Episode 103: Abe Morgentaler talks about mens health, sex drive and the benefits of testosterone therapy
Welcome to stem talk stem stem talk. Welcome to stem. Talk for introduce you to fascinating. People who passionately inhabit the scientific and technical frontiers of our society. Hi I'm your host Don Cornelius and joining me to introduce today's podcast as man behind the curtain. Dr. Ken Ford Agency's Director and the chairman of the Double Secret Sexy Committee that selects all the guests who your parents. Don't talk put on great to be here today. So our guest today is Dr. Abraham Morganthaler the author of the truth about men and sex and the founder of the nation's first comprehensive men's health center which is called Men's Health Boston so abe is a practicing physician and associate clinical professor of urology at Harvard. Medical School whose work has challenged Andrew versed decades concepts about testosterone prostate cancer and male sexuality in his practice specializes in. Hypo gonads them. Which is low testosterone sexual dysfunction male infertility prostate disorders vasectomy and microsurgical Reversal Abe regularly appears in the media on the topic of men's health and has appeared on NBC nightly news. Cbs Evening News CNN with Anderson Cooper and the connection on NPR Kaz clinical work testosterone was featured in the New Yorker and in journals including Newsweek and US News and World Report. But before we get to today's interview with Abe we have some housekeeping to take care of. I we really appreciate all of you. Who have subscribed to stem talk and we are especially appreciative of all the wonderful five star reviews as always the double secret selection committee has been continually carefully reviewing I tunes Google stitcher and other podcast. Apps for the wittiest and most lavishly praised reviews to read on stem. Talk as always. If you hear your review read on stem talk. Just contact us at stem talk at I. H Mc us to claim your officials stem. Talk T shirt. Today our winning review was posted by someone. Who goes by the MONIKER? Banana Lover One. Seven eight eight nine and the review is titled Superfan. It reads I discovered stem talk only a few weeks ago and I've been listening to the episode every chance I get. I actually look forward to drive now. It is such a wonderful and unique opportunity to be able to hear about the most recent discoveries in science right from the source as I listened to this podcast. I'm reminded why I am working so hard. Hope that one day I too can be a guest on stem talk. Well we did too and thank you. Banana Lover Seventeen. Eight eight nine and thank you to all of our other stem talk listeners. Who've helped some talk become such a great success. Okay and now onto our interview with Dr Abe Morganthaler Stem Talk Stem Talk. Hi Welcome to stem talk. I'm your host Don Cornelius and joining us today as Dr Abe. Morganthaler Abe. Welcome to the PODCAST. Nice to be with you and also joining us Ken. Ford Hello Don in Hello Abe. So Abe you grew up in Canada and like all good Canadians. You love hockey other than spending a lot of time and skates on a hockey rink. What were you like as a kid? I did like hockey and unlike now I live in Boston. And our winter Well there are a little tough. But they're not as bad as Montreal but back then when I was a kid. Winter was fantastic. He just to like skating and skiing and tobogganing and whatever else in snowball fights and snow forts. So what was I like his little kid? Well I thought I was going to be a hockey player. That was the dream. I thought I was reasonably good. I played on my high school team. I played on sort of my town. What we call the travel team. We played other towns. And when I got when I got accepted And went to Harvard undergraduate. I just figured I was GonNa play hockey and I thought I'd walk on and I'd be the best player and of course that wasn't exactly right and you find out you know. Big Fish. Little Pond and And then you go to a big pond you find out how good people really are and My goodness I was proud to make the in the end. I was proud to make the freshman team which was a big deal. Harvard was good Good hockey school. Yeah absolutely but I had to give. I gave it up after year. I realized that this was really not my ticket to stardom. And I wasn't that good and I had to really rethink and figure out who I was and what I wanted to do in life so after high school actually just stepping back for just a second. You took a gap year and travelled around Europe. And you even went to work on a kibbutz and in Israel. It sounds as if you had an interesting time. So can you tell us about that year? Sure so you know. I had two friends and We hid degreed in High school that when we graduated we would all take a year off. And you know is this is the beginning of the seventies and that we would all travel together and of course by the time we graduated. They went on to college and I kind of stuck with it and I really wasn't ready to go on to university and I didn't know really what was ahead of me and and so I took a year and I traveled around Europe and My parents who originally came from Poland and were Holocaust survivors and finally came to Montreal. Where I was born they knew people from all over Europe and they gave me this whole long list of names and I sort of nodded at them. I took the list but I know intention of seeing anybody but you know I was in Europe for bed. Six seven eight months and in the end. I saw every single person on their list tonight. Orienteer- up and I got some nice home cooked meals and occasionally slept in a nice bed so that was good and then When my money ran I really? Didn't you know it's funny to think? Now you know I've got two daughters in their twenties and You know this was. There was no cell phones there was no Internet. I don't even remember how I stayed in touch with my family but it wasn't very often and when my money ran out it was kind of appointed prior to didn't want to go back home yet and so. I figured where can I go without money? That will take me where I can work and I went to Israel and I said I'm sure somebody'll I can go work on kibbutz but I really had no plan. I didn't know how would happen and I arrived. And there's the baggage carousel and I had this Big Rucksack with the Canadian flag on it and I just took it off of the carousel and somebody came up to me and said Hey WanNa work on a kibbutz I said sure and it was a fascinating experience. They actually put me up in a different kind of Farm environment was called Moshav. It was in the Negev desert between Beersheva any latte and the moshav differs from kibbutz. In that it's really more of a each family works itself but there's a community some community services and community equipment. They used together and I was there for a couple of months picking Tomatoes and eggplants and Growing or raising gotTa Turkeys and that was You know an incredible experience for me just working on the farm using my body in the middle of the day everybody takes Esta and The person the farmer I worked with head little. I don't know you call Noah scooter like a VESPA kind of thing. And this was a in the middle of the desert and they had a paved roads that went out to where they thought. They would expand for more fields. They didn't have desert but they had irrigation water so that's how they could grow the crops but the places that weren't yet being built were just desert and I would take that thing out in the middle of the day and wearing these tiny little shorts and no shirt and just go zooming out on these paved roads with nobody around and it was pretty incredible. Fantastic I understand that When you were Born your mother had two special wishes for your future. What were they so the the story is? I don't remember it from being a newborn but The story is that when I was born in my mother discovered. I was a boy her to wishes for me. Were one that I learned how to play the violin and the other was that I go to Harvard so I never learned how to play the violin. I guess the second one was my way of making it. The the that works so you were sophomore in college and you weren't sure what to do next but then one day you ran into professor over on Harvard Square. Who asked you how are you doing? So can you tell us what you said? And then how that chance encounter led you to start studying the sex hormones of lizards. Yeah to mazing how life works really Lena thinking back like I told you my freshman year was kind of like being a freshman and my identity was as a as an athlete is a hockey player when that came to an end. You know I really wasn't sure what to do and didn't have any you know. I took some biology science classes. I like that but I really didn't have a path forward for myself. I didn't have an identity and I ran into a professor of biology class that I take in the previous semester the year before and I'd done well in the class. And you know he just chatted with me and said how you doing and I was honest with them. I said you know I was really thinking about leaving school or taking time off and I told them that and I wasn't that happy and he said why don't you come work in my lap Maybe like it and so I- dropped by and I worked a little bit on this project and a little bit on that and eventually it really grabbed me and and the work was being done. His name was David Cruise in a after Harvard. He went down to the University of Texas in Austin. He did really amazing work. Brilliant man and He had a reptile lap and P and had lizards and snakes and The first project I did was really boring but in the end very important which was that he had done a project where they had taken a radioactive testosterone and injected it into the lizards and then when the animals were sacrificed. The take the brain and you could slice it up very thin and put it on a slide with an emulsion of photographic paper or photographic emotionally. What would happen? Is that the radio-activity these tritiated Molecules would basically develop little spots on the photographic paper. And so you could see the cells and you could see where there were as a high concentration of these basically black dots and those black dots represented the presence of the radioactivity which had been injected for testosterone. And so that. First Project was actually mapping out on pieces of sketch paper the thing projected onto the paper and you sort of draw the outline of it and then put in where the areas were that were lit up by the radio activity and that became a map of the Lizard. Brain that showed where to stop Stran- was taken up and it was taken up in a few areas and one that became the focus for my research over the next three years was the sexual center of the reptile brain. Or at least that Lizard Brain and that was the media pre-empted area which overlaps with the anterior hypothalamus. In you know people say why do you work with with lizards like why reptiles everybody's used to research in mice and rats an from an evolutionary point of view to actually a really critical? So when we think about the vertebrates animals that have backbones we start with the fish and amphibians and reptiles and then the reptiles become a branch point in evolution where one branch leads to the birds and the other branch leads to mammals. Both of which the mammals and birds we think of as the higher vertebrates or the most evolved if you will but much of the biology of that brain if we're just focusing on the brain for a second is conserved meaning you Mo- most of it actually functions in Almost an identical way in the higher vertebrates. So we still talk today about the Mammalian brain is having a resilient part of our brain. We talk with human brain is having a reptilian part and the reason we do it is because the the physiology of that area is really almost identical in humans and in lizards or reptiles in general and so whatever it was that we would find there would actually have potentially implications that would ultimately we sort of think of. I think the much of the biology we're interested in is like what does this have to do with us? Not all of a lot of it and And so that was and so once. We had the area that we knew that we wanted to get to and we had a map of the Lizard. Brain the next set of experiments that really took up most of my next several years and then really led to my work over. The next forty years was to look at what happens when we manipulate to stone in the mail lizards and this is really pretty cool. So the list we were dealing with a call to knowle's caroline and sece's the American Chameleon these lizards that you see in Florida and the Carolinas in the Bahamas there about three to four inches long. They sometimes get in your hotel room or you see them on the palm trees and we see them here all the time it agency by the way we see a running all over so if you ever come visit us you'll get a chance to see them exactly. So they're they're easy to find in what happens if you put a male in a cage with the female or they have this bright colored flap of skin under their neck. It's called Delap and the sexual behavior of the male knowle's but a lot of the lizards is to extend that do lap in their head bobs up and down very rapidly almost like a the mail saying. Yay and the female. If her ovaries are intact will do a little very elegant stately. Push back that basically says okay. Maybe I'm interested. Let's see what you got in. The mail comes closer extensive do lap and in the bobs up and down again and they repeated a few times and then finally they mate well turns out that when you castrate the mail which means to remove its testicles which is the source of its. Testosterone. You put that male in a cage with the female again and it does nothing. It doesn't care The female will sometimes to push up as if to say. Hey Buddy. I'm over here in. The mail does nothing. And then we knew that you could put testosterone these little implanted under the skin of the Lizard and recreate. It's sexual behavior. But my project was then having identified the part of the brain that we are interested in was to develop a way to deliver minute amounts of testosterone right into the sexual centers of the brain and then to see what would happen and when I was successful in doing that putting it in the right part of the brain which was a whole you know stick by itself just had had to actually deliver it but when I was able to do that successfully this mail without testicles and without detectable circulating testosterone and its bloodstream would see the female delap would come out head. Would Bob up and down. Yeah Yeah Yeah Yeah. Yeah and they would make an amazing amazing thing. That's fascinating Abe. Just really quick. I was sitting here making sure. I'm touching because I've heard this name David cruise you're talking about he worked with early on David. Cruise was actually the mentor. Advisor for my First Academic Mentor and Advisor John Godwin whose at NC State University and I did work with him looking at Arnie. visa toxin and The Blue Grass and I know David I worked with a bunch of David's students over the years On some behavioral endocrinology studies. So it's a small world. It amazing. I was just in Lisbon at a different conferencing ran into this guy. And who sort of an evolutionary biologist. And we're just chatting and HE TRAINED WITH DAVID CRUISES. Well so that's amazing. So he had a big impact in a Lotta ways and I'm not sure that you know he would know at one of the most amazing things I think. In sort of the world of teaching and academics is you never know what the ripple effect is going to be and how people are influenced by? Your work downstream. That is absolutely true. So for the past twenty five years the greatest fear related to the use of testosterone therapy in humans has been the fear that raising testosterone levels led to prostate cancer and this is largely due to a nineteen forty one paper by Charles Huggins from University of Chicago who demonstrated for for the first time that cancers can be sensitive to hormonal manipulation and he and his co author of the paper actually castrated men with metastatic prostate cancer because castration reduce oxyde phosphates which indicated improvement in the cancer and this was the first treatment for advanced prostate cancer that was shown to work so as a result castration became the standard treatment for advanced prostate cancer and Huggins won the Nobel Prize and also as a result medical students from around the world were taught that high testosterone levels cause prostate cancer. And we now know that that's not true of course but can you take us back to the early nineteen nineties when you began to question the so called scientific fact that high testosterone levels caused prostate cancer. Sure will you you say we know today? Of course that it's not true but I I would sort of challenge. That is that there's still a lot of people who really worry about. This is so in ten years of training for years of Medical School. Six years of residency. I didn't learn anything about giving testosterone all. We learned about testosterone for the most part learn. Just a couple of things. One was at least in medicine. Testosterone was necessary for male puberty. And that if a man lost his testosterone for lost his testicles to cancer or Trauma that he wouldn't be as if it happened early. He wouldn't realize he wouldn't. You know develop beard or muscular definition or things like that and that was pretty much it. And the other thing we learned. Is that when men had Bad prostate cancer is that we lower testosterone so in six years of residency in urology. Which is the specialty that deals closely with prostate cancer? You know many times. We would lower testosterone either by early in my in my training. Either by removing the testicles. Just like I told you. We did with lizards or right around that time came the introduction of these medicines called L. HR h agonists lower testosterone just by injection and so that soon became preferable to doing surgery removing a man's testicles but when I came out of my training in one thousand nine hundred eighty eight. There was no doubt in my mind as there wasn't with anybody I knew the testosterone was terrible for the prostate and terrible for prostate cancer. And we believe that we are taught and we believe that Prostate cancer was caused by testosterone that high levels of testosterone wouldn't would cause it in and create an environment where aggressive cancers would appear and it men who were lucky enough to walk around with low testosterone would never get cancer and so we learn things like men who lost their? Tesco's early in life never got cancer and Unix never got cancer and that was it and there were everywhere in every city there was often one specialist. Sometimes to who dealt with the very very rare cases of men who'd had Patou itary tumors removed and as a result they had you know vanishingly low testosterone. Where like I say. They had lost their testicles. For one reason or another and those cases were rare. There was somebody who usually endocrinologist that would treat some of these guys and it's amazing how this is all changed and so when I started in practice. One thousand nine hundred ninety eight. I was at Beth Israel. Now it's Beth. Israel deaconess medical centers part of the Harvard Teaching System Hospital System. I started specializing in Male infertility and male sexual and back. Then we didn't have much to offer these men in terms of sexual problems. There was no Viagra. There was no Seattle and these guys would come and I was just curious because of my experience with the with lizards and And I just started checking testosterone levels. There was nothing I was trained to do. I was really just curious. And the first thing that struck me was how often the testosterone levels came back low in these men who had you know diminished libido or sex drive or reaction. Proms and it was like wow like I. I never knew that and almost as a Lark I just wanted to see what would happen if men were really liked lizards and I gave some of these men testosterone. I didn't know how to do it because we had no training around that I went to one of these senior endocrinologists I said had he give testosterone and she said. Oh It's easy you give two hundred milligrams Testosterone once every four weeks. That's all in so I had my nurse. Give a few of these guys Injections every four weeks of of this testosterone. And then I saw him back after I said how you doing and the Governor Guy said Oh my God it's Great. I feel better. My sex drive is better my erections. You're better as a and they would say I'm better in ways. You never even told me could even be possible. My wife says I'm nicer to be around. I wake up in the morning with the sense of optimism. It's like wow like what is this. And my first thought was that this was a placebo effect because it was such a powerful response. These guys had and nobody told me about it. It probably wasn't real but the thing that convinced me that it was real and not a placebo. Is that almost all of these early guys? Who had a good response would say so? That's how I feel for the first couple of weeks after the injection but remember. They were getting injections. Every four weeks says Dr for the next two for a week or two before my next Gentian all my symptoms come back like what's up with that and I had no idea and I joke that is kind of like a bad version of a double blind experiment where where the patient didn't expect noted the doctor in that case and just started checking blood levels and it turned out in every one of these men. The testosterone levels were up early in that injection cycle but by day twelve to fourteen. All of them were back to their low baseline levels. And what I got. And there was no way that any of these patients could know that that wasn't easy in from it. Turns out that there was information on it but not much and not easy to find. This is especially before the Internet and before you head product information available everywhere and articles that you can today you can access this but there was no way they knew then and when I got out of that which was true was that man could tell when their testosterone levels were low and they could tell when their stock levels were higher or normal it was real and as I started doing more of this and thinking what like. This is really cool. You know it came back to the prostate cancer issue because now that I was raising testosterone. I was absolutely terrified. That might be doing something bad for these men the same time. So Abe an incredible story and it's really disappointing that for nearly fifty years. No one bothered to look at what was happening in men. When you raise your testosterone and it just reinforces that we as scientists need to always question things especially the status quo and received wisdom. That is in front of us. But that's not easy as it sounds like you. I'm going to get you probably had some pushback as you delve into some of the work that you're doing yell I couldn't agree with you more. You know it seems to me. Having dealt with this over many now. Several decades is that it seems to me that the longer a truth there some foundational concept has been around the less it becomes questioned and challenged. Indeed Science does not best proceed Through consensus know exactly right and once it's been around for a while everybody just says oh we we all know this is true like otherwise. Why would this have been around my? I learned this from my teacher. And he was the most brilliant guy ever knew like everybody just agrees with and then it becomes really hard to challenge it or question it so you know the the work that I did following. That is that I was so worried about. Tell you this story so I am now treating you know. A moderate number men and We have a residency program where the residents Go from one of the Harvard hospitals to another and they basically are like bees cross pollinating different institutions. So there ended up not being any real secrets you know and I was starting to talk about this to the residents in my faculty and you know that these guys are doing well and it was a shock. And there's something really marvelous. How really focus helping these men and it was about four years three to four years after I was Out in practice and at our national urology meeting the America you a American Urological Association meeting. I ran into my former teachers who had been at. Who's faculty at Brigham and Women's Hospital? This sort of assist Organ Sister Hospital and he said anybody here that you're giving testosterone to men. I said Oh my God yet so good. It's like we didn't know. And He puts up his hand like a like directing traffic and he says very dramatically says. Stop he says. I don't think you should do this anymore. I heard you doing it from the residence. I decided to give testosterone to a man his. Psa went up. I did a biopsy. He's got cancer so I don't think you should do it anymore. You're GonNa give these guys cancer and of course that was always the fear and I was already talking to these men. They say what's the risk and there wasn't a whole lot of written experience about this and I would talk to them and say you know what you know theoretically there's concern about prostate cancer. We're going to monitor you as closely as we can. They would say how you're going to do that. And you know the two ways. We Monitor people are. Psa and and we feel their prostate digital rectal exam. We can't and they say well you know. Could you miss it and I would say it's possible. And that's one of the risks and we have these long conversations with these guys before they go on to star in when this former teacher of mindset stop by the sky with cancer. I don't really WANNA stop. I think this is really good. I don't know about that one case that you have. Maybe it was anecdotal. And he says to me says Listen if you're going to do it and I strongly recommend you. Don't I think you should biopsy prostate? I make sure they don't have any existing cancer and that seems kind of radical and invasive prostate you know we do a lot of prostate biopsies but back then it was no fun. We frankly we didn't know how to anesthetize man. It was an unpleasant experience. You know now we do it in the office. It literally takes five to seven minutes. It's not it's not pleasant but it's not terrible and But back then it was a big deal and I to my chief of And I said to him. Listen I ran into Dr so and so and he suggested I do these biographies before I give to stone and I'm kind of thinking. Maybe that's the right thing to do. I don't WanNa you know. WanNa make sure that. We exclude as well as possible. The presence of cancer so it doesn't like grow on them spread and he said fine. Do it and so that became a requirement. Did I made on men before? Giving Him Testosterone Even if their PSA was normal and their prostate exam was norm on other ways they had no known indications. Get a biopsy. The only reason I was doing a biopsy was to make sure that they didn't have an existing cancer. As far as I could tell the prostate that might grow like wildfire if we gave them testosterone. Not every man agreed but a lot did and shockingly. We found cancer right away in these guys and remember that the belief at the time there was based on what was called the androgen hypothesis everything bad about prostate cancer seemed to be testosterone related so high testosterone lead to cancer and the converse was that low testosterone was supposed to be protective. The belief was that men with low testosterone would not get cancer and so right away. I was finding cancers in these guys who had no indication of anything and at the national. Ua meeting a few years later we presented on. I forget it was thirty or thirty. Three men who had these biopsies and we had. I think six cancers and I fellow gave the presentation and this net internationally known figure famous famous Guy. Bob Crane came to the microphone at the end and in addition to being famous he also had one of the biggest booming voices. You've ever heard. And he came to the microphone. And he said this is garbage. Everybody knows high testosterone causes prostate cancer. Low Testosterone is protective and the room is packed and He Says I. I bet you dollars to donuts. You can do another hundred biopsies and you won't find another prostate cancer. So we thanked him for his comments and continued to do it and when we had fifty patients in the cancer rate was there is still high submitted the Journal of the American Medical Association. Jama and something happened. That had never happened to me before never happened to me since I've published two hundred papers. Which is that. The editor called me called me and He said you know our editorial board was just looking at your submission. We were very interested. This is the opposite of what we've always been taught and told and you've got a high rate of prostate cancer in these men. We thought it should be low. But you know you've only got fifty guys and I'm sure these don't come by every day and you know we're a little concerned just that the numbers low but I tell you what if you if you can collect Some more numbers and maybe already have you know. We'll consider it. And so when seventy seven men. Eleven of whom had cancer one seven with a normal. Psa We resubmitted it and they accept it and that was published in Jama Nineteen ninety-six more than twenty years ago. And at the time nobody knew what to do with that information frankly including me and we followed it up some years later with a much larger series that showed exactly the same thing which was that there was a fourteen to fifteen percent risk of cancer detectable just bye-bye ups in these men with normal. Psa But low testosterone and that rate of cancer that for one out of seven or fourteen to fifteen percent when we published it in nineteen ninety six was as high as for men who had known increased risk cancer due to an elevated PSA or prostate Najah. And so. We didn't say at the time. My chief who was on the paper wouldn't let me say that we thought low testosterone was a risk factor. We basically just hemmed hedged a little bit and said that in the presence of low testosterone that may be. Psa in other tools look for prostate. Cancer are less accurate but it was the beginning. It was the first piece of evidence that the story that had been told since the nineteen forties. Was that there was something wrong with it. Because men with low testosterone did not have a reduced risk of cancer. It appeared if anything they had as greater risk and maybe even an increased risk seven and two thousand six flashing forward. Just a little bit. You pulled together all the literature that you could find and wrote a paper that was titled Testosterone and Prostate Cancer a historical myth which show that the data contradicted the Oh believe them more testosterone will lead Tamara prostate growth of all. The papers have written. I understand that this one is your favorite. Is that correct? It is it is so you know what led me to. This was so nineteen ninety-six. We're doing these biopsies clearly. Low Testosterone was not protective. That part of the story was BS and I was treating a lot of men and in two thousand and four together with my fellow. We ended up writing review article on the risks of Testosterone for the New England Journal of Medicine. And just to give you some historical context. The modern era of testosterone could be argued started around two thousand and one with introduction of the first testosterone jail that was approved by the FDA called Andrew Joe. And that was the first time really. The doctors around the country were getting detailed on a testosterone. Product was branded. They were not TV commercials. But they were you know. Ads In magazines and Medical medical journals and stuff and the women's Health Initiative study had come out about women and hormones in two thousand and two that had raised concerns about risks. And so when we wrote this paper testosterone was kind of this new Had Been Around since the thirties but it was kind of a reborn new Item in medicine and there were concerns about hormones and women in one of the things we wrote about in is that we couldn't find it until we until we did that review article. I still believe that high testosterone must be a prom prostate cancer. Like I still believed old. What you're taught doesn't disappear didn't have complete vision right away. It was always like pulling back one extra layer of the onion. I knew that low testosterone wasn't protective but high testosterone must be bad. Otherwise why would we lower testosterone in men with advanced prostate cancer and after we went through about two hundred articles reviewing him we could not find a single article they provide support for the idea that high testosterone was bad for prostate cancer or the testosterone? Therapy was bad. We'd simply couldn't find it. We didn't say it wasn't true but there was a fair amount of contradictory evidence. And so you know I'm on the lecture circuit kind of in Urology talking about testosterone. Now and about you know the the date and the workweek done that showed that may be testosterone wasn't so bad for prostate cancer in this older prostate. Cancer Oncology Guy says to me you know what a your stuff's very interesting but you have to be careful because maybe metastatic disease is different and hugging. Huggins said so so I decided to actually find out what hug and said and in that time when you wanted to get to articles you had to go to a strange building. The House Law of articles. They had a name. You may be heard of it. It's called the library We don't we don't deal with those much anymore. Now everything's on. You can get almost anything online but back then. I walked myself to the Harvard. Medical rb can't way and in the basement. They have these archives of all these articles. They're all bound. The you know volumes of nature going back to the eighteen hundreds you can just pull off the shelf and there was the original article from nineteen forty one cancer research by Huggins and his CO author. Hodges and that was the article that we're he established that he took these guys with prostate cancer metastatic to bone and he removed their testicles or gave them estrogen to lower their testosterone. And he showed that this blood marker called acid fossey's which is sort of the precursor to PSA if you will for prostate. He showed the all in all cases when he castrated these men. The ACID FOS potato would go down and also wrote that. In every case where he gave injections of testosterone the acid foster as would go up and I remember the feeling of reading that and getting so nervous that my brain didn't work right because my palms were sweaty. My heart was racing because by now I've treated a lot of men I've allotted men under my care with testosterone. And I kind of told myself that maybe wasn't true that testosterone was bad but I was worried about him. And here's the patron saint of Urology Charles Huggins saying YEP IT CAUSES. Prostate cancer and the final sentence of that paper was injections of testosterone activate. Prostate cancer. I thought. Oh my God you know I had small children. I had this image of the police coming to my office and taking me away for doing this. Terrible terrible work in in in a moment of very proud of it of self discipline while my heart's racing I kind of forced myself to reread the paper. Answer a few questions that I wrote down for myself and one of them was how many men did he treat with testosterone and the papers are done differently back then they're more a lot more storytelling and sort of anecdotal cases in case histories and as I went through it and read it again and again it turned out that he only gave injections to three men of those three men who got testosterone only gave results for two men of those two men one had already been castrated which today we understand represents a special case where the prostate is you know essentially starving for any kind of testosterone or androgen and in the end the whole ball of wax about how testosterone is dangerous for for prostate. Cancer comes down to this one original paper which itself was based on a single patient. Who is still hormonally intact? Who received stone for only fourteen days? And that Kerr for the acid phosphates in that man goes up and down. So erratically did it is unintelligible. And that was the story of testosterone prostate cancer in seventy years later were stuck with a premature conclusion based on basically one anecdotal story that I think could not only could be interpreted differently should be interpreted different amazing thing and when I did that I then went through every like he was I opening like. Oh my God this is what it's based on this huggins work around testosterone causing prostate cancer. And what I did in that. Two thousand six article wrote where I wrote about. The historical miss was split wrote about that. But also I pulled up all the older literature and all the stories that created what I call the lore of testosterone in prostate cancer. So for example I was taught in training that men who were Unix never got prostate cancer low testosterone prevents prostate cancer. And so I went to find the source of the and the source from you know asking around and residency was. Oh Yeah. They did the study where they went. And they found these surviving UNIX in China and they look for prostate cancer. None of them had well. I found that paper to from the nineteen sixties. And what they had was. I don't remember how many guys they had something. Like twelve or fifteen of these older men and back in China. They used to have something. On the Order of ten to twenty thousand of these UNIX living at a time and they just had from whatever Pruitt ever period it was and You know they took care of the noblemen and the the royal families and and nobody checked them out for prostate cancer. It turned out they did have prostate exams. And some of them they felt the prostate in other words. The prostates were small but they didn't have. Psa's they didn't undergo any kind of imaging. Nobody had a biopsy that paper had nothing to do with finding prostate cancer. And yet the information kind of fit this narrative that we just worked for everybody and in India and just one more piece of a story that turned out to be. I don't want to say not true. But it didn't say what it was purported to say it it just looked circumstantially like it added to the story and the story was wrong. You followed up this paper with one that appeared in the European Association of Urology. It was titled the Saturation Model in the limits of androgen dependent growth. Can you explain how this situation model fundamentally changed the way you think about the relationship between testosterone and the prostate? Sure so you know gone out of everything I've I've told you and and Thank you kindly for your your your patients in hearing these stories it's funny. How Science Advances Right? It's often not from these randomized control trials. They have their place. But sometimes it's just somebody just trying to follow through where things started from so what was clear to me. Was that the data and we had a lot of it. The data that higher to stops Joan is related to prostate cancer. Appear to not be true. Giving two men who have big prostates have higher testosterone than men with smaller prostates. There was all this stuff. And they were animal experiments the same way that it it appeared that for a large range of testosterone concentration scale. If you will that prostate didn't really seem to care at all and yet there's another observation which has really been propelling the whole thing. Which is that. We know that if we can straight men or reduce their testosterone dramatically. Psa's will come down and the PSA's can go from very high numbers down to undetectable. That part's real. So there's a paradox. There lowering testosterone shrinks the prostate and lower. Psa there's no doubt every doctor who seen a man with prostate cancer knows that has seen it over and over again. If you're a urologist and yet raising testosterone didn't seem to do anything and so would occur to me just from some little Pieces of evidence. Some of it from the nineteen fifties and sixties was. It appeared that if you gave tiptoes down to a man who hadn't yet had his testosterone lowered. The cancer didn't seem to change in what had said to me was that there was a maximum amount of stimulation that could That androgen testosterone like substances could provide to the prostate or prostate cancer. And once you reach that maximum. It didn't seem to matter if you added in more and if you withdrew it and you deprived it absolutely you know something happens. You're depriving it of it and so the term saturation comes really from its biological term. But there's a practical version of two if you just had a little scale and you put a sponge on it. That's sponge has a certain weight. If you add some water the sponge will hold onto. The weight will go up yet. A little bit more water way to go up at a little bit. More weight will go up at some point. The sponge can't hold any more water. At which point we say it is saturated and you can pour water onto it but you've reached the maximum weight it's done and it turned out you know. Huggins worked in a time. When we didn't understand how many hormones worked most of them work primarily through binding to receptors so for tips dostram binds to what's called the androgen receptor and it turns out there's a limited number of copies of the androgen receptor per prostate cell. And once you reach the maximum for that you can add in all the testosterone. You want that mechanism can't do anything anymore. It's maxed out. And that's what the saturation model is. And so we propose that in. I did it early in two thousand six with my myth paper but then again together with a brilliant biochemists a colleague Abdul Trish we really provided in two thousand nine article data from animal models from in vitro systems and also from human studies all the data that really supported it and to this day. Ten years later I don't know of a single example in in biology or medicine between regarding staw strong and prostate whatever prostate PSA prostate volume. It doesn't fit into that. It's it's clear that's what happens. There's a maximum amount the you can stimulate it and when you deprive it by all means things get smaller and you don't get the angiogenesis stimulation and that's the saturation. On the importance of the saturation model is is that. It provides a new theoretical framework for understanding the relationship between testosterone and the prostate malignant or benign and then became the basis for which men now or doctors now can provide testosterone safely to men who have previously been treated with prostate cancer. Because if these guys are walking around with a low wish but still some level of testosterone the amount of testosterone stimulation of those cancer cells if there are any is going to be extremely limited and that's allowed an and now many urologists around the country around the world will now offer testosterone to some men with prostate cancer. Especially those who appear to be cured. A The work that you're doing today that really excites you has to do with men who are coming to see you about metastatic prostate cancer and standard treatment for these guys who spent a lower their testosterone as much as possible which actually becomes a form of chemical castration. And I hear that it was a phone call from a ninety four year old gentleman. That guy you interested into looking into men with metastatic prostate cancer. Is that right amazing? An amazing story so this is a several years ago. Now this guy calls me from out of state. He's a scientist. He's got like a hundred patents and despite his age he seemed very sharp on the phone and he got on the phone with his daughter who's a nurse practitioner and they had read a lot of my research and he soon come see you. I want you to put me onto Austrian and he had metastatic prostate cancer. I didn't have a lot of the details yet and he said if I come see you will you treat me no guarantee but I'm happy to talk. I'm happy to talk to you about it and we'll see but you know I can't do much over the phone so he was supposed to seem. You made an appointment seeming like a week or two later and then that got canceled and he came several weeks after that and it turned out that the reason it got. Can't the appointment got cancelled was because his cancer had grown to obstruct the yours carry the urine from the kidney down to the bladder and he needed tubes to divert the urine. There called the frosty tubes. And so when he came to see me and so he was hospitalized for that and he got out. He still made his trip to Boston to see me and when I came to see him he was ninety four. He was pretty looked pretty good. He walked to the cane but he got on and off the exam. Table by himself and brain sharp is daughter. The nearest practitioner was with them and he had this tweety kind of Jack and he had one of the urine bags from his right side in the right pocket of his jacket and he had the banker. The left side in the pocket under left jacket left side of his jacket and We sat down in the in the in my consultation room. I said so. Tell me what. What are you interested into Austrian for and he said well. I used to exercise every day and it made me feel good and now I'm too tired. I don't do it at all and I used to send emails and correspond with my colleagues all around the world and I'm don't do anymore. I'm just too tired. This guy had cancer that had spread to his bones. He had the highest. Psa of anyone. I've ever met at that time. Which was over five hundred? He had blocked kidneys on both sides from obstruction from his cancer. He was in bad shape. He'd lost lottery and He was really what we call. Sort of pre terminal. You know like he wasn't about to die today or tomorrow but you know it wasn't going to be long for him and I said to me I'm not so sure about treating. You have never treated anybody like you. I've treated men with low grade cancers that were just watching. We call that active surveillance. I've treated men. After they've had surgery for their prostate cancer and they seem OK. I've treated men after radiation for their cancer. But they seem okay you have prostate cancer that spread throughout your body and my fear of giving you testosterone is that your cancer will grow rapidly and you could die tomorrow or next week and could cause you pain. One of the things we worry about in urology with advanced prostate cancers it goes to the bones and the spine vertebrae could collapse from a fracture from weak bones and cause paralysis. And I told him all these things and He said I've never lived in fear doctor and I don't want to. I don't intend to now says I know that I'm going to die of prostate cancer. And even if it's not cancer ninety four years old but while I'm here on this planet I'd like to live as well as as well as I can so with Some hesitation intrepid days and and writing a very long when we call informed consent that he signed where he knew. All these awful awful things could happen to him off. He went with the prescription and And his daughter started giving him injections of testosterone at home and within four to six weeks we spoke in. He was feeling better and he started exercising regularly. His appetite improved he gained weight and he started corresponding with his colleagues and he started working on a new patent wrong and he survived almost eleven months and when he died one can say was from prostate cancer which was ultimately but really would cost him to die with his one of those tubes and the kidney had fallen out at home and people can get infections when that happens and he got septic and his daughter didn't want him admitted to the hospital so we got some antibiotics. He wasn't hospitalized and he died about two weeks after that But you know what? I don't know that we shortened. His life expectancy by even one day and during that nearly year he was on testosterone. He had great quality of life and he wrote to me and sent me pictures about his story and his daughter did as well and they not only gave me permission to use his name and his photograph and I've used his photograph in a couple of lectures But they he encouraged me to do it. He knew he was doing something that was sort of new and and the the fact he was doing so well with so different from everything that we had been taught and after he had that experience he gave me the courage to start doing this in a limited number of men with a similar situation and so we continue to to do it and so far. I tell them in this. We don't have the kinds of data that we like and medicine where we have these large control trials and where we can say what the safety risks are and how great the are we. Don't have that but anecdotally. Here's what I can tell you. That's amazing is that not one of the men that we've treated has had any of these terrible rapid of prostate cancer that causes all kinds of morbidity and. Proms just haven't seen it. No It's good. Ask like a great story to and so you use the term. Lo T to describe a condition that is otherwise known as Hypo at them or test around Deficiency Syndrome although people think of testosterone as the primary male sex hormone. It actually is much more significant than that. So can you give our listeners? An overview of the different biological functions of testosterone sure so testosterone is everywhere and works on an incredible array of of Tissues so you know we think about it often around sexuality and male desire and in the brain but also affect mood. It affects the function of the of the Penis in terms of erections. It affects muscle. Which is why the athletes in the bodybuilders. All want something testosterone. Like to help them when they were to cheat with it affects fat to the testosterone keeps our our fat mass down. It affect red blood cell production in the bone marrow It affects nerves in effect liver function and it effects skin and scalp and body hair and scalp hair and skin oiliness and something else. Which amazing we we have this A new a new medical society as of a few years ago. Three years ago called the androgen society where we bring in. All the different specialties into chronology urology primary care and We have a meeting coming up in April in Orlando and one of our speakers in ophthalmologist whose published work. That shows that men with low testosterone actually have decreased production of tears tears so one of the treatments they have for people with dry is is they actually have a testosterone like boy I O ain't that amazing. Yeah Yeah and affects bone so you know we. Everybody knows but women are at risk for osteoporosis. After menopause estrogen levels go down it turns out that men are at risk cross. You prosise to if they're stronach's down and on that note there huge numbers of men who have symptoms of low T. and we know that testosterone levels decline with age and since this decline is a natural part of aging. Many physicians argue. That we really shouldn't be treating people with low T. So what's your response when you hear people say that yeah So that one makes me crazy? So here's the thing so the argument has been because it's a quote unquote natural or normal for testosterone levels to decline as we get older. The argument is it's normal therefore we shouldn't treat it. It's just natural part of aging people should just get used to it. And that's who we are and here's what I would say. Is that almost everything we treat in? Medicine is age related. So what happens as we get older is that we get bad eyesight? We get bad teeth. We get bad joints. We get bad blood vessels. We could bat hearts. We get bad blood pressure control. We get bad sugar control control and we get cancer. Every one of those things is age related which means they become more common as we get older. That's what aging is sucks and we treat. We treat every one of those things either to improve health quality of life derision of life. That's what we do and the idea that we should avoid treating men with float who are symptomatic from low testosterone often miserable. Just because it's more common as we get older makes no sense no sense in my world and we agree with you on that one. Here stem talk is an educational service of the Florida Institute. For Human and machine cognition a not for profit research lab pioneering groundbreaking technologies aimed at leveraging and extending human cognition perception locomotion and resilience another interesting development. There's been a controversy around the role of testosterone and cardiovascular health and one of the most common assertions about testosterone replacement therapy is that it can increase a patient's risk of cardiovascular disease. There's actually paper that came out in two thousand thirteen in Jama. The reported increase cardiovascular risk and men given testosterone replacement and the study compared the incidence of heart disease and eight thousand seven hundred nine low testosterone men in the VA health system who underwent coronary angiography. And it made headlines around the world and you looked into the study and found. The study statistical analysis was seriously flawed and today twenty nine medical societies have called for the retraction of the original. Jama article arguing that the data are not credible. Can you tell us about this episode and the study itself? Yeah this is an amazing story but how science works and how it fails forbid twenty years before the publication of that article. I author is is Vegan V. I. G. E. N. published in Jama Two thousand thirteen for twenty years. There had been a growing body of evidence that having a normal testosterone or maybe even testosterone therapy was beneficial for the heart and for cardiovascular disease and it was based a fair number of studies showed some of which were observational. Where if you just looked at populations did men with the Lowest Twenty to twenty? Five percent of testosterone levels? Were at higher. Risk of having heart disease was associated with severity of Heart Disease. Low Testosterone was associated with increased mortality. And then by the time that paper came out there were two papers not randomized control trials but observational studies where they looked at men with low testosterone who either receive testosterone or. Didn't you know not everybody? Who's on treatment? And those studies have shown that the mortality rate for men who received historic drone was half as high as the men who are untreated half his high. And then this paper came out and it's an observational study and in your listeners will understand that you know when you have a randomized. We call prospective forward looking. Study tryin control everything that you can and you collect data as you go and you've tried to equalize if you will the confounding factors that you may or may not know about on both sides and with an observational study. You're looking to groups who for example you look at one group that got to stop the one that didn't but they all have low testosterone and frankly we don't know why One group did in or one individual may have gotten in one didn't and there may be something that we can't even put our finger on that accounted for that difference in that thing we can't identify might be responsible for differences in outcome right like we don't know and so those kinds of studies are valuable. But you can't hang your hat on too much unless every studies showing the same thing they repeated so this study came out and it was contradictory to this twenty year history. And it was amazing thing. So this this group wrote as you described over eight thousand men in the. Va System All of whom had coronary angiography. That was the group that was identified. Some of them went on to get tossed around prescriptions in some did and what they reported was that there was a small but significant increase in the number of heart attacks strokes and deaths in the men who got to stockton compared to the men who didn't and so the conclusion was. There was an increased risk cardiovascular risk. So when this paper came out I looked at the data as did several my colleagues and the key headline in there that was carried in every news article. And for whatever reason some some of these stories become big news right and they're carried everywhere not just for the the nerds amongst us the health conscious guys but like to the public right. They just become big big headlines. This was one of them here. Was this common. You know. Very increasingly frequently used treatment testosterone. Some people are anti-test Austrian because of the ant. They think we should age naturally like we spoke about some people think it'll cause cancer some people. I'm certain are against testosterone because it sort of promotes sexual function in their anti sacks. But for whatever reason here we are and Oh my God with this common treatment and now we find out that it's killing people that's sort of the essence of the argument and the term that they used in their in their Abstract in the paper was the absolute rate of events and that they said was higher in the men who got testosterone so absolute rate of events is one of the simplest statistics in medicine and science. And it's literally. How many events were there per group? Or how many events were there divided by the number of people in a group so if you had ten events one hundred people? Your absolute rate of events is ten. It doesn't get adjusted for anything like by age. Whatever the numbers are the numbers are and it reflects reality and so it's very comforting to see a study where they give an absolute rate of events. 'cause you understand what actually truly truly happened. You know when when the statisticians get in there. He started Justin for this and adjusting for that. You hope they're doing a good job but the truth is we. We have to sort of just depend on their good practices honor but absolute rate events Israel. When you look at it you can calculate this yourself. And so they actually had the number of men who died the number men who had a heart attack number men who had a stroke and they give you the number of people in each group and you can just do that that calculation yourself in two seconds. You don't even need a calculator for so easy. And when I did that based on their numbers I got something that was completely opposite from what they reported so what they reported was that if I remember precisely is that they reported that at three years. The number of events in the Austrian group was twenty five point seven percent and in the non testosterone group was nineteen point something and when? I looked at the numbers. The actual rate of events in the testosterone group was ten point one percent in the other group that didn't get testosterone. It was twenty one point two percent in other words. The absolute rate of events for the guy who got testosterone was half as high as the men who didn't get it so what they reported was completely wrong. It didn't just have the numbers wrong. They had it reversed so a couple of my colleagues are going. The numbers don't make sense numbers on somebody should talk to jam. We should write a paper. And so I said I'll call and so I actually put in a call and managed to get to the editor of Jama within. I think three days after it was published and we had a very nice conversation. Howard blocked and My congratulated him on his success with this paper and he was very proud of you. Thank me and I said you know. I'm calling on behalf of a number of colleagues in the testosterone field and we'd love to write you know your results are opposite twenty years of data and we'd love to write a perspective on this and he said Well thank you very much but really don't have room and and but we encourage you to write a letter and I sort of got the feeling he was getting ready to push me off the phone and I can. I just show you something in your Abstract he said sure. I've got it open here on my laptop and I went to the numbers with them and I said you numbers are wrong. I said you're authors made a mistake you reviewers missed it. You had somebody right in editorial on this who missed it and I say jam has responsibility. Here you've misreported the data in this paper that's been where the results have been transmitted around the world and there's dead silence on the phone and after a moment he says and clearly. It was obvious to me. He was like looking at those numbers because they're not complicated and he realized there was an area. So I can't disagree with anything you said and we're GONNA get in touch with the authors and I'll let you know what happens and within a few days. I got an email from him where he said. The article has been revised very briefly. And when I went online there was now a revised version of the article and by the way without any indication it was no longer the original article that didn't happen for another two months which is unbelievable to me and they use the same numbers that twenty five point seven percent in the nineteen point whatever it was but now instead of saying absolute rate of events they called it something like estimated probability of events. Using Kaplan Meier curves something very statistical sounding. Because that's what it was. You know we can argue whether or not. That's believable or not. It seems to me. It's not like on authors. There were so many authors on there who are in public health for statisticians and everybody has to sign off on these papers. It's not believable to me that everybody would have missed that basic error if it was really just the wrong term and it wasn't just in the abstract it was in the text as well results and so that was bad enough but we ended up actually writing a letter and we picked up on another area. That was bothersome and in response to a query that we had the authors responded that they had looked at One of the groups and they had made errors in over a thousand individuals Turned out the Nine percent of their all male population turned out to be female. Yeah Good luck with that so just imagine for a second breast cancer studying women. Were you find out that almost ten percent of the population is contaminated by men? Like it's just it's just basically bad and so We wrote a letter and we believe that the data were not credible and it turned out the twenty nine medical societies signed on and Jama declined to retract the article. We thought it was just bad information and so that paper. Still persists in the impact of it is incredible to me because listen I. I don't attribute any bad intentions to the authors. I think they just made mistakes. I think he was just a sloppy piece of work. It happens. I think it was. The first author was a fellow and I think there was inadequate oversight and people get excited when they have a chance of getting into big journal. You can sort of make your career if you will and I think people just sort of slipped past but the impact of that bad article what I would call not just bad information but essentially non information. We don't know what's true or not true in that paper anymore. The impact of it is that in the field. There's now this cardiovascular controversy and there's many doctors and patients who read about those cardiovascular risks being increased and it's very hard to turn that put that genie back in the bottle and so at every meeting that I go to. We have some debate on the cardiovascular risks and we update it and whatever and I can tell you that about a year ago. We published a review paper on cardiovascular risks since that paper and I think they were twenty two controlled. Trials and not one showed increase increased cardiovascular risks. Not One. It's an amazing story. Both in terms of the failure of pure review which we see more and more now and Often the reviewers hardly go through the data even coupled with Remarkably sloppy work on the part of the original authors. More recently in twenty seventeen a trial by bud off a tall was published in Jama and suggested that testosterone replacement therapy and men with low testosterone lead to more rapid progression of plaques compared to Placebo. Can you discuss this paper sure? So that paper was done because of the other paper no doubt right so once you have something that's his. Oh we've got to watch out for for heart disease. All of a sudden there was a slew of papers looking at heart disease and testosterone. As I just mentioned none of them were able to show that they were increase bad outcomes not and several of them showed benefits of testosterone versus the no treatment so the the article by Buddha off now is part of what was called the testosterone trials. This was the largest prospective trial of testosterone ever multiple sites around the country supported by the National Institutes of Health National Institute of Aging Seven Hundred. Ninety men sixty five years of age or older average age. I think was seventy three underwent one year of treatment with Testosterone Gel. Or when you're of treatment with a Placebo Gel and then There was a second year where nobody got treated. But they monitored the men for safety issues. Did anything happen to them? Heart attacks strokes etc overall the number of what's called the major adverse cardiovascular events. We call it. Mace which consist of heart attack stroke and death in year. One for that study. There were seven events in the testosterone arm and seven events the same number in the placebo arm in the second year again. Nobody's being treated but they're now being watched. After that first year of treatment they were nine events in the placebo arm and only two in the testosterone are. If you add up those two years they were sixteen. Events in the placebo arm and nine and the testosterone are clearly no indication from those data. Seven hundred ninety men large study multi-institutional carefully monitored the testosterone increase cardiovascular risk. Right in the magic. If the if the numbers were reversed and there was sixteen events in the testosterone. I'm everybody will say Oh. It may not reach the TISCO significance or they say well. The number of the number of events is still relatively low. But they would say oh. We think there's a strong signal here. There's nobody saying from these data. The testosterone is protective. Although maybe it is one of the parts of that study was they selected a subgroup. And I don't recall how they picked the man who did this. But they picked a subgroup who underwent evaluation of their coronaries with C. T. Skin Coronary C. T. Now What's interesting? Is that as coronary? Ct is used to evaluate heart disease. Now in men and has been for. I don't know ten fifteen years or so and normally the talk but coronary calcium scores and it turns out that the more calcium the higher calcium score the greater the risk of heart attacks like that's clearly established and the difference in the group of men who did get testosterone and into the end of the year. The calcium scores were the same. They're identical they were basically unchanged both groups there was another factor that they looked at though which was called. Non Calcified Plaque. Non Calcified Plaque. So the part that is not calcified and If you speak to cardiologists they don't know what to do with Conan calcified plaque like. Maybe it's important. Maybe it's not has not been shown to be associated with bad outcomes. What the outcome of that study was was they said. Well there's more of this added a non calcified plaque in the men who got stoned than the men who didn't and so people say well we don't know exactly what it is but that can't be good right. Plaque is in good in general we don't know and what's interesting. I think the group was over one hundred hundred thirty five guys or something. There wasn't one single cardiac event in that group not one. And here's the thing is that this was a it's funny. It's it's often called a randomized control trial. It actually wasn't too is something else which is called an assigned people were assigned to groups. It's sort of one step up in a way from a randomized trial because they're trying to make sure that by chance alone that the groups don't get overloaded on one side versus another. So you could you could. In randomized trial ended up with two very different groups who has a lot more high blood pressure than the other for example just by chance and so they made sure on a number of important items. The two groups were equal. We can call it. Randomized has the same effect as randomize. But here's the thing has just because you do that. For a couple of items doesn't mean that everything ends up being equal and so when you look at the baseline level of the non calcified plaque in the two groups one of which got testosterone. One got placebo. They were completely different. So the Placebo Group had almost fifty percent more of this non calcified plaque at baseline at the end of the study. That something like only forty percent more plaque but they had more plaque whatever that plaque is that's non calcified whether it's a risk or not you'd rather not be in that placebo group and because they're not bounced at the beginning to change the delta. That happens over year is I. Think impossible to Interpret because maybe there's just a certain amount of catch up that has to happen or let's call it regression to the mean. Maybe there's certain amount of variability in how it's measured don't know but that's the basis for it and so the booed off is articles often cited as. Oh you see. There's really something happening here. And it's important to recognize that knowing that it had the limitations. I just mentioned to you but in the end the much larger group of seven hundred and ninety men overall showed no difference or no no worrisome trend in terms of heart disease heart attacks stroke her death guys who got testosterone versus guys. Who didn't that's interesting. So you mentioned that There's evidence and more and more over time that testosterone replacement therapy may actually be to some extent protective with respect to cardiovascular disease. Is there strong evidence for a mechanism of action? There is the elevated esther. Dial you might see what what. What do you think accounts for this if it is in fact protective well? I don't think it's terribly complicated. So one of the things that is shown in in essentially every stroke trial is that raising. Testosterone lowers fat mass. We know that fat mass is obesity. If you will fat mass associated with cardiovascular risk it may be as simple as that it decreases fat mass and increases lean mass which is basically muscle and we know that each of those is an independent predictive factor for development of heart disease. It may just be as simple as that as you pointed out earlier. Testosterone not only affects men sexual desire and performance but also their mood their thinking muscle and fat as you just mentioned in short their overall wellbeing there are a number of studies showing that as many as something like forty percent of men over the age of forty five have low levels of testosterone and the average male testosterone levels have declined significantly over the past fifty to one hundred years. I was looking at the Massachusetts male aging study which gathered data on fifteen hundred randomly selected men. In three time periods. The first was in late eighties. The second in the late nineties and then the third two thousand and two thousand four and in this study they Measured their total testosterone levels as well as the bioavailable or free testosterone levels and what they found was that both total and bio available tee levels had decreased more than twenty percent over this remarkably brief period lest one think that this is only a Boston phenomena and I would understand why people might think that having been there a large finish study reported similar findings a man born in nineteen seventy had twenty percent less testosterone than his father at the same age and then finally a two thousand seventeen. Meta analysis not on testosterone but interestingly reflecting the state of the modern mail suggested that the sperm count of the average western male had been halved in the last thirty eight years. I wonder if you had any comments on this current state of affairs and specifically. What do you think is driving what appears to be a rapid change in the level of this critical hormone and the broader societal consequences? Poor men demonize hormone. We're up against it no seriously so you know you know. They've been some really good movies about loss of fertility. What happens in the future and like those few people that can still reproduce your so valuable? There's you know obviously in with there's one thing and women is the handmaid's tale stuff and and then there was this great one about about men in anyway You know listen I think that some of that stuff is probably real One has to be careful for methodological reasons about comparing older and and recent stuff but I suspect it's true. I mean some of these results are we're getting consistent reports and so that makes you think that maybe there's really something there. There's one there's again and not to be over over simplified but I think that obesity is is one of the likely contributors to this so obesity leads to lower testosterone levels testosterone is critical for sperm production spermatogenesis. And I think it it. It may be enough to account for both the decline in in measured testosterone and also the sperm stuff. You know the other argument. That's out there. That people are worried about is environmental estrogens. That certainly may be contributing as well. It's hard to now it's interesting you also see drastic reductions in grip strength among the millennial men compared to their father's. Isn't that interesting it is. Most people are aware of the term menopause. But not a lot of people are familiar with the term Andrew paws which is the male version of menopause. And I understand that you hated this term when you first heard it so why is that? I hated it when I first heard it. But I'm a much more sympathetic to it now. The reason I didn't like it so I in the term. We don't use it as much anymore. But you know it's obviously a term that came up to draw in obvious parallel to menopause right. So you know there's something hormonal that's happening to men in when I first heard it. It sort of became popular in the early two. Thousands was that I thought it was too simple and it was too easy to poke darts at like. I think this business of men having low testosterone about society just individuals that I see where people dismiss this important a medical condition. They don't think it's important. They think it's all made up. They think this is a pharmaceutically-driven false epidemic. Every day in my office I see people who have been evaluated and seen by other doctors. And they're told this is on their head to Saas. Joan levels are fine and just get on with life. This is what it is to get older. And we treat many of those men if their levels of testosterone are low and we only treat them if they levels are low and for some of these people. It is life changing. You know whether I'd one man say to me you know I did okay before but now that I'm treated with Testosterone I. I realized that before I was seeing life in black and white and now I feel like I see it in color like it's it's a different character of what life is like for people in the Andropov thing I thought was too easy to dismiss. Because obviously menopause happens to basically a hundred percent of women at a certain age. It is in the low testosterone doesn't apply to every man it may be a large large number but it's not every man. Menopause happens you know usually sort of Mid Forties to maybe early fifties sometimes younger Limited time in life right like maybe a ten year period where pretty much every woman goes through it and you know testosterone for men. We see guys in their twenty. Sometimes thirties forties fifties. Sometimes they show up in their eighties like there were too many differences there. The reason I ended up liking it better is that it actually provides a brain construct. A way to conceptualize what's happening to men. That is not that different for women so nobody disputes that menopause exist. You can't dispute it it's there. It's hormonally based in the part that is similar is that there are hormonal. Changes that happen. relating to age and men many men that have widespread effects on their biology and their sexuality and the by giving back some of those hormones we can absolutely reverse or resolve many of those symptoms. Those parts are the same in men and women and for that reason I no longer think. Andrew Pause is such a terrible term but we tend to not use it that much anymore so when a man starts experienced symptoms such as low desire and chronic fatigue. He may go to his physician and ask for his blood to BE TESTED FOR LOW TESTOSTERONE LEVELS. But these lab tests can be deceiving. Can you elaborate a little bit on this? Yeah I'll tell you one quick story. He probably tired of my story that I'm going to take this great story. Got Great Guy. The Guy Comes to see me. I think he's forty two. He's married he has no sex drive he's otherwise in pretty good shape any says you know. My wife is really upset that we're not. We love each other. I love her. I'm attracted to her but I just don't have the feeling for sex anymore and she's she thinks it's her she thinks. Maybe I'm having a fair I don't find you attractive. She stays in shape. Like it's really stressful. So my doctor. Primary Care Doctor. Got My blood tests and it was low for a total testosterone. I think somewhere in the range to fifty or so well and almost everybody would agree to fifty as low people debate. What is a low level? But there wouldn't be much debate about his. And he says he got referred to this into chronology Somebody who I know who's prominent in the in the medical community and the endocrinologist says to him. Yup You levels are low but Listen in the old days the Queen's had these men who are wise counsellors and they were UNIX. They had their testicles removed and they trusted them and they were thought to be wise and they had a good life. Your testosterone is so much higher than those UNIX. You're you're fine. You can go now and it would he said to me it was very funny guy says to me. I don't give give I don't even know the right nice expression for radio says I don't care about these ancient queens. What I care about is the princess who sleeps in my bed every night. Yeah Fair enough. So there's two we traditionally we. We did everything based on total Austrian and important for your listeners. To know that testosterone is it circulates in the bloodstream but ninety eight percent of it is bound to carrier molecules and only about one or two percent is free or what we call the part that gets into your cells as the part that is unbounded. We call free. One of the big carrier molecules is called sex hormone binding Globulin. We usually abbreviated as S. H G and the main characteristic to be aware of the testosterone bound to SHP is bound so tightly that when the testosterone bound to that molecule goes past the cell that needs testosterone. It can't be released. It's bound to tightly and essentially that fraction. That's bound test. Each is not biologically available as we get older and in some men for unknown reasons S. H. BG levels can be high and which means that it sops up along the testosterone that still can be measured in the blood and the higher your S. h. e. g. the more your total testosterone is going to look normal and so some of these men are truly deficient in Their free testosterone is low but their total testosterone which is what most doctors measure and trained on looks normal and so they told no you don't have to Saas Jones fine and the sort of the more evolved sophisticated Clinician than will understand the importance of free testosterone and we treat a lot of men just based on their free testosterone being low the other issue that confounded for your listeners. Who think that they may be candidates for this. Want to know is that the laboratories all put out there called reference values. You know sort of what they think is a with the proposes normal values and the reference values for testosterone and free testosterone often. They're put out by various labs. Have no clinical relevance they weren't determined by whether or not people have symptoms at that level or not and many of those reference values go very low which means you have to be crazy low for it to show up on the lab report as being below the reference value right. And so that's a major problem so we don't use lab reference values. We published a paper some years ago. We just query twenty-five labs. We just call them up. What are your reference values for? Total and free testosterone have twenty-five five labs. They were seventeen different reference ranges and the level that was considered low varied by four hundred and fifty percent. So what it means is that you can have a laptop you can have the same value. That one lab will say as normal in the under another liable stays low so for total testosterone. I you know I think everybody United States would pretty much agree. That less than three hundred is low. I actually think in Europe with us. The number three fifty. I think that's a more reasonable of value but free testosterone has gets messy. 'cause they're different assays with different units? I think it's the most common is calculated free testosterone in my opinion and the clinical experience. If somebody has a free testosterone less than a hundred picograms per mille and they're symptomatic than they probably deserved trial. If treatment. I makes a lot of sense in what often gets missed in. These discussions is normal is not necessarily desirable in a population that is overweight. Metabolic sick many cases and so Homer Simpson's normal but homer simpson is not optimal and it's a very good point so in nineteen ninety nine. You founded men's Health Boston which became the first comprehensive men's health center in the United States. And you and your colleagues. Mhp have been among the first to offer a number of new therapies. Can you give our listeners of the background on 'EM HP and also an overview of the center and what you guys are doing there? Oh my God. I'm so glad you asked so one of the things you know. I've done all this work around science and stuff but I was a fulltime faculty person at Beth. Israel deaconess medical center. I was sort of on the academic track. If you will and in one thousand nine hundred ninety nine I realized that I. I was specializing in Male. Sexual issues and male infertility issues. I did vasectomies I dealt with some prostate stuff and I went to the head of the hospital. I said listen I practice. What I think could be considered men's health that term did not exist back then like we had no sort of didn't have any meaning but every center in Boston and in many places around the country. Every hospital had a women's health center and there were no men's health centers and I said I think we should open up a men's health center. I want to run it and I think we can really help guys you know. Sort of. Give them one center of excellence around the stuff and the head of the hospital loved it. We talked for about an hour at the end of the hour. He said this is great. Let's do this. I said how long do you think it'll take? He said well. Listen we're big bureaucracy? I've talked to facilities in nursing. And whatever he says any. I'll take three years could be longer than three years. I was young ambitious and ended up leaving. I still have a good collaborative relationship with Beth. Israel that's still my institutional home and Harvard Medical School but I went out and I did it on my own and it was the first comprehensive kind of men's health center in the country offered testosterone. When nobody else did. We looked at bone density testing. Because of the stonework that nobody else was doing. We looked at muscle and fat composition. Which nobody else was doing? And then I did some of the standard urology type things you know. Like treating people with erectile dysfunction with pills and injections and I did surgery Ford for implants and we dealt with male infertility and then over the years. So we're now said. We just celebrated. We just had a party for twentieth anniversary of Men's health. And and you know where we are now is in in the concept has been did. It's helpful for men to have a place where they can go to talk about the issues that the often are too embarrassed to talk about to anyone else including their primary care doctors and where they're able to get state of the art care for those things sometimes tradition on sometimes some of the newer treatments that are out there. We do clinical trials and now we do cardiology services for the last several years. With Board Certified Cardiologists. We do echoes and stress tests. And you know. There's this huge overlap. We've been talk the cardiovascular risks with testosterone so it turns out that if you have low testosterone or you have a rectal dysfunction which often overlap but both of those items are risk factors for later development of my cardio infarction both of them and if you look at the cardiology population. Some huge percentage like eighty percent of people with coronary artery disease. The cardiologists have either erectile dysfunction and low testosterone. So you know. We're not and so the cardiologists that we have a Evan Appelbaum. Who Superb you know? He sees himself as a preventive cardiologists. And that's part of what it is that we offer sounds like a very valuable service. Indeed absolutely we touched on a little bit but could you talk about the different modes and types of administration of testosterone. This has also led to a good bit of confusion in the community. Yep so they're many ways to give testosterone the ultimate concept though. Is that as long as we can get testosterone up to a good level and have it be up for most of the period of time with treatment? The results are GonNa be the same and so some of this has to do with just consistency of results and convenience. The oldest form testosterone worthy injections I mentioned huggins and The prostate cancer guys. They used to be injections that lasted only a day. So they'd get daily injections. The most common injections now are are. What's called Testosterone scipion eight or testosterone in an and usually we can give those on a weekly or every two week basis They're inexpensive. They've been around forever they get good good. Absorption it's a shot usually in the bum or in the thigh The downside is the levels will go up and they'll go down and so some people feel that and they feel like they're on a roller coaster but it's effective and we can work around one of our favorite treatments that we use than the Are these pellets? So it's like compressed testosterone. It looks like a grain of rice. We take a few of them and we put them under the skin. We numb up the skin of the buttock. And we make a little Nicorette we place these pellets into the subcutaneous fat. And you don't need a stitch or anything you just get a little fancy band-aid slow release Form of testosterone. It'll Released usually over three months sometimes a little bit longer for months. There is a long acting injection. That's been approved by the FDA. It's called Historian on-deck no eight. The trade name is feed and then injection happens every ten weeks so that's not too bad levels. Tend to drop a round day week. Eight to ten of some people needle extra support around that time. There's a nasal testosterone which is a Jimmy. Squeeze it into your nose. You Rub it around for a bit. Very actually convenient levels. Go really quickly go up to very good levels. The interesting thing though is that they dropped quickly so you have to do a two to three times a day. The results are pretty good. And what's interesting is because a lot of the day the testosterone is back down to normal which we would we would think of as not being helpful but it turns out that some of the risks that we monitor in some of the effects of stone like lowering sperm counts and stuff while you're on treatment don't seem to happen as much with that. Nasal Gel so that's interesting and then we have the creams and the jails and that have been around. Andrew Jelly mentioned was the first jail was approved in two thousand and one. I think it was has been the most popular but now insurance companies have made it so expensive that too. That's gone down in the injections have Have become the most popular a lot of compounding. Pharmacies can make historian creams and have done that for many years. That's usually inexpensive. The big issue with the top would call topical says that the absorption is variable. So some people just don't absorb it at all and some people only absorb it a little bit so we don't always get great levels with at the same time for a lot of people's completely noninvasive and that's really when they wanna do and as long as we get good levels. There's nothing wrong with it. Recently was approved in oral testosterone. It's not yet available on the market but expected to show up in the next couple of months and we'll see how effective that is That's interesting I'm also hearing a good bit. Lately of a transdermal Testosterone Applied Typically Allocate Twenty Percent Gel Scrotum early and they're supposedly get very good absorption. Have you heard anything about that? Yes so you know the the very first topical we're actually patches. Before the ANDRO was approved there was a patch and it was applied to the scrotum and and people thought. Oh it's the scrotum because that's where the testicles are no it's because the skin of the scrotum so thin it's so thin so it's absorbed more readily there and so the scrotum can be a useful place to apply some of these compounds one. Here's all kinds of different opinions regarding the issue of a remedies ation of testosterone to estrogen associated with replacement therapy and some folks are very concerned about this and watch it super carefully and prescribe medications to suppress this and other see it as a feature not a bug and. I hear a lot of argument about this. How do you think about this? And are there any risks associated with over suppression of around? Yeah that's an important question so you know. A lot of testosterone work has come really out of the anti-ageing community and there's been a belief that testosterone estrogen dial are kind of like battle. Duke it out for for surpremacy in the body and and the testosterone is good for men and estrogen is bad for men that that's over simplified so it turns out from some very sophisticated studies that men need estrogen to and some of the activity that we attribute to testosterone happens by its conversion to estrogen. Examples are including bone density and also inside the brain and in one study. That looked like We I've I've mentioned several times. The testosterone reduces our fat and it turns out that estrogen appears to play an important role with that too so because of the fear of estrogen and also important to understand especially for your audience. That's a little bit scientifically savvy. Is that estrogen. In men and in women comes directly from testosterone. It's converted by an enzyme called Romo taste. It's one chemical change and so in women that testosterone doesn't stick around that long. There's lots of Aroma. Tasting GETS CONVERTED TO ASTRO DIAL or estrogen in general and in men too so when we raise testosterone in men. We necessarily increase estrogen to you know. We wrote a review of this some years ago and we just couldn't find any important negative aspect of higher estrogen. The one thing that I've seen occasionally is that there are some men who get very high testosterone levels Estra. You dial is very high and for some reason. They're just not getting the benefits we expect and in some of those men if we lower estrogen moderately modestly demand. Make it better Better results with that. So we don't I don't use the aromatase inhibitors. Those the ones that prevent the production of estrogen. I don't use them all men. I use them relatively sparingly but I do use them in some men when it's indicated in or if they're symptomatic some breast tenderness or something and some of those men it can be important. It's important to not drop the estrogen too much. And I see this all the time from people who come in from other centers because it's bad for bone density. We need our estrogen for bounce. Yes so earlier you very nicely explained the plea tropic effects of testosterone in the widespread problems associated with deficiency and I think people in our audience appreciate that and the benefit of normal or high normal testosterone. Has Anybody what he looked at say. Supra physiologic levels instead of twelve hundred or a thousand two thousand. Do we have serious quality studies looking at that? There are a few not many but there are a few where they looked at it especially in older men and the part that interested me and was part of my developing the saturation model is that turned out that the men who got these super high levels or super high doses of testosterone had no change in their PSA compared to the man who got just normal amounts. Your model would suggest that. Yeah but but that helped me actually get to that. Oh I see cancer. It's like it because it was shocking to me so there are two studies that That come to mind around the super physiologic doses of testosterone and one was for I think twenty weeks in the other one for for nine months and nothing terrible happened to any of these guys. You know their levels of testosterone were sometimes three times the upper limit of normal. You know the one thing you have to watch for. One of the risks of testosterone treatment is that the red blood cell count the Madden created. The hemoglobin can go up too high so we don't know exactly how risky it is but it doesn't sound good and the fear is the fear. Is that if it goes up too high. The blood gets more viscous maybe leads the klotz. A lot of it's theoretical. But we sort of stop it at fifty normal is usually up to fifty percent and we stopped difficult to fifty four or we or take blood off the people we sent him to the. Red Cross to donate and so that does appear to be dose related or at least concentration dependent with testosterone. So if you're on injections for example have a higher risk of that elevated red blood cell. Count if you're on gels limit sense so the guy in the supra physiologic part you know we just worry about that but the big thing that people have worried about with the super with the excessively high doses you know. Is there something bad that happens? What about this road rage that we hear about mood stuff and it just didn't happen it just didn't happen now? They weren't huge studies. A lot of the stuff is kind of bogus our defer your listeners. To one of the most entertaining books I ever read but I learned a lot too. And IT'S BY JOSE CANSECO. Who was the Homerun King? Who openly took you know? Anabolic steroids. And it's just fascinating and fun. And he makes the claim in their books. Got Fifteen years old or more. You know he's. He writes in the book that he knows more about all this stuff than any doctor in the United States and I'm sure it was true because doctors tend to not give super high doses of this stuff and of course if here in athlete and you're trying to maintain some crazy high level of performance. You know they may be something to that. I'm sure there is Anyways just an interesting read indeed in your book the truth about men and sex. I think it was a twenty thirteen. Twenty fifteen book. You explain that you were trying to pull back the curtain to reveal men as they really are. The last chapter of the book is titled Men. Are People too now that you would need a chapter like today's world? It's definitely needed to talk about that. Chapter little and what you mean by you know the When I was in medical school I had Two things I was trying to figure out how to decide between two areas and one of them was Surgery which then led to urology which is a surgical sub specialty. But the other was psychiatry. And I've always been fascinated about the mind and relationships and emotions and I kind of fell into this area of the sexual medicine part. Were guys start talking to you about stuff and when I started doing that work and you know I was young when when I came out what I was maybe thirty two and you know is married and I didn't have that much experience around these things and yet guys talking to you and you're supposed to be wise and give them advice and I learned from my patients. One of the things that I learned just by listening is that men were so different from how they're portrayed in the media and in movies and I don't mean to excuse for a single second all the men who bad stuff around sexual violence and stuff that's criminal but you know we're talking about half the population or mail and I'll never forget one very early on. I had this guy walk in my office. Who was like way too cool for school and I had an immediate negative reaction to this guy and like I didn't I didn't I even before he opened his mouth. I didn't like him. And all this stuff and and it within a few minutes this guy's telling me about how he has premature ejaculation and he has a girlfriend and he doesn't feel manly enough because he feels like he can't provide enough sexual pleasure and satisfaction to his girlfriend and he's crying in. I was dumbstruck. And I realized that I'd made this quick judgment and I was completely wrong. And there are a million guys out there like this guy who are really struggling and they're struggling with their masculinity and they're struggling with whether they feel clear worthwhile and the other thing that came out and really is supported by thirty years of sort of you know behind the closed door. Having guys talked you bet stuff is important. It was for men in relationships to actually be good to their partners. You know we're talking largely about straight couples but not exclusively sex for the guys has which is completely opposite of what everything that I thought I knew and you know I see. Sometimes these men who had erectile dysfunction. They've been married for quite a number of years and you know and I've heard this on a few occasions and this one guy says to me I feel like I'm letting down my wife. The sex was always a nice part of our relationship. And now I feel like I can't hold up my end of the bargain. That was shame associated with not for him but with regards to what he was able to provide to his partner so I wrote that book filled with stories from my patients but the theme is really what our guys really like when they opened up around the stuff. And what's it like for men when they lose something important like their sexual functioning and what's it like when we can treat them and they can regain. It was incredibly important. Work that you're doing and you have people flying in from around the world to visit men's Health Boston and meet with you which I know keeps you extremely busy. But when you're not working we'd like to know what you do in your spare time and also. I've heard that you like to play golf. Even though you're not very good at it and is that right I. I'm not sure you're supposed to tell everybody I'm not that good at it but the ULTA I like to think I can have as good a time as anybody but I do. Spend a lot of time on my work. In years ago I was inspired by an ice to struggle with it because I would see my patients during the day. My kids are grown now. But you know I'd come home once they were asleep. I'd work on paper and science and it was just so fascinating to me and and especially with the work that we've been talking about here like you know. I really felt like there was something that I was seeing. In a number of my. I wasn't alone. Of course I've got any number of colleagues that are dear to me and sort of on the same team or wavelength. If you will but that we were actually moving the ball forward you know in an important way that matter and there's a gentleman named Bruno Lunen felt brilliant guy. Who's now I think? Ninety and he started a society called the International Society for the study of the aging male. And it's probably fifteen years ago. He was in his. I don't know late Seventies. Who would ever and I saw him. It's a meeting and some other things some other country and there was going to be a dinner that night and I said you're going to be Bruin. You're going to be at the dinner. He says no no. I got another meeting. I'm leaving. He was going to other countries Brunei. How do you do it? L. D. R. U. He says my life got better. He says when I realized that my work was my hobby and my hobby is my work and that applies to me a lot too and you know some of us are really blessed to find something for me. It's been kissed Australian ever since I was you know with twenty year old undergraduate at Harvard. Tiff find work that we find interesting. That keeps US thinking that feels like it matters and where we actually can with the work we do make a difference and It's been An incredible journey for me and and I've had the best time fantastic anything. We can all say the same in this room for sure and you showed up at Harvard when you were eighteen. And now you're sixty three and you've been at Harvard this entire time for someone who wasn't sure they even want to go to Harvard. In the first place you certainly planet some deep roots on that campus. So I'm curious. Was that your plan all along and it's just one thing leads to another. You know but you know I told you that. My mother wanted me to to both learn how to play the violin or go to Harvard so I think if I were to leave Harvard I would need to pick up the violin. That'd be another hobby down the line but it sounds like you're going to be at Harvard for for quite some time so Eight this has been a lot of fun and this This podcast is very important to a lot of the listeners that we have so. Thank you so much for spending time with us today. It's been fantastic. Really interesting thank you. Oh It's been a pleasure to be with you so much. Skin pep talk stem talk so that was a really important interview when it comes to sex whether it's from the male or female perspective. There are a lot of taboo topics every like that age is trying to help people become more comfortable talking about these topics. There's so much that all of us can learn from as work men's health in particular absolutely and it's really disappointing that a hugely flood paper written in nineteen forty one could become standard medical practice in terms of the diagnosis and treatment of prostate cancer. Net and in discussion with A. We've heard of several such poorly done papers with inadequate period view because of this paper for decades men with low testosterone levels. Were denied treatment that would have significantly improve their health. Workers another reminder that scientists and researchers we all have an obligation to constantly question things particularly received wisdom. It's incredibly important. So if you enjoyed the interview as much as I. Did we invite you to visit the stem? Talk Web page where you can find the show notes for this and other episodes stem talk dot. Us This is. Doc reneged signing off for now. Ken Ford saying goodbye to we. Need again on stem talk. Thank you for listening to stem talk. We want this podcast to be discovered by others. So please take a minute to go to itunes to rate the podcast and perhaps even writer review more information about this and other episodes can be found at our website. Stem Talk Dot. Us there you can also find more information about the guests we interview.