Does testosterone therapy cause an increased risk of prostate cancer? | Peter Attia & Mohit Khera

when I bring up testosterone replacement therapy for men the question I get asked the most is about prostate cancer now I've documented and discussed this in so much detail I think I've probably done two if not maybe three podcasts on the subject including a dedicated AMA podcast on all things that relate to testosterone as far as risks and benefits and um I would say we've spent more time on this than than just about anybody perhaps not as much as you we came away from this analysis with the belief that there was no evidence that exogenous testosterone application was increasing the risk of prostate cancer and there was actually some evidence that hypogonadism may not be increasing the incidence of prostate cancer but may have increased the incidence of high grade prostate cancer furthermore we saw virtually no evidence that exogenous testosterone therapy was leading to an increase in atherosclerotic cardiovascular disease though there was one study that suggested in the short run I.E within one year highly susceptible men might see an increase in the risk of ascvd but that risk decreased at two and three years post-treatment so with that being my current state of understanding can you fill in the gaps let's talk about is this a great topic so so look this this thought that testosterone causes prostate cancer started in 1941 Huggins and Hodges Nobel Prize based on one patient one patient in 1941 when they gave exogenous testosterone the prostate cancer got worse if you look at the different paradigms the American Urologic Association in 2018 came out with the testosterone guidelines guideline on that under Section patients should be informed there's no association between testosterone and prostate cancer strong recommendation so finally patients say I Googled it I heard I can get prosecuted so no the guidelines are very clear based on the evidence no data support it contrast that for a moment with the guidelines on estrogen therapy and breast cancer in women which we're not going to go down that rabbit hole because I get way too phosphorylated but talk about the difference between men and women and how differently they're treated with respect to hormonal therapy and I think a lot of that started with the Whi Whi of course 2003. so you get this big news and everyone's off hormones and later on you get a reevaluation the Whi and say hey maybe we made some mistakes but all that the damage was done right all that noise so we're going to talk about the Traverse trial so I've been one of the involved in this reverse trial the Traverse trial is coming out in June of this year will be coming out the Endo meeting uh about cardiovascular but that was very similar the impetus part of the Traverse was hey we have no large trial in men we the Traverse 6 000 patients randomized placebo-controlled trial largest of its kind will be coming out pretty soon but I want to finish about the test prostate cancer so so so listen so many there's a paradigm shift and the paradigm shift is that maybe testosterone may not only be safe but it may be protective against the development of prostate cancer so I just want to give you an example in 2015 the Hopkins group published a very interesting study on a concept called bipolar Androgen therapy they called it bat who was the lead on that uh it's schwartzer and the the senior was denmead and so in 2015 and I did something very unconventional you walk in with metastatic prostate cancer into Hopkins and what they do is they give you high doses of testosterone to treat your metastatic prostate cancer which is mind-boggling because the standard care for that patient is the exact opposite right it's to give you Androgen deprivation it's too chemically castrated right and the way they would do it they would give you Lupron first to shut you down and then they would give you high doses 400 milligrams every month and it would go up and down and it would basically convert the cast rate resistant prostate cancer to castrate it's a sensitive right and so and so essentially the PSA went down by 50 and what they saw was a radiographic disease went down by 50 that is unheard of to give that metastatic prostate cancer patient testosterone the same group published numerous really impressive studies but my favorite was the one that came out at 2021 called the Transformer trial this is mind-blowing so they took about 200 patients who had castrate resistant metastatic prostate cancer and they said okay and if they became resistant to abiodarone the treatment of care is enzolutomide which is an androgen receptor blocker this is instead of giving everyone enzolutamide we're going to give half the men high doses of testosterone okay so let's see what happens so they gave them enzoluted or high Dosa testosterone they found that the overall survival between the two groups was the same no different but the difference in quality of life was significantly better on the patients but it got even more interesting you were allowed to if you took bipolar antigen therapy you're allowed to switch over to angelutamide if you came resistant and vice versa the patients who did bipolar antigen therapy and then did enzolutamide had significantly greater survival 37 months versus 28 months then enzolutamide which is the standard of care the cost of enzolutomide is 8 000 a month the cost of 400 milligrams of testosterone is about 100 a month right and it had significantly greater survival this is called less than 21. 21. so we're three years two years after that how many men with metastatic prostate cancer are receiving that care now I I think minuscule why I don't know why that's why I did I don't know why attention was not given more attention was given to the study I mean it was it's called the Transformer trial it was really impressive you know as using a standard to care which is enzolutomide versus bipolar energy therapy and then the angelutamine so I think you're going to see a lot more of therapeutic use of testosterone you know um I I also you're going to see a lot of studies there's been some recent studies suggesting that giving testosterone to men after radical prostatectomy may be potentially protective against biochemical occurrence that was Tom Allen's group look I'll tell you what so I have a lab in my lab we do a lot of basic science work with testosterone and prostate cancer one of the studies we did was we took Petri dishes we put Lin cap cells prostate cancer cells and those Petri dishes and we gave each one of those Petri dishes different amounts of testosterone and it is true when you initially give testosterone you see prostate cancer cell growth no question but when you give higher and higher doses of testosterone you see greater and greater suppression of prostate cancer cell growth we call that the inverted U where maybe castrate may be protective eugenatal protective but hypogonadal is dangerous so then we said okay let's do it in animals 200 mice castrated 50 mice we gave a castration we get 50 controls we castrate and give low doses of testosterone and then we get castrate in high doses of testosterone these are pellets in the mice we published both these articles what we found was that if you castrate the mouse you get a decrease in prostate cancer growth no question it helps low doses of testosterone you start getting increase in prostate cancer growth high dose you get a statistically significant decrease an inverted use so if I have high dose Compares how much to the castration essentially it's a eugenatal range essentially Castor if you do castration behaves almost the same as slightly better but in certain cases in the animal case in the petri dish it was it's better but it just varies but the key is this if I have prostate cancer either castrate me or put me in the normal range but do not I think personally put me in the hypogonal range I think it's a danger zone yeah except I would say having watched Men get castrated yeah chemically it's awful I mean I I generally advise men to undergo surgery whenever possible if surgery is an option if you're that Gleason three plus three or three plus four or whatever and and you know it's just a question of having the best surgeon operate on you yes there is a lot of downside of surgery but I think it pales in comparison to the downside in in what I see from men that undergo chemical castration the metabolic syndrome yes and the metabolic derangement that follows yeah from being hypogonadal Beyond hypogonal they're basically eugenatal um not to mention the complications of bleeding that followed the radiation so um again I'm sure there's you know lots of medical oncologists and radio oncologists that are listening to me now wanting to put arrows into the back of my head yeah but uh I don't think I'm speaking with just a surgeon's bias I think I'm speaking from watching Men in the years that follow undergo complete metabolic destruction right and even if they're still alive their quality of life is so poor sure so that's why I would say like gosh if there's a medical way to do this with high-dose testosterone you know certain you're right now certain patients do benefit better with radiation just based on Gleason score and but at the end of the day yes if it's moderate we give them six months if it's severe we give them two years of energy deprivation therapy but we do in my practice treatment after radiation with testosterone is controversial we'll get into this and what dose you're using so typically I will use gel first because I want short acting so I can stop it if the PSA then we'll move on to an injectable but I treat them just like I normally would treat any other patient I don't whether they had you treat them to a level of total tea or free tea just like I would at someone in the normal therapeutic range but there's no data to support that it causes cancer and what kind of consent form do these men sign to undergo something that is so radical and do you need an IRB for this so if you look most clinicians or urologists it was a recent survey looking at urologists 96 of patients of urologists will treat men after radical prostatectomy with testosterone 86 percent of your own after radical after that 86 after radiation therapy right now look there has to be some consent here there has to be someone form decision making the American neurologic Association made it very clear the risk benefit ratio after prostate cancer surgery radiation is unknown right we don't have the randomized placebo-controlled trial so I tell them look we don't have a randomized placebo control trial these are the risks these are the benefits and we have a shared decision-making model but there's something important you have to understand something called the the prostate saturation model it's really important we were taught in medical school that the higher the testosterone the greater the PSA we were taught it was linear and the higher the testosterone the way to go that is not true at some point it saturates we did a study in 2011 we said the saturation was around 250 in the underground per deciliter so if you take a guy that's pretty low it's pretty low but that's where the satch inflection point was and others have shown the same thing roughly around 250 but we're all different but why is that important because if you have a man who starts out with a testosterone level of 190 and you put them on testosterone because PSA should go up it should go up if he's at 290 and you put him on testosterone it should not go up and if you take the guy from 290 and take him to 3 000 should not go up because it's saturated right so it it plateaus so so that's why if I give someone Lupron that testosterone goes down but the PSA goes down right but if you raise the testosterone it's not the more I raise it the more the PSA goes up so the tricky part for me is when patients come to me after radiation therapy because they've been given Android deprivation therapy testosterone is 50. and their oncologist spent all this time taking away the testosterone that's right and when you get it from 50 past 250 you're going to see that rise until you hit saturation and so the oncologist says what are you doing patient says what's going on I have to set the expectation it's going to rise it's going to Plateau I just have to have that understanding with you based on the saturation model we just have to have this understanding [Music]

Channel: Peter Attia MD

Views: 32,227

Keywords: peter attia, mohit khera, does testosterone therapy cause an increased risk of prostate cancer, prostate cancer, testosterone therapy, the drive, longevity

Id: EMVsNKRuMNQ

Length: 11min 53sec (713 seconds)

Published: Wed Jul 05 2023