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How Risky Is TRT Really? - Dr Peter Attia

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Dr. Peter Attia expresses significant concern regarding the rising trend of young men utilizing Testosterone Replacement Therapy (TRT), often driven by a desire to improve mood and overall well-being rather than treating clinical hypogonadism. He argues that many users lack an understanding of the critical distinctions between physiologic replacement doses and super-physiologic dosages, as well as the severe risks associated with obtaining testosterone illegally from unregulated sources which introduces contamination issues. Furthermore, Attia criticizes numerous clinics for capitalizing on this demand without adopting a nuanced medical approach, often prioritizing profit over patient safety by failing to adequately educate users or monitor long-term outcomes in younger populations who may not yet fully grasp the implications of suppressing their own fertility. When examining TRT administered correctly under physician supervision with appropriate physiologic doses, Attia addresses two historically feared risks: prostate cancer and cardiovascular disease (CVD). He presents compelling evidence that TRT does not initiate prostate cancer; indeed, it may slightly decrease risk, citing cases where men who have undergone a prostatectomy for existing cancer safely continue on therapy under strict monitoring protocols. While the data regarding CVD is more complex, he references the recent TRAVERSE trial which showed no increase in adverse cardiovascular events with low-dose replacement. However, Attia cautions against concluding that all risks are settled, noting that the study may not have utilized high enough dosages to reflect real-world scenarios where patients often reach total testosterone levels of 800–900 ng/dL compared to the trial's lower targets. The dangers escalate significantly when TRT is administered at super-physiologic levels or without proper medical oversight, leading to a host of severe complications beyond simple hormone elevation. Attia highlights that excessive dosing can drive red blood cell production to alarming rates, causing increased blood viscosity and potentially triggering Polycythemia Vera, a self-sustaining disease where the bone marrow continues producing cells even after stopping therapy. Additionally, high doses often result in elevated levels of estrogen (leading to gynecomastia) and dihydrotestosterone (DHT), forcing users onto aromatase inhibitors like anastrozole or 5-alpha reductase inhibitors such as finasteride. Attia strongly advises against using these medications for hair loss due to the risk of permanent side effects, including irreversible libido loss associated with "finasteride syndrome," and warns that blocking DHT may not be a viable long-term strategy despite its popularity among men experiencing hair thinning. Fertility represents another critical concern, particularly for young men in their twenties who might consider TRT without realizing it can permanently compromise sperm production within two years of use. Exogenous testosterone shuts down endogenous production via negative feedback loops on the hypothalamus and pituitary gland; while fertility is often retrievable after cessation if started later in life or with good testicular reserve, early initiation can lead to a lifetime dependency on therapy for those wishing to have children in their thirties. To mitigate this, some users turn to Clomid (clomiphene) or hCG injections, which stimulate the body's natural hormone production and preserve fertility by tricking the brain into increasing follicle-stimulating hormone and luteinizing hormone levels. Despite these mechanisms for preserving fertility, Attia remains skeptical of long-term reliance on Clomid due to its potential to increase desogestrel (desol) levels over time. Chronic elevation of this steroid is linked to serious health issues such as an increased risk of atherosclerosis and cataracts, drawing parallels to drugs withdrawn from the market in the 1950s and 60s for similar reasons. Consequently, he advises against using Clomid or hCG indefinitely, emphasizing that while short-term use might be acceptable under specific circumstances intended solely for fertility preservation, long-term application poses unknown risks regarding cardiovascular health and ocular integrity. Ultimately, Attia concludes that the benefits of TRT in the brain—such as improved mood and libido—are best realized when estradiol is allowed to function naturally within a physiologic range, rather than being artificially manipulated through aggressive dosing or inhibitory drugs.
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one of the other things that's been happening a lot recently is the rise in trt usage among young young men um maybe in part due to hoping to elevate their mood to improve the way that they feel what's your opinion on the what appear to be increasing numbers of young men using trt uh I'm I'm greatly concerned by it truthfully I I think it's um I I think again a lot of men I think don't understand the risks of trt and while testosterone is a very safe therapeutic I mean uh if if done correctly it's as safe a hormone as there is uh but you know if you're talking about a young guy who doesn't actually understand the impacts of testosterone on fertility for example later in life uh doesn't understand what a physiologic dose is versus a super physiologic dose and especially in the cases where guys have to get this stuff illegally um that then you introduce a whole new of contamination and uh all sorts of things like that so so net net I'm a little concerned um maybe a lot concerned I also think you know there are lots of clinics opening up that are kind of trying to circumvent some of these issues and again I I I think their I think their their motivation is to capitalize on an obvious interest but they do so without uh you know necessarily A nuanced approach to how to do this take me through through the risks of trt what are they high level so it depends on the on if we're going to talk about trt done correctly do you mean literally trt testosterone replacement therapy or that and its more uh malignant offshoots where people start to push dosages and stuff but take us through you know the range well I would say let's start with what's sort of known in the medical world right so we'll start with kind of appropriate physician administered testosterone replacement therapy for an appropriately aged individual for an appropiately aged individual at an appropriate physiologic dose cool okay so the two big risks that people have historically been concerned with are prostate cancer and heart disease so an increase in the risk of prostate cancer and an increase in the risk of cardiovascular disease both of these have been studied extensively and I think we can make a very strong and compelling case that testosterone replacement therapy is not increasing the risk of prostate cancer at all and it may in fact be decreasing the risk slightly um I've an entire podcast I think two podcasts on just that topic that's how nuanced it is um but again we to give you just one example when we have a guy who has undergone a prostatectomy for prostate cancer he's had his prostate removed um we will still use testosterone replacement therapy in that guy so think about that you have a guy who had prostate cancer you will still give him testosterone replacement therapy if it's warranted or indicated post prostatectomy now do you do it and shut your eyes and never look again of course not you're still monitoring his PSA every 3 months and you're going to look for any sign of recurrence and if there is infected recurrence you would immediately cease it because what we do know is testosterone would feed prostate cancer but the point I'm making is around initiation is there any evidence that testosterone replacement therapy initiates prostate cancer the answer is no there is not and there is some evidence to the contrary the cardiovascular disease question is a little bit more difficult and the data are a little bit more muddled but on balance they come out in the direction of trt does not increase the risk of cardiovascular disease now there's a big trial that was completed last year called the Traverse trial that gave men uh AndroGel so topical testosterone and followed them for I want to say three or four years and there was no increase in the incidence of ascvd atherosclerotic cardiovascular disease but there is so so at face value that study was taken to mean look we have one more study the biggest and best that demonstrated no increase in the risk of cardiovascular disease with trt so the debate should be settled once and for all um I did a podcast on this wrote a long newsletter on this and the long and short of it is that's a in my view that's a slightly premature conclusion because I don't think the Traverse study was done perfectly uh most importantly it um did not give men a high enough dose in my view so the men started out very hypogonadal with a total testosterone of somewhere between 1 and 300 nanog per deciliter but they were only replaced to about 600 nanog per deiler and while that's a reasonable rate of replacement I don't think it represents what's happening in the world I mean we replace patients to higher than that we replace patients to 800 or 900 we're technically tracking free testosterone and not total testosterone but us to get somebody in the range of where we think a good free testosterone is we will see a total testosterone uh that's easily in the 8900 nanogram per deciliter range so it's possible the Traverse trial only answered the question does low dose or as one of my analysts put it does testosterone light replacement therapy increase the risk of cardiovascular disease and I think there we can say the answer is probably no okay and what about testosterone replacement therapy when it's done badly yeah so I think if you even think about it in the medical setting I think testosterone can be given to very super physiologic levels and I see patients getting super physiologic levels all the time they come into our practice they've been treated at some tea clinic and they walk in with a free testosterone of 35 nanograms per deciliter um you know which is like twice what you would consider reasonable and you know part of the problem is we don't really know what the long everything goes out the window with what I said earlier now can I say that that doesn't increase the risk of prostate cancer initiation I can't say that because I don't have the data can I really say that doesn't increase the risk of cardiovas dises no I can't it's also by the way creating a lot more Arroyos so these people are making red blood cells at an alarming rate and they need to be monitored very closely for increase blood viscosity is is that uh I have a friend of a friend who donates blood every month is that that's why because they just making too much and it's too thick correct wow I mean good for the blood donation people yeah and again the question is if you have to give blood every month if your bone marrow is so revved on that you have to give blood every month do we run the risk that you're going to convert into poemia Vera at some point which is a disease now where all of a sudden you can't shut that process off so oh it becomes self- sustaining even once you've come off the trt yeah again I'm not suggesting that that's happening what I'm asking is we don't know right and and there's just a big unknown there the other thing is once you start to get into these super physiologic doses you start to run into other issues around found a lot of estrogen and a lot of DHT so you'll see these men who are on these super physiologic doses of testosterone also showing up on five Alpha reductase Inhibitors which we could talk about why I'm not a huge fan of those and on aromatase Inhibitors which I'm also not a is that to stop gyno and Halos yes right and um obviously I'm not I'm not a guy who takes hair loss very seriously but um you know I I think it's a mistake uh to take a five Alpha reductase inhibitor for hair loss I think there are far better strategies if it matters and um I think you know even though the risk of uh finasteride syndrome or post finasteride syndrome is low it's not zero and it's potentially irreversible and this is this is I think in a young man taking finasteride again if you've been T if you're listening to this and you you're on finasteride and you have no issues you're fine it's something that if you hasn't kicked in within you know 6 months it's not going to kick in but um we do we do see men who have like a permanent loss of libido this is reported in theid syndrome is yeah so so basically there's something about blocking DHT that might not be a great idea permanent loss of libido would be bad um what what else haven't we spoken about when it comes to exogenously increasing testosterone levels fertility yeah well there's another thing that I I think is when you yeah fertility for sure right so at um once you give exogenous testosterone um you you're going to cut down on endogenous production including sperm production and therefore you're going to see a reduction in fertility and at some point that's retrievable uh and at some point it becomes more and more difficult to retrieve so it depends on the person's age when they start and what their testicular Reserve is but you know generally speaking two years of exogenous testosterone can spell the end of endogenous production and therefore a lifetime dependency which which again we do that all the time like if a guy is old enough and decides it's time to go on trt we fully accept that and there's no risk of being on Lifetime tea for life within physiologic doses but for a guy who's young that might be an enormous risk and and we you know we see this all the time where guys who are doing this in their 20s decide they want to have kids in their 30s and they can't what else haven't we said about the risks of trt um I think there's another method of delivery using uh chopine and en en chopine and these are drugs that have the advantage of preserving fertility uh they work by inhibiting estrogen receptors in the hypothalamus that trick the brain into thinking you need more testosterone so now the brain uh via the pituitary starts producing more follicle stimulating hormone and lutenizing hormone and you end up increasing endogenous production um and again I I might be a an unusual skeptic in this regard but my concern with that approach typically centers around yes you raise testosterone but are you getting the full benefits of testosterone because I think one of the benefits of testosterone is the benefit in the brain and if you're now blocking estradiol's impact in the brain um certainly anecdotally there's questions about whether you're taking away some of the benefits of testosterone including mood and libido would you have any concerns for people being on Clomid for a long amount of time is that something that you think shouldn't be used um I would feel very strongly about people not being on Chopin or Clomid for a long period of time for another reason which is it really increases the production of a stero called desol um interest so and the reason for that there's a lot of problems with that including potentially an increase in the risk of atherosclerosis increase in the risk of cataracts and things of that nature so I think long-term use of chopine is probably not a good idea the drug was never intended to be used longterm it's a fertility drug so it's intended to be used shortterm and I think shortterm uh rises in desol are not problematic but lifetime increases or many years of increase I think would be and there's a drug that was there's a drug that increased as mol levels in the 50s and 60s that was actually pulled from the market because of the increase in cataracts and the increases in cardiovascular disease in other news this episode is brought to you by Maui Nei venison Maui Nei delivers the healthiest red meat on the planet directly to your door first off the venison sticks are seriously delicious not gamey at all and unbelievably convenient to eat no one accidentally hits their protein goals and these little puppies will help you throughout the day if you're traveling if you're on the road or if you're just a rushed human like the rest of us these things will help you to hit your protein goals and ensure that you're getting good quality meat throughout the day not only do they provide the most 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