Testosterone and the Prostate

[Music] the the title of my talk is testosterone and the prostate well I have to ARs questions men with low tea when diagnosed with prostate cancer have a lower Gleason score so it's that true/false or you're unsure so and the answer is false so that's what people think alright we'll see if that changes next one testosterone replacement therapy TRT has been shown to flare prostate cancer in men on active surveillance yes no or you're not sure and survey says most people say no all right let me go to my slides now so if we look at testosterone treatment TRT there's a lot of really well-known benefits probably increase in sexual interest erectile function muscle strength decreased central fat bone density improve cognition there's other ones that aren't so well accepted including mood well-being physical performance activity decreased fractures quality of life and life expectancy and then there's the downside the potential risk I would say that the one that gathers the most interest here is the increased risk and severity of prostate cancer we may have and again these are all not really proven exacerbation of BPH polycythemia that's one of the the relatively known side effects it could make sleep apnea worse fluid retention coronary artery disease gynecomastia an imbalance raising testosterone it's aromatized the estrogens and that may affect that's what's in receptors in the breast and leave the gynecomastia priapism and acne but the one that is a major concern is the increased risk and severity of prostate cancer and I would also say the potential for cardiovascular disease all right so it's sort of a the all these vicious circles here low testosterone metabolic syndrome is prostate disease worse or better is prostate cancer if you're diagnosed with with loti worse better indifferent all these things are out there to think about so what are some of the questions testosterone substitution and possible changes in the prostate one does it increase PSA levels I will talk a little bit about that there's probably some evidence that it does and people say it increases it up to what the normal range would be for a you gonadal person at that level does it increase prostate volume perhaps yes again the same sort of thing and does it stimulated growth in previously undiagnosed prostate cancers well that is what one of the major concerns are but there's no data to support the testosterone substitution as a cause of prostate cancer and I think we've all seen men that have gone on TRT whose PSA goes up a little bit and they're found to have prostate cancer actually we may be doing them a favor that we may not have diagnosed that we know that that in a lot of studies there has been subtle changes in the aua symptom score and things like that and we know that in lots of cell lines that when you administer testosterone that it's a stimulus it's a mitogen it makes the cancer grow but did it again the underlying thing is here does it cause prostate cancer and I don't think there's any data to support that and we'll go through it so prostate we know that prostate development not prostate cancer differentiation and maintenance are known to be closely linked with bioavailable BHEL ability of testosterone and other sex related hormones we know that a group of men born in the Dominican Republic who were deficient in 5 alpha reductase did not develop and prostate disease they had a lot of favorable characteristics like lack of acne did not lose their hair did not get the pH and that was the basis as you well know for five our free duct ACE inhibitors and that but we do know that you do need testosterone and you do need dihydrotestosterone for prostate development growth and so forth Along Came Huggins and Hodges in 1941 and they won a Nobel Prize in 56 for discovering not really discovering but for the first time reporting that deprivation of testosterone slowed the progression of prostate cancer and they were optimistic initially that it was sort of like Lazarus and the cure is that men were writhing in pain and that with metastatic prostate cancer they were treated with with deprivation therapy of testosterone through various mechanisms and they sort of got up and walked and we thought wow we've got a cure for the disease but that concern exists at the testosterones risk of converting an occult cancer into a clinical cancer because we know basically we've all heard this that if you live long enough you're going to get prostate cancer if he examined prostates autopsies while soccer did this years ago was done it was done by barns and the UK that there was microscopic prostate cancer that increased with age and this is this throwing gasoline on the fire making things worse by adding testosterone what's always bothered me because most men that we take care of with prostate cancer have normal tea levels and maybe the ones that have low T levels are disadvantaged and I'll talk about that so this is this is sort of the hypothesis if castration makes prostate cancer cells by then shouldn´t raising testosterone make prostate cancer cells grow so there should be a linear relationship these things are going sort of an opposite direction but men dying the prostate cancer are all castrated so there's a lot a lot of confusion and exists here I think it's it's really time for re-evaluation of this based on current evidence so one of the principles of evidence-based medicine is that concepts that fail to withstand scientific scrutiny are to be discarded well it's not happening I think that such a time has come for the belief that T causes enhanced growth of prostate cancer and probably again we're not totally sure about this the cardiovascular issues my good friend met Abe mark Morgan teller who has been to this meeting many times first wrote about prostate cancer and the the whole concept of testosterone just a few years ago and one of his seminal articles was and was in Jim and here's Abe from his little trip to the Galapagos Islands givin me the thumbs up he sent me this a couple of months ago when he was there so he went and and looked at the actually he went to the basement of the library at Harvard and pulled out the original Huggins articles from 41 and 57 and looked at him and in this 1967 review article Huggins set orchiectomy or the administration of estrogens resulted in regression to prostate cancer that's yep we got a Nobel Prize for that whereas in untreated patients testosterone enhanced the rate of growth of cancer and so that was where this fear came from that the if lowering tea reduces your rate and prostate cancer growth raising tea is going to stimulate it however the logic testosterone favours prostate cancer growth is completely inconsistent that I really is robots beta against this so this is the 1941 Huggins and Hodges report that all of this is based on so Abe actually dug this out and what Huggins and Hodges report it and that people sort of passed down from generation that generation and I got that when I grew up in urology is you don't give testosterone to men with prostate cancer it's throwing gasoline on the fire we tell patients that and that this was based on giving some three three men supposedly testosterone replacement and see their acid phosphatase levels go up but you know what I was thinking about this too is that every time we give an L a charge agonist for instance we raise testosterone we're doing the same thing and we see the PSA go up a little bit we don't measure it but there's plenty of data that show that it does and and Burton Trumbull from Belgium has some beautiful pictures of MRIs of men that received agonist where the bone actually gets worse you can see it light up right after they get an LHRH agonist and that lasts for a couple of months that's called a flare but we do it all the time we don't worry about it I guess so what Abe did is he looked at that article a little bit more carefully and and there were three men injected but they only reported on two of them one of them had already been castrated so we throw that out so in the remaining patient acid phosphatase levels rose during 18 days of T treatment but fluctuated widely before and after reaching the same peak levels three weeks after T discontinuation sort of you know the flare thing so the original assertion that testosterone causes prostate cancer and untreated patients was based on unequivocal or rather equivocal acid phosphorus paste results in a single patient and that was passed down and generation the generation the generation of urologist about why testosterone should not be given to men with prostate cancer the Institute of Medicine has said in summary the influence of tea on prostate carcinogenesis and other prostate outcomes remains poorly defined this is some other work that dr. Morgentaler is done and it's the saturation model we do that and almost all steroid receptors is that you give enough and you saturate it you can give all the more you want and it's not going to do anything you know we do this a lot with with vitamins and minerals and supplements and things like that these people when I go to the gym they're drinking all these proteins and and and vitamins and everything else they probably have the most expensive urine in the city because you don't need all that stuff we if you have a good diet and so forth and the same thing with testosterone you can give all you want but it saturates the receptor and you can go up to 700 and it's not going to matter you might get some side effects because you have too much testosterone and some aromatize too estrogens things like that so there is a nice saturation effect and this is where we play around with energy and deprivation therapy in this narrow window here or lo T interestingly think about it prostate cancer incidence increases as you get older right what happens to testosterone level it goes down when you get older they're going in opposite directions where's the association here I've also did a report in in JAMA in 1996 on a group of men 77 and his his rationale was if I'm going to start somebody in testosterone I want to make sure they don't have prostate cancer so I'm gonna biopsy him and that was the time of sextant biopsies and most of these men had PSA sub lesson for a normal day re and he reported a 14% incidence of positive biopsies for prostate cancer where the expected incidence in that population would be maybe 1.8 the 4.5% we actually shared a little bit later from the prostate cancer prevention trial was a little bit higher than that but but his thought was is that decrease androgen status may mask prostate cancer and low testosterone was actually just the opposite a risk for prostate cancer and as we learn later a risk for more aggressive prostate cancer and so this is a table of low T and increased prostate cancer risk we have Morgan Tyler's here we have other ones that show prostate cancer incidence was higher with low T's which that Gleason grades were higher and other things that supported the fact that low T was associated was the worst prostate cancer right now hypogonadism as we talked about markers we talked about it being a marker for Edie being a marker for cardiovascular we talk about low T being a a marker for a more aggressive Gleason score so there's been a lot of retrospective articles that Hoffman massingill and others have looked at prostate biopsies and and shed mild to this to that had Gleason scores of eight actually had lower T's and pretreatment testosterone levels were an independent predictor of extra prostatic disease in this massingill study we started years ago every time we order a PSA to order a testosterone because we know that that that PSA is an androgen dependent marker and you can give somebody TR a androgen deprivation therapy and see they dive almost immediately but if you do scanning and look at the masses and things like that it's still there so we know that it is a marker but it's not perfect so final thought after a radical prostatectomy if you do not replace testosterone levels and hypokinetic men to make them you cannot oh then how can we justify not lowering levels of testosterone and you good I'll amend to make them high poking at all so we have a lot of men out there that are hype again I know that we do radical prostatectomies on and there's sort of an underserved population and we say I've listened to these discussions ad nauseam about the replacement of testosterone and men who have had local treatments and people say oh you gotta wait a year or you gotta wait two years before you do it to make sure their PSA goes up I'm not sure if that's true and so what what we have plenty of we have plenty of data on that when you do tea replacement you have some certain obligations one is you need to check you need to check PSA don't necessarily need the biopsy but and I still do a lot we have other markers we do we talked about in earlier today things like you know the 4k and select them DX and other things we can do to look for prostate cancer and I got to follow as people you gotta check hemoglobins got a phone for sleep apnea and things like that so in summary testosterone treatment there are beneficial effects for multiple systems and that's not what I'm here to argue about I'm here to say that I think it's safe with appropriate medical monitoring there plenty of studies out there that have looked at giving T to men on active surveillance and and also giving T to men that have had seed implants and giving T to men that have had radical prostatectomies and they're considered cured and even if they're not considered cured I don't know maybe we'll bring a failure to light earlier and I'm a believer that early finding is better than later and men with low teas actually are partially androgen deprived if we look at that that saturation thing particularly that's low but in general most of the time they're not and that's maybe why they have worst cancers so ton of Kennedy once said the great enemy of truth is very often not the lie but the myth persistent persuasive and unrealistic and this myth about testosterone is something that has lasted and I think needs to end so Pablo Picasso once said it takes a long time to become young thank you you

Channel: Grand Rounds in Urology

Views: 16,535

Keywords: David Crawford, testosterone treatment, testosterone therapy, prostate cancer, grand rounds in urology

Id: XLg3rasu6jQ

Length: 18min 56sec (1136 seconds)

Published: Tue Jan 16 2018