and then they stop it yeah does their pituitary go back to making GH yeah seemingly it seems pretty flexible in that so in that sense it's different than LH and FSH and the testes making testost yeah and the reason for that I can't help but think there's because there's multiple actions of the pituitary it's not going to atrophy in the same way I would think and this is just speculative but for example people always want to know if I take anabolics or testosterone replacement for years but I don't take HCG or I don't take these fertility drugs will I be able to restore fertility in short order and it seems to be like a use it or lose it kind of thing where not necessarily but it's more difficult to restore fertility and somebody with like severely atrophied organs that has not had stimulation directly for years versus the pituitary does multiple different things so I can only imagine that you know the maintenance of output of other hormones and things are at least maintaining its flexibility to some extent but that that's super speculative let's talk a little bit about the use of GH in uh restoration of tissue during periods of healing so um I think there's some accepted medical use for GH and burn victims for example right so um if a person sustains a significant enough burn um enough of their the body surface area is burnt I mean that's one of the most catabolic activities the human can sustain and therefore the reversal of that is one of the most anabolic demands that a human can sustain as an adult um what about during you know orthopedic injuries so you look at a person who's having either elective or emergent surgery for an injury uh you know I'll give you an example so so we've had patients who have had injuries so like a torn bicep and you know we've looked at the literature found I would say at best modest evidence suggesting maybe for that person um you know an 8-week course of anabolic steroid oids and growth hormone can Aid in recuperation you know the few times we've done this we've seen great outcomes but that means nothing it's so anecdotal we'd have no you know we have no contrapositive uh or or or you know con you know opposite view there what would happen otherwise so do you have any insight either from kind of literature or from just kind of the underground world as to what the use of modest amounts of growth hormone would look like in periods of Rehabilitation yeah it's more anecdotal cuz like you said you could find very yeah there's just no counterfactuals to any of these stories yeah and often times when we're when I'm talking about this stuff I want to say it's not necessarily founded in literature unfortunately it's kind of a mix of extrapolations rodent studies anecdotes in humans stuff like that which is unfortunate I would love to be able to make like hard-hitting factual statements every time I say something on this stuff but with GH anecdotally it seems to be quite effective in Rehabilitation I think that it is worthwhile in an acute time frame like that's where the ROI makes sense in my opinion so I do see people but again it's not like you have a control of that same guy with the injury yep not taking it so we can only go by what you discern to be a reasonable I don't know recovery period and then well it seems like it's recovering quicker than you would have expected expected good probably good yeah I um I I think I may have told you this like year and a half ago I had shoulder surgery and um you know I was so I was you know really this was an operation I had been you know postponing for 15 years um until it got to the point where I I sort of had to have it and I really was so hesitant to give up so much you know because of the size of the tear in the in the um laum it was going to be you know four months before I could really do anything again other than very light movements so I my plan was to take grow I did you know I did a little bit of homework and came to the conclusion that a certain cocktail of nandrolone and growth hormone was going to be the best cocktail so I found that so interesting that you didn't use a base of testosterone with the nandrolone because you could effectively wipe out your estrogen with that combination interesting well I ended up taking it for a total of one week yeah yeah I noticed yeah I I saw that uh your uh post on Facebook where you mentioned how your I think you had a blood pressure elevation and also blood glucose went up my blood pressure went up my temperature was up at night now in retrospect what I realize is I think I was sick I think I actually got an infection gotcha and and anyway so I don't had anything to do with the hormones but my I felt so bad on the hormones that I was like well I'm definitely not doing this so you know I'm the counterfactual I suppose for you know not having done anything which of course means I still know nothing I still have no insight into what this um what this is but I do find this interesting and like you I do find it frustrating that this is a question that isn't studied now I understand that there isn't really a financial incentive to study this because of course you know there's not really a a great um you know it's it's not something that is a new drug you know um Rec competent GH has been around for over 40 years now hasn't it early ' 80s yeah it was like kadav derived in the 80s and then soon they went to rec combinant I think late 80s or 90s or something so yeah so over 30 years so um anyway it is a shame because I've talked to many orthopedic surgeons um and to a person they all said the same thing which is I really wish we knew the answer to this question like it would it would really be wonderful to study this rigorously and know could we make a difference in the outcomes of patients um by using these things in a very narrow um opportunity and and the other question I I guess I'm wondering is do you and I because I can't find a clear answer to this in literature do you have a sense of the use of growth hormone in osteopenia yeah one thing I can say circling back to the justifying if it makes sense or not I think there's certain things you can use to discern if it's a better idea like Baseline igf-1 are you somebody who is in a ketogenic diet and you're trying to recover from an injury simultaneously are you calorie deprived like there are certain things that kind of make it you know that could otherwise be IM significantly influencing your recovery capacity from a growth factor standpoint that you may be able to manually backfill that for another person some people naturally have igfs that are like top end of the reference range or if you were acromegaly had acromegaly you would not use G obviously um so it's definitely context dependent or you know if you had uh insulin resistance at Baseline or something like there are certain things that may otherwise sway you the direction of the ROI makes sense vers not so I'm not going to I feel like that should at least be said so people don't think it's a total blind roll the dice thing that's right yeah that's a good point um as far as its effects on like bone health and and let's throw the same caveat in there so let's say we're talking about an individual with osteopenia or osteoporosis let's assume further you're going to do all the normal stuff you would do so you're going to do all the things you would do nutritionally with respect to vitamin D calcium amino acids you're going to increase loadbearing activity particularly strength training if necessary you're even going to bring on uh you know Fosamax and the type of drugs that may help in that regard but if in the context of all those things an individual has a low igf1 do you think it first of all is there any evidence that in that setting GH Administration will improve bone density yes I can say with almost near certainty that that literature exists but I would even if it didn't I would say almost without a shadow of a doubt that it would be worthwhile especially in somebody with low igf I'd have to Circle back and make sure the literature was not rode and extrapolated but I'm pretty sure that anybody especially with lower igf1 you kind of get into the discussion of can you even sustain adequate bone Integrity especially in I don't know old age where you might have like you're probably most prone to that to begin with like it's almost certainly Justified I would say in that scenario yeah it's interesting um hopefully we I'd like to find that and maybe we can include that in the show notes because I I feel like the last time I looked I didn't find I didn't find anything that s suggested not doing it but I didn't find something that was a a slam dunk home run um you mentioned a couple of peptides so let's talk about these peptides that are kind of Upstream so I can't even keep track of how many there are there's like CJ c1295 samorin uh what are the others uh so on the ghrp side the easiest way to segregate these is by ghrp ghrh so ghrp are the ones that act on gin receptor ghr are the ones that look very similar to ghr and act on that receptor so like that's the easiest way to segregate them in terms of categories and then from there they're pretty different and how they affect things like for example I pamaran is often used in these like anti-aging clinics and whatnot but sorry the ghrp ones are also going to drive hyperphagia yeah so the depending on the compound this is the weird thing about it so even if you are stimulating the Gin receptor the effects on appetite are quite different so for iin for example despite the fact that that's the receptor is working through and it is a grillin receptor Agonist it does not influence hunger to even any reasonable magnitude within Striking Distance of mk677 ibut to Moran the difference is literally like you eating 2,000 more calories a day not by choice but you're just starving perpetually so it's almost like it's inducing Prader willly syndrome or something which is a condition where you have uncontrolled eating yeah like The Willpower necessary to avoid overeating on MK 677 it's so what's the clinical use case for that is that used in AIDS wasting cancer wasting and things like that orally active so adherence is much more reasonable to expect it's the application it's not FDA approved by the way but it is for GH deficient children I believe and we've seen you know restoration of igf to the you know top end of the reference range when using it so going from I don't know like a low-end igf to a 200 to 300 or something it's not going to push you into Super physiologic territory cuz it's working through your endogenous capacity but you can kind of max out what your pituitary output potential is so similarly to a you know an HCG or something you can kind of manually at least stimulate natural production to the upper threshold of Your Capacity y so it seems to be efficacious in that but it also is but not going to have a high application among adults who don't need an extra 2,000 calories no but it also depends cuz some people maybe you have low appetite and you want to gain weight or you're in a state of recovery and could your appetite is suppressed from some other drug you're using because that's you know fairly common depends on the context and that's where unique kind of case specific so what is the FDA approved indication for this drug it is for GH deficiency and Adolescence I believe okay yeah but it's also like even though it's prescribed among you know clinics and whatnot it's not I don't even think it's achieved FDA approval yet it's like in phase two or three so how is this oral how is how does this peptide survive the gastric environment that is a great question but it is the only one I know of that is often referred to as a efficacious option in this laundry list of ghrps to restore igf-1 to highend normal so how the actual pharmacokinetic profile looks all I know is the halflife it's like 24 to 36 hours it be entally coded it's not hepatotoxic from what I remember um it's got to be something that it just survives through you know coding like you said or something of that nature okay any other uh ghrps that are worth discussing yeah I think I pamaran is probably the one most prescribed in clinics and that one seems to be probably more targeted in the outcomes you'd want to see out of like a growth hormone releasing peptide in that you get enhancement of sleep doesn't make you hungry really even though it operates through the same receptor pathway um definitely increases igf-1 uh it is is it FDA approved I believe it might be for lipo distrophy um or that might be Tessa Morin but these are the two t uh iar is the primary one that is prescribed and then there's a bunch like ghrp 6 ghrp too which significantly impactful on Hunger JRP 6 probably the worst one that's what bodybuilders use when they reach a bottleneck of food intake and they can't eat anymore they will mk677 is around the clock but ghrp6 after you inject it it's like you can modulate acutely when you're hungry so if you had an eating contest to win or you were going out for an all you can eat buffet or you're just a bodybuilder who can't eat your 5,000 calories a day that's when you would be' look disgusted as I'm saying it no I just I mean it's uh yeah yeah I I think there's there's so much to unpack there um yeah but iamin is the one that is prescribed most often the other one and that's a daily injectable yeah so is that used by athletes and bodybuilders yeah fairly often Y is it cheaper than growth hormone yes yes depending on if you get the growth hormone underground or not through phy certainly but there are generic growth hormone preparations that are pretty cheap now like you could get 100 IUS of pretty high quality HG from China for 150 bucks uh by comparison what would that cost at a pharmacy I'm trying to think thousands yeah I mean it's insane yeah especially if it's like you know a big brand name yeah like back in the day people would go to AIDS patients and convince them to sell their SOS stem that's what bodybuilders used to do yeah decades ago okay so on the ghrh side who were the big players Tessa Morlin and samorin but I would say Tessa Morin probably more commonly sorland seems to just people just don't really get the results they want out of it and it's more anecdote than any kind of literature that points to it being sub efficacious but um Tessa Morin plus iamin is kind of the primary combo utilized in clinics especially nowadays so I would say that is so they combine them they'll combine Tessa Morlin with I morelan yeah typically and there's also um are the other ones mod uh there's like the CJC 1295 and there's with drug Affinity complex which is basically extends the halflife significantly and CJC 112 uh 1295 X is is is which one of these is it a ghrh receptor yeah yeah and then there's a a shorter version of it it's like M grf 129 and these are not FDA approved compounds these are literally the wild west of compounds right some of them have sorin and Tess Morin are FDA approved I assume yeah some of them have I know I know one of them in particular is approved for lipo distrophy Y and there are some unique applications in which some of them have FDA approval but most of them the ghrp6 ghrp2 hex uh hex Arland I believe and a couple of the ghrs on that list do not have FDA approval and mk677 as far as I know is like off label prescrib it's kind of weird because it's like this stuff is not there's no company that makes a branded you know FDA approv version of it but then compounding pharmacies will still make it there's a lot of questions as to well what are the standards that go into making it then and are you just ordering it from China similarly to an underground lab and just yeah there are no standards I mean there are no standards um that that's the whole point of compounding right is they don't have to they can make sort of anything I mean at this point the real question is where is the the line between um a grass so so so if something has a Gras designation it's generally regarded to Safe by the FDA you can sell it on Amazon right it's it's an over-the-counter um which would be you know what's the most potent grass thing out there is probably DHEA which in other countries would require you know in other countries DHEA is I think appropriately treated as a hormone I think it's like schedule one in Canada is it really yeah really wow interesting why I don't know because actual steroids are not as as regulated that's amazing yeah yeah but in the US DHEA amazingly is overthe counter so that means it has a grass designation I'm guessing that you know CJC 1295 does not have a grass designation so that means you cannot sell it without a prescription but yet it doesn't have an IND it's not an investigational new drug it hasn't gone down the pathway of an approval so I think it's just sort of in this gray area some of them are abandoned it'll be like a drug that was in a pipeline maybe there was an indd and it got scrapped yeah so it's like you know sometimes is it is it Financial is it lack of efficacy is it's um like in some cases there's a drug called carterine it's a PP Delta Agonist which is actually pretty good results on lipid management um it's kind of like one of those exercise mimic drugs but when you look at the metrics that it improves it looks great but then there is some rodent study where the it was like every dose of of carterine got resulted in cancer in these rodents and then I guess the response to that was a public outcry of you know worry concern Etc and it just no reason why publicly it got scrapped but it's weird because it was like pre-clinical rodent literature supposedly caused the ca it to get cancelled after it was already in phase two in humans so it's like some of this stuff and carterine is prescribed through clinics too but yet all the rodents who took it got cancer yeah every dose I mean that would be disconcerting yeah for sure um okay so again talking about this through the lens of I have one patient by the way who came to me having been prescribed sorin from the outside MH um I asked him to stop because I was like look I'm not going to take over the prescription on that because I don't know anything about it um so he did and like I don't know a year a year and a half later he's like look I really want to be back on this I've just never felt the same since I was on it yeah you know it just gave me such a feeling of Vitality and you know he had a lot of reasons why he felt it was the thing to be on and I said look man I I'm not going to be that guy who says no just to say no but but I need to understand this a little bit more and I think we need to think through what are the what are the risks and benefits of this and so we kind of negotiated this back and forth for 6 months where I said look I guess if we do a bunch of really good cancer screening and can convince ourselves that you don't have cancer you know we do the pruvo we do a you know Gallery blood test you know check a colonoscopy like basically to the level of detection of our modern technology you don't have cancer at the moment um I'll I'll be happy to find you know an endocrinologist who's more comfortable with the dosing and we did so we found a great endocrinologist and she was like okay you know and he went and saw her and she's prescribing it to him and he's as happy as can be um and again again this isn't to me like this isn't sort of a there's not a judgment around this it's it's I'm genuinely curious and I I still can't make sense of would you want to be on samorin Tess samorin it sounds like you're saying Tess is better than samorin or but that again could just be anecdotal versus growth hormone and and then of course I you know I never really understood the stacking where you would to stack both compounds so do you get the sense that hitting both targets both receptors is better than just using GH like does it give more specificity you one thing you could say for certain is when you push endogenous production you are fulfilling the full uh production of all spectrum of variant so there's different you know kilad dalan ISO fors of HGH and this they detected in doping and these variable like molecular weight growth hormone outputs that you get from the pituitary we don't know why they are put out in different you know formats essentially for all we know they have different actions in the body that may not be facilitated by the re combinant straight like 22 so when you take a recombinant HGH you are telling your brain like don't make more essentially so you are actually losing the production of those other variants and you were relying entirely on this one got it so what the implications are of that from a health perspective or a performance what have you like obviously we can manually push your igf to Super physiologic which you will not be able to do with the endogenous kind of upregulators of sorts with the peptides and you can kind of manually just choose where you go with it so there's certainly a case to be made just like with testosterone it's like oh why would you use a GnRH Agonist or why would you use a serm or why would you use an aromatase what have you and modulate these Upstream Pathways when you could just take the straight hormone and manually pick where you land and often times that could be the reasonable answer especially for somebody who wants like a very targeted end goal and knows exactly where they want to land on their igf or you know doesn't uh doesn't need or potentially has worse output relative to the input of those peptides because again it's working off your natural capacity so there's definitely potential pros and cons you can if you have good functioning you know entire uh hypothalmus pituitary all the all the output is satisfactory from an infrastructure standpoint to Output natural hormones at an adequate level you know the natural peptides may be useful and you know you're getting all the variance of all the Kil adol and molecular mass variants but with IND exogenous it's just like you know you know exactly what you're getting you can manually choose the what you're getting out of it and I think it's more could be reserved for people who don't want to don't have the natural output that they are trying to get out of the peptides like they don't respond that well or there's just more data too see so is there kind of an analogy here where taking growth hormone endogenous sorry exogenous common and growth hormone is like taking testosterone yeah whereas taking the peptides is like taking Clomid yeah I would say with exception that you're not blocking negative feedback you are positively modulating correct Clomid works by creating a it would be like analogous to probably an HCG and recombinant FSH or more like a HCG probably or you know combined yeah HMG or something so what does the literature say and what does the non- literature say about the role of GH alone not in combination with anabolics in terms of it capacity to help build muscle and uh oxidize fat yeah the the literature is so sparse on being able to say without a shadow of a doubt that it is going to enhance muscle potential muscle growth potential and performance especially like there are very few studies that really show a clear enhancement of athletic performance so I think what is clear in the literature is the body recomp effects so being able to you do gain lean mass part of that presumably is water retention you do lose fat Mass right yeah and for like lipo distrophy if you're able to I don't know liberate free fatty acids and be able to actually improve your I don't know utilization of substrate like you could absolutely improve your body comp fairly significantly with it but you know when it comes to actual protein synthesis muscle acrel it's very uh wishy-washy and certainly not something that you should hang your hat on as the reason why you're taking it in my opinion so from a muscle growth and athletic performance perspective the jewry is out in terms of if it does anything significant enough to justify its use bodybuilders will claim to high heaven that it's you know the some think it it's an expensive fat burner and some think it's actually quite useful and they notice huge changes but but it also very much depends on your response from a you know fluid dynamics perspective it can definitely increase sodium retention and things that you may interpret as muscle growth that may just be volume and with that said the muscle is you know how much water at the end of the day so is that to be ignored from a cosmetic perspective it certainly looks good on a bodybuilding stage it may not necessarily be may not have the function yeah so you may not get enhanced Force production outcomes like you would be seeking from like a true you know anabolic agent but it doesn't improve cosmetic appearance of muscle almost certainly and can help you uh improve your body composition especially if you you know time it well with because if you just use it and liberate free fatty acids and sit around and do nothing you could just redistribute that and not necessarily get the benefit out of it that you're seeking so so do you think that the Liber the The Liberation of fat is the more reproducible finding of ghus oh yeah like that you know you know that's happening when you use it for sure and you will become acutely insulin resistant as a result of that too so based on that knowledge when is the ideal time to take it do people take this once a day twice a day it depends on the dose because if you're using a very high dose you don't necessarily want to and it also depends on your lethargy from it it is very lethargy inducing you could feel you know sleepy all day if you're blasting a high dose of it I say what what would be a high do like what you were taking 6 to8 yeah I would say and when I took it it was mostly in the 2 to four IU range I only did six to eight for like a very short period of time and even that the lower lower but still pushed me to like a 500 igf was lethargy inducing for me personally for how long um man that was so long um I had tried it for full durations of Cycles so you know upwards of a few months was probably the longest I had taken it but did you have lethargy the whole day or was it just like if you took it in the morning you'd feel that way till noon then you had to work out in the afternoon to get around it with the doses I was using and splitting it up the way I was it was pretty around the clock but why is that it seems to have a very intertwined connection with sleep so you have your biggest GH pulse when you're getting to sleep and people find seemingly pretty positively correlated with aging you have a decrease in igf and seemingly deep sleep metrics also decrease precipitously too and I think this is the biggest case to be made on potential attenuation of cognitive decline as its impact on sleep if you're somebody who gets significant enhancement in deep Sleep metrics however you want to track that it's uh I can't imagine you can extrapolate from there that it's helpful for somebody who has you know if you have a crashed IG F and you have horrible sleep as a result of it like there's clear literature to show that igf deficiency will impair sleep so if you're able to correct that to some level the minimum effective dose you don't need to push it to the top end but you're saying with a higher igf you were more lethargic does that mean you were you would think that you'd be sleeping better based on that argument right yeah probably but I was it's also gets conflated with bodybuilding diets too cuz typically when you're using it you're in a calorie Surplus trying to gain a bunch of muscle so you could definitely conflate those findings of it and it is anecdotal but in general people using peptides even and growth hormone will often find that their sleep is seemingly enhanced like it's deeper more restful and during they're more lethargic during the day yeah so almost is it possible then that the that the GH is inducing too long as sleep like you're you're sleeping a lot during the day but you sleep not at night but then it's carrying over to the day like there's a hangover of sleep potentially for sure like it seems to be a hormone that is quite rejuvenative during your sleep and I can't imagine not that I really right into like ancestral history or how your body functions relative to the ancestors that much but it's like the time you are trying to recover and rest the deepest having the highest Spike of GH like it seems to be I think it's it's something you could at least extrapolate as a interesting anecdote nonetheless that I can understand why I might be tired when the deepest point of rest is also the time that this is simultaneously the highest endogenously so if I'm manually creating at least half of the conditions that are associated with when I would otherwise get the deepest sleep maybe I can manually induce that myself if I'm deficient or what have you but as far as timing and the justification for it it depends on if you were trying to use it for lipolysis or if you were trying to use it to enhance sleep or what the conditions are cuz you are going to be suppressed at a certain level regardless so often times the logic would dictate at least in my opinion that you would probably put part of your dose before bed given that you're not going to get the same output when you're using exogenous GH so if I'm using let's just say all of my GH in the morning and then I'm going to exercise to try and you know use the fat yeah which is not a bad idea there's definitely a at least think a justification that part of that dose or potentially all of it when your igf1 or GH output is suppressed that you would actually allocate your dose to pre-bid so it depends on goals too and if you notice an enhancement of sleep or not but you can say without a shadow of a doubt you will be that feedback loop will suppress your natural output you're not going to just get the best of both worlds and so is the would you say more people today would be using the two receptor approach uh the the two peptide receptor approach rather than GH is that a more common approach today I think among those in the clinics for sure because it's less cost prohibitive that's what I think but in the underground you know bodybuilding world they're typically they're pushing super physiological igf-1 levels that's their goal that's what they want to get out of it so they typically try and find pharmag grade GH and if they can't get it they will go generic if they also can't afford it and that's what they're doing so and they're pushing igf to 500 and more yeah typically like that it would be a minimum adequate amount for performance enhancement you know quote unquote performance enhancement would be deemed higher than what is naturally achievable based on typically a Lab Corp reference range is what most people would utilize let's DeTour for a moment just to talk about bodybuilding before I want to kind of go back and talk about anabolics and then maybe this will be a nice dub Tail in to it so um in my gym I have a lot of pictures of kind of bodybuilders nice Black and Whites that I enjoy and there's just a real clear difference between Frank Zayn Arnold Schwarzenegger you know Sergio Oliva um to you know Jay Cutler and Ronnie Coleman and and and and I don't know when that jump took place maybe Lee Haney maybe um Dorian Yates but somewhere in there there was a real transition in physique yeah and um not to debate which of those is the best I think everyone can have their own preference for which era of physique was the most you know was their favorite but what what is the you know if you sort of think of the the things that can impact your physique genetics okay that's not changing uh nutrition and knowledge of nutrition that's clearly evolved training and knowledge of training that's clearly evolved um drug use that's clearly evolved and then maybe just even injection I've talked to bodybuilders today who say that they're actually injecting compounds in their muscles to alter the shape um they're they're injecting like fats into muscles to actually create some sculpting so that again that's probably something new let's put that one aside as far as the like when you so of the three evolution of training evolution of nutrition evolution of drugs how would you rate the relative balance of those three for the difference of you know a 1970s physique versus a physique today of the best bodybuilders in the world probably drugs at the top almost certainly followed by I would say nutrition probably and then training at the bottom and how how much emphasis on each of those like 50 40 10 that's tough cuz these get scrutinized to hell cuz it's like I'm going to put a number on it people will be like how do you think diet is only 20% so um cuz a lot of these things don't live without the other so you could definitely lean heavier and say well if you eat nothing the drugs aren't going to do any so I would say just in order of importance fair if you did perfect diet perfect training with all of the modern knowledge that we have now your ceiling for muscle growth potential could be as much as 50 to 100 lound lower as a natural depending on height depending on genetic response and by the way I don't want to forget on the GH stuff one thing that is interesting is even in acromegalic patients the incidence of death seems to be cardiovascular almost like significantly more than cancer incidents so if there's anything to discern from actual human literature it's a good point significantly chronically elevated igfs into even you know 40 years old these individuals are dying from um congestive heart failure and things like that as opposed to and that's really interesting so not even atherosclerotic disease it's they're also probably I I have to look into this actually that's a very good point I should look at the acromegaly literature the one of the interesting things is how much fluid retention they hold and the stress that has on the heart too yeah and that's very interesting they also probably would be I'm guessing maybe more prone to aortic dissection because they probably have larger connective tissue um and things like that yeah okay so you're putting drugs at the top of the list and then nutrition and then training I think was the order you had them in so let's talk about the drug use so I've spoken to 70s bodybuilders and was if they're being honest with me and I have no reason to believe they're not right like what do they care you think yeah like what do they care I was shocked at how little drug use was going on back then amongst the best of the best and and we're talking like 1 to 200 milligrams of testosterone a week yeah eight weeks at a time you know eight on eight off eight on eight off one to in other words they're basically taking trt yeah they're not telling the truth you don't okay so that most of them almost certainly are not when you're saying you're taking a like borderline female HRT Dianabol dose it's like back then that's what it was prescribed for um or like muscle wasting in Old AG or whatever some of the old like sea diable ads are hilarious by the way but those dosages are almost impossible to wrap your head around producing outcomes that they are like you might as well have stayed natural almost at that point so you know I too bought into the idea of oh they seem to have consistent stories they seem to have all taken one shot of Primo a week and you know one to two dianal or what have you and it's just not an outcome that you see as reproducible ever in those dosage quantities so you know maybe on the hyp extreme outlier scenario you might have a guy who a total weekly dosage of you know a few hundred milligrams across everything he's using he may hyper respond and get huge but I would say the majority of the guys competing at the Olympia level were still like I've heard of people slugging dball by the bottles like it's even back in the 70s it's just certain people are more outspoken about you know their abuse than others seemingly and seems like the ones that are outspoken are more like this guy Pete Grim Kowski I don't know if you've heard of him before but looked incredible but the guy used like thousands and thousands and thousands of milligrams and I can understand why you would arrive at that logic to take that because there was nothing to tell you otherwise so if you're competing against a guy at the highest level and there's relatively high stakes you see a guy like Arnold getting movie roles and stuff it's like the peak of achievement as a bodybuilder back then you couldn't do social media couldn't do anything you would try and emulate presumably what he was doing or something of that nature to think that you're not going to escalate your dose past one to two Dian ball and a shot of Primo or what have you or a shot of nandrolone because you didn't want to like hurt yourself like shut up dude yeah I feel like I heard I saw a video kind of recently of Tom Platz discussing this oh he had changed the story yeah with that said his original breakdown was relatively conservative still but he's done public presentations about drug use back in the 80s 90s and he you know you could tell he was pretty reserved even back then he handled the situation very delicately you could tell he was picking his words carefully as he spoke but more recently he came out and said his dose was like I don't know a third of that or something it's like okay maybe like you know in 40 years or something I don't expect you to remember exactly what you took but to say your Peak dose was onethird of what it was I don't know like I just I just don't really believe you well at the other end of the spectrum I've spoken to one bodybuilder who and I couldn't believe it but he said at one point he was up to are you ready for it yeah 50 grams of testosterone in a week that's there's no way you would not inject that much I I mean I was like how is that possible run out of inje how are you managing I think a lot of people just don't know what they take to yeah cuz often times you ask people on trt even what's your dose they're like oh I took like you know a half as we noodle with patients between 100 and 120 milligrams a week like literally we would we will make movements that fine 20 milligrams a week yeah yeah I think a lot of people they just go by oh my doctor told me to take this much of a syringe and then they kind of just remember some rough number but often times they don't know how many milligrams per per milliter what they're using is they don't know what their dosage is they just take some scheduled protocol and they stay on it for years and then they don't even know what they're doing but 50 GRS is like it's impossible like you just you would have to dedicate your life to injecting essentially that would be your full-time job just sitting there pitting like 5 to 10 CC barrels of test all day oh God yeah so um given how remarkable the physiques were in the 70s at the top of the you know at the top of the food chain in the Olympia you would you agree with me that it's a different like something dramatically changed in the late 80s early 90s yeah and it seems to be the emergence of growth hormone and Insulin abuse as well as the escalation of drugs to an even more extreme magnitude and the availability potentially like granted they were prescribed readily seemingly but people also seemingly push the limit more and there's the emergence of under around lab preparations and things of this nature so um my understanding at least is and there's no literature to document like oh you know this dosage equated to this and therefore this is why it happened but it seems to be dose escalation of anabolics to some extent but more so the implementation of growth hormone coupled with exogenous insulinas and they're using insulin because of how anabolic it is well that's the uh that's the the goal is what they think it is and obviously if like there's terminology that may not be exact on that but it's like that is uh what they believe it's doing is shuttling a kind of like super physiologic amount of nutrients into the muscle because also when you take GH you are acutely insulin resistant so you need a little insulin to overcome that yeah they're almost like doing both things at the same time as the goal and often when you're using really high doses of GH and fortunately this isn't as problematic in replacement dosages so I don't want people to extrapolate out oh GH equals you know chronic insulin resistance necessarily but at the dosages people are using they will they could induce you know diabetes essentially like you could end up a diabetic from just your GH abuse and often times to relieve stress off the pancreas and the beta cells they will use exogenous insulin so you don't have to produce as much endogenously to actually accommodate the amount of carbohydr intake and just overall nutrients because these diets get to you know to maintain a 300 lb physique you're pounding 500 5,000 calories a day sometimes so the the Advent of or not really the Advent of but the introduction of growth hormone with all of its benefits presumably which we've talked about are yeah and it's so it's funny because right as we finished talking about how it's not performance stand saying now the thing that causes the 20 to 30 lb lean mass jump is supposedly GH and Insulin you know it's uh it's interesting to say the least but um continue well I was going to say so we have that issue going on um you've also um talked a little bit about kind of what we see in so so so my belief used to be all this GH and Insulin use is why we're seeing these big abdomen on not just uh bodybuilders but also on athletes so you know you you you'll see track and field athletes who are insanely muscular insanely lean but they have huge protruding abdomens that do not appear to be fat because you still see a six-pack ripped on top of it but from the side they look pregnant and again the thinking was well is this just organomegaly right are there organs just getting bigger now you've you've talked a little bit about an alternative hypothesis right yeah I think think it is multifactorial but there is seemingly I think the largest cause of it now is significant distension caused by the excessive food intake and the result of significant gastrointestinal issues that result from the Absurd diet models because to get that many calories in get that much protein carbs off and especially Perry workout when you're using insulin and you need to make sure you don't go hypoglycemic in your workout they'll be slamming like you know 100 to 200 g shakes that have hydrolized way in them uh Branch cyclic dextrin plus yeah aminos plus creatin plus glutamine plus this and often times they're essentially in a state of like I'm sure you've had a cheat day where your stomach was like incomparable to you know days when you're fasting for example it's a massive difference you can't you could fasting you could do a vacuum and see you know completely invert your stomach almost versus when you have a giant cheat day and just go off the rails you couldn't keep your stomach in for the life of you you have to be flexing just to keep it not looking like you have a gut when you're sitting down like that is a Perpetual state of reality for bodybuilders Who weigh that much to sustain that food intake and the physiques that they have because it's not a normal amount of muscle to hold so it requires a not normal amount of food to accommodate the the nutrients required to grow further or even like sustain it like there's a good example of that is Ben pulski he makes you know like I think more Health focused content now but he's a former highlevel ifbb pro I think he won the Arnold Classic even at one point and one of his biggest criticisms was his distended gut and you know for certain the guy was using all the same drugs everyone was using at the high level but he was able to reverse it seemingly in a relatively short period of time in his like the latter part of his career by reducing his food intake significantly seemingly and he actually showed up one year later with uh a vacuum on stage which a vacuum for people who don't know I don't even know if I could explain it but it's like you suck your stomach in and it creates like an almost like an inverted yeah it kind of goes in you can see your rib cage and like your seratus lines and stuff and most bodybuilders wouldn't be able to do that nowadays no no if that's a big notable uh differentiating factor of 70s and like '90s bodybuilders the amount of people that could do a a vacuum dramatically so many could in the 70s and it looked great and in the 90s you'd be hard pressed to find somebody who has like an aesthetic vacuum and except for presumably natural bodybuilders are more likely to or yeah yeah because they don't have to they don't have the food demand yeah it also depends on like what they're eating because people with gut issues could have issues too but it's more common in people who are pushing food extremely hard and then the drugs on on top of that like when you have hyperglycemia chronically you might have impaired intestinal motility and like all these things that could compound the issue significantly so and you have people with sibo and you know bacterial overgrowth and all the stuff that can influence the um distension that is kind of like a Congregation of bad digestion insane amounts of food um poor choices of food that don't agree with your body because it's simply the only way you can get the calories into to meet the demand of the muscle um Etc but anyway Ben pulski he he showed up with less muscle but he had completely reversed his gut distension so it seemed as if the food was a large dictator of okay to get the biggest physique you ever got you had to eat some diet that was not conducive to the most aesthetic non-distended appearance and if he had organ growth is it reasonable to assume that it's he could have reversed that yeah like I I don't think is in again it's really is another example of something that's very frustrating to me this is knowable like literally take the bodybuilders throw them into an MRI scanner you can get organ volumes on everybody like we could and we could compare that to you know controls and and also look at them off drugs on drugs all that stuff so again it's just an example of there's so much so many of the questions that we have here that we're not getting resolution to are knowable it's not like we're asking is there life outside of the solar system we're never going to know the answer to that one thing I can say is on autopsi bodybuilders that did die young or what have you often times now with social media those results are released publicly and people dissect them and whatnot and kind of you know make uh I don't know interpret what like you learn things from bodybuilders that have died that you might have not even known because back you know not that long ago 10 plus years ago people were saying where are the bodies no one's dying from steroid use Etc but there are guys dying with heart three times the size of what they should be so there's certainly you know organ enlargement systemically for sure so we could say that I don't know if it's necessarily you know pushing on the stomach wall to actually cause I see what you're saying got it but I I can say with near certainty there is organ growth for sure I just it again multifactorial maybe it's part of it so yeah it's a great point so let's talk about the death of bodybuilders and we're going to again I want to come back and do a long discussion onto anabolic steroids but um what uh there was a bodybuilder that died kind of recently right yeah yeah that was a shocking one too he was a 30 years old one of the biggest social media influencers too and this what was his name uh Joe Lindner okay live American or German German that's right yeah yeah yeah yeah so with him the scariest part was he was one of the guys who was um doing all the right things at least from a blood work standpoint so he would get blood work done literally every two months if not more frequent and was very very rigorous about trying to oversee his health status and his blood work wasn't perfect always but it certainly wasn't somebody who should be dying at 30 years old regardless of you know back in the day or not that long ago even it would be unheard of for somebody to be dying who's if he wasn't a massive bodybuilder by industry standards for Fitness where we have this warart perception of what is Big versus not he was like you know uh probably like 50 pounds off of what you would consider a top level open class bodybuilder who would compete with Ronnie Coleman or something so he was more of like a jacked fitness model by Fitness industry standards and less drug use significantly less drug use less food intake he was always in a calorie deficit shredded year round the guy did lots of cardio at least like 10,000 plus steps a day ate clean like there was no reason objectively at least why he should die at 30 like you might expect that his lifespan would and what are the known circumstances of his death so apparently his and this is the thing I don't even know if you're going to want this in the podcast dude but it's he got apparently the vaccine and two boosters on top of it I believe might have even been more but after he got it done apparently he went and saw he got his blood work done just routinely and they saw uh supposedly that the blood they pulled out was like really coagulated and weird looking and I forget exactly his terminology but there was he literally did a podcast maybe a week or two before his death how he got a blood test done and they were telling him that he needs to get a plasma fesus to clean his blood because it was so messed up from the the Vex so he did it twice apparently and then supposedly his D dier went back down because it was super elevated in his blood work and they said he was fine now and he cleaned his blood and you know reintroduced it back into circulation he would be good he made a long trip to the US I actually met him for the first time like a couple weeks before his death um and then when he flew back to Thailand which is a really long flight and yeah there's you know some uh uh clotting risk you know associated with that on top of all the other things um which is speculated to be something that's a you know another variable but he got back seemingly fine and then apparently a few days after he got back he was complaining of neck pain and his aunt supposedly died from uh aneurism in her neck that is what we have been told we have yet to see a you know autopsy report on his situation but his girlfriend at least reported that his aunt died from the same thing and had a aneurysm in her neck whether it like you know in her neck or in her head yeah it it was apparently neck specifically which I would think is kind of unusual yeah I won't even speculate without an autopsy I think but again uh tragic obviously but um hopefully an autopsy sheds light on that I mean it's there's um it's not difficult to know if someone dies of an aneurysm on autopsy would you Scope that out with like a perovo scan before you even like hypothetically if somebody yeah that's actually one of the reasons we we really do like whole body MRI is you do I mean the incidence of aneurysms you'll see on a whole body MRI is about depending on the series I mean somewhere between one and seven cases per thousand now not all of those are aneurysms that pose risk meaning they're not all aneurysms that if left alone would ultimately rupture but um a number of those require intervention so we've probably in the last seven years had two patients and you if you think about how small our practice is two patients who have had incidental captures of inra cerebral intra cerebral hemor pardon me um aneurysms that were both large enough one in one case large enough in another case growing quickly enough to a large enough size that um they needed to be coiled uh preventatively so um but again the aneurysms that typically kill people are you know in the head behind the stomach um those are those are the ones that you kind of want to look out for um also as far as you know if he had a deep vein thrombosis which would certainly be a risk factor on a long flight um that could obviously kill you with a pulmonary embolism again very easy to diagnose on autopsy so by the way what's your current flight stack for so I don't fly that much anymore and when I do um I I Mo most of my stack is around sleep right so that's so so kind of like what I'm thinking about when I'm flying is how do I eliminate jet lags so I went to London I don't know a few months ago so you don't control for like clotting potential anymore with like I mean I take baby aspirin although the literature suggests that it's not necessarily helpful against DVT um I've also I used to take something else Nat can yeah that's right I used to take that for for DVT nowadays I just use compression hose hydrate like crazy um and basically I've got straight legs most of the flight because I'm like laying down okay um but I honestly I think like hydration probably plays a greater role than most things uh you know at one point I was like so ridiculous I was taking Lovenox injections so Lovenox is uh like an unfractionated uh um or it's like a type of Hein basically um but after one time I took it where I injected it and hit a blood vessel and had like the biggest bruise on my I was like a this is just not worth the hassle anymore um but yeah most of most of my effort really focuses around how to not get jet lag okay which I've turned into a science I have to ask you about that later yes yes I I I can I can I can go to eight hour time zone away be 100% functional the minute I get off the plane that's awesome get right into routine and Rhythm um but traditional bodybuilder Des like this was a bit of a unique one CU a lot of people well until the autopsy comes out no one really knows but yeah it might be that this is just a tragic death that in someone who also happens to bodybuild then it might have nothing to do with in general what I've seen from the autopsies available on some pretty young bodybuilders it's almost always a cardiovascular issue and and not necessarily athrosclerotic but more cardiomyopathy type death yeah so like left blood pressure unchecked and had you know heart function just destroyed essentially and hearts that are way larger than they should be I don't know if you've ever heard of Rich Pana but he was a very famous uh and influential bodybuilder in the fitness industry and he died in his 40s with uh I think it was like a 660 gr heart and then Dallas McCarver probably the most notable one he was like a a mass monster by ifbb Pro standards which is like one of the guys on the Olympia stage who's actually the biggest the guys on that stage his heart was like 860 gram or something wow and I think uh like an athlete heart is like what onethird of that or something or maybe a bit more than that okay yeah um how Mike mener died young as well didn't he yeah but he had and again it's not like we ever he had known atherosclerosis didn't he have uh she was also I and I don't want to speak at a term but I've heard he was pretty into amphetamines on top of that so was like stimulant abuse on top of potential you know anabolic exposure plus I do think that that's one of the the difficult things to ascertain with respect to bodybuilding is you so much poly Pharmacy well it's the poly Pharmacy and there's also like there's the psychological component that's very difficult to disentangle that's part of the part of the profession so um all right so let's let's go on and talk about testosterone and androgens in general you've already thrown around a lot of names that are going to be foreign to people but before we kind of get into the different anabolic steroids um you want to just kind of do a quick review of the relationship between the hypothalamus the pituitary Ling cells you know basically you know CI cells like what's the whole relationship between those hormones testosterone production and uh and maybe we can even talk about DHT Androgen receptors an estradi for that matter so the body has a pretty it's complicated but it seems to be pretty well regulated way to know how much hormone to produce based on needs in tissues especially too so your hypothalamus will create something called gonadotropin releasing hormone and just like the name suggests this is the hormone that goes to your pituitary to actually stimulate the production and release of gonadotropins ganot tropins are the uh hormones that work on your gonan to produce testosterone um as well as assist with spermatogenesis and kind of sustain fertility so the genotropin that come out of the pituitary they elevate upstream and g&h as well in response or lack thereof to adequate and there's so many to lesser magnitudes but primarily Androgen receptor activation and estrogen receptor activation um and then there's also like some stimulation of progest receptors that causes negative feedback as well um among other things too but the primary that are to be noted probably for this discussion Androgen receptors estrogen receptors when those are satisfactory or in a adequate amount um stimulated it will tell your brain okay we have enough testosterone as well as DHD and estrogen that we don't need to make more essentially because we have you know A Satisfied amount of estrogen receptor activation in the body so we need to like clamp down and not make as much hormones cuz we don't want to have too much so that will give negative feedback to the hypothalamus pituitary testicular axis to not produce as much G&R and LH and FSH until those levels fall to where there's a need to make more hormones so it's this like finely tuned system where your body regulates how much it assesses how much it needs Waits until it needs to produce more and then it produces more more so the top of that is the G&R stimulates pituitary output of LH lutenizing hormone which acts on ladic cells in the testes and follicle stimulating hormone that acts on cly cells as well and this is the and this will definitely get into that email you sent me about you know fertility and whatnot those will go down to the testes and stimulate the production of intratesticular testosterone as well as assist with the production of sperm and maintenance of ility so those levels I think that that's probably a good summation of how you end up with testosterone probably yeah so then what's the fate of testosterone the fate of it in terms of metabolites and yeah like once it gets out there you know it's it's how much of it is converted into estrad DHT yeah and this is where a lot of people who neglect lifestyle and diet don't realize all of the backhanded consequences of being too obese or something like that you could have for example aromatase strongly expressed an adapost tissue so if you are too obese and this is problematic especially in adolescence too if you have a disproportionate amount of Aroma taste expression because of how much you know how fat you are essentially you could otherwise be producing more estrogen than you would have if you were lean telling your brain kind of in a indirect way that hey we have enough estrogen so don't make more testosterone because I use testosterone to make estrogen and to I probably should have preface this with testosterone converts primarily to two hormones through the five Alpha reductase enzyme five Alpha reductase 2 DHD dihydrotestosterone which has a significantly greater potency for binding and transcribing activity at the Androgen receptor and estrogen estradi that will be the primary estrogen receptor Agonist in estrogen receptors around the body so those two hormones regulate kind of a balance of androgenicity and estrogenicity in the body and it's like a finely tuned system and this system is also regulated by binding proteins produced by the liver and the differential between you know like females versus men it also works in the same way it's just the difference in how much of these hormones are produced is quite different and also the binding proteins to regulate that you stay feminine versus you have like a masculine profile so ultimately the balance of free Androgen to free estrogen in the body is almost the thing essentially that dictates if you are feminine versus masculine you know and you could flip-flop back and forth almost manually if you really wanted to we see this in bodybuilding where females will literally masculinize themselves to hell in order to win a show by using you know super physiologic amounts of drugs so and also in you know transition people are trying to transition from male to female or vice versa and some of these changes are permanent of course on the masculinization front if you have a deep voice it's almost certain that you're not going to get it you know high after going on female hormone therapy but at the end of the day this is kind of like the primary hormones to understand as far as the spectrum of androgenic male to estrogenic feminine like it's not a female hormone because they exist in both sexes but DHT the primary Androgen that dictates androgenicity and sexual differentiation and maturation testosterone the main anabolic hormone and drives a lot of the uh neurology kind of the psychoactive effects um and then estrogen is kind of like it's a big Balancing Act essentially yeah so let's again just make sure people understand the difference between androgenic and anabolic because we will come back to this more and more with other compounds as we talk about the profile well this one has slightly more androgenic Behavior this one slightly has more anabolic Behavior yeah so the androgenicity or androgenic activity of a compound or your endogenous hormones is essentially how masculinizing it is so dihydrotestosterone the five Alpha five Alpha reduced metaboli of testosterone is the most androgenic hormone in the body and can significantly inhibit estrogen's activity even in RNA transcription at the receptor site like it's very potent in what it does and even if you had like to frame how important is you could have a male if you wiped out DHT before puberty he would basically that's the how you end up with a micropenis essentially like you have individuals who will not undergo full maturation unless you have the Pres words if you took a male before puberty put him on just put him on dutasteride or finasteride and zeroed out his DHT but with making no change on his testosterone he would have the same amount of muscle if not slightly more but that's debatable but no temporal recession probably not as much acne not as much body hair micropenis he would be probably visibly male his voice probably not as deep as it should be yeah but that is uh and we see this in pseudo hermaphrodites that have a mutation in the gene that encodes for five Alpha reductase so this is kind of the Advent of you know these enzyme Inhibitors and how we even discovered how they work and whatnot but yeah DHD the most androgenic hormone in the body the most masculinizing testosterone still very masculinizing too and estrogen on the opposite side of the spectrum zero masculinization very feminizing I think that's the easiest way to kind of summarize so we talked a little bit and I've discussed this on many previous podcasts but just in case folks haven't listened right so testosterone or DHT make their way into the cell cell into the cytoplasm where they bind to the Androgen receptor to your point DHT does so with far far greater Affinity I mean it's on the order of two orders of magnitude sorry one order of magnitude more maybe 20 times more binding um efficiency to the Androgen receptor this new complex of testosterone or DHT bound to the AR makes its way into the nucleus where it acts as a transcription Factor binding to DNA and uh imparting on it effectively uh trans transcription translation that's how we make stuff it's how we make protein so that's how it impacts muscle protein synthesis um guess one thing I should have said is androgenic because you did actually ask me this is not anabolic so androgenic masculinizing but does not necessarily equate to muscle so you could have severe masculinization with a relative absence of actual muscle growth or you know translation to I don't know bone integrity and what have you so by the way how important is DHT post puberty seemingly uh it depends because from a cognitive Health perspective from a balance of estrogen standpoint from a Vaso dilation in the penis standpoint like there are certain things where you could say it's pretty critical but then there's also you could just as easily say it's not necessary or mandatory like you will survive and likely Thrive just the same with a lack of DH h t almost entirely like even when you a lot of people will demonize 5alpha reductase Inhibitors and justifiably so in some cases but even when you look to literature that compares Placebo versus finasteride versus dutasteride side effect profiles are pretty similar even yeah dutasteride finasteride being Two drugs that block five Alpha reductases used initially for reducing prostate size because DHT disproportionately drives prostate growth uh but also used for I think I would say used more for hair loss now yeah um but yes and we have talked about this on two podcasts previously about post finasterid syndrome um which is a debatable idea in other words there is not a clear consensus in the Urologic literature about even the existence of this let alone the prevalence let alone the reversability of it all of these things are really unknown and um actually it's created quite quite a bit of a a conundrum for us because we have a number of patients who take finasteride or dutasteride uh for hair loss and um what's your stance on five Alpha reductase Inhibitors just at a yeah I mean look I think uh I'll I'll be honest with you I never really paid enormous attention to it until about a year ago um and I I think right now our stance is I probably wouldn't start somebody on it mhm um and if a person so in other words if a person has BPH we're not going to manage that anyway but a urologist has far better tools to manage BPH than five Alpha reductase Inhibitors so I feel pretty strongly that if you're presenting with BPH you should not be on a five Alpha reductase inhibitor it's simply unnecessary it's like if someone came to me and said you know my apob is too high and I gave them a bile acid sequester circa 1981 I mean it's just not necessary there's no upside mhm if you're talking about it from a hair loss perspective again not something I obviously know much about I would say and they're going to go and see a Hair Doctor Who's going to try to give them 50 different proprietary compounds yeah which by the way want to come back to that in a second I would encourage them if they've never taken it before not to because I think there are enough other compounds oral minoxidil topical minoxidil topical five Vala reductase Inhibitors PRP transplants I think there are enough other tools that you can do to avoid the small but not necessarily zero risk of something going wrong in terms of sexual side effects that in the worst case might not be reversible what about you what do you think I think that several of the drugs you just said have either comparable side effect profile like topical finasteride you end up with the same burden of 5 Alpha reductase inhibition systemically despite the fact that it's marketed otherwise topical dast ride is interesting because it may have some capacity to stay local especially if you do mesotherapy which we'll get to in a why do you think that's I wasn't aware of that difference yeah it's uh thought to be the molecular just hydrophobicity it's more the molecular mass of the drug so there's this like it's like an arbitrary rule but if the drug if the molecule is greater or less than 500 Daltons I believe it is off the top of my head it's been a while since I've Revisited it but there is a lesser or greater ability to actually absorb it and get systemic circulation and distribution over across the body with dutasteride it's like I think it's like 600 or 700 and with finasteride it's like 300 or 200 something that and to be clear you're right I mean I don't think that you know systemic minoxidil is necessarily a benign drug and the other thing is nobody really can give an explanation for what the right dose is if you look at how people are dosing oral minoxidil it's insane so um yeah I don't again I I don't like to be in the business of prescribing things for which I don't have a great understanding which is why I'm not in the business of treating hair loss uh not because I don't think it's you know something worth you know addressing if it bothers someone but I think the bigger issue is um it would be really awful if in trying to treat a cosmetic condition like hair loss you induced um a devastating consequence on your endocrine system that that's really where I find myself concerned now it also appears that if you've been on finasteride for a long period of time and you're not experiencing any of these side effects you're probably fine so I also don't want this to turn into like someone listening to this who's been taking propa for 10 years who's never had an issue going like oh my God I got to stop this stuff I the literature would suggest and there is a pretty good review we'll link to that if you're going to have these side effects you're going to have them in about six months yeah yeah my in general when it comes to hair loss the problem is often times the treatments if it doesn't actually interact with the AR or inhibit the potential for stimulation or agonizing the AR through DHT reduction or even systemic anti-androgens not that I ever recommend that you are essentially just putting a Band-Aid on the issue so if you stimulate growth with Minoxidil you are still not preventing further loss if you get a transplant you are putting hair on your head but you're not preventing further loss of you know your actual existing hair so often times it's like you're almost trying to row against a current or something and it's like you are continuously getting pushed back and eventually you're going to get to a point where you have so few visible hair follicles even left that are healthy that it's doesn't matter how much you've been on minoxidil or what have you and oral minoxidil it's like you know it's definitely effective um but I think it should be reserved for people who have weak response topically um because topical seems to be far more tolerated side effect wise and a lot more predictable with like hordes of literature and great outcomes and there are ways to enhance that and also turn yourself from a non-responder to a responder which we can get into but finasteride in itself it seems to be like I don't want to try and come out and say I'm a proponent necessarily I try to play a balanced uh take a balanced approach to it but the prevalence of side effects is not nothing but it's quite overblown by the opposite camp that wants to assert that you know why would you ever inhibit you know a hormone that is the primary enery you rely on but similarly why would you inhibit I don't know apob or something like is a clear outcome whereby there's benefit and when there is you know DHT and somebody who's prone to hair loss it's hard to overlook that this is the primary thing dictating if you go bald or not and some people that that hair loss some people care a lot more than others obviously yeah I guess so so I do think there's a difference because I think apob serves no benefit we would actually if if someone created an anti- sensolo nucleotide that knocked out apob all it would do was guarantee we don't have heart disease in our species we wouldn't suffer we would still be able to use all the hdls in the world for cholesterol transport which we currently use LDL for um but I think to take your your analogy a step further what you're basically saying is if a person cares as much about hair loss as they do about heart disease and by that logic DHT is causal which sounds absurd but let's just you know run it I would posit that there are lots of people who care more about hair loss and heart disease the the psychological stress for some people is significant and should not be overlooked by the um seemingly like uh you know the silliness of oh just lose it just shave it bro it's not a big deal there's tons of successful people who are bald it's like yeah sure but maybe I just deal with although I think I think there's a statistic that no bald person has ever been president of the United States W so there you go so there's there's a couple of there a couple of occupations you got to take off the list um now you mentioned when you were going through your insane anabolic steroid use you at a very young age if you're in your early 20s were already starting to lose your hair so how did you reverse that so part of it was just dropping the dose significantly and eventually just going down to replacement therapy but it was the introduction of five Alpha reductase inhibitor initially finasteride and then thereafter I introduced a and I wouldn't necessarily recommend this blindly but a topical anti-androgen that's experimental never actually received FDA approval there are some that are in the FDA pipelines right now that actually look promising and have safety data behind them and whatnot that I'm watching closely and hope one comes to fruition because these are essentially compounds that compete for the Androgen receptor locally but do not have systemic anti-androgenic activity so you can maintain all systemic Androgen levels with just localized activity in the scalp essentially so I use a topical anti-androgen coupled with a five Alpha reduct those were the main two needle movers for me I also use a ketoconazol shampoo but it's like a very mild anti- anderen it's mostly just a good shampoo but those two things and decreasing the burden of vanderen significantly were fairly effective at getting me not to Baseline but you know meaning you never regain no no no yeah and that's the thing with hair that's the sketchy thing is even if you're trying to decide oh you know maybe I should treat it maybe I shouldn't I'll think about it for a bit I'll see if it gets worse the visual representation of loss is typically not apparent until you've lost a lot of ground cuz you could pull a handful of hair out of your head and see no difference whatsoever once you finally notice duse thinning or recession it's not something you've been looking for carefully because you've never dealt with it so often times once you actually notice it in a picture or in heavy down lighting or something you've already lost 20 30% plus of your hair and there's no guarantee that's coming back so preventing so you're saying so did you regain hair that you had lost with this protocol or just completely stop the some some regrowth but expecting yourself to get back to Baseline where you had you know like 17-year-old Immaculate perfect hair if you've been exposed to androgens at a level where you're like visibly noticing it it's relatively unlikely yeah yeah so that's not to say it's impossible like if I took minoxidil as well as micro needle did a bunch of other stuff I could probably get a decent amount of the way there but it's uh the longer you wait and let hair follicles miniaturize the more permanency you are risking so getting making back ground is way harder than preventing yourself from losing in the first place it's almost like maybe analogous to building muscle when you're younger so then you don't have to try and build it in old age when you have like anabolic resistance or what have you so what are again the names of Cu people are going to I don't let's make sure we give people the names of these compounds you're using so so finasteride is like the main primary five Alp take one milligram of that daily I take dast now so you take 0. five milligrams isn't that is that5 0.5 a day so that is a soft gel that essentially wipes out systemic DHD um and your DHT level is close to zero it's like worse than a teenage girl yeah it's terrible so but I seem okay at least now I think one of the guys with the highest IQs on the planet has been on dast ride for decades if that's notable for anyone okay so then what else are you taking besides dast ride dast ride right now is the only thing I take more of convenience because a topical application schedule can be quite burdensome when you were doing that when you were doing that big Salvage effort in your early 20s what was the rest of the stack oh it was topical application of something called ru58841 it's was like a experimental anti-androgen so so I don't necessarily recommend people use ru58841 when there are actually Alternatives with human safety data on the horizon with that said it's also hard to tell me you know however many years ago that wait you don't you only have so much time right so I'm not going to sit around and what are these things that are on the H that have more safety data coming down the pipeline company called kintor has a compound called pyramide and it seems to be pretty well tolerated and comparable outcomes of hair count increase to dast ride if I recall off the top of my head which is pretty substantial given that there are very few things that produce outcomes that are even make it worth taking another drug like right now the most effective things are going to be five Alpha reductase Inhibitors and minoxidil on top of that everything else is like little sprinkles on the cake essentially like some people might get better benefit from you know PRP than another person or what have you but in general the main meat and potatoes are going to be minoxidil potentially micro needling with monox if you're not a good responder or have low sulfo sulfotransferase enzyme activity in the scalp and the inhibition of free androgenic signaling in the scalp whether you do that through five Alpha reductase inhibition or anti-androgen activity locally that's kind of up to you or some people are going to couple both of them like I did but those are the main needle movers ultimately and some people go super hardcore and like the most crazy hair loss reversals you will see are always in men transitioning to women who use female hormone therapy I would never recommend anyone do that but it's a pretty interesting data set to like pull from from so estrogen and progesterone would promote hair growth I mean we do see it in women actually during HRT especially progesterone can really thicken hair progesterone this is in women I mean I have no idea yeah I would more more uh I'm more talking about anti Androgen plus estrogen so somebody transitioning would typically use a cyproterone acetate bicalutamide something of that nature plus exogenous E2 or a synthetic estrogen and the first two which I'm not even familiar with are drugs that just block the Androgen binding to the Androgen receptor or Cerone is a very potently anti- gonadotropic I believe so it's like it will actually prevent it will actually inhibit you from producing I see you know uh G&R so it's it's it's a it's effectively a chemical ceration that's like a steroidal anti-androgen and then there's a nonsteroidal one and yeah it is effectively chemical castration um the non-steroidal variant by camine seems to be a bit better tolerated it's not as liver toxic and it will actually raise your hormone levels on paper your test levels go up it's just you can't actually interact with the receptor because it's occupied by bicalutamide so it's like a silent Androgen receptor antagonist and yeah those are like extreme options they like essentially Irrelevant for anyone watching so maybe I shouldn't have brought it up yeah yeah um okay so let's let's go back to kind of trt then so we've kind of established what's going on um when are you starting uh yeah we're going to talk about that my My Little My hor I'm actually doing my blood again next week so we'll we'll see how how far my levels have continued to fall so I was going to actually talk right about that right which is let's talk about quote unquote what's normal MH so I've never found a compelling table for normal levels of free testosterone that are stratified by age so you can find these data quite easily for total testosterone level um but I've only really seen data for broad chunks you know prepubescent pubescent post pubescent here here are the here are the percentile ranks for free testosterone whereas for total I can show you by decade or something like that I guess it's worth putting some context to this right so if a person's total testosterone is 800 nanograms per deciliter um most of that is bound and sexor binding globulin and albumin probably do the Lion's Share of binding um and if a guy's got 2% of that as free or Unbound that would translate to 16 per deciliter of free testosterone um that's estimated by the way it's not calculated it's very important people understand when you go to the lab and you get a test done they're measuring testosterone that's a that's direct measurement by the way we should talk about Eliza versus lcms um but they're estimating the free based on the measurement of the binding proteins so that's introduction of potential error number one so you don't really know how much fre has testosterone you have the other thing is you don't know how many Androgen receptors you have so you really don't have any idea how much whatever amount of testosterone you have is saturating your andrin receptors or not are you playing below your weight or above your weight um so what what do we know about the amount of total testosterone over time in a guy's life um I know that after it Peaks you will have a steady as opposed to women where you see like a plummet in after menopause for man it's more gradual and you can expect I believe it's about 1% drop in total test per year with a an approximate 2 to 3% drop in free each year as well so at the same time you would a 1% total te drop 2 to 3% free and this occurs well it depends on age you know lifestyle but in general like post AG 30 35 you can kind of expect a little bit of a the decline to start but that's not to say I haven't seen 70y olds with like a th000 total te sometimes so you can certainly retain high level uh production I don't want anyone to think oh now that I'm 45 my levels have probably dropped you know 20 plus% at this point I should probably get on trt might not be the case so in general those are kind of General numbers of decline that you can expect based on literature but I think it's reasonable to assume that a lot of people can retain good production as well it's just a matter of you know how well do you produce genotropin how well do you respond to them at your testes because there is some level of function that's declines with age2 even in response to the genotropin um and that's an expected outcome unfortunately but that's kind of where you get into the Nuance of it's trt justifiable for this person based on pituitary output lifestyle diet nutrient intake sleep hygiene is there sleep apnea Etc and then also actual testicular response because there's an argument to be made if you have very good testicle response like why would you ever be on exogenous trt2 because you could top out your natural signal even is there an advantage to that so I guess maybe before we get to that let's let's talk about the rationale for trt so what what do you think is the most compelling case for it um and and how often are people you know expanding that use case I think the most justified use for it is people who have primary hypogonadism so that is when you have Ganan tropin going to your testes but you're just not responding to them so LH and FSH are you will see these as high in your blood work but your total te is still bottomed out like that could be somebody who is you know you should probably check do you have a varicus seal do an ultr sound of your testies see where things are at structurally functionally Etc before you make any rash decisions cuz is there could be something you're overlooking and I do think a lot of people do Overlook certain structural abnormalities that may otherwise be rectifiable kind of depends but typically testicular failure in response to adequate signaling would be like the the obvious more no-brainer versus if you had low LH and FSH maybe your testicles are fine so why are you ha aurely getting on testosterone when maybe it's a lifestyle thing you know and so you know typically when we see that pattern the second pattern you've described which is low testosterone but in the setting of low LH and FSH the most obvious things that usually show up there are poor sleep uh and you know basically High glucocorticoids um which can also suppress the pituitary and you'd measure the glucocorticoids through like you would yeah usually you're in actually we used to use saliva long ago but yeah so using a Dutch test cool um interestingly those are not the easiest things to fix because people have to change behaviors which is a lot harder than you know taking a medication um so let's just say we go down the path of we believe that trt is the right thing to do and we believe that it's primary hypogonadism um what do we know about the dose response of testosterone and do we think that it makes sense to use fixed dose Ing and increase dosing or Target to certain levels because again most of the studies and we might talk about the Traverse trial um you know they kind of just use fixed dosing yeah um which is at least for me one of the criticisms of that approach by the way is I you especially when you're using something topical and you have variable absorption but what do we know about this yeah I think in general like an accepted if you're going to be treating with exogenous testosterone an accepted entry level dose that is on average safe and well tolerated and will get you to a reasonable total te that provides symptom relief for the majority of people is like I can't see a more logical start Point than for example like 100 to 120 migs a week or something of that nature and just seeing what happens to the guy's total te free te this could also be you know variable based on does he have a super high shbg you know what should we should we be evaluating that cuz maybe he just has a low freey instead of his total is fine in that case you could have brutal symptoms but you're your production is still good it's just being bound up severely and why is that the case do you have like severe liver issues or something so after you flesh all that out and you determine the guy needs T I would like imagine a reasonable starting place is typically like 80 to 120 a week and then kind of you know go from there see how you respond to that and any advantage to dosing it once weekly taking that dose and dividing it by two and doing it twice a week taking that dose and dividing it by seven and doing it every day yeah it's and I don't necessarily know that like for example when patients come to you I'm sure they're looking for the highest level of optimization hence why they're with you so maybe it's more reasonable to expect them to pin more frequently say pin I mean inject but there is a halflife associate like with the drug depending on the Ester chosen typically testosterone cypionate will be be prescribed at least in the US that's the most prescribed one which is a halflife of 10 days if I recall off the top of my head depends on the person of course where it's injected blah blah blah but that halflife you could you know extrapolate out from that okay it's going to take 50 days to achieve steady state serum concentrations in the blood and that's going to look on like a steroid plotter you could check online and see this kind of like you know spiking until all of a sudden there is the same amount of droing of the drug clearing out of your system you're getting an equal amount of Spike backup like there is no accumulation of drug burden after you've achieve steady state serum concentrations so the advantage to injecting more frequently and this is going to be determined largely by patient adherence more than anything because some people simply refuse to inject even more than I've seen some in like insane stuff where people will let themselves drop to literally hypo going at little territory and then remember based on their dick not working I'm going to okay now I take my test but in general once a week is like bare minimum I would say but that's certainly not optimal and I would say that two times a week at least for somebody seeking good quality oversight you know preventative medicine whatever if they're coming to you or to somebody who believes in the same things you do twice a week I think is kind of minimum for decent steady hormone concentrations yeah we've sort of arrived at the same conclusion that that's The Sweet Spot we do have a couple patients who do daily injections and interestingly in these patients we see much less for the same dose of testosterone so you take oh like 15 milligrams injected a day which is actually very difficult to do you have to be very thoughtful about what kind of needles you're using to actually get such a small volume in but they they will have much less FSH LH suppression H which suggests to me that the bigger the the higher the peak the more the fshh suppression I don't know that there's anything physiologically relevant to that other than I think it's the study is when you look at trough level T levels and I say trough I mean like the lowest point of hormone concentrations after an injection often times these studies assessing dose response will look a week after your injection so what you see in the literature isn't necessarily reflective of what's going to be in patients trying to optimize anyways but what I see personally and in miral and through all my blood work that I've seen over the years Etc the more frequent you get there's a diminishing returns for sure but you can lower the aromatization spike and five Alpha reduction by going more frequent so if you have a bullus administration of I don't know 150 Mig once a week you are literally spiking your tea into Super physiological territory acutely and concurrently you are getting super physiologic conversion to estradi DHT you also have a very very aggressive Spike and free endogenic signaling which can crank your sympathetic nervous system up impair your Sleep Quality like there's so many consequences people don't and you'll see more hematopoesis yeah so when I had Mo Cara on here he was talking about nesto which is the nasal formulation which has such a short halflife that it's actually a TI dosing schedule wild so it's 7 milligrams of testosterone injected inally day for more than a year and still tell me it's cool and fun to take so if you end up doing that for trt you got I probably will not but what his point was two two two interesting points with with nesto the first is they don't have the hematopoesis so you know you you these are not people who are making too many red blood cells that you have to actually be careful of and have to go and get them therapeutically flotoma gets over 50 um secondly it's a FDA formulation that women can use right because if a guy is taking seven milligrams in each nostril three times a day clearly a woman could take one of those every other day and and by the way it's sort of an on demand libido uh tool for women in particular so so there are lots of interesting things around that also they're doing a clinical study and we're sort of observing what they're doing where women are using intravaginal use one you know one application of that intravaginally before sex to enhance orgasmic function nice so again pretty pretty it's always desirable to have an FDA formulated product when you can kind of avoid the the the the Dark Side of compounding is my view I think the best way to conceptual Iz for The Listener to why this frequent protocol or getting a more stable level is even why is it result in a lower side effect burden to it's the most the closest you can replicate natural function the more you will replicate natural side effect profile which you know should be nothing if you are physiologic so with you know Nesta which is like in and out acutely like so fast you were not getting this huge Spike to like you know 1,500 2,000 NR per deiler Total Tea there is no situation ever in which your tesses would just blast you once a week with a hammer of test and all of the associated metabolites and backend and consequences of that you would have little pulsations over you know a dial Rhythm and this is why you you know you would test your blood as a natural in the morning when your testosterone is spiking and it's going to EB and flow over the day your test level in the morning will not could be 300 nanograms per deer higher than later in the day like get fluctuates so to expect that it's reasonable to jam yourself with an absurd amount of test in one go and then hang on that as it declines of your body and then crank it to the stratosphere again once a week it's just an not representative of a physiologic state whatsoever so the more you can replicate that dial Rhythm through the synthetic Administration route the closer you're going to get to a lower side effect burden like I've seen some guys that get gynecomastia from trt dosages go to Ed everyday dosing and get off their AI like that's how significant to translate that into English you've seen guys you've seen guys who can take a weekly dose of testosterone and in doing so they make so much estrogen that they have to take an androgen inhibitor uh pardon me an aromatase inhibitor to prevent them from getting breast tissue gynecomastia and if they take that same dose and divide it daily they can come off their aromatase inhibitor together yeah and some people it's it's problematic cuz they will give feedback to their doctor or just give a state a give a judgment to what hormone therapy was like for them based on what is maybe a not the right dose but also just not even close to an ideal dosing regimen and injection frequency when we you know when I got back into the practice of medicine and was learning about HRT I couldn't find doctors who weren't prescribing anything different than twice every two weeks that was the standard have you seen the European susten on I mean it's just no I have not but but so the standard was 200 milligrams every two weeks and um which immediately I I was actually I remember going through lewellen's pharmacology and looking at the pharmacokinetics and being like this is an awful idea um so yeah uh any difference Clinic between cypionate and ananth eight um obviously one of the advantages of an anate is there's a commercial product called zad for people who are squeamish about injecting that comes in a pre-loaded pen so we have some patients who just don't like the idea of having to draw up a syringe and they just kind of want something that's a little more TurnKey so zad which is a slightly different uh form of testosterone but but Clinic I I I sort of remember at one point there was some difference that might be age specific but I don't recall now yeah the halflife in anate is often thought to be a long Ester which it is relative to like propionate or phenol propionate but it's kind of like an in between of cypionate and propionate it's like a halflife of could be as short as like four or and a half to 5 days I believe off the top of my head whereas cypionate could be twice as long in some people so it depends on your individual metabolism of the drug um often so and also if you're pitting subq or IM like you could kind of like bleed out the effect more so with I would say if you're injecting frequently enough it's essentially irrelevant but with these auto injector pens which is typically the auto injector the the zad protocol from the FDA is once weekly oh is it which is actually I mean we still recommend people do it twice a week and just use a lower dose the difference of not using your what you're supposed to take versus using it like obviously frequency is of a lesser concern than you walking around with no test so if the if it's the difference between a guy taking it versus not you know okay take your you know once a week if that's what it's going to take I don't know if it's is the preloaded dose you can't can you modulate you can't meter it that's what's so annoying about it yeah it's such a racket because and I always tell patients I'm like look if if you're completely cost incense I guess fine but otherwise like getting you know cypionate in a jar is a fraction of the cost if you're just willing to be the guy that meters it out um but the enanthate I think only comes in three loaded doses of zad so you also you also have less wiggle room if you're not happy with the output I would assert with near certainty that you are not optimizing your hormone status if you are I want say optimize I mean just like dialing in the stability of it and the side effect profile and potentially quality of life as much as you could if you did a more frequent schedule especially with an anate so once a week is a little bit meaning you you you you the more frequent you're giving it the better yeah like I think the diminished returns are there's a significant drop off when you go from every other day to every day but like one week to twice a week like I'd say there's a pretty dramatic difference that's worthwhile to Y um let's talk about the difference between subq and IM um again I I I have always advised patients to do subq um for the belief that it has as you point out kind of you bleed out the effect a little bit longer uh but I I have to be honest I don't think I've seen data to support that I have seen and I think this is an extrapolation but I believe it to be true is when you look at subq dosing you'll notice the total T levels are higher and then people take away from that oh subq is like you get more out of your test but the reality is when they measure total test levels it's often a week after your shot it just lasts longer so I think you are almost giving yourself a sustained release kind of through administering into the fat tissue rather than intramuscular which is more readily absorbed quicker blood flow Etc just like if you did like an IV Administration it would be like in your blood immediately not that you would ever do that of course but yeah the difference in pharmacokinetic profile of like IV to I to subq like you can change the same drug dramatically in onset of action through that so you think that subq is probably a better Administration and so if you were I think once you get to every other day dosing it's almost it doesn't almost matter yeah but I think especially for people who are doing and again it depends on the amount because if you're doing once a week is that going to be too much of a a Bolis like to sit in stomach fat depends on the person yeah but you know I would say especially for infrequent you'd be better you know sub ideally if the volume of oil isn't significant enough that it's like creating lumps and stuff let's talk about aromatase Inhibitors so there was a a study that I don't think gets enough attention um I think it was 2014 might have been 2013 in New England Journal of Medicine that looked at um 10 groups so it took a it took a group of men and um chemically castrated them and then gave uh divided them into two first half of them get an aromatase inhibitor half of them don't and then within each of those groups there were four escalating doses of testosterone plus a placebo so what you have are five groups times two one with estrogen inhibition one without and and five escalating doses of testosterone so you end up with 10 outputs which are ranging from low to high testosterone with high and low estrogen and the outputs were body composition mood libido a whole bunch of you know rectile function these things and the punchline was you were better off with more estrogen and more testosterone so the best outcome in the best outcome group was the high T High E Group now the high E Group wasn't that high I'd have to go back and look how high the e was but you know I don't I think it was probably in the ballpark of 50 PS per milliliter mhm um but this was an important study because I think it's suggested that estrogen is not the bad guy right I think there's probably a lot of people out there thinking if you're taking testosterone you need to be taking an aromatase inhibitor and while that might be true at some doses um what I guess let's start with normal physiology and then I'm kind of curious to hear what the bodybuilders are doing yeah so back in the day we thought that regardless of the dose of Androgen you should lower your estrad to 20 to 30 cuz it's in the middle the reference range is for a man and that's where you get the best like there was no thought of balance it was kind of like this is a bad hormone to have above the reference range even though our androgens are literally like 10x the reference range so it's like how we concluded that what what were your testosterone levels when you were back in the Heyday I never got lcms testing when I used my highest dosages so it would get capped at like, 1500 or something but it was you know in the thousands for sure um but but yeah with estradi there is and I've seen these you know studies too where it shows neurotoxicity when you add it in vers you take it out and there's a protective effect so like neurotoxic outcomes are higher when aromatase is inhibited and less neurotoxicity when it's taken out on the exact same input of testosterone and I think it's pretty clear at this point that there is a role of estrogen in the body not just from a cardiovascular standpoint but from a neurological standpoint too there's like serotonergic activity there is um so many things that regulate mood as well um I think even like temperature control too is going to be variable based on that it's kind of ties into the postmenopausal um stuff but for men it is certainly important and to crush it arbitrarily based on a reference range is kind of like old brol lore and I think most people even in the bodybuilding space are pretty aware now that estrogen is important for cardio neuro protection and I think another thing that's really important for is bone health yeah and so that's the thing that I think worries me when I see and by the way when I you know you asked me earlier about when am I ready to start my trt protocol I think I'm more troubled by the fact that my estral is so low oh yeah because you know my tea is routinely between about 3 and 400 nanograms per deciliter and my estrad is never above 25 pgrs per milliliter H which is normal right that would be you know normal for such a low T but to me one of the big advantages of having a t of a thousand would be that I'd hopefully have an estra dial of 40 and this is not to derail but five Alpha reductase inhibition when you don't have conversion to DHT you Branch off more T to estr and estr will reliably increase by 15 to 20 2% on finasteride or dutasteride some people who are very low aromatizer and have like a hyper endergenic State those people that's where like unique individual variability comes into the consideration for drug implementation so a guy like that even for actual you know quality of life sometimes that like modulation May yeah that's just in the side yeah I mean I'm actually going to do both tests side by side next week where I'll do um like enzyme based Test Plus lcms for DHT testosterone an estrad so I'll probably have a better sense of what they look like cuz we can talk about how often enzyme based testing gets estrad wrong yeah no yeah I've seen some brutal overestimations using EA when it was like single digit yeah we've seen guys come back with estrad levels of you know we're using like say Boston Hart and which is using an enzyme based system and they'll come back and they'll have an estr dial of 100 and we're like this this can't be right and then you send them to lab core and specify CMS and you you get that they're at 31 yeah and this is like especially important I think in um you know especially hypogonadal men who have relatively low estrogen to begin with like actually identifying where it stands is pretty important for sure okay let's talk a little bit about the other hormones right so for most of the medical needs is there any reason to be considering a hor hormone Beyond testosterone for male sex hormone replacement um I think it depends on the person for sure that's like such a general answer but well well let's say this not if you're just talking about health benefits and not performance benefits because we're going to talk I'm sure about lots of others and I'll give you one example so way back I used to be um I used to sort of be a little bit more liberal and creative so one of the things I used to do was if guys had normal testosterone the example used a minute ago a guy who's got a testosterone of a th000 milligrams or nanograms per deciliter but his shpg is 100 which for a guy is very high and his free tea is like eight nanograms per deciliter so he's like you know 8/10 of a percent free instead of say two yeah so you could use a very very low dose of oxandrolone and you could eradicate his SBG because it has such a high binding affinity for oxandrolone and of course it also will inhibit if you give too much you'll inhibit testosterone production so there's a very fine balance where you might give him like 10 milligrams twice a week or three times a week of oxandrolone you knock that shbg down and you double his free testosterone you haven't given him any testosterone I don't do that sort of thing anymore I feel like it's just not worth a hassle truthfully and um but but you know that's one example of an area where you can manipulate another part of the system without having to to go beyond that but if you maybe take examples like that out if you're just talking about the use of these other steroids what's the case in some individuals adrenal hormone replacement sometimes may be justified but it's going to be based on blood work more and you say adrenal do you mean DHEA yeah so like DHA if you have like a bottom DH maybe you would look to a DHA replacement um if you have low pregnanolone that might make sense but it's more for like neurological kind of cognitive perceived quality of life effects not necessarily because there's any evidence to support that it's necessary um in general the main needle mover is going to be your test and how much it five Alpha reduces or aromatizes into the two metabolites and from there like you would never manually use more DHD you would never almost never probably manually use estral on top although it's not impossible so it's like Upstream to that in the story to Genesis Cascade where might other stuff plug in I've seen progesterone use in men on trt actually reasonably effective in Sleep Quality kind of depends on the progesterone like the same amount as women like 1 to 200 milligrams you don't have any hbta suppression cuz you're shut down anyway so it can be impactful on quality of life because you get the downstream conversion to some of those neurosteroids that you know maybe inhibited in post-finasteride patients wow yeah I never I I i' never heard of that um that's super interesting yeah no not common or you know but it's uh why would it why would it not work why would it work in women and not work in men if you had you know like a reasonably low progesterone level you know yeah um and you're not expected to have a skyh high progesterone anyway but it's some of the downstream neurosteroid metabolites that you make through 5 Alpha reduction and whatnot that are very gabaergic and anotic and can help certain people and maybe that's useful for a specific guy who has a low shbg and is in a state of high sympathetic drive on his test and needs to calm down or like there are certain use cases that are more individual dependent for sure and not necessarily dictated solely by let's like lab resulted out and anywhere we just look for red and then replace it yeah yeah um so I don't really know the history at all of anabolic steroid so I'm guessing like testosterone's probably been around since the 30s or 40s right presumably yeah I think the when it was first synthesized is remains Up For Debate maybe but I know it was uh it it goes back nearly 100 years at this point and so what was the first anabolic derivative of testosterone the first one I can think of off the top of my head is diabal um there might have been like methyl test or something but you know I could be misremembering but essentially what they did was they took the testosterone molecule and found they could finagle it and re you know manipulate it in ways to create testosterone derivatives like dianab Bal meandro stolon which is you know supposedly The Breakfast of Champions according to Arnold it's one of his famous quotes um boldenone on uh is a very commonly used drug as well still um it was prescribed to horse I believe for a while and then I don't think it ever had a human use but that is a testosterone derivative as well and there's other ones that came thereafter like Halo testin which I think famously one of the presidents the United States was on some aggressive dose of Halo testing for I think I forget what it was maybe fertility or Androgen therapy but some of the protocols back then made almost no sense but Halo testing um and through there they also found oh if we take the five Alpha reduc DHT testosterone converts to DHT you would take that DHT molecule you can manipulate it and create more anabolic compounds that are tissue selective like the idea of actually tweaking and modifying it to begin with came from the utility clinically to implement in muscle wasting in Androgen sensitive individuals so you're not going to give a child testosterone who has you know like a burn patient you're not going to give him test cuz you might masculine the hell out of a female child for example so you have to come up with novel Alternatives that are going to be anti-catabolic preserved tissue um keep somebody from wasting away in a state of you know fill in the blank without causing extreme um viralization so the kind of like arms race of creating the best anabolic agent was from numerous pharmaceutical companies and came an array of compounds that you know now to be you know the dianab balls the bonon on the DH d side you had you know the uh oxandrolon one of the more refined more recent although decades ago at this point um primabol in also a very refined one it's a metenolone um proviron I think still used actually to interact with shbg it's probably one of the most potent drugs at binding shbg is mystone um but yeah the ideal scenario would be you're trying to segregate the anabolic from androgenic activity because testosterone is essentially equal at least based on rodent studies you would find an equal amount of anabolic activity in muscle relative to Androgen like activity masculinization so you would try and take the compound manipulate it to give maximum anabolic outcomes with a relative lack of androgenic outcomes to create something that men women children anybody could take for muscle wasting purposes and preserve tissue and they never successfully did it um but an array of compounds have come out but if if if sort of one to 10 would be testost let's just make this scale up so five is testosterone so it is halfway between completely anabolic and completely androgenic M DHT would be closer to one right it's much more androgenic than it is anabolic yep what what is the furthest example you have that's closest to 10 meaning the most anabolic primabol probably so I mean that so so one would think that that would be like the drug of choice if you're a bodybuilder right it often is too so typically men will take I'm not saying it's the only drug cuz it depends on what else you're trying to get CU sometimes the side effects as absurd as it sounds are desired so with Dian ball for example heavily water retentive so that could help like cushion your joints when you're doing heavy lifting for example if you have better leverages on like a I don't know a max out you're going to be better with more water retention around your muscle belly than if you or in your muscle belly than you would if you had like a dry compound that is not a substrate for aromatase and like primabol and is extremely refined and specific in its action like it's like a pure like protein accretion compound with a relatively less burdensome androgenic profile but the side effects of it it doesn't interact with aromates cuz it's a DHT derivative so it's not a substrate for aromatase it does not 5 Alp reduce into a bunch of different things too so it's more predictable in its outcomes but that's not always the desired outcome some people want to look cosmetically inflated with water some people want to lift more weight or prevent injury and sometimes that water can be helpful depends on the person um but yeah that's like skewing the furthest direction of anabolic relative to anagenic you probably have like primabol and anavar yeah and I remember um again just sort of reading like anavar also highly prized among athletes because technically sarms are actually even further if I was to give The Most Extreme Anabolic relative to so let's talk about sarms then what are tell tell folks what those are okay so selective Androgen receptor modulators these were kind of designed some people might be more familiar with serms which are you've talked about Clomid tamoxifen on this podcast before um selective estrogen receptor modulator so these will interact in a tissue specific way with estrogen receptors in various areas of the body so you might have a you know inhibition of estrogen receptor activity in the breast for somebody who has you know breast cancer for example um versus you would have like pro- estrogen activity in other areas of the body like bone which is what makes the selective action of it desirable because you can actually sort of choose where you get the activity you want but also don't impact the health of other tissues and other areas of the body so the same idea was kind of adopted for sarms and they tweaked and modified anti-androgens actually to make these compounds that would interact with the Androgen receptor in a way that was tissue specific and try and get like pure anabolic activity with almost no androgenic and proportionally it's more successful probably than anabolic steroids but the sealing of anabolic activity seems to be lower so when people use sarms they do not gain as much muscle as when they use anabolic steroids and often times in their quest for achieving a similar muscle building outcome the higher and higher the dosage gets the less selective it becomes so almost like certain I don't know uh like uh beta blockers for example as you get higher and higher they become less uh receptor selective and you get more like broad spectrum you know what what are the typical sarms or what are the most potent or commonly used SS lgd 4 43 three probably it's called ligandrol it was actually it's these compounds often get traded around companies so often that they have new code names every time I check I think the most recent one was I think it turned into vk5211 by Viking Therapeutics was the last company I'm aware of who had it and it was in I think a phase two trial for hip hip fracture patients um ostarin also known as in noo sarm was probably the most well-known sarm but but it has not been FDA approved and seems to have not hit their target end points that they wanted although it looked effective and oftentimes women who are trying to achieve like a physique to step on stage to try and like bridge the gap between not using anything and using steroids they will go for something like an Austrian and they don't viralize themselves when they take it and um yeah it's funny I always thought that was a serm I didn't know it was a serm these are um are these band compounds in natural bodybuilding y so they're considered and they're super detectable because they're not supposed to be in your body at all so how does one get these are these if they're in phase two uh same way you would get so it's all underground but compounding pharmacies some of them make them yeah that's true I've seen compounding phies make a lot of things wild nutty stuff just like oh yeah I'm prescribed Tren it's like what do you how's your Pharmacy make Tren yeah let's talk about Tren where does that fit into it's uh so that's actually classified as a steroidal s interestingly enough so it was prescribed to women in the 80s I believe um and was also used to beef up cattle and might even still be um but it is super anabolic but it also has very odd progestogenic activity so it interacts with the progesterone receptor causes severe night sweats it's called Trend sweats um it also has this weird side effect called Trend cough and it's like one of the only it's no one can be sure of what is causing it but it's the one of the only drugs associated with a prevalence of a severe coughing fit like you're having an allergic reaction or something after you take it so you inject it and you feel all of a sudden this tightness in your chest and then within 20 seconds you're on the floor hacking up a for 2 minutes yeah it's great I had a patient come to me a little while ago who was seeing some Doc in La who had him on a pretty high dose of Tren and GH that's crazy and um again there's always like you know how do you get people off these things and luckily he wasn't on it for very long those compounds are more suppressive too because they interact with the progesterone receptor significantly so it's like you get the negative feedback not just through AR ER but PR as well so let's just kind of recap where you were on some of those so did you did you talk about Deca and androne and deca is close to the more pure anabolic side it'll it's not near you know the selectivity of a sarm at a therapeutic dose but it is probably the interestingly enough the only steroid that you can probably use at a dose that is will result in bodybuilder level results without hair loss because it has unique interaction where it's and this it gets so complicated when you think of the pharmacology of the stuff because it's like it will five Alpha reduce into a DI hydron androne which is almost no androgenic activity so in the muscle where you have a relative absence of 5 AR you will retain the anabolic properties of nandrolone where you want it but then in your scalp it'll five Alp reduce into this metabolite dihydro nandrolone where it has almost no andity so you get like the muscle building without the hair loss and it's just very interesting how you have to so do bodybuilders even take testosterone at this point or do almost always so why are they taking testosterone when they have all of these more designer anabolics that seem to have an advantage over testosterone in every way because testosterone is the base because it provides your estrogen base layer of neur protction these things provide aromatization none of these some the only other compounds that could act as replacements for test are things that are potent substrates for aromatase 2o but even then you get these synthetic estrogen metabolites that have less predictable activity so for example dball converts to like methyl estrad which the potency of it at the estrogen receptor it's it's not as predictable and your body doesn't really know exactly it it doesn't have as predictable of outcomes in terms of providing the base layer of what you want from like a broad spectrum perfectly balanced androgenicity converts to estrogen where you wanted in tissues you know it protects the brain to some extent granted at Super physiologic dosages you're a neurotoxic territory certainly you're not going to protect yourself with you know a base of test but it's better than no test for sure or no estrogen I should say when you're saying it's super physiologic doses you mean Super physiologic doses of all of these other hormones yeah cuz I guess there's no actual physiologic level of them but it's more just like the Androgen burden on your body is exceeding what it would be from a natural testosterone production standpoint so what is a bodybuilder if you let's just talk about an ifb you know like a a top 100 top 50 bodybuilder in the world um what percentage of the year is he on some anabolic steroid 90 to oh anabolic steroid including testosterone presly 90 to 100% so so they've they they basically have accepted the fact that they've completely suppressed and lost any endogenous production for life and it's now just a question of how they cycle up the testosterone plus or minus the other anabolic sort of but there is I've seen firsthand multiple bodybuilders who've been shut down for decades come off and restore natural function and then the question comes up and they're using you know presumably FSH and just some of them just HCG just coming off the drugs and waiting long enough m but often times you you can then it begs the question are they would they have been there had they not used the drugs until then is that just what is representative of where they decline to naturally or is it like a permanently lower ceiling potential because you've inhibited organ function for so long yeah you can't really say for certain I think it's almost certain that you've inhibited some level of do we have data on people who have been on anabolic steroids for five years or greater and the ability to forget spermatogenesis just regain endogenous testosterone production yeah it's sparse but it exists and data are sparse or the frequency of people who do it is sparse they like there's not almost there's almost no literature on it but I believe I believe there's a study that shows the recovery capacity and there are people who recover function it's just like relatively arduous if you don't know what you're doing too when it comes to post-cycle therapy cuz you might have clearance of hormones and go to a like a crashed hypog ganata level that you're dealing with until you hopefully kick in ganat tropins and hopefully respond to those well and hopefully restore production to a level that provides symptom relief and that process isn't instant like you have to bleed these hormones out of your system if you're using long acting compounds too which most people are so there requires a lot of thought around bridging into your recovery and how you go about doing that so people have to be implementing as the androgens clear be implementing H well you'd hopefully be on HCG to begin with to preserve testicular function but you'd be using HCG to preserve are these guys taking HCG the entire time they're on these other drugs to just maintain some testicular volume nowadays it's becoming more understood that it's probably important but back in the day and even me I didn't do it because I was just told it doesn't matter you will just recover fine when you want to when you want to come off so you know I think more people are becoming aware though that stimulating activity in the L cells is of reasonable importance almost certainly to retain an easier transition back into recovery while you're on drugs so at their lowest time throughout a year they'd be on how much testosterone they'd be only on testosterone and they would be on it yeah some people they think that they're cleaning out by taking like a month off but in reality it's like the drugs have almost some of them worked their way out of their system by then but they've been on grams of stuff that's achieved steady state and you're just clearing 80% of it or something and then you've never actually gotten out of your system and recovered function which could take months so often times they have either residual androgens in their system or they're just like for the time they're trying to clear or most of them are just staying on a base of trt to bridge between blast phases which are like your high exposure points so those bridges though of trt typically it's not actual trt it's like Fitness industry trt where everyone's dose is 200 minimum yep and they cycle up during contests obviously um professional bodybuilding is not tested so the understanding is you're going to take anything and everything as as often as you want yeah um they're do they take sort of a more you know middle of the road set of compounds as they're bulking up and then move to the more pure an iic less water retention as they're leaning out or I mean what there just must be so much Nuance to this yeah yeah in in general in an offseason when your goal is protein accretion building muscle they are using as they still use a ton of stuff but they will use less than when they are preparing for a contest and the thought is when I am trying to diet down aggressively yeah when I'm in a calorie deficit I need more help on the anabolic even like what threshold is it to preserve tissue at the end of the day typically a fraction of what they're using but to build muscle they will typically be using a base of testosterone plus one or two anabolic agents in general it's going to be you know a primabol in and an androne or something or and how many total milligrams because they're about one to one to one right no it depends on the person how sensitive they are EST because there's also interaction with for example DHT derivatives they also compete for aromatase seemingly so you could I've seen people on the same dose of testosterone with and without a synthetic DHT derivative have significantly lower estrogen without an aromatase inhibitor so they're actually lowering their estrogen input through competing for aromatase simply by using a synthetic anabolic on top so it's like get to modulate that accordingly too so it's like you know often times if you're a very estrogen prone individual or you get gynecomastia easily the male breast tissue development these are things you are concerned of when you are pushing your dosages to levels that your body cannot regulate on its own to prevent tissue formation so some people at trt levels most people will have no issues with gyom Masia development if they have a good protocol in place and they're not obese or whatever but at Super physiological doses of test not necessarily the case but you might be able to modulate that activity down by actually competing for Aroma taste with your primobolan or your drostanolone and then you get to the progestin like nandrolone which seem to have like a an additive effect because progesterone receptor agonism seems to be a stimulation it actually provides uh stimulative input on breast tissue development too like there's other things besides estrogen that stimulate breast tissue so you have GH also and igf-1 stimulate breast tissue development um estrogen progesterone um prolactin so like these are all things you have to consider when you're using which drugs how how do these guys navigate this are there are there not well typically even at the pro level yeah they just take random often but I mean when you look at the guys on the Mr Olympia stage they responding well does not equate to health often oh clearly no I mean like the optimal choice of drug and the most logical scientifically isn't always the one you can there's multiple ways of skin a cat and you can still gain similar amounts of muscle with all these compounds in general but the way you arrive there just might be more side effect burdensome or problematic in filling the blank area so how many of these guys require surgery for gomasa most they typically preventatively proactively do it to make sure they don't have to because one of the things that's brutal is guys who choose their drug protocol based on how gyo prone they are are to those drugs so I've seen people use abusive dosages of aromatase inhibitor serms just to tolerate the Androgen input some of the drugs that are substrates for aromatase so it's like to use the drugs I need to gain the muscle I'm going to get gyno development which I can't have on stage because it looks cosmetically not pleasing and I'll get marked down for it so I'm going to use aggressive Nova deex and aromatase Inhibitors while I'm using the androgens to prevent gyno so I can gain the muscle without the estrogen but it's like you can just imagine the androgenic signaling plus no estrogen it's like uh like horrible constellation of negative problematic factors it just seems like such a complicated regimen I'm really surprised there aren't more Health consequences of this yeah I think they typically manifest um in you know like we see early deaths all the time in the bodybuilding World granted we see early deaths in all places but these individuals are at least you can say you know lean they're typically following meticulous diets and training regimens so at that point it's kind of just body weight and Drug exposure because their sleep is usually dialed to at least as much as it can be relative to their drug related side effects so you know but yeah we did when people say where are the bodies I'm surprised we don't see more deaths I think it just hasn't been as documented as it should be cuz it's like there are a lot of people that you will never hear about cuz they're not a big name in the industry that had heart failure at 27 or something wow yeah um let's talk word about sort of how you measure this stuff so um if you're taking testosterone you can check testosterone if you're but which of these other compounds show up on a testosterone check and how do you know if you're many of them through amuno aay testing so if you use for example testosterone plus nandrolone it is derived from testosterone and often you will see a cross detection so you might have an elevated testosterone level through a standard amuno assay that is not reflective of your testosterone dosage you're using and similarly we see things like estrogen metabolites that are synthetic artificially inflating your estral on ecla as well so like I've seen um uh boldenone which is and there are certainly a group of supplements that seem to aggravate this problem although it's not been clear to me which ones aggravate which uh the artificial reading of enzyme based testing of estrad yeah yeah there's uh certain things that you shouldn't take before a blood test even like biotin I don't know yes biotin being yeah there's some basic stuff that really messes up readings but um yeah like in general if you're not getting liquid chromatography with tandem Mass spectrometry it's like the highest sensitivity of testing you can get for total testost tone and free testosterone this is something I haven't Revisited in a while but I recall equilibrium dialysis was like the gold standard and if you don't use those you will end up with cross detection like I've seen on amuno assay for total test and then the calculation for free tests numbers showing that I'm in the reference range for testosterone when I did nandrolone monotherapy which like for you if you stayed on that Deca almost for sure your test would have ended up in the gutter asadal in the gutter and you would have just had nandrolone there's no nandrolone test so you should have just had like a hypogonadal looking testosterone profile and estral but if you got the cheap you know entrylevel amuno aay testing it probably would have been oh look at that my test is in range still I'm not suppressed on nandrolone I guess 100 migs of nandrolone isn't enough yeah yeah so that's like what some people might conclude so it's very nuanced and you know it's not like you're taught to look for the stuff but often most people aren't going to be prescribed this stuff to begin with so it's a bit less relevant but in the bodybuilding World especially pretty important I would say to know especially where your estrogen is at thinking that you're good when you might have a DHT derivative competing for romaas and your E2 on paper looks in range and it's actually like crashed into single digits problematic brain damage cardiovascular disease bad yeah bone loss yeah um let's talk a little bit about Clomid and HCG um so I guess you know maybe tell folks how they're used and we can we can talk about some of the pluses and minuses of each so human chonic genotropin is presence in pregnant women's urine significant quantities and often it is pulled out as absurd as that sounds and purified because it can be used to stimulate the luteinizing hormone receptor similarly to what endogenous LH does so it looks similar like very it's like nearly some people say it's like a complete it's a mimetic essentially I think is the best way to put it like it mimics the effects of luteinizing hormone in the body and this is why it is commonly used in fertility regimens for men because you can essentially replicate the LH signal to your testes that may be suboptimal if you have low genotropin output or non-existent if you have hbta suppression from your exogenous testosteron you're using so if you use trt you can pretty reasonably expect that your LH fation will go down to either non-detectable or close to there depending on what you're using and the dose and replacing that LH I would say is of pretty high importance if maintaining fertility is important to you so you will experience testicular atrophy if you do not replace the LH somehow whether it's through recombinant LH which is almost never used or HMG which is typically not used either the most cheapest lowest barrier to entry predictable thing is HCG so that's what it is often used for which still is not that cheap if you're using the Branded yeah HCG is much more expensive a clamp down on it recently too in the compounding World um and then Clomid I guess the primary clinical use is in women for fertility for IVF prep but in men it acts and this is how it works in women too but it's just like for fertility purposes in men it's a selective estrogen receptor modulator so we talked about sarms earlier and I mentioned you know serms and how they use that idea for serms it interacts with the estrogen receptor in either a positive or negative way in that it could stimulate activity or prevent estrogen from binding to it and interacting and providing estrogen related activity in certain tissues and it's selective in the way it does this so Clomid is has anti-estrogenic activity in the hypothalamus so it kind of tricks your brain into thinking it's estrogen deprived so the response to that is we have low estrogen so we need to make more testosterone to aromatize into estrogen so you uptick your G&R output to the pituitary which will increase LH and FSH which increases test and then you can sort of intervene with that compound to trick your body to make more tests I yes is the best way to put it um and interestingly I don't know if you want to cut down the rapit hole of encline versus Clomid but Clomid has two is it stereo isomers I believe yeah one one is basically a mirror image of it yeah so it's like zline and encline and encline is seemingly the more selective and actually antagonistic in the hypothalamus so it's kind of like doing the thing you want from the Clomid whereas the zuuk chopine is like anti-ad like it's providing uh almost like a anti-androgenic type activity in a way that is not as selective as like a pure serum so when you think serum you're thinking something that antagonizes estrogen receptors purely in the hypothalamus but then leaves estrogen activity everywhere else bone Integrity is maintained cardiovascular Etc like you all everything is kind of back filled accordingly except for right there in your brain where you want your brain tricked into thinking make more testosterone so en chopine it also has a shorter Half-Life significantly less I think it's 10 hours off the top of my head and zuuk chopine is like days or something so the actual ability to maneuver the drug like pharmacokinetically too if you have a bad side effect or something can't even get off it as easily with clade because you have this big chunk of it as zuine so the idea and presumably creation of you know trying to get FDA approval on and chopine was this is a more pure version of the drug that does what we want and there's been at least one study that showed improved outcomes in women who took en chopine but it never made it through through FDA approval but despite that it doesn't stop people from prescribing it and people from using it I don't think that's a sustainable treatment protocol for your entire life probably I think the reality and it's not as easy to adhere to but I would probably assert that stimulating exactly what you want to do directly with an HCG plus recombinant FSH is a superior outcome rather than in like perpetually inhibiting estrogen activity cuz there is going to be some there's no drug that's purely selective exactly where you want and it's perfect yeah and that's the only issue I would also have with it where I I actually don't think like I think if you took two individuals and one of them you put on exogenous testosterone and one of them you put on chopine and they they were identical in every way in terms of redout mhm equal testosterone free testosterone and estradiol I think there's still an argument to made that the guy who's getting it from exogenous testosterone has a better outcome yeah because he's not getting the central inhibition of estrogen yeah so his libido is better his mood is better his sleep is better oh some of the mood disregulation on Clomid wild yeah I mean we never saw this stuff but again I think we're a very small sample size right because like we're not a you know we're not running like a clinic on this stuff and we're using micro does compared to where I people are going but nevertheless you might not actually if you're not asking those questions you also might not get it yeah and these are often even when people report that these are often people who are on the precipice of hypogonadism already with very low you know quality of life as is presumably to even get on the therapy going on something and then noticing a decrease in vitality and notable anti-estrogenic activity like you are going from a baseline that is not good to be in with so it's like comparing that to the outcome of trt I feel like is often a misrepresentation just for the sake of you're maintaining adequate function or you're maintaining the testicular axis it's like okay does that is that at the end of the day uh a thing that I need to maintain in perpetuity just for the sake of having an LH and f that comes from my pituitary instead of just manually doing it probably not if it's at the burden of permanent antagonizing one of the most important receptors in your body I would say yeah I I I think as a general rule if you start to muck around with receptors in the brain you should have a pretty good idea what you're doing yeah um let's talk a little bit about fertility so you you let's compare a guy who's on testosterone versus a guy who's on HCG so if you're on a high enough dose of HCG you're going to see FSH and LH suppression yeah yeah this is what I found I dug into this specifically based on that case that you mentioned uh so what is it it mean so you've got two two guys one guy's on testosterone one guy's on HCG and they both have a very high testosterone they both have completely suppressed LH and FSH MH obviously in the case of the guy on high testosterone his ladig cells are doing nothing yeah and the guy on the high HCG his ladig cells are cranking out testosterone but in both cases there's enough testosterone being made that the pituitary has stopped making LH and FSH yeah so what happens to these guys when you stop testosterone let's let's assume they've both been on their protocol for several years the guy who has sustained organ function is almost certainly going to have a smoother transition because he has maintained the natural function and output of the organ responsible for intasc testosterone the entire time versus the other guy has literally deprived the tissue so significantly that it's a fraction of the size so trying to compare a guy recovering with testes half the size or less compared to a guy who has fully functioning testes that have been maintained that guy just needs to discontinue and get rid of that feedback inhibition and he's likely going to return to Natural function within short order pending his gatr and output from the pituitary is satisfactory so it's to be determined if that guy is going to have adequate pituitary output given bunch of other factors lifestyle Etc but probably that guy is going to be okay I would say the question then is why did that guy go on HD to begin with because it's presumably because he had low LH output so maybe if that guy got on with low LH output on HCG that's probably the main reason he would have he's probably going to go back to low LH output unless something dramatic has changed in his Baseline you know lifestyle diet and he's older now with less testicular function just as a result of age so there's that for sure that is a major factor but he at least has more potential to recover to whatever his Baseline was than the other guy in my opinion who's going to have a longer more arduous road with okay you have to have enough you have to not only get the test testosterone out of your system to stop having negative feedback now you have to get the pituitary output back hopefully to some satisfactory amount which if your Baseline was low cuz presumably it was if you got on trt like why else would you unless you had like testicular failure and that guy would have never got off test because that's the only option he has essentially that guy is going to have to have enough LH output to stimulate him back to Baseline testicle size to match the capacity of the other guy just from a morphologic standpoint so I would assert that the HCG guys is almost certainly going to be better off than the test guy and do you think that there's a way around it the HCG guy if you dose him more frequently like you take the same dose we typically dose HCG twice a week so kind of starter dose would be like 750 units twice a week uh or 625 I think makes the math easier I think 625 twice a week allows them to go whatever eight weeks with a vial or something like eight yeah something like that um and then generally we just stop if you're if you're not getting an amazing response at 2,000 twice a week which almost you would never I mean we would never go above that M you're wasting your time and you're wasting money um curious by the way what doses are bodybuilders using typically it's to well most aren't using it but the ones that are are typically well even the ones that are using it aren't following like a literature recommended dosages but at least from what I've seen to maintain intasc testosterone at 100% while suppressed on exogenous androgens I think the dose is about like 375 IU every other day approximately okay so not not hurtes at all but this is also assuming you're starting at full function and you're not trying to get back up from zero to 100 so you know that'll be a bit of a difference on that but um yeah there is uh that guy who is on HCG will you know I would I would assert probably have an easier transition for sure but we can definitely get into the FSH suppression and the you know the frequency of administration that's what you ask so if you pin you know more frequently versus twice a week the halflife of HCG I believe is 24 to 36 hours off the top of my head I'd have to double check but if you are going to an everyday schedule you're probably going to maintain more stable serum concentration so you're not going to get as aggressive spikes and light Excel Activation so you're going to have probably more representative of natural output of test but at the same time if that level of test is satisfactory to achieve the hormone levels that your body needs from an androgen and EST should shut down yeah then you should shut down so the only way you wouldn't is either a HCG was too low B your response to the HTG was too low or C your dosage frequency was so like not ideal that you had little blips of time that you had deprivation essentially and your body reacted to it which is not an ideal outcome either so yeah that's uh the frequency thing I think it's more so uh I would recommend more frequent probably for just stability and side effect profile but you know based on the adherence of the patient and how realistic is that yeah couple more random things before we wrap up we've been going a while and uh uh I feel like I'm about halfway through the stuff I wanted to talk about but um we didn't there was one peptide we didn't talk about which is bpc157 do you know anything about that peptide yeah yeah one thing I should say before we get off to HG though because you had that specific example of if FSH is suppressed how do you know if the negative feedback is through the HCG dose uh amplitude Etc versus the testosterone that comes from it I found a really good study that was it used HCG at 4,000 IUS in men who had normal gadal function and those who are poor like non-responders to HCG so you can discern from that if it's the testosterone of the HCG yeah but in addition the people who responded they use Clomid on after so this is the interesting thing so it suppressed FSH in the people who responded to the HCG but not in the individuals who don't respond so from that you can discern it's not necessarily the LH interaction and more so the downstream Androgen receptor activation and subsequent to that E2 estrogen receptor activation the negative feedback so that's pretty elegant so that actually tells us that it's not that you've shut off LH it's that you've ramped up testosterone that is turning the system down L yeah basically but in addition it's not that HCG is too much LH yeah the LH receptor doesn't kick tell your brain stop making tests it's the testosterone output y y and to confirm they applied Clomid in the responders to HCG to see if they could attenuate the FSH suppression and they could so in that you can assert that an estrogen is OB obviously a huge negative feedback regulator if you can maintain FSH at Baseline with a high 4,000 IU dose of HCG with pushing your total T way up and use the serm concurrently and prevent FSH suppression it's like okay it's really up Downstream to the LH activation because it's literally the testosterone output and the estrogen because you're still maintaining FSH with the same Androgen signal and the LH receptor signal so from there you kind of then need to discern okay the one thing I can say from the literature I've seen too is intasc androgenic signaling seems to be the primary determinant on spermatogenesis far and above FSH receptor Activation so if you have a guy who has in and one of the ways you can kind of conversely assess this to is Finas and dride reliably kill don't kill but it decreases significantly uh sperm quality and count like it's something that is just reliably decreases all metrics of fertility from a seen parameters aspect so the int testicular free Androgen signaling seems to be the main dictating variable on spermatogenesis and you can find even in people who have minimal or no FSH at all uh getting them fertile on HCG only and maintaining it now there are certain people who don't seem to respond as well off five Al for reduct a inhibitor though or well still on no that's I'm just saying in general like people who are on 5 Inhibitors you're diminishing your possibility of fertility like almost certainly so because again it's not just int testicular testosterone it's also presumably and this is how you confirm what the five Alpha reductase inhibitor applied is when DHT goes down T goes up 15 to 22% there's nothing changing about output of testosterone production other than DHT goes down when you have a five Alpha reductase inhibitor so if fertility goes down when DHT goes down it's not just the testosterone it's just broad androgenic signaling so the more androgenic of environment you have in testicular seemingly is the main dictating variable on when DHT goes down testosterone goes up by how much if it's finasteride about 15% and you are inhibiting upwards of at best if you use a 5 milligram prar tablet for B prostatic hyper you're getting a 70% Sy systemic DHD inhibition which pushes your tea and estrogen up by 15% which is so interesting because regular te conversion to DHT is not that High I mean it's rarely more than 10% so it's like you're getting you're disproportionately getting a bump in Te to the inhibition yeah yeah and I'm sure this is probably something i' have to almost like right out but I'm sure if you get into the modulation of how much DHT is occupies shpg and then how much free testosterone there is Rel that free increase in testosterone not total test that's total but DHT also the activity of it is going to be inhibited dramatically more proportionately to test because of its affinity for shbg is like 5x so I'm sure there's something there if I wrote it out it would make more sense than me just trying to think all the way Upstream but in general the takeaway that I've seen is having high intratesticular androgenic signaling is the only that's mandatory for spermatogenesis and FSH receptor activation with some level of FSH you can still maintain or achieve spermatogenesis with minimal to almost no FSH and in those individuals that still need a push they either lack androgenic signaling or there's too much uh oxidative stress potentially they need to utilize things like ubiquinol Knack like I don't know like sometimes supplements actually make a difference cartine or get off their five Alpha inhibitor or a myriad of things but a little bit of FSH Rec combinant on top of that base of ensuring you have adequate intratesticular testosterone can be the differentiating factor on fertility for a minority of people but it's not mandatory and at the end of the day when I hear people talking about well maybe we should get back to you know we should use Clomid instead of you know HCG because we're seeing FSH suppression I'm like I'm thinking a little bit of FSH it's cost prohibited but it's probably a much better alternative yeah what's the cost of recom an FSH depends on the pharmacy but I heard the other day there was a pharmacy in Texas that prescribed 1,500 IU vials for like a couple hundred bucks which to me sounds cheap I've heard it's extremely cost prohibitive and I think it depends if you're getting like gonal or if you're getting like you know which brand you're getting and I would have to I could check after a typical dose would be what 50 IU every other it depends you can go as high as 75 every day if you need to it's still significantly cheaper than growth hormone oh yeah probably I mean everything is okay um all right a word on bpc 157 which you know is yeah a peptide yeah yeah so body protection compound I think is what the acronym stands for 157 it's like a it's a peptide that's produced endogenously in your gut and it seems to have some like angiogenic properties that can be useful for injuries but it's like I've seen some pretty remarkable improvements in like minor not complete tears um and certain injuries that are like of lesser I don't know won't I don't know like I'm not I'm not overly familiar with it to a point that I could say with any certainty that it's going to be efficacious for filling the blank thing but it seems to be something that if I had an area with low blood flow like a I don't know a tendon issue or something that's when I would be looking to something that's pro-angiogenesis because it's like I also worry about cancer cell proliferation from something that's PR growing blood vessels so that is a concern with bpc for sure because I see something and does it need to be injected locally for it to have maximum efficacy so let's just assume you tear your rotator cuff um it's thought like this was one of the Bro myths we were taught back in the day inject it right into the injury site and I now don't believe that to be the case it seems at least the last I heard that you don't need to do that and do we hold out any semblance for hope that we might get a study that would shed light on this CU how could we ever possibly know the counterfactuals here and how could we possibly disentangle you know the single user experience on all these things yeah I don't think so I think it's something that so many people use at this point like I imagine you can't like patent anything or make any money off of studying it you'd probably know better than me off of how pharmaceutical pipelines work but I imagine it's kind of at a point where so many compounding phes sell it the problem I see mainly I don't really think it's not good to use like I would probably use it if I had a minor injury to somewhere I needed more blood flow but I do think a lot of people use it proactively far too often for something that is directly intertwined with increasing I think it's veg F and is like super correlated with cancer growth like to me that would freak me out people who are using it like preventatively a lot of athletes use it as a preventative measure to avoid injury or rehabil Rehabilitation when it's not necessary and I think that's Overkill and risky as hell personally got it yeah um you know I think because there are so many other things I want to talk about that we should just we can do wrap this up and hit a part two sure because we haven't talked about any of the stuff I want to talk about around nutrition around appetite appetite suppression again I think we've talked a lot about how bodybuilders use drugs and I think for many people that's a pretty foreign idea but bodybuilders also I think in a way through their own very empirical study have really figured out the science of how to get lean and how to do it with the maximum preservation of muscle this is something that I they got that dialed they really they really do and that's why um I can't imagine a demographic that better understands how to do that even if it's not necessarily the healthiest way to live um but but I think we could all take a page out of the book if we're saying you know God I I could stand to be 10 pounds lighter and wouldn't it be cool if I only lost one to two pounds of muscle in the process when you see a guy with like 50 lbs more metabolically active tissue demanding nutrients starve himself to 5% body body fat and step on stage it's like okay I can lose the 10 I could you know cut my calories by 300 or find some way that is more satiating to hit my hit my goals like it's uh definitely something to take from that yeah so I want I want to dive deep into that I also think we could spend some time kind of talking about you know ways that people can um help I don't know prevent themselves from being fooled by you know all the charlatans out there but these people wouldn't be as popular they are they wouldn't be making tens if not hundreds of millions of dollars if there weren't people who were sort of falling for what they're talking about so probably there's something to talk about as far as like what are signs that maybe what this person is telling you might be too good to be true and and maybe there's uh maybe there's a bit of a buyer beware um anything else you want to add to round two when we uh when we do it which maybe we can do in the fall or something um off the top of my head um I think the fertility discussion I think we kind of scratched the surface on what you know an ideal protocol might look like and things to be mindful of banking sperm you know uh concerns that people might have getting on trt beforehand how to vet if you need it even like criteria that would be worthwhile to know because Discerning often times people are told especially at the clinics you know oh your total te is 400 that's low get on test it's like you might have High AR content and expression like you don't know that you need more tests to actually achieve I've seen some of the most Jack guys I know have 450 total te's and feel fine there's a lot of nuance that goes into that too and knowing not just identifying content charlatans but like medical providers you know even your own doctor potentially knowing who is looking out for your best interest educating yourself at a base level I think is almost a necessity nowadays to Wade through the nonsense so I would love to dive deeper it sound awesome man I look forward to it Derek this was uh this was a ton of fun and I I look forward to uh continuing the discussion awesome thank you for having me [Music]

Channel: Peter Attia MD

Views: 1,007,445

Keywords: Peter Attia MD, Dr. Peter Attia, Early Medical, The Drive Podcast, The Drive, Longevity, Zone 2

Id: JNpgqpyzW98

Length: 210min 34sec (12634 seconds)

Published: Mon Oct 09 2023