Dr. Abraham Morgentaler
Appearances
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And the New England Journal of Medicine had published maybe the biggest paper of this century in 2002, which was the Women's Health Initiative, which was about hormone replacement therapy in women. It was the largest placebo-controlled trial at the time. It was something like over 20,000 individuals.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And everybody at that time had thought that hormones in women were great, protective about all these things. And the headline from the 2002 paper in women was that HRT, hormone replacement therapy in women, was actually associated with increased risks, increased. And it really affected that field.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Today, you know, there's lots of follow-up studies from that, and it's clear the scare stories from those initial headlines weren't true. But in 2003, as testosterone was just becoming more popular, We contacted New England Journal and we said, are you interested in a review paper on testosterone? They said, yes, we're interested in a paper on risks.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So we worked with them and we pulled together all the papers we could find on testosterone and prostate cancer. And one day our nanny comes to me and we've divided up the papers and he's a very confident person. Confident man. And now he's a very prominent urologist in Porto Alegre in Brazil. And he looks nervous. I'd never seen him nervous before.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And he says, Chief, do you have the papers that show that high testosterone is dangerous for prostate cancer? And I said, no, Nanny, I thought you must have them. And what we found and published was that we couldn't find one single article that showed any good evidence that high levels of testosterone or testosterone therapy were associated with anything bad with prostate cancer.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Higher prevalence, higher stage, the higher mortality, nothing. And we were shocked. The editors at New England Journal were also shocked. And I was relatively young. This is more than 20 years ago. And they were uncomfortable publishing the paper. So they sent it first to three urologists who gave it high scores. But they didn't believe this thing about the prostate cancer.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
It was taught everywhere in the world. So they sent it out for another three reviews, this time to endocrinologists. The endocrinologists didn't mention any papers that we'd missed either. And they gave it high marks. And they still weren't satisfied. And they sent it out for another round of reviews, this time to oncologists, who also couldn't find anything.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And so they published, took about a year to publish it, and it got published in 2004. And that was the first time that any kind of major journal questioned or challenged this idea that high testosterone or testosterone therapy was dangerous for the prostate. So that's 2004. We're now in 2024. It's 20 years later. And I can tell you that there's been a lot of research in the last 20 years.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
We have three large randomized controlled trials now, as well as numerous large observational trials. None of them Not one shows anything bad about high levels of testosterone or raising testosterone and prostate cancer. But still, there are many parts of the world where you never, ever, ever give testosterone after the man's had radical prostatectomy or radiation therapy.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
The AUA guidelines actually were the first to allow, for 2018, first to allow there to be, to give some cover, to say it's okay, or at least that there's not a contraindication, to give it to men with low-risk cancers where there appears to be what looks like a parent cure.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But, you know, there's still nothing documented anywhere that says maybe we can give it to other men or men on active surveillance or men after radiation. And the argument to not do it, I think, is based on nothing.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So in the late 1980s, early 1990s, what we had available was mainly the short-acting injectables, testosterone, cipunate, testosterone, and anthate. There was a pill, methyl testosterone, which wasn't used. It was known to cause some liver damage. It's still available, but doctors are discouraged from using it. Dangerous in most cases. So that was really what we had.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
The first real advance in terms of the new technologies branded things was a patch, testosterone patch. It wasn't very successful. You needed to apply it to the scrotum. And so you had to shave your scrotum. And it didn't stick very well because people get sweaty down there.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So, you know, I have a nurse who had been with me for now for 20, 25 years, and it was his job to teach people how to shave their scrotum and how to apply the patch. Not a great part of his day necessarily, but so that didn't work. Then there was a patch you could apply to the chest. And then really the first new popular treatment was the gels. Androgel was the first.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
followed by another gel called Testim. They're now all generics. And then later in about 2008 came the pellets. And urologists tend to use a lot of pellets. They're good. Interestingly, pellets were one of the first forms of testosterone, was available after testosterone was synthesized in the 1930s.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And it turned out that there was a pellet called Testopel that was approved by the FDA in the 1970s, but it wasn't marketed. I didn't even know that it existed until a company brought it to the attention of some urologists at the Sexual Medicine Society meeting in, I think it was 2008. It's called Testopel, and it turned out to be very good.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So, you know, subsequently we had long-acting injectables like testosterone and decanoate. Then we have the self-injectors, testosterone and anthate that you inject into the fat of the abdomen, zyasted. And now we have three oral testosterone that are safe, that have been approved over the last several years. And it'll be interesting to see what happens with market share and how doctors use those.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So we're lucky that we have all these different, we have a lot of choices, right? And I was always interested in trying the new treatments. I wanted experience with them. I wanted to see if they would work, how well they worked, who they would work in. And in the end, really, I tried as best as I can to match patient with treatment.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So in urology, there's a lot of kind of macho stuff that, oh, injections are the way to go. We get high levels, the patients are happy, it's inexpensive. But you know, there's a lot of patients that don't want to do injections. It's an amazing statistic, but in a couple of studies, the percentage of men who are still doing injections...
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
at the end of one year after they started, is only 15%, one out of seven. People stop it. So a lot of urologists I know say, oh no, my patients stay on it. But unless you actually look at your numbers, There's a lot of bias involved with that because we know that we see the patients that come back to us. We don't see the patients that don't come back to us. And we may not remember them.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
We see them once, maybe twice, and off they go to learn how to do self-injections. So unless you're keeping statistics on your own, folks, it's hard to know. So injections are fine. It's a good form of therapy. We would give patients the choice of doing self-injection which they could do once a week, usual starting dose is 100 milligrams or half a cc.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Or if they didn't want to do it, we would inject them in the office. They'd come in every two weeks. Once a week is too much for, you know, a lot of people have to take time off from work and fight traffic in a city like Boston and Park and all that. So we'd have them come in every two weeks and we would inject them starting dose 200 milligrams or one cc. And we can adjust the dose after that.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
The gels, people say, oh, the gels, the topicals, what a nuisance that is. But there were about, I don't know, 10 plus years where the leading testosterone product in the United States, at least, were the gels. And they have advantages that it's not an injection. There's nothing scary about it. Patient has some control over doing it. They just apply it themselves.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
They feel like they have control too. Like, you know, there's nothing really bad that happens with testosterone therapy, but you have the sense if you're applying a cream or a gel every day that you can stop it. You know, if you're worried something's happening, then you just stop doing it, whereas the injection, it's in there.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So, you know, the longer acting treatments, pellets, and the longer acting testosterone injections, testosterone and decanoate, you know, they have advantages, which is that the treatment is less frequent. But there are issues around insurance or cost and, you know, there's a lot that goes into what actually will work for somebody.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
No, I think the data are quite clear that it does not cause blood clots. You know, we just had published over the last year or so the TRAVERSE trial. So TRAVERSE was the largest randomized control trial ever with testosterone. It involved more than 5,000 men randomized either to testosterone gel or placebo gel. Mean follow-up was 33 months, so a little bit less than three years.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Mean time on treatment was a little bit less than two years. And that's a big study, 5,000 men. And the original intent of the study was to look at major adverse cardiovascular events, heart attacks, stroke, and death. And it turned out that was fine. There's no difference between testosterone and placebo. They also looked at prostate cancer, and there was no difference there either.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But one of the things they also looked at was venothrombotic events, VTE, which is pretty much pulmonary emboli and DVTs, makes up most of it. And there was no difference there either. And we've had a number of observational studies too. A minority of them showed maybe some increased risk with testosterone. Most showed none. But the best is a large RCT, and there was no difference in that.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So it doesn't cause increased blood clots. I'm pretty comfortable seeing that.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Jose, I got to tell you that I was nervous most of my, almost all my career. And it's very hard to give up concepts that you were taught as a trainee. Very hard. You know, the smartest people that I knew in my training, and some of them were brilliant, taught me that testosterone is dangerous for prostate cancer. It was completely unchallenged. It was just... It was just one of the rules.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And so when I first started treating my guys, I mentioned that I was doing biopsies to make sure they didn't have cancer, but it's still thought that they might develop it. But after a while, what happened is that, so for many years, at least in the Boston area, I was the only doctor. that was offering testosterone therapy to otherwise healthy men. They just had low levels of testosterone.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
They didn't have pituitary tumors. They had two testicles. And people were making me nervous, right? Like my urology, my patients would go for a second opinion. And they were told, that guy Morgenthaler is crazy. You're going to get cancer from that. And I had colleagues stop me. I had one colleague, one of my former teachers, stop me at the AUA meeting one year.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
I was just out of practice a few years. out of training a few years, and he says, what you're doing is dangerous. You have to stop. And I was brought in. I gave grand rounds in my own hospital to the endocrinologists. And a day or two later, I get a call from the Human Subjects Committee, the IRB, from the chief of the IRB. He says, Abe, we'd like you to come and talk to the IRB.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So they arrange a time. I go in. I don't really know what it's all about. He says, we heard that you're practicing dangerous medicine. And it came, I know it came from one of the endocrinologists that I had spoken to. And you know what's funny is that that was early days.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And the most dangerous thing that I had done then, which was part of my lectures, I mean, I was giving talks on this thing because it was interesting to people. was I gave testosterone to men who on prostate biopsy had been diagnosed with PIN, with high-grade prostatic interpithelial neoplasia. At that time, we thought this was a pre-cancer.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And if a biopsy showed PIN, we automatically scheduled the next biopsy because we were sure there was prostate cancer hiding in there somewhere. Today, we barely care about PIN. Even if somebody has Gleason 6, which was absolute diagnosed cancer, at least that's how we thought of it then. Now we know maybe that doesn't deserve the designation of cancer. And in any case, it's low risk at worst.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But what's funny now is that this dangerous workout I was supposedly doing was because we've given it to 20 guys with PIN. and published it. And one guy eventually was biopsied and had cancer, but that was one out of 20 with, I forget what the follow-up was, but there wasn't much. So that was the dangerous work.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But what happened is that I developed a reputation around testosterone, and it's not just about sex, right? So in the mid to late 1990s, there was a movement that really emphasized health and wellness for people. The idea was that sort of the standard medical training was hospital-based, and that was really for what some people might call sick care.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
You know, heart attacks, cancer treatments, things like that. But there were a lot of people who didn't need to be in a hospital, And they weren't feeling that good. And it wasn't just sex. You know, sometimes their mood was down or they felt weaker. They didn't feel like themselves. Energy was down from people who otherwise had led vigorous lives.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
One of the things that the orals have transformed is the concept that you have to have a continually high level of testosterone to get the benefits. And clearly that's not true. And the safety seems to be improved, the safety profile, by having levels that fluctuate some during the day, returning close to or even to baseline.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And a group of physicians and the public sort of figured out that maybe there's a way to feel better. And they really created the first movement around desire to normalize testosterone levels for quality of life. And they were right. They were right.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And today we know from studies and also just from seeing patients that, you know, what I say to people is that having low levels of testosterone is a reduced state of the human condition. You know, there's a lot of stories that are very colorful of men doing what we were always characterized as foolish things in the past, looking for the fountain of youth. Yeah. Oh, those men are so foolish. Yeah.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
You know, Jose, it's actually, it's an amazing story. So I finished my training in 1988 and joined the faculty at one of the Harvard teaching hospitals, Beth Israel Hospital. Now it's called Beth Israel Deaconess Medical Center. And at that time, It's hard to imagine, but people were so scared of testosterone.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
There was a guy in the 1800s who was tying off the vas deferens on one side because he thought it would help rejuvenate men by blocking the outflow of sperm, right? They knew that testicles made sperm. And you could think of it as chi or energy or whatever. And so he kept it within. And one of the people who had that procedure done was Sigmund Freud. Another was the famous poet W.B. Yeats.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And people say, how could such intelligent, educated people be fooled in this way? And we ridicule, we mock men for this. But in fact, what I see is that these were people who knew what it was like to be not successful, but sort of to be at the top of their game. They had an A game. And How important, and clearly they weren't feeling that anymore.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And how diminished they must have felt in order to actually try something as dubious as what was being offered. It reflected on how important it was for them. Not that they were stupid or foolish or just looking to be sexual, but there was something that was different to them. And we know that about having low levels, especially very low levels of testosterone. The effects can be profound.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So as the years went on, I took on what I thought of as riskier and riskier situations. And when you asked if I was nervous, I was always nervous when I did something like that. So first was the guys with PIN, where we thought they had pre-cancers. Then it was guys after radical prostatectomy who appeared cured.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Then it was guys with radical prostatectomies where they had higher great Gleason scores, higher risk, radiation therapy. Then guys on active surveillance. Now, I wasn't, these guys would seek me out. I wasn't saying to anybody, listen, you really should be on testosterone. No, no, no, no. They came to me, they said, will you give me testosterone?
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Because they knew about it, or some of them may have been on it before their cancer diagnosis, and they knew how much better they felt. And in the end, I was also giving it to men with metastatic disease and biochemical recurrence. So in 2021, I think it was, we published on 20, 22 guys. who had either biochemical recurrence of their cancer or frank metastatic disease.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And some of those men were on testosterone for years with metastatic disease and not much happened to them. It was just astonishing. So I was nervous with all of them. The first guy that I gave with metastatic disease was an 84-year-old man. And he came to see me. He had widespread METs. His PSA was over 500. And he had done standard treatment with androgen deprivation, and he hated it.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And did I say 84? He was 94. But his brain was sharp. And he came from out of state. He said, I've read all. He was a scientist. I've read all your work. I want to come to Boston. Why don't you give me testosterone? And I said to him over the phone, I'm happy to see you, but I can't promise you anything.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And when I saw him, he was mentally sharp, and he could walk, and he had one nephrostomy tube in the pocket. He wore a jacket. He had one nephrostomy tube bag in one pocket of his jacket, another one in the other pocket. I said, what do you want testosterone for? He says, I used to exercise every day and it made me feel good.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And I've got colleagues in science around the world and I'm just too tired to correspond with them. He says, those were the two main things that gave me pleasure in life and I'd like to be able to do them again. And I said, you know, I've never treated anybody like you. You could die in a week tomorrow if I give you a testosterone. And he said, I've never lived my life in fear.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
They believed testosterone would cause prostate cancer almost in everybody if you raise testosterone. So what that meant was that there was no testosterone therapy being used in the United States except for the rarest of cases. Young men who didn't go through puberty because they had pituitary problems or hypothalamic issues or they'd lost both testicles or some genetic issues like Kleinfelter's.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
I don't intend to do it now. He says, and besides, I'm 94 years old. I'm going to die. He says, I've got metastatic prostate cancer. I'm probably going to die from that. But he said, while I'm alive, I'd like to live as well as I can. And he said, I'll sign anything that you want. And so I wrote this very long handwritten note in his chart. And I treated him.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And within a few weeks, he was exercising. He gained weight, which he needed. He was very skinny. His appetite came back. He started corresponding with his colleagues. And he had a bunch of patents. He started to work on a new patent. He had a good year. And we died at the end of the year. But I don't think we shortened his life expectancy by one day. And he died of prostate cancer.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
His PSA would rise and rise and rise. So he gave me the courage to do it in younger men. You know, I stopped seeing patients a few years ago. But by the end, it was clear to me, and it's even clearer now from the literature, that I simply do not believe anymore that testosterone makes prostate cancer grow unless the levels are severely low.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
below the saturation point, in which case there still is a little room for testosterone, you know, to cause some growth of the cancers. But once you reach the saturation point at around 250 nanograms per deciliter on average, I don't think it does anything negative.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Most, but I don't think all, most had been on ADT and didn't like it. There was one guy who had basically lost his personality. It was just like flat affect. And he'd had a few strokes, and I thought his lack of responsiveness was because of his strokes. And I didn't treat him right away. His wife brought him in and said, this isn't the man I married. I don't recognize him. And I put them off.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
I said, maybe stop the ADT. Maybe his testosterone will rise and he'll feel better. And they came back months later and said, we stopped it. He's no different. Please, we want to have him go on testosterone. And they came back a few months later, and he was like a new man. Yeah. He was funny. He spoke fluently. Before, it was just one yes or no. It took a long time for the words to come out.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
When I first saw him, he needed help to stand up and to be examined, and now he just stood up on his own. That was an amazing thing. So ADT, people often misunderstand my thoughts about this. So androgen deprivation does work, especially the newer agents that lower testosterone even more. I call them super ADT. And they've shown that progression-free survival is improved.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Overall survival is improved. It's good. There are many men who don't like what happens to them. And there are significant health risks, including mortality, non-prostate cancer mortality, that happens to these men. They become obese. Generally, they put on a lot of weight. They're at risk for more heart attacks and strokes. And they just feel like crap.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And so there's a lot of men that sort of fall outside the system. They just stop their ADT. They're lost to the system. And I'm not saying they should all go on testosterone. So I don't believe that ADT is bad or that it's dangerous. And in the proper circumstances with informed consent, I think it's totally the appropriate thing. But there is a cost.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And sometimes the cost is often decreased quality of life. As a rule, almost everybody that I treated with advanced prostate cancer who came to me and wanted testosterone, they almost all said the same thing, which is that this life that I'm leading now, it doesn't feel like much of a life. And even if it shortens my life, I'd like to live better.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And that was the justification for them wanting to go on testosterone.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And it was understood that those men needed testosterone in order to complete puberty and become virilized. And some men who had completed puberty but had some of those other issues I mentioned too, but those were the severe cases. And they only got testosterone until they hit around age 40, 45.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Yeah. So I treat them as a normal patient because it's a little bit like you can't be a little pregnant. You either are or you're not. The fear, it's taken me 30, 35 years to come to the conclusion that I have around testosterone and prostate cancer. And it took me a long time. And I don't expect people to have a sudden epiphany about it.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So there's no difference in terms of what we were taught about risk, whether you give a little testosterone or normal amounts of testosterone. It was supposed to be dangerous no matter how much you gave. So you may as well just treat them. And what kind of treatment you give matters. It's sort of what the doctor's comfortable with.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
I think some people may be more comfortable with gel initially because the levels don't get as high. You can stop it if the PSA goes up and it makes you nervous, then you can stop it. But once you have a little comfort with it, and the easiest patients to start with are the people who had lower risk prostate cancer before definitive treatment, Gleason 6 or Gleason 3 plus 4.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
maybe with negative margins, undetectable PSA afterwards, or even radiation therapy, again, with lower risk disease. And I think once you start seeing that lightning does not strike either the doctor down or the patient, that people get more comfortable. Amazing thing happened to me, which is, so at this past year's AUA, I moderated a plenary session.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And the question was about, the debate was on whether or not you could reasonably treat a man with testosterone who was on active surveillance. And it was a case of, I don't remember if it was Gleason 3 plus 4 or 4 plus 3, but it was Gleason 7. And so we had good debaters and they debated it. And then I asked for a show of hands from the audience, you know, and it's one of the plenary sessions.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
They've got a couple of thousand people in the room.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Yeah. And about a third of the audience put up their hand saying that they would have treated the case that we had. Now, that's amazing. Amazing. Because just a few years ago, it probably would have just been maybe a couple of hands. So it's shifting.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And part of the reason it's shifting is that so many urologists now and doctors have experience treating men after radical prostatectomy or radiation. They've seen that nothing happens. So then we go on to the next group.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And there's a way of thinking about this that I think is very effective, which is that if you had a patient in that situation, prostate cancer, treated in whatever way, but it's not metastatic, and he had a normal testosterone and felt good, nobody would talk about lowering that person's testosterone.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So if you can imagine as a urologist, as a physician, that there'd be no point in lowering a testosterone in a man with normal testosterone, then what's the danger in raising it to a normal level? It's the same chemical. So the cells that need testosterone cannot tell the difference between testosterone made by the testicles and testosterone that we inject once it hits the bloodstream.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Because they were entering the prostate years and people were afraid that testosterone would cause cancer. And the belief that that was so was stronger than the idea that smoking would cause lung cancer. Like that would pale in comparison. And today it's, in looking back, it's not that long ago, right? It's like 30 years, 35 years. You know, today it's laughable.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So for example, many of the risks of testosterone that we used to talk about probably aren't accurate anymore. We had the Traverse trial, the biggest randomized control trial ever. that I think disproved the idea that cardiovascular risks were increased with testosterone. They were not paired to placebo.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So they all have all these names, right? Like testosterone, cypionate or enanthate, they're esters. But what happens is that when they hit the bloodstream, there are enzymes that cleave off those side groups and what circulates is testosterone. It's the same molecule. So that's one way to think about it.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So the most important thing to understand about PSA is that in order to interpret a PSA level, you actually have to know what the testosterone level is. And the reason I say that is PSA is its production. It's a normal prostate chemical that is androgen dependent. So you can take healthy volunteers, which has been done, and give them an agent that lowers testosterone.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Their PSAs will go down usually to zero. or close to it. When their own testosterone recovers because you've stopped that medication, as the testosterone rises, PSA will rise. until it reaches a maximum. If you give finasteride or dutasteride, we know the PSA drops by about 50%, right? We compensate for it.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So it's a testosterone sensitive chemical that we use to monitor men with prostate cancer or to assess their risk. But if you've got a testosterone less than 250, less than the saturation point, the PSA is going to be suppressed. It's not a real testosterone. It's not its real PSA. If they're less than 250, you don't know exactly what it's going to be if you raise it above 250.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
This is true whether men have prostate cancer or not. So if you have a guy with prostate cancer and his testosterone is, let's say, 200, and he goes on testosterone, so there's two versions of this. One is, let's say, they've had radiation. Most guys with radiation have some measurable amount of PSA. The PSA will go up in that circumstance.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
If their testosterone is above 250, it probably won't go up much at all or maybe zero. If they've had surgery and their PSA is a very low number, or let's say it's a sensitive assay, right? Let's say it's, I don't know, 0.01, right? Still below the sort of recurrence level if you want.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But there is a chance, especially with a very low testosterone, that the true value of that, which you'll find out when you give testosterone, might be above 0.02. Or 0.2. And so you have to see what that is. And it sometimes changes the status of somebody. But if somebody has a measurable PSA and their T is less than 250, it's almost certainly going to go up.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And it's important for the doctor to know that and also very useful to let the patient know that. Because when it comes back at a month or two months or three months, if you don't tell them, everybody's going to worry that the cancer is growing. So it's expected to go up if the testosterone was less than 250. And the new value at about three months becomes the new baseline.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
That's the true baseline. And we only worry if it goes up from there in a consistent way.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Correct. And the funny thing is, is that even though we've been taught, it's been drilled into us, testosterone is dangerous, testosterone is dangerous. Most prostate cancer guys, they don't measure a testosterone. They don't even know what a testosterone is. They don't know whether it's normal or low.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But part of the, because everybody, well, not everybody, there's a lot of millions of men on testosterone. And we now have a lot of data that shows that it doesn't increase the risk of prostate cancer. And part of the reason that that belief persisted so long, testosterone came out in the 1930s.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And that's not a criticism of them because the truth is, it doesn't really matter for the outcomes we care about with prostate cancer. It doesn't really matter.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Well, it matters if they're symptomatic and you're thinking about giving them testosterone afterwards, for sure. Yeah. And then you have to, if you're using PSA, you have to know whether the testosterone has let the PSA max out to whatever it's going to be, or if it's somewhat inhibited because testosterone is too low.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Yeah. So it was one of the great advances in testosterone therapy is the development of these oral medications, pills for testosterone. And, you know, we used to say until they came about, maybe about, what, three, four years ago, that oral testosterone was bad. And the reason we said it is because they were alkylated. They had a side chain.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And when you swallowed them, it had a first pass effect with the liver and it turned out to have some liver toxicity. The new pills are all made out of testosterone undecanoate, which has this long carbon side chain of 11 carbons. And it doesn't get absorbed the usual way through the gastric and through the intestinal vasculature, but rather it gets absorbed through the lymphatics.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And so it bypasses the liver altogether and doesn't have toxicity. The product that I'm most familiar with is called Kisotrex. They're all made out of testosterone and decanoate. And what's nice about the pills are that... You know, the most popular treatment for the last, I don't know, 7 to 10 years with testosterone have been injections. People learn to inject themselves.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But the truth is a lot of people don't want to inject, right? Nobody looks forward to it. It may be worth it to them, but nobody looks forward to it. And people are used to pills. We take pills for all sorts of things, Tylenol for headaches and whatever else. And so the pills are taken twice daily. They all have different dosages.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
For Kisotrex, the usual starting dose that most urologists are using now is 400 BID. So it's two of the 200 pills taken twice a day. The testosterone levels go up and then they drop. And then you take it again and it goes up and it goes down. And the symptomatic response is excellent.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And one of the interesting things is because the body goes back to, because there's not the sustained high testosterone level, some of the side effects or the things that we worried about with testosterone don't happen as much. So there's less suppression of the gonadotropins LH and FSH, which are the hormones that act on the testicle to make sperm.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And in 1941, Charles Huggins, who went on to win the Nobel Prize, figured out the first treatment, first effective treatment for men with metastatic or advanced prostate cancer, which was castration or what we might call today androgen deprivation. And he deserved his Nobel Prize. Because that was the first time anybody had shown that any cancer could be hormone sensitive.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So I don't know this has been shown yet, but anecdotally, testicular size doesn't shrink the way it does with some other products. And I think we're waiting on some fertility studies. But the early indications are is that this, we used to say testosterone always is, you can't do it if you're trying to make babies.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So it's going to drop your sperm counts to zero or close to it if you're on injections or pellets. Should recover, but not always. But with the oral, I think that's going to turn out to be not as common a problem. So that may be very, very helpful.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Is that more or less accurate? What an interesting idea. So the question I think you're asking about is what about trying to give them a little daily boost without really changing much? I think that's a very interesting idea. I'm not aware that anybody is trying that yet or has reported any data on it, but it's a very interesting idea.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Yeah. You know, so one of the things that the orals have transformed is the concept that you have to have a continually high level of testosterone to get the benefits. And clearly that's not true. And the safety seems to be improved, the safety profile, by having levels that fluctuate some during the day, returning close to or even to baseline. So for example...
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
You know, many of the risks of testosterone that we used to talk about probably aren't accurate anymore. You know, we had the Traverse trial, the biggest randomized control trial ever that I think disproved the idea that cardiovascular risks were increased with testosterone. They were not compared to placebo. And the same is true for prostate cancer.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
I think the data is now becoming overwhelming that testosterone does not increase the risk of prostate cancer. But one of the things we've always worried about is polycythemia, the risk of getting a high hematocrit, which can happen in up to 20% of men who do injections. And the rate with the orals appears to be more in the 2% to 3% range.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
It doesn't happen as much, almost certainly because the levels of testosterone aren't sustained at the high level, and yet people still get the benefits.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So to be able to have levels of testosterone that provide men with whatever it is they need, like the testosterone level they need for sex drive, for vitality, for mood, and at the same time to have fewer of the adverse effects or potentially fewer, that's a pretty good trade-off.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Yeah, so the words of wisdom is don't be afraid. Realize that the goalposts have shifted a lot over the last 30 years. It used to be you can't do this ever, give testosterone to anybody. Then it became you can't do it to anybody who were worried about prostate cancers, had prostate cancer. And now that's clearly not true, right?
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Because there's so many people who give it to men after radical prostatectomies with the parent cure. And it's just, it's an old story that just needs a little bit more time to die maybe. But I'm very hopeful.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
You know, I gave, I was at Tulane and I spoke to the residents there and Wayne Hellstrom is at Tulane and he's been, you know, very highly involved with the testosterone and prostate cancer story. He runs a course at the AUA on testosterone. And the residents have learned from him.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And I was just chatting with them before I started my presentation and said, you guys treat guys in the clinic that you see with testosterone? They say, yes. I say, you treat after radical prostatectomy? They said, yeah. I say, what about guys on active surveillance? You don't do that, do you? They say, oh, yeah. I say, what if it's like Gleason four plus three?
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And he went on to work also with ovarian cancer, breast cancer, uterine cancer. But he created the difficulty because he saw this as kind of like an either-or situation. If you remove testosterone, prostate cancers would shrink. And the biomarker they used then, which was called acid phosphatase before PSA, would go down just like we would expect PSA to go down.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Like they're looking at each other like what's the problem? And the reason is that they now have the experience of treating these men and nothing happens to them. There's a baseline level, of course, of recurrence and progression, but they're not seeing some terrible thing happen. One of the reasons that testosterone was not used for about 50 years after Huggins published his paper
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
was because everybody was so scared that there were no doctors that had a large group of patients on testosterone that they could say, now hold on a second, I have experience with this. I've got all these patients and they're not getting prostate cancer. Nobody had that experience and so it lived on without a challenge.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Once doctors have clinical experience with this, it becomes impossible to tell them something that isn't quite true. Like the idea that just a little sniff of testosterone is going to create some trouble makes no sense to somebody if they're already treating and they haven't seen that problem.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So I think that urologists are already well on their way with the younger generation to recognizing that testosterone really appears to be quite safe in most, maybe not all circumstances, but in most circumstances of men after prostate cancer.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Right. It's the little things. Those are the little things that give us pleasure in life and make us feel like this is a life worth living.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And if it was present, he believed, or if you gave testosterone, he believed that it would make the cancer grow rapidly. Today we know, and I'd like to take some credit for it together with my colleague Abdul Tresh, we know that there's a limited amount, limited ability of androgens to stimulate prostate cancer growth or prostate growth. And that limit is achieved at a pretty low concentration.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
We call it the saturation point. Prostate tissue needs androgens like testosterone for sure, but it can only use a little bit. And once you have enough, that's it. It's kind of like a plant with water. If you deprive it of water, it shrinks. If you give it back water, it'll grow. But once it has enough water, you can pour water into it all day long.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And let's say a houseplant will never grow to be the size of a tall tree. Because... It's not water that's limiting its growth anymore. So it's just unbelievable how things have changed. Unbelievable. And what's amazing to me is, is that we know that a lot of the original beliefs I guess this is a family show, so I'll be careful what words I use, but it's just not true.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And yet we still have major restrictions on how we're supposed to use or rather avoid testosterone, especially in men with a history of prostate cancer. And I don't think any of those are scientifically based.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
How did that happen? It's a good story. So, listen, you know, when I was a young urologist, All I really wanted to do, when you finish your residency, you're not a complete urologist or surgeon yet, right? Like you're hopefully reasonably safe, but you're not skilled. And the challenges then were to do things right, to learn how to do, to become a better surgeon, more efficient.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
I wanted to be a good surgeon and I wanted to learn how to treat all these different things. I started off in male infertility and male sexual issues. And part of the reason I picked that was there were some new procedures for sexual dysfunction that required microsurgery or they were just interesting cases. So, you know, arterial bypasses for erectile dysfunction. We hardly do these anymore.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But that was exciting back then. And so I started seeing some men who had ED or decreased libido, and they were desperate, some of them. And this was 10 years before Viagra would show up. And so a couple of these men would say to me, don't you have anything, doctor, that you can help me with? My wife's going to leave me or my girlfriend is really unhappy with me.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And as an undergraduate at Harvard, I had worked in a laboratory for three years with lizards, the kind that you find in Florida and in the Carolinas, the little guys that are everywhere. And the experiments involved testosterone. And my project was to put testosterone into the brains of these males.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
If you castrate a male lizard and you put him in a cage with the female, normally if they're not castrated, they have this whole sexual behavior. They've got this bright flap of skin that comes out. The head bobs up and down quickly and they mate. And if you castrate them, you put them in the cage, they don't do anything. They don't care. They have no libido.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
and my project we had mapped out where in the brain testosterone was taken up and we knew which of those areas were likely to be the sexual centers and i had a my project was to figure out a way to put little testosterone implants tiny tiny tiny into the sexual centers of their brain and when i was successful and it took a few years to figure this all out even though the male had no circulating testosterone that we could detect
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
The male would see the female, and the flap of skin would come out, head would bob up and down, and they would mate. It restored all their sexual behavior. It was incredible. And what I learned from that was that testosterone was, amongst other things, a brain hormone. It worked in the brain, and it was enough to regulate the entire sexual repertoire of these lizards.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
The deep part of our brain that's also involved with sexual behavior, we still call the reptilian portion of our brain. And we call it that because some of the old parts of the brain are conserved. You know, the processes are identical or almost identical, going back to earlier vertebrates in evolution, like the reptiles.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So having done that research was the only reason I ever conceived of testosterone. All I knew of testosterone was it's dangerous. If somebody has bad prostate cancer, we lower it. Castration was a common procedure I did as a junior resident. And then the LHRH agonist started coming in towards the end of my residency. We started using that. But it occurred to me that maybe men...
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
were like lizards. And I took a few of these guys who were pretty desperate, and without knowing what the effect would be, I just gave them some testosterone. I told them, you know, there's a risk of prostate cancer, and they were willing to take whatever risk it was. And you know what? It worked for them. And it worked for them sexually, and it worked for them in ways that I hadn't anticipated.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And these men would tell me stories like that they have more patience to play with their small children, that their wife likes them more, that they wake up in the morning with optimism for their day, which they hadn't had in many years. And it was rather remarkable. And so I stuck with it, but I monitored the prostates extremely carefully.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And before too, too long, I actually started doing biopsies of the prostate just to protect myself and my patients to make sure that they didn't have prostate cancer that might grow. And this was prior to the PSA or PSA was already... PSA was relatively new, but it was there. So... You know, in academic centers, we were already using PSA. But as you know, PSA isn't perfect.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
So I was doing biopsies in prostates of men with normal PSA, normal digital rectal exam, only because their testosterone was low. And my first paper relevant to this to the prostate cancer story was actually the first piece of evidence that the testosterone and prostate cancer story wasn't correct.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Because not only was it believed that high testosterone caused prostate cancer and made it grow quickly, it was also believed that if you had low levels, you would never get prostate cancer. As a resident, we heard, eunuchs never get prostate cancer. It's not exactly true, and one has to wonder, how do people know so much about eunuchs and prostate cancer?
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
How many doctors were around who had a large population of eunuchs that they would follow for 50 years or so until they were in their 70s or 80s and decided, yep, there's no cancer? Nobody. I mean, it's not real, but that was a story. And so these were men that we were biopsying before testosterone. And the only reason we were biopsying them was because they had low testosterone.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
PSA normal, digital rectal exam normal. And we found prostate cancer right away.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
This was called, it was a sextant biopsy. We only took six cores back then, and it was totally random. Ultrasound guided, but random. And one out of seven of these men had prostate cancer. Most were Gleason 6, which we were still worried about back then, seriously worried. And some of them were Gleason 7.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And I'll tell you this little story because I think it tells us a little bit about how things work. So I had 50 patients. Now, that's not a ton, but these were probably the first 50 patients that underwent prostate biopsy because they had low testosterone. So I was hoping to treat them if their biopsies came back negative.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
and submitted the paper, and I've published my share of papers, and this never happened to me before or since, which is that one of the editors called me on the telephone and said, you know, our editorial board just discussed your manuscript, and it's very interesting. It shows the opposite of what everybody has believed. You have a group of men with low testosterone, high rates,
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
Of prostate cancer. So we're interested in this. It's very curious. But you know, you only have 50 men. And I tell you what, if you accumulate more men and you do biopsies on them and the numbers hold up, please resubmit your paper and we'll consider it very seriously. So when I had 77 guys, I resubmitted it and it got published in the Journal of the American Medical Association in 1996.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
And that was the first time that, and it was clear then, that low testosterone was not protective. And we followed that up a few years later as I started doing more of this with another 345 men and the results were identical. So part of the story was BS. Low testosterone was not protective. These guys had as high rate as prostate cancer as anybody.
BackTable Urology
Ep. 188 Testosterone Therapy Today: Clinical Advances and Safety with Dr. Abraham Morgentaler
But I was still worried about high levels of testosterone. And I'll tell you how, can I tell you how that? Yeah, yeah, go ahead. No, no, I'm enjoying this. This is also amazing. It's sort of funny how these things happen, right? So I had a fellow from Brazil, Hernani Rodin, and he had pulled together a lot of research data for us. We published some.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it wasn't just, and where the things went awry is the idea, not just that lowering testosterone to severely low levels was beneficial, but it got thrown in with this idea that testosterone must be dangerous. And that's where things are off.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. So here's how that happened. And just to lay the background a little bit. The reason nobody challenged it is because testosterone had just started. We didn't think about it the way we think about it now, right? So there's a lot of physicians now who are very pro-testosterone. Let's find these guys who are doing poorly in one way or another.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Let's make them feel better and their health better, right? But that wasn't true back then. It And there was no doctor who had a huge number of patients in his practice that could say, now, hold on a second. I've treated 200 guys. This doesn't happen. They don't get prostate cancer. Those things didn't happen because it was a self-perpetuating concept.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Like, if you really believe it, you're not going to use testosterone. Why would you put your patient at risk? So nobody did it. And the only reason I did it was because of my experience with lizards. And the desperation of some of these men. So I lined up when I started. I wasn't trying to change the world and I had no idea if testosterone would be good for him. No idea.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But they were willing to try. And I told them this could cause prostate cancer for you. They said, Doc, I'll sign anything. I don't care. I'm in trouble right now and I'll do whatever it takes. And so we tried a few things. And right away, what these guys said to me is, yeah, not only was sex better, sex drive, erections were firmer, but they said things to me I had never expected to hear.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I didn't really know what to do with it. They said, my wife likes me again. They said, I have four small children. I've never had so much patience with them before. One guy says, I wake up in the morning, I swing my legs over the side of the bed, and I'm optimistic about my day. I haven't felt that way in 15, 20 years.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I wondered, maybe this is, you know, in medical school, you learn a lot about placebo effect. These guys were getting the male hormone. 30% should improve. And maybe this is a placebo effect, the non-sexual part. But what convinced me that it wasn't was that when I had to find out how do you treat men with testosterone. So I say nobody gave testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
There were exceptions, but they were rare. And they were treated by endocrinologists for these young men generally who didn't get through puberty. even though they were in their 20s, because of genetic issues like Kalman syndrome, Klinefelter syndrome, or they had pituitary tumors, or maybe they had lost their testicles, both of their testicles, to trauma or cancer.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So in every city, there would be a handful of men with these rare conditions, and the endocrinologist learned how to treat those guys. But the idea that you could treat a regular guy without a pituitary tumor with two testicles wasn't known. But I went to the endocrinologist, the senior person. I said, how do you treat with testosterone? At Harvard or somewhere else?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, at my hospital, Beth Israel Deaconess Medical Center. And she said, oh, it's easy. You give 200 milligrams of testosterone, cipionate every four weeks. So that's what I did. And the patients came back. And what I told you, all the good stories they had to say were true. But every one of these first guys I lined up said, but doctor, I got to tell you.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
For a week or two before my next injection, all my symptoms comes back. What's up with that? And I joke that it's like a bad version of a double-blind experiment because the patient didn't know and I didn't know. I didn't know what was going on. So they feel so much better and then they don't until I started checking blood tests on these men.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it turned out by two weeks, everybody's blood level of testosterone had returned to their baseline low value. And so what I learned from that, from the first three patients was that, because there's no way the guys knew what their blood levels were. I didn't know, right? I said, guys can tell when their levels are good and they can tell when their levels are low.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It changes almost on a daily basis. They can tell the moment that they drop. So I said, this is real. This is no placebo effect. And so that gave me, and they didn't get prostate cancer. Were you worried? You must have been. Oh, I was terrified. I was terrified. I spent most of my career terrified.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Oh, it's great to be here with you. Thank you.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Well, I'll tell you. So I pushed the envelope in a lot of different ways. So the first hurdle was just, can you give testosterone without making it so these guys get prostate cancer? Where it went next was that there were men who had like pre-cancers, we called them.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
A technical term is prostatic intraepithelial neoplasia, PIN, which we used to think meant if somebody had a biopsy and they had PIN, we said, oh, there's got to be a cancer hiding in there somewhere, and we would re-biopsy them, like within weeks. And I gave testosterone to these guys with these pre-cancers. Nothing happened. Published that data.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
and then gave it to men after they'd been probably cured of their cancer by surgery. There's about a 15% recurrence rate after surgery, so you never know. And then eventually, near the end of my career, even gave it to men who had metastatic cancer or their cancers had come back. And at every point, I was still worried that maybe something bad is going to happen to her. And? It never happened.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Never once. So this metastatic cancer thing is amazing. So today the controversy is, so I think everybody is clear out in the medical community, pretty much, that giving testosterone does not increase the rate of cancer compared to a placebo. The biggest study that we've had is called Traverse, came out about a year and a half ago in 2023. Numbers of cancers in the testosterone group were 12.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Thank you. You know, it's hard for me to accept something like that, but practically speaking, I think that that's right. And, you know, I started doing this at a time when everybody thought testosterone was going to absolutely give people prostate cancer, like pow, right away. Just a little whiff for a week or two, prostate cancer. That's the fear that we had. And I got interested in it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Number in placebo was 11. This is over 5,000 men, three years of follow-up roughly. It's the same. It's the same. And so that part is kind of clear. Giving testosterone to men who have prostate cancer, that's still controversial. But I've treated many hundreds and hundreds of men like that. Never seen anything bad happen.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I can't think of any condition where that's a problem. You know where it comes up is there's still some debate about venothrombotic events, DVTs, pulmonary emboli, things like that. I think the data are clear. I've been involved in a couple of studies around this, and the Traverse Trial 2 showed nothing with that. But I'll tell you how people think and what they do.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
There was a guy, there's a doctor who has published on testosterone and this venous thrombosis risk. He's published a lot on it. And he believes testosterone increases that risk. So there's a epidemiology-type guy who invited me to participate in research that he was doing looking at this problem, and he invited that other doctor who thinks that it's a problem to be an author on the paper.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The study comes out, or the data comes out, and we're all just discussing it. It's written up, and it doesn't show any increased risk, none. And this guy's a very, his name's Jacques Bayargeon. He's a very accomplished sort of public health researcher. And the fellow who thinks that it's a problem looks at the data and says, well, you didn't look at this and that.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I think if you do, we're going to find more of these events. So Jacques goes back and he re-looks at the data the way this guy wanted him to and nothing. at which point there's an interesting conversation with the other author and says, listen, if you don't want to be an author on this, I'll understand it, but these are the data we have.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And to that fellow's credit, he said, well, listen, you did the analysis, and if that's what it is, I'm happy to be a part of it, which is really the way medicine and science should work. So a credit to him. But where his original work came from is he took people who already were at risk for having DVTs and PEs. Like you can have clotting problems, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Exactly. So some have the slide in five factor that predisposes to it. And so some people say, well, maybe you shouldn't give testosterone to those people. But this is not clear thinking. So people who are at risk for something are at risk for something.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
If you then add in something like testosterone, which has not been shown to anything, yes, they can get clots again, but it's not because of testosterone. It's because they were at risk for it, right? You might as well say- You just stick a margarine. Let's see if that happens. Exactly. Exactly right. Yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So the answer is, listen, the big ticket items that we've worried about, prostate cancer, cardiovascular risk, Those are now clean as far as I'm concerned. There's just no data to show that there's a problem.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I'd love to tell you how I got started. But my work has really been about using testosterone and showing that it didn't really cause prostate cancer. I didn't know that before I started, but that's what happened. And as the barrier to testosterone dropped because people weren't so worried about prostate cancer, then all sorts of things opened up. And here we are 35 years later.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Oh, yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, it's an amazing story. So, I started publishing data showing that this old relationship we thought existed between testosterone and prostate cancer wasn't true. And even published in the New England Journal of Medicine.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
No, no, no. But we published doing the Journal of Medicine together with my former fellow or nanny Roden that this in 2004 that we just could not find a single piece of evidence that supported this idea that testosterone was dangerous for prostate cancer. We couldn't find it. We didn't say it didn't exist. We say we can't find it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And the editors at New England Journal, they didn't want to publish that. That was a crazy idea. Everybody was taught this around the world in medical school. It was a foundational concept in oncology that testosterone makes prostate cancer grow. It's bad. You can't use it. And they sent it out over the course of a year to three sets of reviewers.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
First urologists, they couldn't find anything wrong with it. Then three endocrinologists, they couldn't find anything. Finally, to three oncologists. And listen, when we did it, I was relatively young. I thought maybe we missed it. I mean, I believed it until actually I pulled all those papers. I believed That high testosterone must still be a problem in some way, even though I couldn't define it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But that's what I've been taught. And then nobody could find any fault in what we'd written. So it was published, 2004. It took a year. And so I'm kind of on the lecture circuit within medicine and urology. And I'm talking about how we couldn't find the evidence, blah, blah, blah. And there's a great prostate cancer specialist named Paul Lang. And he was on the same faculty at this thing.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I think it was at Vail. And we're talking afterwards. And he says, listen, Abe, this is really interesting stuff you got, but you better be careful. Because it could be different in metastatic cancer. Huggins said so. So I'd heard, of course, of Huggins. Huggins is probably the most important, biggest character in all of urology. Prostate cancer is our biggest topic.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
He's the prostate cancer guy, Nobel Prize winner, the only urologist to ever win the Nobel Prize. So everybody knows Huggins. But we didn't have access at that time to articles online the way we do today. You can pull up Huggins' article now in 20 seconds. I'll give you a couple of keywords. You'll have it. But not then.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Where articles, especially old literature, existed was in bound volumes of published journals. And in a department of urology or any department, surgery, gastroenterology, whatever, people would have their bound volumes behind their desk. But it's stuff that they had collected. And maybe it went back there in practice 15 years. They had 15 years worth of bound journals.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I was very proud when I started getting my own journals bound. But nobody had articles that went back 40 years. Right. To do that, you had to go to this crazy building that housed old stuff. It's called the library. People don't even know. Never been. People don't. Yeah. And down in the basement of the Harvard. And so I went because this guy, Paul Lang, said to me, Huggins said so. Excuse me.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Well, we knew about it, but I'd never read his articles. I knew what people said about his article. I knew what my former teachers taught me about his article. So at some point I said, I got to see what he wrote. I was nervous about it. Armpits were sweating is the whole thing. Well, to be honest, I had a good thing going around this testosterone product.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
My patients were happy and I didn't want to mess it up. And in the end, I said, I got to do it. So I go down to the basement of the library. There are all these old, dusty volumes. You take it out, you have to blow the dust off the top. And there it is, 1941 Cancer Research. And there's the article by Huggins and Hodges. And I read through it. And I had two small children at the time.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I'm thinking, I read through it. And the last sentence, the last sentence of the article says, testosterone injections activate prostate cancer. And I was sick to my stomach. I was awful. My hands were sweating. And I had visions of the Harvard police coming and arresting me then and there.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it being a big Boston Globe front page story that my kids would see, you know, the Harvard doctor like arrested for, you know, ethical malpractice by giving testosterone. And so I forced myself to reread the article. And just wrote down a few basic questions. How many men did he treat? For how long?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it turned out that the number of men he had treated, most of this was about the guys he'd castrated. The number of men he treated was only three. Only three. Of the three he had treated, he only actually gave any information about two of them. One of those men had already been castrated, which today we know is a special case.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So this whole idea that testosterone causes, the general concept makes prostate cancer grow, or as Huggins said, activated, was based on one guy who received testosterone for only 18 days. And his curve is uninterpretable. Goes up and down, up and down, before and after testosterone. It was amazing.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Acid phosphatase.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. What can we learn from that? Yeah. I'm so glad that you're underscoring this point because, you know, I've done research for 50 years since I was 19. Since yesterday. And all different kinds, right? Like randomized trials, pharmacokinetic studies, animal studies, basic science studies. My greatest discovery is
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
was actually figuring out, finding out that Huggins based this whole thing on one patient. And he was wrong about it. There was a misinterpretation of that information. And that's the basis why people around the world have learned for 80 years, have been told that testosterone... activates prostate cancer, and later it switched.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Huggins never said this, but people started to believe that testosterone actually caused prostate cancer, which it doesn't do either. There's no evidence for that, none, zero. Nor does it make the cancer any worse, unless, here's the thing, unless you're already castrated, which only happens if you've already been treated for advanced prostate cancer. And that's where people have messed up.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
You know, so the field has moved. I'm proud to have been involved in some of that. But man, it's hard. I've been railing at this point for so long. I've been debating on stage at the national urology meetings, prostate cancer stuff for so long. And that's probably not a comfortable place to be. Well, I have to tell you, there's a part of me that enjoys that. I do.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Especially because all the arguments are on my side. It's an amazing thing to try and get people to open their minds. But these ideas die hard. I would say that the myth about testosterone and prostate cancer is the most persistent myth in medicine. It's been pervasive. And just the other day, I had somebody that I know who's in his mid-70s. He's got an uncertain spot by MRI of his prostate.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So we went to see this prostate cancer specialist. He says, listen, we're going to biopsy it. I don't know that we're going to treat it necessarily, given your age, and it may just be a low-risk thing. But if we find anything at all, you're going to have to stop your testosterone, which he's been taking for about 10 years with great success. Now, this is an academic center in a major city.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
There's no reason, it makes no sense that academic people are still saying this garbage to people. It's based on nothing.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But that's a whole other topic. So you know who said it best is... So old ideas die hard. And there's this guy, Max Planck, who won the Nobel Prize for physics somewhere in the 40s or 50s. And he wrote about new ideas. And I'll try and do the quote credit because I think it's great. He says, new scientific concepts do not triumph because the opponents to it have been convinced.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And now they see all of a sudden see the light. It's because they die. It's because they die and a new generation that's familiar with it grows up with it. And the short version of that is that science proceeds one funeral at a time.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. So it's just amazing. People hold on. And what happens is people don't like new information. They don't like new concepts that differ from what they've been taught. I've had people, you know, early days, I had people walk out of my lectures. I gave grand rounds at important places like UCLA and elsewhere. And there was an older chief.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And the chief always has the last word after the guest speaks. And I remember at UCLA, Gene DeCernian, who was a famous and very important, brilliant man. So some of the stuff I'm talking to you about today was not nearly as, it didn't have as many supporters as it did then. And he said, well, this is all very well and good.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But, you know, I remember back in the day, we had experiences that were completely different with that. So I'm not going to take it too seriously right now.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And that was it. He had the final word. The students are there. The residents are there. The other faculty are there. And it's just hard. Some of the old ideas have to just... The people who hold them don't want to change their minds.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
There's a lot of evidence that people confronted with evidence that contradicts what their beliefs are actually double down and they hold their beliefs even more strongly.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. So part of the challenge is that testosterone is still considered by many to be fringe medicine. And the reason for that, in my opinion, is that it's not taught in the medical schools. Still. So people, you know, we have remarkable amounts of information, wonderful scientific data about testosterone. What's amazing about it is that it's a natural chemical in the body.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it's also true in all these different animals, all the vertebrates have testosterone or something very close to it, including fish. Right. And so we have natural models to even look at testosterone. The wealth of research into testosterone is phenomenal, right? And yet people... We have studies in the top medical journals in the world, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
New England Journal has really liked all the RCTs about testosterone. JAMA has published it. We have stuff in Lancet. All the top journals have data on this. And sort of the regular physician who wants to keep up with the literature, you know, they trust those journals. But it hasn't impacted what they do.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so what we have is we have a medical condition, testosterone deficiency, used to be called hypogonadism, where people have too little of it, men or women. Men get most of the publicity around this, and it's better studied in men, but it's true for both. And do you know that testosterone deficiency either predicts the development of or is associated with
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Oh, my God. So, listen, thank you for that. And it's kind of amazing sometimes I sit here and think back like on all the changes that have happened and. And we went through things. And truthfully, it did require a certain amount of courage because I was doing something that was considered dangerous.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
many of the most important medical conditions we deal with in healthcare. So obesity, diabetes, the metabolic syndrome, cardiovascular disease, mortality, dementia, osteoporosis, these things are all associated with the deficient amount of testosterone in the body.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And beyond that, these men, let's focus on men for a moment, these men have symptoms that often make them, I say the testosterone deficiency is a reduced state of the human condition. There are data. I told you there was a golden period of testosterone research from the late 1930s to about 1940.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
1940, this guy, Dr. Joseph Aub, AUB, writes an article in New England Journal of Medicine that says this is one of the most potent medications that we have in our armamentarium. And they described men who were basically, they called them broken men back then. Broken men, that was the term. There were these men who just, they lacked confidence. They were quiet. They were introverted.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And they got testosterone and they became better. Now, I suspect that we didn't have blood tests back then, not till the 1970s. I suspect that many of these men who underwent these trials had extremely low levels. And the lower your level, the more of a benefit you're going to see, right? And the more the low level is going to impact who you are and how you carry yourself.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But men, this makes a huge difference in how people live their lives. And so the fact that it's not yet accepted by what, you know, I'm a mainstream doctor, but I'm going to call this not accepted by mainstream medicine is our number one problem. And what gets compounded then is that because there's a tremendous need, people now know that testosterone deficiency exists.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
They know somebody, they heard of somebody who got treated. They say, maybe I can get some too. If the And so some of the docs that are doing this are docs that the sort of, I'm an academic guy, you know, it's like science-based, but the academic docs see those groups of physicians and they say, I don't want to get involved with that. I don't think that well of those practices.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Part of testosterone's problem is it has a bad rap.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It has a bad rap.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Blood vessels. Blood vessels.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. No, we're treating a tiny fraction of the men who have it. And it's funny because in some ways, testosterone is, the men who really need it don't get treated, not enough of them. And a lot of the men who don't need testosterone are getting it, right, through whatever, gyms or, you know, there's a trend to give it to people who aren't even deficient. Can we talk about that?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But I always felt like what I was doing was in my patient's best interest and with open communication and discussion of what the potential risks were. So the story originally begins, if I may, when I was 19 years old and I was an undergraduate at Harvard. And I was supposed to be a hockey player. Like in my head, I was going to be like a professional hockey player.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, I have feelings about that.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, good. So I think there's broad agreement, and I certainly agree with it, that people should be treated if they have low levels of testosterone, they have either symptoms or what we call signs of Symptoms are things that people experience, like my sex drive is down.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Signs are something you can measure, like their hematocrit, their red blood cell count is reduced, or their bone density is down. Something you can measure. So traditionally, all the guidelines say you should have both. The challenge is, what's a low level of testosterone? And critics of testosterone therapy say, the experts can't even agree on what a low level is. And that's true. And that's true.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And part of it is that some of the decisions about what a low level is has been arbitrary. So the FDA uses a number below 300 nanograms per deciliter. And if you look at any of their writing, they have no citations for that. There's no reference that says where they got that number from.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So the urban myth that I think is true is, based on talking to people, is that when there was a first new testosterone product brought to the FDA in the late 1998, I think it was a patch, the FDA said, well, you have a drug that's supposed to normalize testosterone. Please tell us what a low level is. Fair. I mean, that's totally fair.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so they had a very senior expert and he said, well, people disagree on the number, but some people think it should be 400. Some say 350, some say 250. And free testosterone was not discussed. Nobody's talked about, we have to talk about free testosterone, but nobody's, that has been part of the conversation for forever.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But, and so this guy said, apparently to the FDA, I think 300 is a fair number.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. Could we treat them? Well, of course you can if they have symptoms, in my opinion. First of all, the idea that there's a single number that separates everybody is just anti-scientific, right? We don't work like that. Our bodies are not clones of each other. You do research in animals like rats. They're all the same genetic strain. They're all basically identical twins.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
That's not true for humans. And we all have different set points for a lot of different things. People can tolerate cold, heat, pain. We're all different with all these things. And true also for when people become symptomatic in terms of having low levels of testosterone. But it's worse than that. It's worse than that because what a low number is, is defined by specialty and by geography.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And geography. Geography.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. So get this. So in the United States, the endocrinologists, their guidelines say you have to be below 264. Urologists say 300. FDA says 300. Guess what happens in Europe? In Europe, they use 350. Wow. I ran a expert panel on testosterone some years ago, which we published. And we had a couple of European guys.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And there's one guy from Europe who says, if they have symptoms and they're under 400, I'll treat them.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it turned out I could play at a decent level. I played freshman at Harvard, which is a good school to play freshman level. There's no way I was going to play varsity. And in my second year, I didn't know what I was doing. And I ran into a biology professor from whom I'd taken a class in Harvard Square. And I was completely lost. I was just a lost sophomore, not sure what I was doing.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
No, it's not guidelines. So if you have a guy like 310 in the United States, you go to a primary care doctor, he says, it's normal. I'm not going to treat you. If you go to Europe, they say, oh, yeah, you're low. We'll treat you. Well, that doesn't make any sense. Because if you go see an endocrinologist, they say, you could have a testosterone at 275.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The endocrinologist said, according to the guidelines, you're normal. I shouldn't treat you. But the same endocrinologists that write that have also performed many of the most important studies we have, where they use values under 300. Or in some cases, they had one, they said, we wanted unequivocally low levels, 275. But that's not even what their numbers are now. Now it's even lower.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So what is, and also age doesn't matter, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Well, according to guidelines.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. So, you know, listen, I'll give you my take on guidelines. Guidelines is an important, has been an important step forward in the last, it's really only in this century, you know, the last 20 years or so. And it's really, they provide guidance, but they're not the rule of law, right? And in the end, it's a group of individuals. You could have 10 people sitting in a guideline panel and
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And they all might practice differently, 10 different ways. But they have to come up with basically a consensus document. So they might say, okay, let's say 300 is the number. So they put that out. And maybe they have other requirements too. How many times do you check? Does it have to be morning? Does it have to be afternoon?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And at the end, after putting that out, they all go home to their practices and they can still practice differently than the guidelines, 10 different ways. But people think, oh, it's guidelines. There's a clear way, right way to do things and wrong thing. And you can't deviate. No, not at all.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I think guidelines are helpful for the novice, in my opinion, that gives you a general sense of what's probably safe to do. And in almost all circumstances, conservative, But I think once a physician or a healthcare provider gains a certain amount of clinical experience, clinical experience can, in my opinion, often outweighs what the guidelines say.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. So let me use that question to get back to solving the mystery of testosterone and prostate cancer. Like, how is it that lowering it is helpful, but raising it doesn't seem to be dangerous, right? And the answer is the term that you used, which is saturation, that I came up with in about 2007. And then together with my dear colleague, Abdul Tresh, we really put the finishing touches on it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And what saturation means is that if you started out either prostate cancer cells or prostate cells or animals or humans... with essentially zero testosterone. You give them more testosterone. Prostate tissue does need androgens, testosterone-like substances, in order to grow. True. It's a requirement for them. But it turns out that the maximum ability to grow
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
maxes out at a relatively low concentration of testosterone, which looks like it's around 250 nanograms per deciliter. So there are studies, and I'm a part of one, Mokira, that you mentioned, published another one, where if you have men who have levels below 250 and they get testosterone, the PSA, which is a marker of prostate activity, goes up.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And he said, how are you doing? And I told him, actually, I'm not doing that well. I don't know if I should just stop college, just drop out. And he said, why don't you come work in my lab? You might like it. His name was David Cruz. And he changed my life and put me on a track from age 19 to here I am 50 years later. It's unbelievable.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
If they start with a testosterone above 250 and you give them more testosterone, nothing happens. So that saturation, imagine a sponge with water, you can put it on a scale, has a certain weight. You add a little water, it absorbs it, the weight goes up. You add more and more water, at some point it's saturated. It can only hold so much water. Adding any more water doesn't do anything, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So it's maxed out. And different prostate, it looks like the saturation point is around 250. Different tissues are different. So, you know, men who are castrated or undergo treatment, so medical equivalent of castration, get hot flashes just like women in menopause.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It turns out, and we call that vasomotor instability, like the blood vessels and whatever is sensing it centrally in the brain goes crazy, right? But it turns out that if you let a guy's testosterone get back to about 100, which is an extremely low number, it's gone. Very low. No more vasomotor instability. So whatever that is, that saturation point is probably around 100. Prostate's around 250.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But a lot of guys at 250 still have symptoms from testosterone deficiency, like low libido. And some of that probably gets satisfied at numbers around 500, maybe 600, depending on who the guy is. That's saturation for that symptom in the brain.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. Listen, my lizard stuff. Testosterone is a brain hormone. Yes, it also works on muscle and fat and all these other organs, but it's a brain hormone. Absolutely. So one thing that's interesting is that is so the question comes up. If somebody who doesn't have low testosterone takes testosterone, what's going to happen to them? Great question. Yeah. Sorry, I didn't mean to take your time.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Wonderful. No, no, you're doing great. Forgive me, forgive me. Please.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So what I mean by not low, in some ways, the easiest way to define it is it's certainly well within the normal range and that individual has no symptoms, right? They just say, I think I might be better in some way with testosterone. So if you have a guy with, let's look at sex drive, for example, a guy who's upper end of normal, we often define as around a thousand, okay?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So if you have a guy who's 900 compared to another guy who's 700, Which they're both well within the normal range. They're going to have, on average, the same amount of libido. As a matter of fact, you can take the same guy. Let's say you could manipulate his hormones at 700 to 900. Nothing changes for him. Not erection, nothing. Because his testosterone is normal.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so he had a reptile lab and he was interested in sex, hormones, and the brain. And so the first project, I worked on these little American chameleons. They're all over Florida. If you've been there, you see them everywhere on the walls, on the sidewalks, inside your hotel room sometimes. Terrifying.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The one area that does not seem to max out is muscle. Is muscle. And that's why the bodybuilders, the athletes who are taking anabolic steroids that are all versions of testosterone-like compounds, versions of testosterone, why they can have muscles on top of muscles on top of muscles. Right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So anybody that's on normal amounts of testosterone therapy, just trying to get them maybe to the upper, into the normal range or the upper end, or even if they might slip a little bit above it here and there, it's not a problem. I've treated thousands and thousands of men. There's nobody who walked into my office looking like just regular muscular, who walked out like super built.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
you need to get levels that are 10 to 50 times higher in terms of testosterone equivalents to start doing that.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So here's the thing. Most of these people don't actually use testosterone or maybe part of their regimen. So they stack. They use multiple agents that do this. And some of these agents have never been really tested in humans. They've been used in cattle and horses, for example, like Winstraw.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And they seem to be more potent for the muscle effects rather than sort of the libido effects and things like that. But in terms of testosterone equivalency, in terms of muscle potency, some of them are more potent. And the reason that testosterone works differently in muscle is muscle has an extra receptor for testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So for almost everything testosterone does in the body, there's one receptor, which is a chemical that binds it. It's called the androgen receptor. In muscle, there is a second receptor that's bound to the cell membrane. It's called a G-protein coupled receptor. And it's hard to see. I'm not sure that there's an upper limit to how much you can get with testosterone through that second mechanism.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And you put a male in the cage with the female, and they have this bright colored flap of skin that comes out. It's called a dewlap. And the male sees the female, the dewlap comes up and their head bobs really quickly. It's almost like the male is going, yeah, yeah, yeah, yeah, yeah. Like he's interested. The female does a little stately pushup that says, okay, buddy, what you got?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, I'm so glad you asked. So, you know, the everyday scenario that I hear about is that somebody goes to the doctor and they have symptoms of low testosterone and their testosterone comes back in what is called low normal range, right? So let's say it's 310 or 320 or 350. And the doctor says, well, you're normal. almost all of those men will have low levels of free testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And the short bullet is that free testosterone is the most reliable indicator of a man's testosterone status. So I hope I don't get too sort of nerdy with this, but... But your viewers can handle it, I'm sure. Yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So listen, so when you measure total testosterone, what they do is they take a certain amount of your blood and they measure how much testosterone in total is there per little unit of blood. So it's measured in nanograms per deciliter, a tenth of a liter. But testosterone circulates in three forms. More than half is bound to this carrier molecule called SHBG, sex hormone binding globulin.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And what's important about that binding is it's so tight that testosterone can't come off it. So if the testosterone attached to SHBG is just floating past a cell that's saying, hey, give me some testosterone, I'm hungry for testosterone, testosterone can't get in there. That portion is not biologically available.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Most of the rest is attached to these other proteins in the blood, like albumin, but it's weakly bound. So it goes on and comes off, goes on and comes off. And so when that cell is saying, hey, I need some, there's enough of it coming off of that that it can get in there. And 1% or 2% is free, which means not that the test doesn't cost you anything, but that it's unbound, unbound.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And what gets through that cell membrane is the free testosterone only. So testosterone is lipophilic. It likes lipids. All cell membranes are lipid bilayers. It's like like, likes like, and it can just go right through it. It doesn't need any carrier proteins. It doesn't need sodium channels, calcium channels. It just gets into the cell that needs it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so the free only makes up one or two percent of the total. So as we get older, our SHBG rises and it tends to bind more of our testosterone. And so most of that isn't available to the cells. The total can look normal, but actually the free may be low.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And then the male comes closer and repeats the behavior and then they meet. So if you castrate the male, which means removing the testicles, which was the first procedure I ever did in anything, not knowing I was going to go to medical school, let alone become a urologist. But if you castrate the male, you put him in a cage for the female, they don't do anything. They have no interest.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. So SHBG is, the beauty of free testosterone is it's unrelated to whatever SHBG is doing. So SHBG is binding up a lot of the testosterone that gets measured in that blood test. But the free testosterone is just hanging out doing its thing. So it is whatever it is. It's either low or it's normal, or potentially it could be high if you're on treatment. So it's unrelated.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But what it means is that women who have been on birth control pills, and women in general tend to have higher SHBGs than men do, it means that their total testosterone is even less reliable in women than it is in men. And so in order to properly interpret what a man's status is, you either need to get a free testosterone test, or we always measure SHBG.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And you can actually, there are these online calculators. You just put in the SHBG value, the testosterone value, and it'll spit out a number for you for the free testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. I mean, so what happens is that the total testosterone number when SHBG is generous or high is unreliable. It's going to look like it's fine when the person is really deficient, right? But if you give testosterone, the free will go up and the total also goes up.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so when I have somebody where there's a discrepancy, so most of the time when there is a man who has a lot of symptoms, we say, oh man, his blood tests are for sure going to show low levels of testosterone. And his total comes back within the normal range. It's almost always explained by having low levels of free testosterone. which usually goes along with generous levels of SHBG.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The treatment is the same. The treatment is the same. And the goal of treatment is not to get the total testosterone into the normal range. The goal is to improve the symptoms that the man is having and hopefully resolve them. And they will resolve if it's hormone-related.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But because these guys with elevated or generous SHBG levels already may have good total levels, I always tell the patient, and I put it in the record because other doctors will see these notes, that the total testosterone is likely to be very high with treatment because we're treating a free testosterone level.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. I have a very prominent patient who has a lot of doctors, and he's just like that. His total testosterone is fine. His doctors didn't think he needed anything. His free testosterone was low. And his total testosterone was mid-range normal. I don't remember the exact number. It's many years ago since we've started treating him. Let's say it was 500, yeah?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And most people say, oh, that's robust, right? But he had all the symptoms. He had low free testosterone. So we treated him, and all his symptoms got better. It's interesting. This is a man who you and I would think that everything he's done, he should be on top of the world. But he wasn't. He's a guy like everybody. And when testosterone is low, he wasn't who I thought he would be.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The female will sometimes do her push-up and say, hey, buddy, I'm over here. But their testosterone is gone. And then my project was we'd mapped out where in the brain, the itty-bitty brain of these itty-bitty lizards, where testosterone was taken up and what was likely to be the sexual centers. And my project that took three years to do was to put tiny implants of testosterone powder
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
He was really struggling. Yeah. And life is hard. It just is, right? We have challenges every day, whether you have small children, elderly parents, difficult relationships, work. Life is hard. And what I see testosterone doing for a lot of people even if they're not like out and out miserable, is they lose what I call the critical 5%.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
There's a certain way that you, for example, are successful because you've got drive and passion and skill. But if you lost 5% of you, you could get through your day. You could do podcasts. You could write. But it would be a chore for you. And you would lose some of what it is that makes you, you. And that's what I would see with a lot of these men. They'll lose their sense of humor, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
They lose their sense of play. They lose their reserves. People think testosterone makes people irritable and aggressive. It does not.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But irritability happens when people don't have emotional reserves. And they lose those reserves when their gas tank is approaching empty. So... Yeah. So I'm sorry for that little. I think it's really important.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But in the end, what I'm really saying is, you know, here we're talking about numbers and they're important and they're going to help people out there who are listening and hopefully health care providers, too. But in the end, what we're talking about are people. We're talking about people.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I've had discussions with prominent endocrinologists and other academics, but why don't you take this testosterone business more seriously? We've got great research. And they say things like, I remember this one conversation, this very, you know, academically important person said, well, I think we'll take it more seriously once we have studies that show important differences in outcomes.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And what she's talking about are mortality rates or complication rates of this, that, or the other. But what gets lost in all of that is the individual person. The individual person. And one of the most gratifying things for me, and part of why I fought on with the testosterone story, especially early days, is that I was making a huge difference in the lives of these individual people.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I didn't have an agenda to show testosterone was good. I was working hard just to be okay at what I was supposed to be okay at. I was learning surgical skills, trying to become an expert in all these things, but I had these patients.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And it turned out that these guys who had low levels of testosterone, some of them just low free testosterone, if I treated them, they'd come back and they had the most marvelous stories about how their lives were improved. And when I was, especially early days, what was amazing, I felt like I was seeing, because nobody, none of my colleagues were treating with testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It's not just that they weren't treating, they thought I was doing dangerous medicine.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I caught a lot of flack. I had some tough situations. But what kept me going was I was seeing something that wasn't being described in the literature or that I had been taught. I was seeing something. It was like these guys saw all the best-known urologists or endocrinologists like in Boston where I was without success. And they'd see me. I said, well, your testosterone's low.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
into those little sections of the brain. And when I was successful in doing it and putting it in the right place, these males that had no detectable testosterone, just testosterone in their brain, would see the female, the dewlap would come out, head would bob up and down, yeah, yeah, yeah, and they would mate. It was the most amazing thing. And so my first publication on testosterone is in 1978.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Let's see what happens. I mean, I didn't have any guarantees. And they'd come back and they'd say, oh, my God, like my life is better. Let me tell you one story. This guy came to see me. He was a surgeon. He didn't care about it. I don't know whether sex wasn't an issue for him in his life, or he just didn't care about it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
He says the problem is that he's up all night operating, and the next day he has full clinic, a full day of seeing patients. And he says, you know, for the first 15 years of my career, that's not a problem. He says, now I find that I'm falling asleep the next day after being up all night. And I'm just wondering if it could be testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
His testosterone was low and I treated him and he came back and follow up. And I said, how's it going? And he said, well, I don't fall asleep anymore the next day. So he was like happy. I said, well, that sounds great. He says, but it's more than that. He says, since I started with you. He says, I've reorganized my entire division. I've written three papers. I've made two educational videotapes.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Like this guy had gone to town. That's who he was before. He had stopped doing that. What got him is he couldn't stay awake, right? Like that's what brought him to the office. But in fact, this guy was a superstar. He was a dynamo and he'd lost part of his dynamism. And that's what testosterone can do for people who are deficient.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
You know, I'm chuckling. So listen, testosterone is the most interesting chemical.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
No, it's true. The amount of stuff that's involved, it's everywhere. We had a talk, we have an annual meeting, it's called the Androgen Society. We had an ophthalmologist come and talk about effects of testosterone on the eye. Turns out that the number one cause of office visits to eye doctors is dry eyes. Guess what testosterone does? It makes lubrication for the eye or helps to enhance it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So people who have dry eyes often have deficient tear production. Wow. Testosterone's involved with that.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
They have. So according to this guy, they use some ointment that has testosterone in it. They use that for the eye. Time me up. Right? My kidneys are going to be super sharp. Yeah, and it happens more in women who have less testosterone than men. I'm not saying that testosterone is the entirety of that story, but it's a contributing factor. Yeah, so testosterone in women.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So I started years ago a men's health center, and so I saw exclusively men.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, thank you for saying that. You know, it's funny. So I was so proud when we opened it up in 1999. And men's health was hardly a concept back then. And I was full-time faculty at the hospital, Beth Israel Deaconess Medical Center, one of the Harvard teaching hospitals. And I go to the president. And we have all these hospitals in Boston. They're all these high-powered places.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
They all compete with each other. And I went to the president. I said, listen. Every hospital in Boston has a women's health center. Nobody has a men's health center. I say, I think I practice what could be termed men's health. I do male infertility, male sexual stuff, testosterone, some prostate. I think the hospital should open up a men's health center. I'd like to run it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And we had a couple of conversations. And at the end of the, he says, oh my God, this is great. Let's do this. And I said, super. And I said, how long will it take? And he said, four years. And I said, what? He said, listen, we're a big institution. We're a bureaucracy. We can get this done, but it'll take a lot of years.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so I left my sort of lab research stuff and I went out on my own and I thought it was a great idea and it worked out well for me.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And that was the start. And then when I went to medical school, I learned almost nothing about testosterone. It was important for puberty. That was about it. It was important for men to sort of be functional. But we didn't learn about testosterone deficiency or anything like that. And then I go on to practice and I start dealing with men with sexual problems. And some of these guys were desperate.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And that was 1999. It was called Men's Health Boston. It still exists, but I'm not part of it anymore. And but what's funny is that men's health. These men's health centers have now gotten a little bit of a wonky reputation. And so I used to be so proud of it. I don't always mention it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But the idea was to have a place that really focused on various aspects of men's health and to do it in a respectful and way with expertise. And I still think it's a great idea.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. So these centers are often, they advertise on radio, on sports radio, things like that. They've gotten a reputation for not necessarily practicing the best medicine. And yeah, a lot of churning is sort of what you hear about. Now, there's a funny part to that, I have to tell you. So I don't share those criticisms completely.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And the reason is, is that within what I would call sort of more institutional medicine, right, mainstream, you know, you're here in Houston with all these tremendous academic centers. If you go see an average doctor, Houston may be different because there's some key individuals here who have popularized use of testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But in most American cities, you go to a hospital-based doctor or hospital-affiliated with symptoms around testosterone, male or female, and you will not get treated. You'll be shut down. So even at my own institution, the endocrinology folks, I'll never forget this. Can I tell a story? Yeah, please. All of them. So I would see a lot of second and third opinions, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Like people were shut out somewhere else. And this one guy comes in, he's in his mid-40s, 45 or so. And he's married. And his problem is he has no sex drive. And his wife is complaining. And he feels like it's wrong. He's not holding up his end of the bargain, if you will. And so his primary care got testosterone levels on him and they were low, really quite low.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
How did you choose urology? It wasn't obvious. I didn't know anything about urology, really. I was in general surgery. And I loved operating. And I thought surgeons had, if you'll forgive the expression, the biggest balls in the hospital. And I said, I want to do that. But I didn't like being up at night. And a lot of the emergency operations were at night.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so he got referred to the... I need to be careful about how specific I get. He goes to see an endocrinologist at one of the teaching hospitals in Boston. And the guy says to him, looks at his labs and says, you absolutely have low testosterone, but I'm not going to treat you. He says, why not?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
He says, well, in ancient Egypt, there used to be eunuchs, guys who were castrated, and they were regarded with great respect. They often had important positions in the queen's coterie, and your testosterone is a lot better than any eunuch, and they did okay. You don't need it. And when the guy comes to see me, he tells me this story. And he says to me, very funny, I thought.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
He says, I don't give a rat's patootie about some ancient queen in Egypt. I care about the princess sleeping next to me in bed every night. So we treated him, and of course he did very well. It's actually not rocket science, and I know some rocket scientists.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It's not that complicated. You just need to know a couple of key facts about how to treat, and we improve the lives of people. And the argument to not treat them is mystifying to me.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so getting back to these men's health centers, the reason I'm not so critical about them is, although I don't agree with necessarily everything they do, they often are giving three medicines instead of one that they need. And they throw in all this other stuff too, is at least those patients are getting treated. I agree with you. I agree with you. At least they're getting treated.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I think most of the other stuff may not help them, but probably doesn't hurt them. So I can't give them my wholehearted blessing. But geez, Louise, I mean... It's better than nothing.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So free testosterone gets complicated because there are different units that are used for measurement in different tests. But the most commonly used test is now called a calculated free testosterone. The lab reference ranges are useless. None of them will say that you have to be incredibly low to be categorized as low.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Appendectomies, gallbladders were dealt with, perforated ulcers. And so I looked for a field where they did good surgery. And they were nice and they had very few nighttime emergencies. And the urologist that I encountered had told the best jokes in the OR. And they were, some of them, superb surgeons. I said, I'll do that. But I really didn't know much about it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Anything less than 100 picograms per mil is, together with symptoms, in my opinion, bears treatment. And that's what I used for 30 years.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So women have about one-tenth the amount of testosterone that men do. Free testosterone is more important in women as it is in men, maybe even more important because they have so much SHBG. And the data in women, there actually is many very good studies in women. And some of them go back also to the 40s and the 50s.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
You know what happened in women is that... All their hair fell out.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It's rare. It's one of the risks in women, of course. But what happened is there's no FDA-approved testosterone product in women. And FDA has a funny relationship to medicine. FDA does not regulate the practice of medicine. They have nothing to do with what healthcare providers do or how they manage things except for making pharmaceutical products available on the market.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
they govern the pharmaceutical industry, and they will say straight out, we are not involved in the practice of medicine. Somehow, along the way, some kind of institutional part of medical education got tied into the FDA in a way that I think is actually unhealthy. So for example, I organize and speak at a lot of continuing medical education events.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It is part of the requirements, we call them CME, part of the requirement before that all speakers say whether or not they're going to be speaking about anything that is considered off-label. Off-label means using medicine in a way that the FDA didn't say is okay. So let's say a drug like, I don't know, the new GLP-1s. Great example. So they start off with whatever the first indication was.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I don't know, weight loss, diabetes. Diabetes, yeah. But it could be, it turns out there's incredible data that some of these medicines are good for other things, right? Like kidney function and- Heart disease. Right. But unless the drug company has applied for essentially permission from the FDA to state that as one of the benefits- then it's not, then the FDA won't give that as an indication.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So every drug, every time you pick up a medicine, it's got a label inside, right? Inside the box or whatever. And with a lot of fine print and all these scary things that can happen. And part of what it says is indications. That's what the FDA says the pharmaceutical company can promote that drug for. But that doesn't change the ability to use it.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so physicians have discovered that all sorts of medicines have benefits and uses beyond what the label says. So at these conferences, and many of them are in guidelines.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So, for example, one of the treatments in my field, erectile dysfunction, is for people who don't respond to Viagra, Cialis, often the next line is medicine that the man injects in his penis that gives him an erection, more powerful than Viagra. And what is that medicine called? So usually it's a combination. The most potent is a combination of three, and we call it Trimix.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But Trimix has never been approved by the FDA. So it's off-label. You can't pick it up at a pharmacy like Walgreens or Rite Aid. You have to go to a companion. You have to go to a companion. But it's been around now since the 1980s. It's standard treatment.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And then it turned out to be perfect because especially with my lizard experience and then human sexuality, that was a fit made in heaven. So these guys come to see me and they'd say, Doc, I'm desperate. This is 10 years before Viagra. This is 1988. And I said, don't you have something? My wife, my girlfriend, she's going to leave me. Like, I'm desperate. I'll try anything.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So if I was giving a lecture that involved a comment about that, I would have to say ahead of time to the organizers of a CME event, I'm going to be discussing something off-label. But the off-label part for a lot of people say, well, that's kind of iffy. No, it's not. It's standard medicine. Often. Often.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
In women.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Exactly.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. Well, in some cases, if their testosterone is low, testosterone would be perfect. Testosterone. But it's not indicated for us. There are no products for it. So... Well, Addi. Yeah. We just got approved. Yes. No, there's a couple of products that are used for that, but there's no testosterone products. Exactly. Right? So listen, Addi is a non-hormonal treatment.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The medicine is called flabanserin. The data are actually very strong. It is FDA approved for that. Right? Mm-hmm. For a woman who is postmenopausal and has basically her gas tank for a couple of those sexual hormones is at zero, testosterone can help. Some women who are pre- or perimenopausal may have low levels of testosterone. They can benefit from it too.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And women's symptoms are often very similar to men's. They have fatigue that isn't sort of normally explained by activities, right? It's out of proportion fatigue. They don't feel right. Their energy, their zip is gone. Libido may be down. And testosterone works for them, just like it works for men. There are differences between men and women, but we have a lot that's so similar.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Easier to get, easier to... So I mentioned that institutional medicine or academic medicine has this weird, I think, unhealthy... They bow down to the FDA as if the FDA is some arbiter of something. It's not. Well, it is, but only with regards to what their mission is, which is to make sure that the drugs approved in the United States are safe and effective. That's their mission.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It's not to regulate how medicine works. And yet, there are too many people within the medical community who say, well, if the FDA doesn't list it as an indication, I shouldn't use it. Our studies are just as with or without an FDA approved indication.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The studies are the studies and the studies show testosterone therapy in women can be highly efficacious and safe for women who have symptoms related to low testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The data around women and actual levels are less strong. Yeah. You know, and what's funny is that they're... Well, there's a whole other topic, so I hesitate to take you too far afield. But, you know, the world of endocrinology is based on blood tests of hormones. And to treat people who are too low or too high, right? Whether it's thyroid or whatever it is. In order to decide what's normal...
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I thought to myself, could testosterone work in men? Could men be like lizards? How far into practice were you? Just starting. Just starting. Just starting. I'd come out of residency. In six years of residency, two years general surgery, four years of urology, never once did we ever give testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
You have to have a control population. And so in men, this is really hard, but they've tried, like who's the control population, right? Is it 80-year-old men? Is it 25-year-old healthy guys? Is it the average assortment of people you might see in a doctor's office? Or is it an idealized group of individuals with no medical conditions whatsoever? Right. People struggle with this.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The reference ranges for laboratory tests for testosterone, for example, I mentioned earlier they're useless. They're useless because they all differ, their reference ranges, and they're not based on clinical symptoms. So there's been an effort with testosterone to use young, healthy men with no obesity, no medical problems whatsoever, and to say, this is our reference population.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And then what's funny about that is it is a central tenet of laboratory medicine that if you had, let's say, 100 individuals in your reference population, that the central 95% of them are categorized as normal. That's how labs work. For any blood test you want, with a few exceptions, like where there's targets like cholesterol, PSA.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Otherwise, whatever it is, hemoglobin, hematocrit, liver tests, they have a reference population, and they say that the lowest 2.5% are low, By definition. And the highest 2.5% are high. So if you have a condition where the prevalence is, let's say testosterone, let's say low testosterone, let's say you had a perfect reference population, whatever that is.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It would be fine if the lowest 2.5% of the population had that condition, if the prevalence was 2.5%. But what if the percentage is 5% or 10%, but only the lowest 2.5% are getting categorized as abnormally low? It means that you're missing and miscategorizing in the 10% prevalence, which I think is a conservative number for adult men.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
You're mischaracterizing 75% of them as normal when they're actually low.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so a lot of people don't understand what reference ranges are and how we use them. They're a guide, but they cannot be used as some rigid application of anything. So with women, the data on levels and symptoms have been harder to find correlations with than in men. So I know I have a lot of my colleagues in the testosterone world do treat women with testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
All we heard every week, like on weekly rounds, grand rounds, testosterone causes prostate cancer. You give testosterone, you have prostate cancer. And of course, we were treating, get this, we were treating men with advanced prostate cancer by removing men's testicles, not lizard testicles, men's testicles.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And they won't base it generally on a level. They say, well, we just base it on symptoms. And that's not necessarily wrong. But the world of, and those, I'm not an endocrinologist, but maybe I play one on TV. But I'm a frustrated one.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Thank you. Yeah, my wife is a clinical psychologist, Marianne Brandon is a clinical psychologist and sex therapist. We met at a sex therapy conference where I was lecturing. And so we have a lot to talk about. And so we talk about that in our show, The Sex Doctors. It's fun.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. So I've used, over the course of my career, every available form of testosterone for my patients. I always wanted to know what the story is with them because everybody wants to hear what I have to say about it and I want the experience. And I'm a firm believer that until you actually get some clinical experience with something, it's hard to know what's real and what isn't real.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
In terms of, all of these products work. If we can raise testosterone in men to adequate levels, they respond. And it doesn't matter whether they got it through a pill or an injection or a pellet or a cream. And the beauty of the orals is that most men are used to taking medicines by mouth. So the orals have been a great advance. That's just the last few years. We have three of them.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Kysotrex is one and the one that I have the most experience with. It's got the easiest dosage. Dosages, by the way, have some weird numbers for the others, but they all work. And, but what's interesting about the orals is that they have the potential to have fewer side effects too. So what's interesting is if I give somebody an injection once a week or every two weeks, levels go up.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
They usually go above the normal range and then they decline over days to a week or two. With the orals, you have to take them twice a day because the levels go up and stay up only for about six hours or so, four to six hours. They come down. And then you've got to do it again. There's a part of that day where the levels are back to normal.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But the guys respond as if their levels are good all day long. So that's very clever. The fact, though, that when we – the fact that it comes back to normal for part of the day – It means, though, that the body isn't getting the experience of there being excessive amounts of testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
If I give an injection, one of the side effects of testosterone therapy, we say, is it reduces fertility for men while you're on it. Because the body of the brain, hypothalamus and pituitary have a sensing mechanism, and normally they send chemical signals to the testicle to make testosterone and make sperm.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And this is part of why there's a misunderstanding, so much misunderstanding about testosterone and prostate cancer, which is... And I'll just tell you, some of this was obvious and impressive. There's a relationship, clearly. So back then, PSA was just beginning to be introduced. We didn't have a blood test to screen for prostate cancer. And so...
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
If the sensing mechanism gets the feeling that there's too much testosterone, it stops sending those signals. And so the testicles basically go to sleep. They take a nap. They hibernate. And so sperm counts go down. And some men may notice that their testicles are getting softer, a little smaller.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Most guys, if they're in married relationships or stable relationships, or they're over the age of 45 or 50, they don't care. The single guy who's out there dating might care some. And so there are ways that we can deal with that. But the orals don't seem to suppress those pituitary signals as much. And I think there's a study that's undergoing now looking at sperm counts.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And I think that that's probably going to be positive. In other words, that the guys will still have sperm. Whereas with injections, usually we get guys down to zero or very close to zero.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I don't think we have enough data yet to say definitively those studies. If they've come out, I haven't seen them yet, but I know that they're underway. And I think that's pretty good. The other thing that we worry about as a risk of testosterone is what's called erythrocytosis. The red blood cell count goes up too high. So here's a fun fact.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
No, I'm just kidding. No. So here's the thing is that men and women... Lots of controversy around that. Yeah. But just in terms of our regular biology... Most labs will say that the normal red blood cell count, hematocrit, is between, let's say, 38% and 50%. Slightly off depending on the lab, but roughly that. It turns out that there's almost a clean cut between women and men.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And that clean cut happens around 44% or 45%. women tend to be 44 or less, men tend to be 45 and higher. And that difference appears to be related to testosterone. So when I see men who are testosterone deficient, Their hematocrit are often in what I would consider the female range. And some of them actually, if your count is too low, we call that anemia.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
If somebody says you're anemic, it means your red blood cell count is too low, below 38 or whatever the number is for the lab. So there now have been two large randomized controlled trials where often when people are anemic, nobody knows the answer. It's called unexplained anemia, right? You're not bleeding from anywhere. You don't have a genetic abnormality.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The doctors say, we don't know, but it's not dangerous. So you're okay. And it turns out that testosterone is better than placebo in these trials at making people not anemic anymore. Amazing. Because testosterone increases the rate blood cell count.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I had a guy years ago, a young guy, who just before he'd seen me for sexual symptoms that turned out to be related to low testosterone, he'd had a whole big GI workup because he was anemic. They did this whole workup. They looked with a telescope from above. They looked with a telescope from below. They did these other tests. Final diagnosis, we don't know. But you're okay. We don't know.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And when I treated him with testosterone, his blood count became normal. And he said to me, if I had seen you before them, would I have needed those tests? And the answer is no, you wouldn't have, right? He would have had a normal hematocrit. So because testosterone can raise the hematocrit, some people may go up beyond what we want them to do. And so we say that's one of the risks.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But the truth is we don't know anything hard, hard evidence that that's dangerous. The Endocrine Society has helped everybody in this way. They're normally a very conservative group. And they put a number at 54, which actually gives a lot of room for people to go above the normal range of 50. And they say it shouldn't be above 54. It's an arbitrary number.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
But if somebody is at 53 or 52, I don't think you need to do anything.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Almost everyone diagnosed with prostate cancer back then was diagnosed when it was already metastatic. And they'd come into the emergency room with terrible pain, pain in their bones. Prostate cancer goes to the bones preferentially. And sometimes we would operate on them to remove their testicles. And the same night after surgery, their pain was gone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah. Yeah. And, you know, there's a, so in medicine, as I've discovered, there is a lack, often a lack of what I would call common sense. So it turns out that people who live at altitude have high hematocrites, right? If you go and you live in the mountains of Colorado, their normal range for these things can be up to 54, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So guidelines say, well, don't treat anybody whose hematocrit is too high. But these people live with a hematocrit that's too high, and no one has ever shown that they're at any increased risk of anything because of them.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So the Colorado docs are cool about this. Amazing. I know a couple. They come to the meetings. One in particular says, it's an everyday occurrence for me to see somebody not on testosterone with hematocrit of 54. So why can't I treat them with testosterone? They're already used to that hematocrit.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So the labs don't really make that distinction. That's why I say the normal range is usually between 38 and 50, and it applies to both men and women. But listen, I don't think that having a somewhat higher hematocrit does anything. The concept is theoretical. It's not based on anything. The theory is if you have more red blood cells, your blood may be more viscous, more thick.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And if it's more thick, maybe it's more sluggish, getting through tiny vessels. I don't know that that's true. Testosterone, by the way, has actions on the endothelium, on the lining of the blood vessels, that may in fact make them more pliable. Even if it were true that the blood is more viscous, it doesn't show up anywhere in studies.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It's just not so that people with high hematocrit because of testosterone have been shown to have any problems at all.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So I've written four books. The one that's the most popular is called Testosterone for Life. And it's basically a primer for non-medical people about how testosterone works. It's not dumbed down, but I hope I've made it easily understandable. And I've had a lot of doctors tell me—it's a paperback, you can get it off of Amazon—
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And a lot of doctors tell me that instead of discussing everything about testosterone with their patients, they just give them a copy of my book. I've had physicians who tell me that what they've learned about testosterone they got from my book. So it's intended to be, it's full of patient stories and it talks about levels and things like that and free testosterone like we talked about.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
The book I'm most proud of was originally called Why Men Fake It. And it was stories from my practice and what we learned about what I learned, a true education about men and sexuality and how men are very different than their stereotypes. Its current title and paperback form is The Truth About Men and Sex. It's got some amazing cases and stories.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And, you know, the bottom line that I would just share with you is that men have, I say testosterone has gotten a bad rap. I say men have gotten a bad rap too. It's a difficult period, the last, I would say, 20 years for men. Somehow they've become a punching bag. And we think of men as if they're all 19-year-olds on spring break, out of control.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And that's not my experience of men having seen them behind closed doors in the doctor's office. By and large, with relationships, especially sexual relationships, there always are some bad apples, of course, but by and large, men are trying to be the best people they can in their relationships. And they may not always do it the right way.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And so the story made sense that lowering testosterone helped these guys. And if lowering testosterone is effective for guys with advanced prostate cancer, then raising it has to be dangerous. Like that story kind of made sense until it didn't. Until it didn't.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
They may not do it, they may not express themselves or behave in a way that their partner would like them to or that suits them best, but they're trying. And that feature of men and their interest in service, and I use the term in the book, and don't laugh at me, an effort at nobility, I think is something that has been under-recognized and unappreciated.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Thank you.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Gabriella, it's an amazing story. I mean, it's really, and it tells us not only about testosterone and prostate cancer, but how medicine works. and how medicine can often fail us also, how you get these crazy bad ideas. I remember when I was like 10 or 12 or something, I'm at the beach with my parents, and I had lunch.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And then my dad says to me, my dad was a physician, he says, so you can't go swimming for two hours. Because you ate lunch. Yeah, because I ate lunch. I said, why? He says, well, your digestive system needs the blood supply now that you've eaten. And it made no sense to me. But that was taught to doctors at the time who then told everybody else. It's just nonsense. Like, don't eat eggs, right?
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Yeah, absolutely. The cholesterol thing turned out to be wrong. But for a generation often, these things are wrong. The testosterone story is wrong for 80 years. For 80 years now, it starts with 1941, a guy named Charles Huggins, together with his co-author Clarence Hodges, took, based on experiments in dogs, they thought there was no treatment for metastatic prostate cancer.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
So guys would come into the hospital regularly through the emergency room in pain, like I mentioned.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
That's how they found it. Yeah. And so it shows up on x-rays, plain x-rays, as denser than bone, which is unusual for cancer. So you could make a diagnosis almost exclusively on that. And they used a blood test. They started to use a blood test called acid phosphatase, which we don't use anymore. But that was big for Huggins. And what he did is he castrated these men.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
And he showed that this blood test acid phosphatase came down when he castrated him. He also claimed that raising testosterone made the cancers grow more quickly. And because of that work, 1941... people stopped using testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
It was first synthesized in 1935, became available soon afterwards, and there was this golden period of about four years where people wrote these amazing articles about the benefits of testosterone. Amazing articles. They were using it for men and women who had angina, chest pain from exertion, right, where you don't have enough blood flow to the heart, with remarkable detailed case histories.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
I think the largest series was 99 individuals. That's a pretty big series for the late 1930s, right? And very convincing and compelling. In 1941 comes this story about testosterone more or less causes prostate cancer and makes it very dangerous, and everything stops like cold. So that by the 1980s, when I was a resident, we never, ever, ever gave testosterone.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
Right. So that's true. But what made it compelling, the castration part, And they also used estrogen treatment also, which they didn't know it lowered testosterone. They thought it just antagonized how testosterone worked.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
No, they gave estrogen as a form of blocking the testosterone effect. They both worked. But what was compelling about it was just like I told you that I saw with my own eyes, just talking to the patients who came in when I was a resident, and we would remove their testicles and their pain would get better. This was the first treatment for these guys. Otherwise, they just got pain meds.
The Dr. Gabrielle Lyon Show
The Science of Optimizing Your Testosterone | Abraham Morgentaler, MD
There was nothing else. And Huggins rightly won the Nobel Prize awarded to him 25 years later. He didn't just work on, he was really the first or one of the first to ever show that any cancer could be sensitive to hormonal manipulation. And so other doctors did what he did and they saw with their own eyes that this worked. So that became the thing.