What is the Low T Syndrome? Is Testosterone Supplementation Safe?

[Music] thank you so much it's a real pleasure to be here and to talk about this topic which have become very interested in for a lot of reasons I'm an endocrinologist and seen many many patients who are asking about testosterone supplementation safety all kinds of issues so I've become very interested in the topic I have no disclosures or conflicts of interest with regard to this topic so just very quickly testosterone it's a hormone that means it's a chemical that's made in our body in the testa sand and other places but mainly in men and the test is it goes from the test is to the blood stream and goes really throughout the entire body and its main actions are occurring in the nucleus of the cells that are in the target tissues for testosterone it interacts with a nuclear receptor and there's a lot known about sort of the biochemistry and the molecular biology of this important receptor in our bodies but when testosterone interacts with its receptor it changes the genetic programming of the cell in question and sort of way way way downstream from that interaction comes for example masculinization of the body male reproduction and many many many other processes so testosterone is sort of made through a really very elegant endocrine system and it really starts up here in the brain in the hypothalamus where a protein called Gennady tropen releasing hormone GnRH is made that goes down here to the pituitary gland at the base of the brain and the pituitary puts out the hormone FSH follicle stimulating hormone and luteinizing hormone and men and women have all of these hormones but because the test is specifically responds to these in a certain way you make testosterone and the lytic cells of the testes and over here in the tubules of the test is do you make the sperm okay and all of that happens under the influence and the control of that important pathway now what we've learned over the years is that you need to secrete that GnRH and a pulsatile way to go through puberty for boys for example and also for girls and then this leads to pulsatile production of those hormones well that's wonderful that's a normal process if you put out those hormones GnRH continuously down go vegan editor opens that stimulates at estes and and it's a very elegant system and why that's so important and why sort of the biology is so important is if we can mimic this with a medication like an analog for GnRH for example we can sort of biochemically turn off this production of those two hormones and then shut down the production of testosterone and it's a very commonly used treatment for carcinoma of the prostate for example so we can use it's kind of a biochemical if you will castration and it's reversible in general so this is an elegant axis that controls the production of testosterone by the testes but it's sensitive to many many things any kind of high intensity stress can shut down this axis if men are acutely ill or chronically ill in the hospital it can shut down if there is some kind of psychological severe psychological stress it'll shut this down if there's malnutrition if there's a chronic opioid use for example many many things can shut down this pathway so this makes it difficult for us sometimes to tell well is this really a low testosterone state or am i dealing with an illness that's led to this but many many things can influence this axis so testosterone you'll see in a moment a picture of a sort of hypothetical man but it has many many effects in the bodies of men so we've already talked about needing it for sperm production to reproduce boys if they don't have adequate testosterone don't go through the normal stages of puberty with all the changes in the body that take place in puberty and then testosterone is needed to sort of for men to gain the the physical characteristics we call them secondary sexual characteristics of being male male like testosterone maintains lean body mass and in men and and perps it happen for example in women and it promotes muscle to stay healthy and develop and it takes away it helps to decrease the amount of fat that people have so it's got lots and lots of effects and this figure right here just shows you some of the main target organs for testosterone so the skin and the skin it can cause facial hair growth and hair growth in other parts of the body for example that women don't have testosterone is doing that it's responsible for what we call male pattern one of the things responsible for male pattern baldness in the brain it affects the level of aggression the level of energy the level of sex driver libido and we've already talked about muscle being strongly influenced in its growth development size and power by testosterone in the kidney it makes a very important hormone called Depot or erythropoietin that determines the level of red blood cells in the body so important in the kidney it also affects the bone marrow enhancing the production of stem cells there it affects the growth of the bone even in young boys as they're adolescents and grow to their full height but also in men who are mature who aren't growing anymore testosterone is important as a source of estrogen as well to maintain bone health so it's important all the way through life and then the male sexual organs the sort of changes that occur with puberty that occur in the male genitalia the production of sperm and the growth and function of the prostate and in addition in the liver it has effects on protein synthesis so you know just almost every single tissue in the body has some response and these are the big ones if you will for testosterone actions in the body so you may have heard about the low tea syndrome there's a lot of information in the media about it we we kind of struggle a little bit to define exactly what it is in medicine we know that the levels of testosterone should be low in this syndrome but it's hard sometimes to know exactly what numbers constitute loti syndrome so we typically call low t something that's happening in older men and I I was kind of nervous to put an age in here you know not to be you know offensive to anybody but we're not exactly sure when the low T or the fall and testosterone occurs you'll see some curves in a moment but it's a very gradual process that continues pretty much through to the end of life and the symptoms that have been attributed to low t include effects on energy well-being sex drive being low not being able to maintain normal erectile function the muscle mass changes that occur and the gain of fat that that sometimes accompanies this loss in low T syndrome and sometimes it's been called andropause kind of to give it a name similar to menopause and women andropause for men so that's kind of an effort to kind of try to define it functionally a little bit so as I said we as physicians and endocrinologist we we struggle with getting an exact definition for it so I sometimes say that if the levels of testosterone in the morning are very very low and the man is healthy he's not stressed he's not you know very very overweight or obese he's not on opiates and he's not drinking heavily then it becomes easy then you can eliminate all those things that can affect the level of testosterone and you know that you're dealing with a low T or a low testosterone it's a true low tea syndrome but that's pretty much in what I do the rare case okay and some of the problems have to do with the fact that stress happens and and many other things happen in the course of health and illness but it but as well we have difficulties sometimes getting accurate measurement of testosterone the assays that are available and many of the laboratories aren't perfect and there's a rhythm of testosterone that goes on in the course of the day that you know stymies some of these assays and so the levels can vary as much as 30% maybe even as much as 50% in a given man on a given day so you can see that that makes it pretty tricky and then the other problem the other part of it just about every symptom that I had on those those slides that we call low T can overlap with even natural healthy normal aging so you can see it becomes very difficult here's some bad news here this is what happens to the testosterone levels by age okay and let's say something in the range of 275 or so is considered the lower limit of normal if you look at a good reference laboratory you can see the total testosterone in blue it's going down all the way here to practically the bottom of the normal range in in healthy men and it's hard to find healthy men at the age of 90 and 95 to actually get these measurements so we can actually put these data up here and so that's total testosterone in the blue and the red is the free testosterone so if you if you're having these levels measured yourself you know that you might have seen on the lab slip total testosterone free testosterone they parallel each other you can see they both go in the same direction down with with age so that's that's a tricky part of all of this and then the other part of it is that when you go to like the guidance from a good reference laboratory like this is this one is from a good one you don't see much guidance for what the testosterone level should be decade by decade it just gives you one big normal range here and it's left to you know whoever ordered this test your doctor or whomever to kind of interpret this in the context of the age and the patient and even the free testosterone we don't get much guidance from the laboratory so we've got to use experience and and so forth to kind of figure out is this normal for the age of that man that you're seeing and so forth and it can be it can be very challenging okay so that's the medical side of things when we come to the media and we come to you know the Internet and we look at all these different websites they haven't got any problem fine telling you what a loti syndrome is okay it's sex drive is low orgasm less strong less energy losing height decreased enjoyment of life feeling sad or grumpy falling asleep I like that one the best holding to sleep after dinner is you know they've got that associated with this and work performance so no sweat they have to figured out what it is and you can get all of these symptoms and you know find you know support for it in the media that that's low t and if you look up low T on the internet you will find there's many many many thousands of pages there but here's just one example we are yours this is a San Francisco low tea clinic we are your solution are you currently experiencing fatigue loss of sex drive difficulty concentrating depression or low mood loss a muscle mass and gain of fat low sense of overall wellness erectile dysfunction and then they go into everything and then they go on to want to sell you a certain kind of a formulation geared for your specific you know problems you're experiencing and there's loads of this here's at this one I put a few pages in here because it's it was pretty remarkable so this one goes if you're a man in your mid 60's you want to pay close attention to what I'm about to tell you at this very moment a hormonal shift could be taking place in your body that for all intents and purposes could be destroying your manhood but before I go any further let me ask you does this sound like you do you have flabby thighs a spare tire or extra belly fat do you feel zapped of energy do you find it hard to answer questions does a low sex drive leave you struggling to satisfy your partner if you answered yes to any of the above the real cause of your symptoms may be a lotus our own level and these are just some of the other headlines that go on on on and on through this website the seven enemies of your manhood you don't need to put up with the draining effects of a declining testosterone one day longer it's time to take back your manhood and your life don't let testosterone testosterone steal it next page don't worry I'm not going to ask you to take a testosterone shot that will mess with your hormones and so what this site is about is some herbal combination remedies a natural breakthrough always good right the big side effect could be that women much younger than you will feel very attracted to you I did not make this up could you feel 10 20 or even 25 years younger here's the picture that goes with it for many men supporting their testosterone levels is the secret to restoring their youthful vigor their energy and their excitement for life and so on and it continues and continues and and so the marketing has worked right I mean they've defined the syndrome and they are marketing it now out there and so you might say well why do you why do you think that it works well take a look at the prescriptions here so this is the year 2010 up through 2013 this comes from pharmacy data that's collected around the country and these are the number of men on prescription testosterone this is prescription this isn't going to the low-tech clinics and all those places somebody's doing a prescription it has practically doubled in this four year period of time doubled so the disease hasn't doubled in this period of time and this Green Line is men between the age of 40 and 64 so it's it's just that age group that's got many of those concerns okay oh well the market from 1988 testosterone we spent about 18 million dollars a year in this country on testosterone it has gone up a hundredfold in that period of time so the marketing in fact works so the media has an innocent succeeded with this so the real disease as I told you that we try to find out figure out and diagnose and treat as endocrinologists is a is a condition that can really be coming from a whole different from a whole host of different disorders in the body it can come from problems in the pituitary gland that produces those kanata to opens i talked about that stimulate the test us either tumors there infections there inflammation issues in the pituitary function can come from hypothalamic disease higher up in the brain right the same kinds of processes could affect that and it could come from direct problems with the test is for example someone who's been exposed to a lot of chemo a lot of chemotherapy sometimes that's toxic to the test Asst radiation for maybe a tumor that was you know much much earlier in life trauma mumps both on both sides for example can cause testicular dysfunction and and a lack of testosterone cancer genetic disorders like the Klinefelter's syndrome men who have had a lot of alcohol issues chronic alcoholism can sometimes really destroy testicular function and then men who take that kind of therapy that shuts down norm that normal axis for prostate cancer for example can really have bonafide if you will hypogonadism low testosterone due to a pathologic condition so when we're looking for that we usually will get a total serum testosterone level and in hypogonadism it's going to be low and low t it's going to be low but you've got a factor in the age we sometimes get and i put this in here only because often times people say well should i get that should i be looking at the total testosterone or the free testosterone it should be the free testosterone should also be low if the level is going to be measured it needs to be measured early in the morning between 8 and 10 ideally fasting so if you happen to be getting this make sure that you get it checked under the right conditions where the level can be interpreted and have meaning and because of that up-and-down variation in testosterone you want to get at least two and preferably three levels separated out by time so you get some idea of what's going on over time a little bit and you want you want the individual not to be stressed and that might be difficult but that's you you want to interpret that level in a in a man that's not under stress and if the tea level is low then we go ahead and do further things like measuring those gonadotropins and so forth and then we go and try to look and see if we can understand why okay so let's say one has made the diagnosis of that or we're considering testosterone replacement and you notice I have the word replacement in there I don't have supplementation with testosterone because we're keeping this at the level of what would you do if the testosterone really in fact were low and there was a reason for it we've got a lot of options we've got testosterone injections which can be given on a variety of schedules we have a gel that can be applied to the skin pretty easy to take and and quite reliable for its delivery of testosterone we have a patch that can be put on once a day and we have tablets that can go in the mouth and slowly release the testosterone so we have really good reliable treatment options if replacement of testosterone is needed and and the other part of all of this is you know if you're going to give testosterone is it safe and and all of the marketing and all of the discussion about the low tee syndrome has led a lot of men all those men taking those prescriptions I showed you too it's led a lot of men to be taking testosterone even if they don't have a disease of the pituitary gland or the hypothalamus because a doctors measured a level it's low it's low for their age and many times a sort of a therapeutic trial gets initiated and so this has led a lot of endocrinologists to kind of look at whether this is a safe thing particularly in the older age group and so what we're gonna look at very fairly quickly are a couple of studies that in that are that we're done to try to inform us is is is there a safety signal here do we have a safety issue to be concerned about and this is just just to remind you that there's lots of different kind of studies that can be done but the ones that people respect the most are what are called randomized placebo controlled trials so I've tried to show you a couple of those here as we come along so we're going to talk in a moment about some of those trials which have taught us about safety of testosterone and effectiveness but I just wanted to also set the stage for the fact that all of those replacement options I mentioned were all tested in good randomized trials but most of them were in younger men so what do you see in younger men who have hypogonadism low testosterone from whatever condition with testosterone replacement you see a lot of good things happen you see the maintenance of secondary sexual characteristics you see improved sexual functioning in many different domains muscle mass and strength increases bone mass increases in fat goes down so in the younger man under say 50 you can really measure all those different things improving with testosterone but again the big question is what about older men who are experiencing that decline in testosterone so this study came out a few years ago now called the Tom trial testosterone in older men and the idea here was if you can improve muscle function if you can improve energy vigor strength etc maybe for older men who have limited mobility this would be a good thing and we could see something good come out of you know controlled or moderated testosterone replacement so this trial looked at men with frankly low level our levels at the lower limit of the normal range again randomized them to the gel they put it on every day and they looked at a variety of parameters they looked at muscle strength and then they looked at side-effects because that's pretty important if you're if you're initiating this therapy and men in their mid 70s you want to make very sure they are not causing side effects and what they found and this received a lot of publicity was that there were some cardiovascular safety signals early on in the trial and the FDA stopped this trial so just looking at did did testosterone in fact work on some of the things that that they were testing and and these are just some studies looking at muscle strength and so this is the leg press these are the placebo men and then on placebo gel and men on testosterone you can see that leg press strength improved chest press strength improved and then they measured power climbing stairs and that all of those things all of the green bars are the men on testosterone showing that they in fact improved muscle strength muscle function but this was muscle testing it wasn't proof for example that they would fall less or be stronger in in activities of daily living and less disabled and so forth so it's a it's a interim kind of measurement but the one thing that stopped this trial and has let everybody to pause and think about this we're some of the cardiovascular signals and I won't mention the skin but I'll just show you that in this trial they collected cardiovascular events in the men on testosterone versus placebo this lowered black line and the cardiac events were greater 23 events it was a small study so 23 events in the men on testosterone just five in the men on placebo but when you run the statistics this actually became quite significant and that's why the FDA stopped the study and same with some of the skin findings so this led to everybody's stopping and thinking about is is testosterone safe in this group of older men with loti some of the other adverse events or side effects if you will are a high red blood cell count and we monitor this carefully when we give men testosterone and and this is just a summary but in in a whole bunch of studies a bunch of trials this signal turned out in fact to be a significant one in other words that effect on red blood cells has to be carefully looked at because it does go up with testosterone and you'd think that's a great thing I mean having more red blood cells it's got to give you more oxygen be able to do more the relationship between that in older versus younger men isn't the same and so in older men this may actually you know accelerate the chance of having a heart attack or a stroke so there's a lot of attention being paid to this what about the prostate we know that the prostate is a testosterone sensitive tissue right so in all these trials and I've just put a little red line down the middle here when any of these lines cross that red line that means it's not statistically different so basically in all these trials they basically have established that testosterone therapy even though the prostate sees that testosterone doesn't cause prostate cancer and statistically it actually doesn't worsen lower urinary tract signs like frequency and and so forth and these are in that and in men of that age but still we monitor PSA prostate specific antigen and men on testosterone but it doesn't look like it's dangerous in that sense and there's a there's a small effect on HDL cholesterol and in men who have obstructive sleep apnea we have to take care of that sleep apnea before we give testosterone because that can may be worse than the sleep apnea so those are some of the things that we've learned from a lot of these trials and in the next five minutes I'll just show you this last set of trials but just frame it around you know the concerns that that Tom trial raised about cardiovascular safety and then a lot of the other trials also raised the concern of are we actually getting any efficacy out of giving testosterone to older men and so the National Institutes of Health sponsored a bunch of trials that they called the T trials or the testosterone trials and specifically targeted older men and we won't go into the details we just don't have time but just eight about eight hundred men were enrolled in these trials and you can see all the different parameters this cost us a lot of money I'm sure but all the different parameters that they looked at in these different seven different testosterone trials and the men were all over the age of 65 and again it was the gel formulation and each of the studies was one year so they succeeded in raising that testosterone levels you see the men in the placebo stayed low the whole year and men on testosterone raised that level into the mid normal yeah young mid normal range so what did it do well this little red line here tells you the men on testosterone and it tells you about sexual functioning so it in fact did improve no surprise really there these men over the age of 65 could walk a little bit more but it didn't quite make statistical significance maybe way out here but it was not significant over here and there was no and they'd studied a lot of these things by questionnaires no effects on the sense of vitality reported reported from a questionnaire but mood got better in terms of adverse events I'll just summarize that by saying and they looked at everything very carefully the safety looked okay in that one-year study they looked at sexual functioning and about 500 men and all of these were men who on their initial intake complained of a low libido and they looked at it with different instruments for testing this and they found that 10 out of the 12 aspects of sexual functioning got better but one thing and many men complain of this in this in this age group certainly is a rectal function it didn't change erectile function and that's important because we have other other treatments for that they also looked at cognition so you know memory function and so forth and we'll go straight to the bottom line here no difference between testosterone and placebo and these were these are considered the very best tests for checking these things they looked at bone mass and 200 men and bone strength you can estimate that from different kinds of imaging tests and that was positive in other words these men increase their bone mass and if you calculated strength from the bone mass measurements strength improved so bone was positive bone was and and sexual functioning positive now what about cardiovascular and that's the big-ticket question that we all have working in this area so there were only a hundred and seventy men in the cardiovascular trial again it was the same thing I've told you about the gel for a year versus placebo and they looked at cardiovascular health by doing coronary artery CT angiogram is a very precise quantitative very detailed imaging technique and they also did coronary artery calcium scores and cutting quickly to the chase these things I've highlighted in this orange color those things actually did worsen over over that one year of therapy so non calcified plaque in the coronary arteries did go up with a year of testosterone and the total amount of plaque also increased so plaque is not a not a good thing and this kind of plaque is thought to be sort of the bad kind this may or may not be you know may may just be hard plaque that you accumulate so I think this led a lot of people to really be thinking maybe that original Tom trial was telling us something true they did do the coronary artery calcium scores and in that one year they didn't see a change now with this small a number of men couple hundred you can't count heart attacks in a year there wasn't that high risk of population so we we can't say anything about events heart attacks strokes etc they can count them but it's too small a study so just to sum up quickly what about treating older men with low T well the T try I think our going to be for a while the best data that we have I think they're very helpful you know they're very well done and and carefully done but they're all short and cardiac events and vascular events often happen over time and and they couldn't capture because the study was the studies were small real endpoints real hard endpoints which are I think the biggest concerns we have and because they weren't designed to be safety studies and they're in the real sense of exposing a lot of men and following them over time they don't establish safety all you can say is here's what we saw you can't say this doesn't mean you aren't going to see a heart attack if you follow men for five or ten years so they can't establish safety this is what we're probably going to have the testosterone by no means is a panacea for aging and definitely beware of the marketing and look very carefully at supplements that are set up to augment testosterone or give testosterone look very carefully at it so the jury is still out he's thinking very hard about about these data and maybe over time he'll come up with a better answer than I have [Applause] [Music] you

Channel: University of California Television (UCTV)

Views: 220,124

Keywords: Low T, testosterone, training, Endocrinology

Id: KToBZpy82Mo

Length: 32min 53sec (1973 seconds)

Published: Mon Apr 30 2018