Is Your ED A Symptom Of Something Deadly? The Truth About Heart & Hormone Health - Roundtable #210

The penis predicts the first heart attack by three to five years. Healthy men should not have ED. It's a symptom of something going on. That's a symptom of depression, cardiovascularities, prostate cancer, diabetes. If you have low T or ED, look at what the cause is, because it could be potentially life-saving.

74% of Americans are either overweight or obese. Every decade by decade, the T levels are going down. And if you match and look at obesity in the United States, obesity is going up. The good news is, cut 10% of your weight. All of a sudden, boom, T starts going up, more T available for your muscles, for your energy, for your sex drive. Now you're starting to make gains and your T gets better and better.

He may lose it, but he may gain it back again. And sometimes these patients need to use the testosterone in conjunction with the lifestyle modification to get the best outcome. It gets them to the gym. It keeps them in the gym. It gives them a different mindset. Yeah, the lifestyle modification is great, but sometimes you need something to get them started. And testosterone really does help.

We don't talk about the elephant in the room, which really is the stigma. It's not any longer what testosterone does. I mean, you are all still clarifying and teaching the science, but the stigma is so heavy.

Other people are going to feel horrible. This is a fact. But I feel like every man should know. Well, this is the first ever roundtable, and we have Dr. Larry Lipshultz, Dr. Toby Kohler, and of course, Dr. Makara. Welcome.

Thank you.

Thank you. It's a great idea.

Um, well, it wasn't mine. I have I have a great team.

We need to talk about penises.

Oh my god.

I know. And um, and it's it's funny. We joke about this, but there is a disconnect between the science, men's health, andrology, and of course, the public. I think that there is quite a big disconnect, but you guys are changing the narrative and also, I think even more importantly, changing the science. So with that being said, I have a few questions of my own.

Good. Um, when I was in residency, we weren't even testing for hypogonadism for testosterone. And I did a fellowship in geriatrics. This was something that when you think about sarcopenia and muscle mass, I wasn't, we weren't even looking at. Was there, um, a moment in each of your residencies, and obviously this is the way back when, because I'm sure it shaped to where you are now, that you got wrong?

But we got wrong. I know it's a bad word, but that you got wrong in your training? Because even right now, there isn't an ease where a patient goes to their doctor and says, "I have low libido. I have erectile dysfunction. I have low muscle mass." There isn't this ease of conversation as opposed to, you know, um, I'm having headaches or I'm having shortness of breath.

Yeah, but you have to look at the time. I mean, right now, I think it is fairly common. When I was training, it wasn't. People didn't talk about it at all. So, I think it's different now for you guys because you're, you know, younger and you've been brought up in the practice where you do talk about it.

Yeah.

I don't think it's a taboo topic. I and there's so much in the media about testosterone and hypogonadism. I think it's fairly common.

Oh, for sure.

What about your both of your experiences?

Yeah. Well, go ahead, please. Well, he trained me. So everything I learned, everything I learned was from him.

It's like a father-son situation here.

But we learned a lot along the way. Look, the past 25 years, we learned about the fact that, you know, patients who come in with low energy, low libido, erectile dysfunction. We were taught check a T level. But the reality is that same patient comes into a psychiatrist, they check for depression and only depression. That same patient walks into an endocrinologist office, they just check a thyroid, right? So we're all in our silos, and we're now learning that, no, we should be checking TSH, check make sure they don't have depression, check a T level. So we're broadening our scope of what could be causing these symptoms. We learned a lot about side effects. We learned about erythrocytosis now. We've learned about estradiol. When we were training, we thought men don't need estrogen. Women have estrogen. Let's bring it down with some Arimidex. Men absolutely need estrogen. They need estrogen for libido and sexual function. And, uh, we know it's a mistake to shut them completely down. But we didn't know that back then. So our education has really evolved over the past 25 years.

And it still takes quite a bit of time to then get out to someone who is perhaps trained like me in family practice.

Oh, yeah.

I think family practice is our biggest problem in terms of, you know, educating primary care doctors, because, well, they never had it in their training, and it's just changed so much, as Mo said.

Mhm. So, I mean, that I think, you know, a lot of my patients come in and they've been inadequately treated by their primary care doctors, but I think it's changing.

Well, I've had actually the same experience because, and Dr. um Kohler, you talk a lot about, and you, I remember this, I watched a lecture that you did at the Andrology Society where you talk about Chad.

Okay. And I'm not usually good at names, but I remember Chad. And there was this evolution of the idea of testosterone, the testosterone culture. And where I'm going with this, in the 80s, there was, um, like a roid culture, and this discolored testosterone and testosterone replacement, both in men and women. But in terms of in your training, so I'm sure there's been an evolution from what you.

For me, testosterone has been, uh, guilty until proven innocent instead of the other way around.

Guilty until proven innocent?

In terms of causing bad things, right? It's like, for some reason, the proponents of the evidence has to be, we have to prove that it's safe. And there was this switch that got flipped 80 years ago when, you know, the work of Huggins and some, you know, based on one patient. It's amazing the work of one patient has changed how testosterone was a wonder drug and essential and vital for both men and women to being, you know, characterized as the devil or fuel for the fire. And so through my career, when I was at the VA in training, you, we still worried about testosterone making prostate cancer worse. But it's so interesting about how long it takes, like ideas and medicine to evolve. Because when I was a resident, fourth year, I heard a Morgan Tower speak for the first time. He's like, actually, no, it's the opposite. Looks like testosterone may actually be totally safe or actually even helpful for prostate cancer. This was for me 25 years ago, and every year it diffuses a little bit more. But the vast majority of people are still afraid of this prostate cancer testosterone myth, even though it's completely debunked with excellent science. Just takes a while to get out there.

Yeah. But I think Dr. Kohler nailed it. You know, you asked why family practitioners do not prescribe it. They're still reticent. It's fear. It's fear that it causes prostate cancer. It's fear that it causes worsening of BPH symptoms. It's fear that it causes cardiovascular events, heart attack, stroke, and PE. Right? That's the fear. We know today that's not true. But that takes time to get the word out. You still ask primary care physicians, why don't you prescribe? I don't want to give my patient a heart attack. I don't want to give my patient prostate cancer, but those are myths. Those are not true.

They are myths. I will say that when I started in clinical practice, I was terrified.

And I knew that they needed it. I knew that they needed both men and women. And I would call mentors and I would call other people because I had not learned anything about it. And there's risks if you don't treat. And I, I just want to mention one other thing is that people consider testosterone a lifestyle drug.

Originally, that was right in the 2080s up to the 2000s was a lifestyle drug, meaning something nice to have. But essentially, it's not. It's essential. It's an essential hormone for men and women, right? And we know that men with low testosterone levels are much more likely to have a heart attack. Non-negotiable. Men with low testosterone, much more likely to suffer from depression. Non-negotiable. More likely to break a bone. Osteopenia, osteoporosis associated with anemia. You show me another blood test that's associated with so many medical conditions in men. There's no other blood test. It's the best marker of a man's overall health.

And, you know, you have to be careful though about throwing out the term lifestyle drug and saying, "Well, we don't want it associated with that." Because there's nothing wrong about changing your life, which testosterone can do. And I think the idea of a lifestyle drug, uh, gets a little bit punitive or something, but it does change your life, of course.

So, I mean, I don't have a problem with saying it is a lifestyle drug, but it changes your life. It's not a, like icing. It's very essential. And, you know, as humans, we get older, there are invariable changes that we're all fighting against, right? And like these things I'm wearing right now, like my eyes were just fine 20 years ago yesterday, but now I can't see anything. And nobody gives a second thought to getting a prescription for glasses and seeing better. And so to to demonize testosterone is like, well, it's low. We shouldn't fix it because it's kind of fighting the natural aging process or however you want to think about it. I think it's completely wrong.

And that's what everybody's doing now. They're fighting the, you know, it's all about not aging.

We don't have any other hormone. If your thyroid was low, you'd replace his thyroid. If your cortisol was low, if your insulin was low, if there any other hormone, women, estrogen is low, we replace the hormone. Right.

Right. But why can't we replace?

And I don't like the word replace.

Yeah.

And I think that's gotten way off course because we're not replacing testosterone. We're using it as therapy and we're making it more normal. But men always have testosterone unless they're castrated. Women don't. They stop making estrogen. And I think that TRT, the female was the HRT, and now we go to TRT, but I don't think it really is. I say this all the time, but it's never going to change, but I don't like the term TRT when it comes to performance enhancement. So, if we're talking about lifestyle medications, and why is this so important? Because if we don't talk about the elephant in the room, which really is the stigma, it's not any longer what testosterone does. I mean, you are all still clarifying and teaching the science, but the stigma is so heavy. It's a Schedule 3 medication with ketamine. But if we're really going to unpack that and make it accessible for both the patient and the provider, where, you know, your patient doesn't come to me and then I put them on testosterone, well, not yours, but a proverbial patient comes to me and I put them on testosterone, and then they go to their cancer doctor or they go to another physician, and the other physician's like, "I cannot believe this doctor put you on testosterone." And hence, you see patients undertreated. So, just understanding that the relationship between testosterone and then normal life versus performance enhancement.

Yeah. And, you know, it's interesting, you make a distinction between if I drive up my T naturally. I eat better. I exercise. I focus on sleep. I mitigate stress. I accept the fact that stress is like a powerful force in my life that's going to help me, not necessarily a bad thing. If I do all those things, my T goes up and nobody says, "Ah, you're doing something crazy, right?" But there's some of us where the testicles are kaput. They're not doing the job anymore. Just like the eyes aren't seeing anymore. Sometimes it needs to be replaced.

It's very reasonable.

And you're not replacing it.

You're supplementing it.

Okay. Well, you're normalizing it.

Yes.

Um, there was something else also very surprising. These are just a couple numbers, and I stand to be corrected. Number one, there is this idea of age-related decline. So, age-related hypogonadism. And then when I looked up some of the numbers of testosterone deficiency, so I would love to kind of clarify age-related decline. Is there a normal age-related decline versus deficiency? And then is it true that 5 to 6% of men are diagnosed with, depending on their age, low testosterone?

Yeah, that sounds very.

I just don't understand. Why has there never been a study looking at decades and the average T?

I agree. So, we know it does go down, but you're right. Specific decade by decade. We know it goes down, but aging alone does not cause the testosterone to go down significantly. A healthy 80-year-old man is not going to have a significant decline in his testosterone below 300 if he's healthy. When the patients develop diabetes, obesity, metabolic syndrome, the acquisition of comorbidities, that's when you start dropping your T levels. Right? So this age-related hypogonadism is a misnomer. Right? Healthy patients should not have a decline. You're right. 5.6%, 6% of patients between the age of 30 and 79 are going to have, uh, low testosterone diagnosed by low T and signs and symptoms. If you just look at low T, that goes up significantly higher. But low T signs and symptoms, up to 20% of those patients never get treated. So, it's an important number to think about.

How, I'm not sure I'm not sure about this, that it doesn't decline with aging because when examining a lot of men with fertility concerns, you notice that as men get older, the testicles get smaller.

Yep.

And softer.

Yes.

So, I mean, and they could be very healthy guys. They just don't have the same testicles as a 25-year-old.

No, I agree. So something's changing. I mean, it's, and I don't think they necessarily have to have diabetes or hypertension.

2% per year starting at 20. You're right. So there'll be a decline as we go on, but it shouldn't be enough to throw them down significantly unless they have some illness. Like I agree, aging will drop it, but it's not enough to make you severely symptomatic, but unless you have something. And Toby Cers used this, and I use it again. It's like the kind of like the check engine light. If you have ED or you have low T, check what else is going on because something is causing those to go down, right?

We know we have a decrease in post-LH release when we hit our 30s, and it goes down a little bit per year in men, but you can mitigate how bad it is for you, and you can certainly make it a lot worse if you don't take good care of yourself, right? So, there are some age-related changes. We're not going to live forever, no matter what we do, unfortunately. But if we do all the right things, we can still have a super high T, super awesome erections in our 70s and our 80s, as long as we take good care of it.

Mhm.

Does the idea of age-related decline, if we think about statistics, if 74% of Americans are either overweight or obese?

Mhm.

74% are going to have, I mean, that's a comorbid condition. But if it is defined, and I know this is a little bit of nitpicking, but if we don't have the conversation, it will remain age-related decline. And we are seeing 50% of adolescents and youth that are either overweight or obese.

Mhm.

How do we imagine that if kids and people are getting obesity and other comorbid conditions earlier, then this, in my mind, becomes an essential treatment.

Yeah, it's there's no question that every decade by decade the T levels are going down. And if you match and look at obesity in the United States, decade by decade, obesity is going up at every age group, right? And weight increased fat increases the risk for having hypogonadism. 10% you gain 10% of your body weight, you're going to actually drop 85 nanograms, you gain 15% of your body weight, you drop 270 nanograms per deciliter. So it's bidirectional. And so the GLP-1s have helped. So you lose weight, you actually can maintain and increase your T levels, but obesity has a bad profound effect on T levels.

Yeah, and it's a, it's a feed-forward or, you know, reverse-forward cycle. The heavier you get, the more fat you have, the more you convert your testosterone to estrogen, the less testosterone you have, the less energy you have, and you get more and more and more heavy. But so that's the bad news. The good news is, cut 10% of your weight, all of a sudden, boom, T starts going up, more T available for your muscles, for your energy, for your sex drive, and now you have more, and now you're starting to make gains and your T gets better and better. So it goes both ways.

But I, but I think, you know, we have to face the fact that, look, you know, I am older than you guys. I hate to admit it, but I am, because I trained Mo, right? But I mean, my T has gone down. And I don't, I don't have any comorbidities and I'm not obese.

Yeah.

So, I mean, you know, it is what it is. You have to deal with it. I just don't think you can say, well, if I do everything right, my T is not going to go down. It's going to go down.

Yeah. I think you can decrease the slope, right? So, it's going to go down. It's just that how fast is the slope?

And mine's gone down slowly.

Yeah. Which, in good health, I'm in good health, but it's still not what it was.

And now the question is, if it is low, should I be supplementing? I mean, do I want a T of a 40-year-old, or is it more, or should I have a T of whatever age I am, which won't?

But, but I have a question. Why would there be a even a consideration that either you would or you wouldn't? And what do I mean by that is if a 40-year-old testosterone level, which I again, I realize that it's not based on age, some people will have a baseline. Um, and to be fair, many people listening only think about the total T. So if a free testosterone when someone is 40 is anywhere from, let's just pick a number, 500 to 700.

And that's normal for them.

And as you get more mature, notice how I said mature. I like it. The, um, idea that you would replace that of your 40-year-old self, that there would be some hesitation to me.

You're saying why would there be any hesitation?

Yeah. To me, as someone who has been a legacy provider and prescriber.

Right.

Why would you even have a second thought?

For a long time, I resisted.

But, uh, then I decided I wouldn't.

But I, I agree with you. I mean, like the reality is, if you knew that there was a drug, let's call it drug X, that decreases your risk for diabetes, T4DM, large study, prevented the risk of progressing to type 2 diabetes and reversed diabetes. If you know there was a drug that helped prevent, reverse diabetes.

Oh, yeah. T4DM. Just say this again.

So, this was the T4DM study. It was a study out of Australia, over a thousand patients randomized to either long-acting testosterone or placebo. Over the course of the time, they found that these men who had the testosterone actually reversed diabetes or prevented the progression of diabetes. Large study, one of the, we call it the big three, it's one of our big three studies, T4DM. So if you know that there's a medication that could potentially reverse diabetes or prevent the onset of diabetes, the medication could actually prevent or help prevent osteopenia, osteoporosis. You knew the medication could actually help with depression. You know that theoretically there's some cardioprotective effects, but we can talk and debate that. If you knew that, forget it, and it also helped with muscle mass and preventing sarcopenia, and you were low in that medication, why would you not consider taking it?

But I think I agree and I, I just always worry, wonder, worry, uh, whether or not people who are taking testosterone are doing so many other different things that they didn't do before. I mean, they're eating better. They're probably exercising better. They care more about themselves, or they wouldn't have taken the testosterone.

Yeah.

So, it's almost a self-selected group to become healthier.

Sure. But I'll take it.

Yeah.

I understand. But when you look at studies like that, I mean, do they control for every other variable?

Yeah. T4DM, you're correct, was testosterone versus placebo, but both groups did lifestyle modification, exercise. But the T plus the lifestyle modification was much stronger than just lifestyle modification. But I think, I think if somebody has low T, and you want them to exercise as part of lifestyle changes, uh, to help with their natural improvement, then if you give them the T first, they're going to be more likely to exercise. So, it's kind of, you know, a self-fulfilling prophecy.

Yeah. Of course, you not only will you likely have more energy, be able to get up off the couch, but actually, if you do start moving iron, you're going to see progress and be like, get excited, and it's going to be a cycle, right?

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I have, um, another, maybe it's a little bit controversial, and I mean it's not really, we're all friends, but if we are seeing obesity, and it's not a treatment for type 2 diabetes, right? At least for women, we don't go, you have type 2 diabetes. If I had to make a decision of your first-line intervention, it's, and I had to choose between two drugs, GLP-1 and testosterone, it's never going to be testosterone.

Right.

Um, we see, I am not sure that we are going to get a handle on obesity and metabolic syndrome. We do have an increased use of GLP-1, but as a provider and as someone who's trained in nutritional science, I don't know if we're going to get there.

Mhm.

That means some individuals are probably going to be more likely at an earlier age willing to look at testosterone. And then this becomes kind of a dance because I remember when I had a patient and they were in their 20s, they went to urology. This was in New York City. They went to urologists, and the urologist didn't want to treat that 20-year-old with testosterone because he didn't want to affect his lifelong fertility.

So, how do we then normalize making decisions at to what age would you actually begin treatment with testosterone when it's low?

But they were in their 20s and there was like.

But was it low?

It was low. Well, then you have to, I mean, it's like Mo was saying, I mean, if they had, uh, low thyroid, if they had, uh, problems with diabetes, you would treat it. So why are you not treating the low testosterone? I mean, we've shown that you can, you can prevent them from affecting their sperm production. We know that.

But the fertility aspect is taken. The fertility aspect is extremely important. You know, a 20-year-old, if you want to put them on lifelong medication, it's a long time for a 20-year-old, right? So the reality is there may be other ways to do it, and you could do lifestyle modification, but also lifestyle modification helps each one helps individually, but, but, but sometimes just weight loss will make it, but you can't, it's hard to sustain. That's what I'm trying to say. You say, Mr. Smith, I need you to lose 10% of your body weight. He may lose it, but he may gain it back again. And sometimes these patients need to use the testosterone in conjunction with the lifestyle modification to get the best outcomes.

Yeah, that's what I think of because I think it gives them, it gets them to the gym. It keeps them in the gym.

Yeah, I agree.

You know, it gives them a different mindset.

Yeah.

And so I think, you know, lifestyle modification is great, but sometimes you need something to get them started. And testosterone really does help.

Yeah. But you're not touching the elephant of the room. The elephant of the room is the GLP-1s loss because it causes a significant decline in muscle mass, right? And that's important, right? Because if you restrict your caloric intake, you're not going to only lose fat, but you lose muscle. And some studies will say up to 30% muscle mass. Well, that's a problem, particularly if you're older and you get sarcopenia, right? There are now new companies coming out making GLP-1 plus SARMs or medications to raise T levels. Why are they doing the combination? The combination because they're hoping that the T levels going up will increase muscle mass in that patient that's losing muscle mass with the GLP-1.

Yeah. I, I think, you know, the bottom line is food is too delicious.

Yeah.

You know, that's why 95%.

For yourself. I guarantee you.

That's why 95% of diets fail. So, I'm all, I'm very in favor of GLP-1s. And I think there is a danger of sarcopenia, uh, with extreme quick weight loss, but it can be mitigated. Protein intake, exercise, sleep, right? There are powerful trials showing that if you're sleep-deprived, uh, and you lose weight, it's mostly muscle. But if you're sleep-replete, you're sleeping adequately, you lose much, much less muscle. Right. So all these.

Protein is so important.

Yeah. Sleep, protein, exercise, all all the pillars that you need. But just the GLP-1 alone. Yes. I, I would be worried about muscle mass loss. But you don't give one in isolation. You tell the patient, listen, I want you to eat 100 grams of protein a day. I want you to work out with resistance training at least twice a week. I want you to focus on sleep.

Yeah.

And then you won't have that, you know, extreme muscle loss. When people lose a lot of weight, they also lose muscle. Even if it's not from GLP-1s, it's just from starvation. So.

Are you seeing an improvement in testosterone with the use of GLP-1s because of the improvement in obesity?

Yes. T levels do go up.

Yeah.

Clinically significant.

Clinically significant and sustainable. In other words, when I, when the GLP-1s were not around, they would lose the weight, then they would gain it. Then they lose the weight, and now it's sustainable weight loss, and the T levels stay up. So why would it be sustainable once they stop the GLP-1s?

If they stop the GLP-1s then and they gain the weight back, T levels start going back down again. Right. Right. So, but these patients stay on the GLP-1s. I have most of the patients I start on GLP-1s go on maintenance dose. So they get to their desired dose, the level of, uh, weight, and then they say, I'm not, I say 85% of patients gain every pound back if they stop unless you've changed your lifestyle modification. Most patients say, Doc, keep me on a maintenance dose. But do we know, do we know, I know I'm asking a question I know the answer to, and that is, do we know the long-term effect of staying on GLP-1s for years?

No. But we do know the long-term effect of being obese for many years.

And what about low testosterone? Can we touch on some of the perhaps a little bit unknown consequences of having low testosterone? And then, um, maybe before we do that, defining what is actually low.

Yeah. I mean, there's a definition that's been the community is 300 nanograms per deciliter. I disagree. I think most of us disagree. There are patients who are at 320, 350, 390 who are symptomatic, that may, uh, benefit from testosterone therapy. You can't have one number for everybody and say that everyone below this number must feel bad. Everyone above this number must feel good. There should be some kind of range. And, uh, quite frankly, if you give a patient a three-month trial in medication and they don't get any better, and you could argue maybe this is not for them. But if they do feel better, then you could consider. So, my threshold is a little bit higher than the 300. I may go up to almost 400 in patients, particularly if they feel as well.

Talk about the the tiles from the guidelines.

Yeah. So I'll give you an example. So the AUA puts out guidelines. The guidelines say that the patient should be between 450 and 600. That's what you're shooting for. So a patient came into my office the other day and said, "Dr. Cara, what range should I be in?" I said, "According to the AUA guidelines, you should be between 450 and 600." He said, "That's great. I'm at 390, so can you raise my levels?" And typically, you're supposed to say, well, no, you got to be below 300 in order for you to put you on T, to put you into the normal range. That makes no sense.

That makes no sense.

Really, the cutoff should be the lower limit of the range you're trying to get them in. So, the cutoff really should be theoretically 450 if that's where you're trying to put them. But I think another thing that another thing that patients don't realize and a lot of the primary carers don't realize that although the FDA has approved 0.5 as a drug dose that they, you know, with a with a commercial testosterone.

Can you, can you explain to me what do you mean 0.5?

Well, there is a commercial product, FDA approved, and its maximum dose is 0.5.

100 milligrams a week.

Of testosterone.

I see.

Okay. And the thing about that, if you give that to somebody and you measure their testosterone two or three days later, it's over a thousand.

Yeah.

So, I'm in this business of looking at at the endpoints. You have to decide, are you going to look at the nadir before their next shot?

Yes.

Or are you going to get it in the middle?

Right.

I mean, and I'm, I am not one that's hung up on numbers because I am treating a patient with symptoms.

Yeah.

And so, and not.

How long have you been in practice?

I'm not going to tell you. Why? Because what I've noticed is, um, and there, I think that there's a natural trajectory of a clinician. When I was early on in my practice, I was a stickler for the number, like this is the number. And it takes 20 years of practice. I think you're right. But it takes 20 years of practice for me who, you know, I still am uncomfortable if it's outside the number. But then maybe if I've been in practice 40 years, I'm much more flexible. But that means there's a huge cohort of physicians, and most importantly, primary care, the first line of defense. They're going to feel very uncomfortable if someone comes to them and goes, "Doc, you know, I'm at 450. I feel like crap."

Let's say I'm living in the middle of Idaho, and I, you know, I'm in a very rural area. You know, no offense to anyone who's from Iowa, but maybe it's a rural area. And then it's unfair that both the physician, cuz we all as physicians look back and gosh, I really wish I would have treated that patient.

Yeah.

And then 10 years later, this patient goes through life, and then it becomes 20 years, and then finally the patient gets treated when the doctor's caught up.

Yeah. But it's very different than putting a level, putting someone in the normal range at the upper normal and then sustained supraphysiological levels.

What's the danger of supraphysiological?

Well, there's a lot of erythrocytosis. There's going to be cardiotoxicity, cardiomegaly, uh, ventricular hypertrophy. Uh, there's been increased MI risk. I mean, he's done more work on this than anyone I know. We're going to talk.

Yeah. So, I mean, he's, I mean, and so, but that's sustained supraphysiological levels. I accept that if I give someone an injectable that there'll be a transient increase in physiological levels at the beginning and then it goes down. Pellets, it'll go up a little bit slightly higher and then it'll come down. But to sustain supraphysiological levels, I personally get concerned. I mean, there's been very good data that you've presented on.

But, but I also think we get, we do get too caught up in the numbers. And I think those of us like you say, that was a great point. The longer you're in practice, I think the more you realize that it's not as important as the patient's symptoms, because that's why you're treating them to begin with. But I have a patient with Klinefelter syndrome, which, you know, is a problem with testosterone. They do not make high levels of testosterone. He's a football player in college, right? So we had to get permission to treat him because he's playing football, which we did because, you know, he has a genetic abnormality. He should be treated. So we were treating him with, I don't know, maybe 75 a week. He's huge, you know, like 6'10" and, you know, 320. I mean, just a big.

Is 75 enough?

Well, wait a second.

Okay.

So then I get a letter saying that I am overtreating the patient. He should only be on 0.5.

Yeah.

I said, "What, what happened? I mean, why did this is after, you know, three years of treatment?" His parents say, "Well, somebody new entered the, uh, council, whatever they use for the for the athletes." And I said, "I will bet you it's an endocrinologist." It turned out it was an endocrinologist. No one has ever looked at this person. They're just getting a report with a number, and they think the number is too high.

Yeah. I mean, we know there's biological variability between humans, right? Somebody's T at 400, they're going to feel great. Other people are going to feel horrible. This is a fact. Whether it's testosterone sensitivity, whether it's the free T and not the total T, there's all these factors that can make you different in how you feel. Maybe this is contentious, but I feel like every man should know what their testosterone level is when they're at their peak in their life. When they're 25 years old, they're healthy, they get their baseline T. So yes, I felt amazing when I was 25 with a testosterone of 450. That's a very powerful piece of information because if your T is 450 at age 55, very unlikely that that's the problem. If you're feeling off. If, however, your T is normally at 650 when you're 25 and now you're coming in at 400, to your point, yeah, it's probably another thing that I think we overlook is patients' weight, body size. I mean, there's a lot of literature on treating people with higher doses because they weigh more and they're bigger, right? You know, someone, you know, a 150-pound man does not require the same injection as a 250-pounder. I mean, they're different.

No, you're right.

And we don't pay enough attention to that, I don't think, when we see patients. Do you? You see?

I do. I do think about it. And then I think about this idea that actually I've learned from you guys over at Baylor is this idea of CAG repeats.

Yeah. And, you know, in my mind, when I think about obesity, so in skeletal muscle, there's this anabolic resistance. So muscle becomes resistant to this normal stimuli and less efficient. It's less efficient at recognizing, utilizing amino acids and protein, and also, and this might be a little controversial, but obese muscle, when fat is infiltrated, it's not as responsive to exercise. There's myostatin. That makes sense. It does make sense. And then that makes me think about the receptors and testosterone, where it's this fine balance, and I don't, I don't know the answer. I'm hoping that you guys can shed light on it for me, that if someone is obese, do they require more testosterone to then feel the effect or even get the effect? And, and I'm sure you worry about estrogen and this, um, just this dance, but is there, to say this succinctly, a change in the amount getting to the muscle from the with the utilization of testosterone? Do they require more in obese patients?

I think it's two different topics. So one topic is the sensitivity of the testosterone receptor. So it's called the CAG repeat. So in Baylor, when I started with Dr. Lipshultz, we started this doing this, we do it today. We take the blood, we send it to the lab, and they give us the sensitivity of the androgen receptor. If the CAG is greater than 27, the androgen receptor is insensitive, and we show that those patients need more testosterone. Makes sense. If it's less than 27, it's sensitive. They need less testosterone. And we're all different. So, everyone has their own CAG repeats. So, that's different. What you're referring to is the acquisition of obesity. And obesity in itself has many mechanisms why it shuts down the T. It aromatizes, increases leptin, it increases cytokines. Each one of those take a hit directly on the pituitary and the testicle to shut down the ability of the amount of T we make. So, you have to give those patients more T in order for them to compensate for the loss. On this side, when they're insensitive, you got to give more T because they need to be higher levels to feel the benefit. So, they're a little bit different, but both categories need more T to feel better. And this creates a huge, um, I want to say, red tape because providers might not feel comfortable with the dosing.

Can we touch on, um, how, and you guys have talked about this, uh, quite a bit, but the idea of how do we determine a dose of testosterone because you don't necessarily look at all the numbers?

Well, I look at the numbers to start treatment, but my point is I don't follow the numbers in terms of what I'm going to do when he returns. My patient returns in three months. I'm going to see how he feels. That's my most important guidance is the patient's symptoms, not the blood test.

So, I have to push back on this just a little bit. Is that, for example, I don't feel comfortable increasing the dose of testosterone over 200. Even if a patient comes to me, and I'm not a urologist, if a patient comes to me and I, and even if I suspect CAG repeat, because for the general population, it's not as easy to get. And I remember I have this, um, patient who's a part of Homeland Security, and I am only willing to provide 200 milligrams of testosterone because it's outside my comfort zone, and I know that he needs more.

Mhm.

But that's your problem.

No, it's your problem because I'm sending him to you.

But I mean, the, I don't have, I don't, I do not have a problem.

But you would be more, would you do that?

Uh, I typically don't, but, but I'm not looking at, I'm not looking at the amount I'm prescribing. I'm looking at his blood level, right? So, so I'm looking at the blood level. And so if the blood level, typically, you're right, at 200 milligrams a week, I don't need to go any higher, right? So that's, you're right. But for some patients are eating it up faster, metabolizing it faster, and he needs to go higher potentially. But the reality is, depends on when you're looking at the level. Testosterone is a game. You whenever you check the blood in relation to when you give the medication, you can make that level look like whatever you want. And that goes for anything, a pellet, an injectable. I check and give someone an injection today and check their blood tomorrow. It's very different than when I check it in a week before they give their next injection. So whenever I tell the residents, when you check a blood level, right underneath that, you write when was the last dose given on whatever you're giving, because that's going to change the level, right? It's very important. But to that point, what we're seeing, what I'm seeing now is more patients are dividing the dose and more patients are microdosing.

Microdosing has become very popular.

Where the patient takes, let's say we're going to give them 200 milligrams. They divide it by seven and they do a subq injection every day, or they divide it into three.

Yeah.

Because I, we're seeing fewer side effects.

I agree 100%. And the whole reason is you drop the erythrocytosis rate because you're not spiking, right? And that's helpful. Some people are showing a drop in hypertension rates. You drop the mood swings. So, it's a little bit of a hassle, but I think it's so much. The patients like it because a lot of men get very tired with intramuscular injections because it's painful, and it's much less painful with subq.

Yeah.

And if you know with the syringes I use, they'll send the patients a larger needle to draw it up and then a smaller needle for them to inject. So, they're kind of on the same page. And you can drop the dose. So, 80%. So whatever you give IM, you only have to give 80% subq and get the same blood level.

You get the same blood level. The I do want to touch on the risks of testosterone replacement. And really where you were talking about was supraphysiological dosing. And in my mind, if you do IM, technically they would then get a quote supraphysiological dose once once a week.

Transient, transient though. It's transient, but still over time, it's kind of like if I'm eating a cake, I don't know, you know, I, I know you like cake. If I'm eating a cake once a week, listen, because you're sitting next to me, so I get to pick on you.

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>> But um if even if it's transient, is that without risk?

>> Well, there is some risk because the spikes do cause an increase in rth of cytosis,

>> which is >> higher increase in red blood cell count, right? So heat goes up and theoretical risk if it goes above 54. There's a theoretical cardiovascular risk. I use the word theoretical patients in Denver and then that's exactly right. um hemoglobin matocrate are above 52 easily >> and this is called secondarythroytosis and there's never been there's been only one paper to show that secondary ariththroytosis increases risk of cardiovascular this is out of the University of Miami other than that there's no data to support this all this data comes from the polyythemia vera data which is a blood disgrace which is different >> it's a cancer so it's very different but we've extrapolated the polyythemia vera data to the general population which is a mistake saying that oh if you have a high hematocate you're more likely to have a MI So the day I think that that data is evolving, but there's not great data on secondarytosis causing cardiovascular events. So I think that's important to keep in the back of my mind.

>> I've been I've been trying to figure out that number that people want like what is too high? What's the level that's too much?

Couple things to think about. So I looked at 100,000 men at Mayo Clinic over the last 20 years. And it's actually pretty rare to physiologically exceed a thousand nanogs per deciliter in healthy men. It happens occasionally >> in testosterone.

>> Yes. Testosterone levels above a thousand naturally is pretty rare.

>> Naturally.

>> Naturally.

>> Naturally. Right. Okay. So that's an interesting tidbit. Right. So if you think well if very few men get above a thousand naturally it's intuitive to think that an average level of testosterone should be below a th00and right. The other thing to think about is okay well what about people like really super physiological we know a lot of bad things happen heart attacks these kind of stuff >> at what is there a number >> well the data is not great right there's only seven trials where they look at men getting tea levels higher than 100 consistently right and they have a lot of the things that Mo talked about you know acne heart disease changes in lipid profiles you know problems with sperm production these kind of things but the bottom line is the FDA uses is 1,800 >> as the safety cut off >> 1,800 >> 1,800 for trial. So when you're doing testosterone trial, if you exceed 1,800 any point, >> you're that seems a bit high.

>> It's generous, right? But they're taking into account the fact this is an this is a one time level, not an average, >> right? So, you know, I think a T level in the 5 to 800 range in my my read of the literature is reasonable, especially if you're one of these people who are very insensitive to testosterone, if you have the keg repeats, if you have all these other mechanisms going on. So, that's my read of the data. You know, that's just an opinion.

>> But that 1,800 and he's what he's saying is it's in a trial. So, they'll allow for someone it's 5% will go above 1,800. That's not they're not allowing it to go to 1800. say they have to titrate it down. So if you're trying a new drug out and just learning more about it, but that they're not saying that's acceptable.

>> That's like the hard stop.

>> We don't really have a hard stop yet, right?

>> And you know something I see a I I see a lot of athletes and they take testosterone for you know whatever what were you calling it before?

>> Performance enhancement.

>> Performance. I was wondering if you were going to say it. I was like, >> and I send them and I send them to the cardiologist at some point. I have not had a single cardiology problem identified in these guys. Not one.

>> Is it a length of time then?

>> I mean, it could be. They're younger guys, right? And I I haven't done it yet, you know, at 5 years, but they don't stay on these performance-enhancing drugs for long term. I think the men who stay on testosterone long term are the the older patient with classic symptoms of low testosterone but the ones who are doing it performance enhancement I think it's fairly transient uh but again I have not seen anything and I measure lipids and I measure hematocrits and I measure CMPs regularly on all these people.

>> Seems odd that an athlete would come in and think about performance enhancement and again we're not talking about super physiological levels, but then they go, "Oh, my sporting career is over. I'm going to go off of testosterone." It just seems a bit counterintuitive. And maybe it has to do with the FDA restrictions. So, there was recently um a removal of uh the blackbox warning with the traverse trial.

>> Um and you were involved in the traverse trial. I'd love to hear a bit about that.

>> Yeah. Can I just I just say one thing and that is what when these when these people are no longer doing whatever they wanted to do for which they wanted the hire testosterone I will talk them down I will not continue high dosing in people.

>> What do you consider high?

>> You know over one cc.

>> Over okay so.

>> 200.

>> 200.

>> A week okay.

>> Yeah. The traverse trial is interesting because it's like before 2010 numerous studies showing men with low testosterone levels much more likely to a heart attack. Numerous studies showing that >> numerous studies before 2010, those below 300 >> were more likely to have increased mortality, more likely to have a heart attack. Also, numerous studies showing that if you give testosterone, it may decrease the risk of a heart attack before 2010. 2010 to 2014, four studies come out suggesting that you may have an increased risk. Three of these studies are not randomized, no placebo, no control. their retrospective database studies 2015 2014 the FDA has a meeting and they decide that there may be an in it's inconclusive based on these four studies whether testosterone increases the risk of cardiovascular events and they strongly recommend a large study called the traverse trial the largest randomized placebo control trial 5,246 men took us 6 years to do it very expensive trial what did it show no increased risk in heart attack in those men taking testosterone and it was a gel Don't get me wrong, it was a gel versus placebo, but there were sub studies. No increased risk in BPH, no increased risk in prostate cancer, uh a slight improvement in cardio um depression. Uh there was also improvements in uh sexual activity as well. So big trial, a lot of money spent on it. And based on the reverse uh the results of the traverse trial, big day was it was February 28th, 2025. The FDA announced we are now going to remove the cardiovascular warning from the label. was 10 years exactly later where they decided to remove the warning. So, it it took us a while, but it's it's now off the label.

>> Was that one of the biggest moments in your career?

>> Huge. I remember exactly where I was and I saw the thing come up pop up on my feed. It was a big deal because, you know, we published the first paper in 2023 showing there was no cardiovascular events and then it was silence for 2 years and I thought maybe I hope they're going to what if they don't do anything? What if they don't take it off? It was just silence. And then two years later they announced, okay, yes, we will take off the cardiovascular warning.

>> But I have to be the devil's advocate in that. I'm not comfortable with the dosing on that study.

>> Yes. So let's talk about that because people look at the range of 350 to 750 and they say, "Well, 350 is sub therapeutic. If you got someone at 360, it may be low." But what most people don't realize is this is the only study where those numbers were the troughs. They weren't the peaks. They were the troughs. So the tea trial which came out in 2015 uh 2016 sorry those were actually uh peak levels.

>> So what so what was the average tea level in the traverse study?

>> Average increase in the tea level was 147 nanogram per deciliter but this was at the trough. So we didn't publish the peak levels but

>> You have it.

>> We can look at it. We still have the data but those were the trough. So everyone that looks at say Cara 360 that's so terrible. I say if it was a peak yeah I agree that's a trough. Yeah, but there's not as many peaks and troughs with topicals >> because because you do it every day >> and it's constant. These were not injections.

>> Do you prefer as a provider? I mean, most providers pre at least I can speak for myself prefer injection. Is there a reason someone would use uh a gel or you used a gel? Was it just ease of access?

>> Well, it was also the sponsor. So, the sponsors were basically gel sponsors and so we used their formulations. But I agree with Dr. Luke Schulz. I mean gels and injections are different. So you have to be very careful in using the injection the gel data to be apples to apples for injection data. But if you talk about prostate cancer it's safe because the reality is we talk about a saturation point. So if you put someone above 250 I don't

>> Can you pause on that? The saturation point most people listening to this don't really understand that component the saturation point of um prostate or PSA. Right. So yeah, the prostate acts like a sponge. It takes up all the testosterone that it wants and finally it's saturated. Then it doesn't care how much more you raise the testosterone in the blood. It's not going to change the PSA. It's not going to change the prostate volume. And so when you uh we think the saturation points around 250 in the end peril roughly. Meaning if someone has because one of the biggest um restrictions for primary care is I don't want to give you testosterone because it's going to cause prostate cancer.

>> Right. Right.

>> That's changing. I mean, don't you think?

>> Even on the traverse trial? So the traverse trial actually showed 5,246 men no increase in high-grade prostate cancer regular prostate cancer or BPH. Big study randomized placebo. But remember if you take someone whose testosterone is 150 and you put them on tea, that PSA is going to go up. You better believe it. it's going to go up, right? If this PS testosterone is 290 and you put them on tea, PSA is really not going to go up. You're above the saturation point, right? So, if you're on an injectable or a gel, we've gotten beyond the saturation point on both. So, I'm not really concerned when it comes to prostate cancer and BPH. Cardiovascular is a little bit different, right? An injectable can cause higher ariththroytosis, potentially higher hypertension. So, there could be some parameters that are not apples to apples. I think the traverse trial gives you a good idea, but it's not exactly the same with an injectable.

>> And can we just say one more thing because this is so in nutritional sciences when a study is funded by an organization, whether it's a a beef company or the dairy council, people there will be very good science >> and instead of looking at the science, people will say, well, there's funding behind that. And I don't know if it's like that in the world of andrology and pharmaceuticals. Is it?

>> Yes.

>> It is. I mean, but quite frankly, without the funding, we can't do the great science.

>> So, I wanted to hear you guys.

>> That's the issue. I mean, this traverse trial would have never happened without the funding right now. The way the funding works typically, it's an unrestricted grant to a group of scientists that do the study, but yes, the money comes from a industry to help support the trial.

>> I don't remember in that study whether it was whe the brand was announced or incorporated.

>> No, but it wasn't. Um, but AB was the major sponsor and we had other sponsors as well but again all the money went to a central repository at the Cleveland Clinic. Uh and that study was done with nine investigators but there was

>> And wasn't at that time the uh all of the topicals generic.

>> Um, I don't remember because it's 2015. So the

>> Well, they are now.

>> They are now. So, I mean, you know, you couldn't have profited >> because, you know, your brand was not out there being advertised.

>> It's a it's a big misunderstanding with the general population and even people that are very interested in science and then the researchers because there has to be money for funding and ideally it is given to and provided to excellent scientists and excellent physicians and the data is the data.

>> Yeah. And that I mean that becomes really important.

>> Is it unethical to not treat with testosterone? So from what I've read is that if someone has low testosterone, there's an increased risk in for example high-grade prostate cancer.

>> Mhm.

>> So you think I think the word uneth >> to not treat.

>> I don't know whether the word unethical is the right word. It's uneducated.

>> A little too heavy. Well, I mean, yeah, but it's not ethics, you know, when you're treating patients. It's what's right, what's wrong, what's, you know, the currently accept acceptable way to treat standard of care. I think right now most people would treat.

>> Yeah. But I think we knowing what the three of us know now,

>> I would say, look, if it was a loved one, brother, my brother had low tea, and I'd say, look, I really want you on this for your not just for your sex drive, your libido, it's for your overall health. Yeah.

>> And I really want you on this.

>> But how about if he has no symptoms?

>> Uh well I agree. So it depends on how low is low. Like it's clearly under 200.

>> That's a really good point.

>> Yeah. You know that's a really good point. Let's see.

>> That's why I worry about testosterone screening. People are all talking about testosterone screening and if they start screening when do you treat? Do you treat because the numbers lowish? Yeah.

>> Uh you know you have to be it has to be well thought out agree when you're going to treat.

>> I think if you're severely hypoganatal and I use under 200. Yes. I consider that severely happy. Then I worry and it usually it's pretty rare that someone under 200 is not symptomatic. So let's be fair. But the reality is I worry about what's going to happen to you. Osteopenia, osteoporosis, what cardiovascular risk. I worry about lipid profile. So I would in that case say look I realize your levels low and you may not be symptomatic but these are the things I'm worried about.

>> But it's pretty rare for someone to be below 200 and not symptomatic. I know, but I just saw a baseball professional baseball player >> comes in te's are consistently under 200.

>> Yeah.

>> And he doesn't really have significant symptoms.

>> But, you know, I worry about him.

>> I worry.

>> First of all, he was very thin.

>> Yeah.

>> And I I just don't think he had enough muscle mass. Practically speaking, from a patient perspective, if you go to your provider >> and you have symptoms, your testosterone is low or borderline low, it is totally reasonable to seek a second opinion if that physician or care provider is uncomfortable writing for testosterone.

>> I know, but how many patients know that? I mean, you know that.

>> Yeah, but that's that's why we're saying these things, right? I mean, you have to take the initiative and be like, listen, this doesn't seem right to me. I'm going to get a second opinion. Or ask them, you know, I understand you're not comfortable running for testosterone. Could you please refer me to someone who is? And there are plenty of people to do that, but you have to like kind of take the bull by the horns and say, "Listen, this I I I don't feel well and this is the blood level. If you're not willing to give this to me, can you send me to someone who is more educated about it? Let me give you another, you know, playing the devil's advocate. Lo centers. I don't know what it's like where you live here. They're on every corner and they will treat anybody. I've never seen anybody who was turned away by a low tea center. So then you have to ask yourselves, I mean, is this right? Is this >> is this a license to hurt people? I mean, there has to be some judgment.

>> Yeah.

>> As to I think they've gotten a lot better though. But you're right. But a lot better. But in initially, but now they're because now, you know, just you worry about screening for elevated prolactin. Did they check you check the prolactin? You check talking about really infertility. the education uh initially was a little worrisome, but I think it's gotten a lot better. But but Larry, think about this also. They're doing a lot of now online tea like like uh announced uh that they're selling Kais, you know, so pe people can they don't have to go see a physician anymore. They can do it on their app and it's asynchronous. I put in information, someone puts in information, my tea shows up the next day uh at my house. So, you know, that's another venue that a lot of people are using. Who would you not treat with testosterone? Because you had mentioned that it raises blood pressure, is it um clinically impactful? So if someone has a low blood pressure or low blood pressure, if they go from 110 to 120, still in the normal range, if they go to 120 to 130, because we know as age happens, you know, as a geriatrician, we wanted to see blood pressure at 130 for peripheral um profusion, for cerebral profusion.

>> Yeah. So, who would we not treat? I mean,

>> I get very nervous about treating young men at a very early age if he's 21 years old uh for fertility and long-term having to be on the medication. So, I would like to talk him out of it or see if I can use other medication clomidg something else and just to kind of, you know, 21 those young patients I'm resistant. Um, so I think that's that's probably my biggest. I feel that testosterone I personally believe is cardioctive. I think there's many benefits. People say, "Oh, he's he has a lot of cardiovascular risk." Well, the traverse trial was high risk cardiovascular patients and I Yeah. And so, yeah, he had to have cardiovascular events or three of the eight cardiovascular risk factors and I think it may be part cardio. So, most clinicians say, "I'm worried he has a bad heart. I don't want to put him on testosterone." I say, "I believe the opposite. I'm worried if you don't put them on testosterone, it's going to make

>> Well, there's a difference treating someone with heart disease versus preventive treatment.

>> Yes. Yes. I mean, you're not going to be worried about preventive.

>> No, I mean we're preventive, but she's saying, "Is there someone you're worried about?" And someone say, "I'm worried." Most people say, "I'm worried about someone who has high risk prostate cancer. I'm worried about someone who has increased cardiovascular risk factors." I say, "I'm not. I believe the opposite. I think that testosterone also may be protective against prostate cancer. I think that, you know, the hypogonatal range is a danger zone. We call it the inverted U. Castrate may have some benefit. Ual high levels of tea have some protective benefit. I personally believe that it's the middle zone, the hypoglyanatal range, which I believe increases chemical recurrence for prostate cancer, increases the risk for higher risk prostate cancer. So I I really believe the same with cardiovascular disease. It's the inverted U. That's that's very much.

>> And we're also now seeing drugs that stimulate the patient to make their own testosterone >> like what?

>> Well, the clom clomophene and its derivatives like you know and clomophene.

>> Uh so that I think is a good drug for younger guys.

>> Easy. It's a pill. um use off label, but still helps raise natural testosterone, helps raise sperm counts. Um yeah, I think it's a great drug.

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>> Can we touch on if everyone is comfortable just touch on peptides because that's kind of all the rage. Yes. Right now.

>> Like what are we touching on it? Um I I don't want to talk about necessarily the GLP ones, but the other peptides like

>> I think they're going to become huge.

>> Like CGC and

>> I think they're going to become because

>> tessamine.

>> As far as we know they don't have side effects that are worrisome.

>> How does that make sense?

>> Why? Well,

>> They're protein hormones. They're act, you know, they're attaching to the cell membrane. Um, I don't know. I mean, why would they necessarily have bad side effects?

>> I'm going somewhere with this. I was leading you into somewhere. So, you're going to trap me.

>> Oh, I was going to have you explain that. Um, because this is my understanding that um testosterone is recognized by the body as such, but these other peptides, these string of amino acids are not um recognized. Again, this is my understanding by the body as that entity, meaning it doesn't have downstream effects that would be negative.

>> Did I explain that well or

>> As far as I understand?

>> As far as I understand, they're naturally occurring substances. They're extracted from other fluids.

>> CJComorin is a natural.

>> I mean, I can't I cannot tell you which ones. There's one that comes from the placenta. There's one that comes from gastric. The BPC is gastro extraction. I don't know all the other ones, but uh they are theoretically they're called naturally occurring substances and they have very specific action. It's not like you know you give somebody testosterone, it does many different things. Peptides are very specific and I think the more specificity the less chance you're going to have of side effects. Yeah. And we're not seeing any yet, but I mean, it's way too early because I, you know, the places that are making them are they're coming from compoundingies and not all compoundingies are equal.

>> So I think we have to be careful at this point in time. I agree with

>> Prescribing because we just don't know enough about their sourcing.

>> Uh but I think it's going to be something very big in the future.

>> Yeah, we use this word peptides very loosely. There's a lot of peptides, you know, so you know, but the peptides most people are talking about are growth hormone peptides or they're talking about BPC, which is a gastrop. That's what they're talking about. They're not talking about all the other peptides. GLP is a peptide. That's not what they're talking about.

>> And the peptides of peptides.

>> Yeah. So, so when you say peptides, be specific. What are you talking about? We're talking about growth hormone peptides, gastropeptides. And these peptides, uh, some of them are FDA approved, some of them are not FDA approved. The ones that are FDA approved, for example, are Sir Morlin, Tessa Morlin,

>> Been around for a very long time.

>> Very long time. And if you have data, and if you look at the data, what do they really help with? The three things they help with are increasing muscle mass, decreasing fat deposition, particularly trunkal fat, and actually uh can help with sleep. Right? That's it. There's no benefit in sexual function. My libido went up when I took that CJC. No, there's no data to support. Now, it may have, but show me the data. But there are some that are theoretically uh oriented towards sexual function.

>> Like brelanide PT-14ide. Tell me about that.

>> So breaotide is well here it's it's it would came out for women.

>> Visi it's for women pt41 but when people say peptides they're not talking about visi but but you're right there are sexual function.

>> I do use PT I do use it for men.

>> Yeah we do. It's a off label. It's very effective. But I think when people are using the word peptides, they're not talking about vile. They're talking about give me that CJC, give me that BPC, give me my epomoralin. And you have to realize that they're not FDA approved. And there could be some safety concerns. And if you look at the FDA website, they say that they're not intended for human use at this time. Fine. And so I just think it's important to know that Sir Morland's FDA approved. Tessa Morland FDA approved. What are there was it clinical indication tessa morland for >> HIV lipodistrophy and sir Morland was for uh pediatrics for growth deficiency >> but if you look at the data on tessellin the studies are pretty good studies yeah >> from when it was launched >> is it co and it's an injection is it daily injection yes >> tessor yes >> is it cost prohibitive or covered by insurance >> I think it's I think it's too expensive right now uh I don't think it's expensive to make or source so I think we're going to see prices come down on peptides >> for for sale for a compounding pharmacy to make a peptide it has to be under 40 amino acids. TessaN is 42 amino acids. So theoretically it should not be compounded for human use because it's above the but if you you can buy commercially if it's not no insurance it's about 7,000 a month. It's

>> But the 40 amino acids is for classification as peptide versus a biologic. Yes. It doesn't mean that if it's a biologic, you can't make it or sell it, but there's stricter criteria for biologics than there are for peptides. In Europe, some of the peptides are sold as supplements. You don't even need a prescription.

>> So, I don't know what's going to happen here with peptides. I mean, there was a recent announcement that 14 were going to be approved uh for manufacturing uh under a new FDA ruling, but it's not yet actually done. So, whether it will actually happen,

>> I don't know. But uh Robert Kennedy did come out and say he was trying to get them approved. And then the followup with that will there be more do you expect more randomized control trials with these type of >> if they get approved they'll be easy if you get it approved it'll be easy to get those trials up and running >> but the trials will be from people like you they won't be from pharma >> because apparently there's some reason why they they can't um copyright them or what's not not the word what is the word when it's a drug patent >> they can't patent it because it's a naturally occurring substance. and and there's so you know big farmer can't make money on it and since studies are so expensive who's going to pay for the studies that's that's the big problem with peptides.

>> So this is a really interesting statement here I'm just going to read it says erections as medicine the cardiovascular conversation.

>> Did you make that up?

>> I didn't why I'm making it because it's much better than anything that I could that I could make up then quite frankly.

>> Um

>> It's a really important point and that's what I think Dr. Coler brought up this phrase I still use. It's called the check engine light on. Essentially means ED is not a disease.

>> It's a symptom. It's not it's a symptom of something bad going on. Right? A healthy man should not have ED. Right? ED could be because he has depression. That's a symptom of depression. Depression of cardiovascularities, a symptom of prostate cancer, diabetes. It's a symptom of something going on. And your job is not just give him the viag and say goodbye. find out what the problem is as opposed to just giving them their body.

>> And in in all honesty, I would bet the majority of men who show up and say, "Yeah, my erections are just not as good as they used to be." And you give them back, you don't get a study on these men.

>> There you go.

>> Why? Why not?

>> Because it's cost prohibitive. Every man at a certain age is going to tell you his erection is not as good as it used to be. So if you and talk about lifestyle drugs, I mean, then you Viagra is becoming a lifestyle drug. So, you know, and daily sales.

>> What do you mean lifestyle drug? Meaning there's Because in my mind, that would improve uh blood flow. So, that would not necessarily be a lifestyle drug, but improvement.

>> Well, but the end point what I'm talking about is what they're trying to get is a better erection.

>> Um they're not it's they don't have a uh a terrible symptom, you know. Well, yes, it's a terrible if they can't get erections, but just to make it better, which is so often what the patient says.

>> But but we do investigate everybody who comes to me with a problems with erections. We check a testosterone level, right? That's what we were talking about in the first hour here.

>> We ask about a family history of cardiac disease. If that's there, uh we do much further investigation. We typically check a cholesterol panel. Uh we check a sugar. So these are all the kind of like other check engine lights that should be.

>> I was thinking more more of a duplex.

>> Duplex ultrasound is certainly down the road but if a guy comes to me with ED >> I'm telling you I'm just saying he says my erections are not as good as they used to be. It's not that he can't get an erection >> and it's very subjective. I mean.

>> Of course it is. However, it could very well be the sign of something going on that we should investigate.

>> Uh you know there's powerful data. We know clearly that you know vascular ED that is classically lack of blood flow to the penis predicts heart attacks by three.

>> Say that again.

>> So when you have blood flow problems to the penis that cause problems with erections cuz sometimes it's psychoggenic, right? It's not true vascular problem.

>> The penis predicts the first heart attack by 3 to 5 years.

>> Okay. So

>> That is really profound.

>> So we know that as a fact. Okay. But now there's even more data that shows that men even with psychoggenic ED that is the plumbing is fine. We do the Doppler uh that we just discussed to check the blood flow and the blood flow is fine. But we know that men who aren't getting erections because they're anxious because they're nervous because they had a bad day, bad night, and now it keeps happening again. Those guys actually have more heart attacks, too. It's crazy data, but think about it. The average man thinks about sex 18 times a day. There's a study out of Ohio State in 2012. And if this person doubts they're going to get good erection, that means they're going to get depressed and anxious 18 times a day. That is a setup for more anxiety, higher blood pressure when somebody cuts you off in practice. Uh worse sleep. These are all a formula to set you up for other metabolic problems and and disease.

>> So I think erectional dysfunction should never be ignored and always should be further investigated independent of the cause. So if you think about what he just said, so a man walks in with ED, he's 35 years old. So we know that if he comes in with ED today, 15% chance he'll have 15% of those men have a heart attack or stroke within 7 years.

>> 15.

>> 15% within 7 years. We know that he's three and a half times more likely to suffer from clinical depression, which you're not even touching on. And there's a 30% chance he could have diabetes or pre-diabetes that you're missing. Now, let's say you do nothing and you just give him the Viagra and he did have cardiovascular disease or he did have diabetes and you picked it up 5 to 10 years later. That's 5 to 10 years of pounding on the vessels and which you could have picked up 10 years earlier. Now, if you think that young man, he has hypertension, you say, "Hey, well, I want you to go in and get screened for your blood pressure every year." He's saying, "No way. I would have never gone at 32 years old to get my hypertension." But if he has ED, first thing tomorrow morning, he's at my door and he's going to say, "I I what's going on?" So ED is a great way, a gateway for men's health to get them their blood pressure checked and to get their blood sugar checked. It is a gateway to bring men in. But I think it's a disservice when you have a particularly a young man to say, "Here's your viagra. See you later."

>> But that's what's happening in the in the world. That's what's happening.

>> I mean, because most of these patients are talking to their primary care and they're saying, "My erections are not good." They give them Viagra and then

>> That's it. Right. We only see them when I mean I think the ones that we see are the ones that don't respond.

>> So the primary care refers them or they don't get erections which is a lot more severe than it's just not as strong as it used to be.

>> But but what an opportunity to actually >> screen and get baseline numbers in these patients. I mean awesome. You see this guy like when you're a young boy or girl uh you see your pediatrician. What happens to girls? they get handed off to their obgyn doctor. What happens to boys? Nothing. Nothing. So, they don't come to your office for 20 years. In the meantime, they have high lipids. They're pre-diabetic. Maybe they have a cardiovascular risk. And we're completely missing that.

>> We talk about this, you know, I have this webcast and we talk Amy and I talk about the fact that >> no one is seeing the guys. I mean, the women have their gynecologists when they're going to start birth control or they start having periods and they go and they get checked. There's no place these guys are just floundering around for until they're 30 easily because we see them as infertility patients, right? They've never seen anybody. And and the culture continues like the phrase, I haven't seen my doctor in 20 years. I'm healthy as a as a horse. I mean, that's just lunacy. Who who buys a Porsche and then never changes the oil, checks the the air pressure, right? I mean, like, that's just crazy. the human buys this amazing machine and screening like really helps to prevent heart attacks, you know, diabetes, etc., etc., etc. Yet, there's this desert of men's healthc care that is completely there's this there's this phrase now toxic masculinity, right? And that's these guys, you know, it's they say, "Man up." You know, I'm having headaches. Man up. You know, the father tells his kid, "There's nothing wrong with you." And this is built into the society uh as we know it right now is that guys don't they think it's bad to go to the doctors because they're admitting there's something wrong with them. So when girls start menrating they go to obg you know obgyn is there an age that so for example the normal age for erections to become more frequent is what >> 14ent puberty >> puberty >> is there going to be an indication where okay you've hit 14 you're a boy we're going to send you for even baseline testosterone um or whatever >> how about just to talk about sexually transmitted diseases is >> preventing pregnancy. I mean, they're not there's no health education in the general education system right now like there used to be. So, they don't talk about it. I mean, no one talks to these guys.

>> It's tragic. I think it's terrible.

>> Will there be um I mean, is that anywhere in the guidelines what you were talking about >> screening?

>> Yeah. No, but we're trying. When we went to the FDA back in December, we talked about the fact that and every man over the age of 40 was what we thought about. Every man should over the age of 40 should have a testosterone level screen annually because it's the best predictor of a man's overall health. And when we thought about it more, I think the number maybe should be lower.

>> I mean, I think I mean, I want my levels when I'm at peak performance.

>> Yeah.

>> 25. Yeah. just just pick a number, but certainly earlier than age 40 because again when you're 45 and things start to fall apart and it may be too late. Also, the things that caused you problems at 45 could have been addressed when you were 25.

>> It shouldn't be an annual screen.

>> I mean, and everybody knows what their cholesterol level is, right? If they're going to the primary doctor, nobody knows what their testosterone level is.

>> But you young guys don't go to primary care unless

>> That's the problem. No, I know.

>> That's the problem. But but but then again you have to think about primary care. Primary carees are just inundated with patients. It's very difficult in Houston right now to get a primary care appointment.

>> Mhm.

>> And that you know they have 10 minutes per patient or whatever. It's a very short period of time >> with so many things to discuss.

>> Yeah. It's such an important point you just mentioned. Right. So the reality is it's like 18 minutes. My wife's primary care cure. She says look I got to go through diabetes, hypertension, hyper lipidmia, OSA. How am I going to get to ED and testosterone? You start with it early.

>> Yeah, you could start with it early. You could, but she's like, well, then what if I can't get the diabetes, right? Like I got this is what I got. I got to get everything in. And I said to her, well, you need it's an important predictor of their could be suffering from other things. And she said, look, where did I get the training? I didn't get the training, right? And he put out an unbelievable paper se several years ago saying that only 50% of

>> What is it called? Well,

>> It was a what journal it was like a couple years ago where you and the Mayo Clinic put out an article showing that if you look at education, I think Dr. Dr. Hilo was the first author showing that the only 50% of medical students and residents got formal training >> 15 or >> 50 50% got formal training on uh sexual medicine like how to you know sexual medicine and how to approach ED. Of those 50% that got training 50% said their training was lousy.

>> So So h how do you feel comfortable coming out talking about someone's erections when you got no training?

>> I mean, it's it's a really good point. And then um to your point on primary care before we even get to diabetes, hypertension, cardiovascular disease, perhaps when they're 18 or 15, I mean maybe 15 is a little too young to get a baseline cholesterol and baseline testosterone level.

>> I think it's really important. Yeah.

>> And we start early. What about um >> birth control? So vasectomies. You how many you've performed over 2,000? I mean

>> Yeah. You're doing it in your living room. Come on guys. How many?

>> I have no idea. I mean, when I was in the army, I had to do five every Friday for two years. I mean, you know, it's just

>> Do I he's done a tremendous taught many fellows, over 130 fellows how to do them.

>> What about reversals?

>> He's done a tremendous amount of reversals.

>> 130 patients. I mean, 130 fellows have been trained and a lot of them go out and they don't do it because they don't have the the patient population. But we do a lot of uh rever I had three people come in yesterday for one office hours to talk about reversals.

>> Is that um effective and is it a common procedure in general?

>> It's not a common procedure because not that many people are trained. I mean if if we trained 120 130 that's you know that's who we trained. I mean they know there aren't more and people retire. I think what's happening though, I think there I think there's been more with more divorce uh people are forced to change their mind because their new spouse is often younger. The woman's often younger and she wants to have a family. He has two kids and he will have the reversal so she can have a child. And I think that's becoming increasingly common with the high divorcy. Yeah.

>> Is there something that men and women should know prior to undergoing vasectomies? I don't think it's really discussed that much.

>> I think I just think the message is that tell them it's permanent even though we

>> So stop coming to you for reversals.

>> No, I would love doing reversals. But I mean the point is people should not be told this is a temporary procedure. They have to realize that it's hard to get it reversed because there's not that many people doing it. But don't you think you want to educate people when they come in for a vasectomy that it's not temporary?

>> Yeah. Two points. Also, his point is also you only want to go to a center of excellence. People who have high volume that know how to do this because sometimes you can do something more complicated like an epidmovastomy which is more complicated. So it's a more complicated type of the procedure and you don't want to go to someone who's doing one a year or two a year. You really want to go to someone at a high volume. And more importantly, if you're going to give one message out about reversals, the sooner you do it, the better. If you come to me in three years or five years, the outcome is much better than you come to me in 20 years. Right? So that's a really important point. It's time dependent on outcomes.

>> But people don't always know when they're going to get divorced and they only, you know, so you know, I think we have to just do it when they need it done. But we counsel them that the results are going to be better if it's been under 10 years.

>> Okay.

>> Um, you know, I was misguided. I thought it was a very common procedure.

>> What a reversal. Yeah, I thought it was very

>> 6% of all men who get vasectomy inquire about vasectomy reversal. That's the number I remember.

>> Okay. So, it it's not quite frequent at all. And when it comes to male infertility, uh I'm curious as if you all agree on the one cause if you could pick one. I I know you hate the one.

>> I mean, you you he was the one who invented Veric Casil because the one who caused Infertility's paper.

>> Um, so it's probably the most common problem.

>> And it's the most and it's the

>> What is

>> It's enlarged veins around the scrotum around the testicle.

>> Could someone see that or it's under ultround?

So you can see it in some cases, and we grade them as you know, small, medium, and large, or grade 1, 2, 3. And the grade three, you can literally see. I'm sure you've seen patients with these large. You know, that I'm asking for that, you know, for those guys out there. Um, is there anything?

So, I think I think that you have to remember that 18% of all men, 18, have varicose veins of the testicle, but not the legs. It's the testicles. It's right around the testicle, and it overheats the testicle, and heat is bad for sperm production.

And wait, you got because I don't actually know this. So, the varicocele causes an increase in heat production?

Yes.

It because it's retrograde flow, and it sits around the testicle. So you don't have the blood leaving. It's just pooling there.

Sounds painful.

No, it can be, but I mean, that's not the most common thing we see.

Okay.

It's like a factory where, you know, you're the workers are making sperm, and somebody like takes out the air conditioning and turns the temperature up 30 degrees. The productivity of that factory is definitely going to go down.

Oh, that's huge.

That, that's a great, that's a great analogy.

I picture these little men like smile. So when, so he's very stoic, and then when he starts to smile, you know he's coming in with an analogy or something.

Right, right. But anyway, so when a man comes to see you, the fact that he has a varicocele is not necessarily known in the

Well, it's also and yes, but it's also not necessarily the cause of his low sperm production because it could be true, true, unrelated. He could have a varicocele since 18% of all men do, and he could have another reason for his infertility. Uh, but I think in general, most of these men will end up having their varicoceles corrected because it is such a common, uh, problem with, uh, testicular failure.

Mhm.

Is it one of the causes of low testosterone or ED, or erectile dysfunction in younger men?

Low testosterone. Yes.

Yes. Yeah. Low testo, not erectile dysfunction, maybe indirectly testosterone goes down, but low testosterone. Yes. The problem is that if you fix the varicoceles, you see about a 85 to 100 nanogram per deciliter increase, which some would argue is not clinically significant. That's not that much.

So, yeah, so if I started at 250 and you get me to 350, so it's not currently considered an indication. Like, you wouldn't fix someone's varicocele to help raise their T to a normal.

People do, let's be honest, they do. But I don't think it's, I don't think it's clinically significant. But you, you'll know if you, if a man checks his own testicles and one's really small and it used to be the same size as the other side. So there's something called testicular hypotrophy. The testicle gets smaller from that factory exhaustion thing, right? So now there's little men taking riding, and the factory is actually getting smaller. I think you mentioned something very important that was having men check their testicles.

And they don't, and they should. But again, there's no education to young guys that, you know, between 25 and 35, peak years for testicular cancer. So, you know, I tell my patients, you know, once a month in the shower when everything's nice and just make sure there's no lumps or bumps on the testicles, and if there is, come on in and we'll check it. But it's really important. But if they don't, testicular cancer, what is the, the mean age?

Between 25, 35 is a bimodal distribution. So, in either young men below age 35, and then older men like about 50 or 55.

Yeah.

And then, you know, when you're, when a guy is feeling his own testicle, he has to know what's going on there. So there's this olive-like structure, and then there's this thing on the back. It's like a backpack. That's the epididymis. It's where the sperm learn to swim. Swimming school. And

It has to be bigger than an olive, please.

It's a, it's a very olive.

It's a huge olive. So 20 cc's or so.

Yeah.

And then what you're supposed to do is gently roll the testicle between your fingers and learn what normal is. So the epididymis is back there. What age should they start testicular exams?

20s.

Well, 18. Some 18 to 35.

18 to 35 is like.

That's a big, that's a big range.

18 is when you start.

What you're looking for is if you're walking down the street and you picked up a stone, like a pebble, right? It's jagged. It's hard. If that's living inside your testicle, you feel like, wait, there's an irregular border. It feels very hard there. That's

Cancer to prove otherwise.

Y.

That's cancer. Tolerance is very important. And we've all experienced seeing these guys who come in, nice guys, married, unmarried, and they've just, their whole testicles replaced by cancer because they just, they just don't. I know, but they don't know or they, you know, but refuse to face the fact that something bad.

Early diagnosis of testicular cancer is great, life-saving.

I mean, 99%. Ask them to make a fist, and you tell them between the knuckles is exactly what a normal testicle feels like. You just press down. It's normal testicle. The knuckle is identical to what a cancer feels like, right? You want to feel between. You don't want to feel the knuckle. That's a very simple way to tell someone what they're feeling in their testicle.

What is the lifelong prognosis if it goes undetected or untreated?

It's, uh, high, high mortality if you, it gets because it can get metastatic very quickly. There are a lot of good drugs right now for the, the man with, with testicular cancer, but you don't want to let it get to that point because the drugs all will all, as a group, will cause infertility.

And so, you know, you don't want to, you don't want to let it get so far that you need drugs. And you also need to know that you can bank your sperm easily and not expensively if you have to have treatment for testicular cancer. And can someone still maintain fertility because it's not always, is it usually bilateral? I don't want to say bilateral, is that the right term?

Yeah, it can be. It can be. And one of our partners has a case coming up that's bilateral. But in those cases, you have to make a decision. You know, do you have, it's saving their lives, but we do something called oncofertility. And oncofertility testing is when you remove the testicle, you work with the pathologist, they line out where the cancer is, they show you where the good tissue is. We take the good tissue out at that time and we go bank it and save it so they can do IVF later. And then we give the cancer to the pathologists, but it takes a team to get that done.

There's a whole subspecialty medicine called oncofertility, preserve fertility with cancer for both men and women.

Wow.

Right. So often when patients start, when young patients are told they have cancer, first of all, uh, survivability with people, young people with cancer is actually quite good. But you get blinders on. You forget about these things like fertility, because you're just like focused on, I need to get this treatment. I need to get this treatment. But there is always time to talk to an expert about this and say, either bank sperm or do ovarian cryopreservation in women, or potentially move around where the ovary is if they're going to shift it out of the radiation field. There's always time. It should be considered because if you don't treat it before the cancer treatment starts, it's too late.

Now Anderson is trying. They do have two women over there full-time.

Yeah.

But it's mainly addressing the women.

Yeah. But they send their survivors.

They do. They do. And I have one last question regarding this before, uh, we wrap up.

With smoking, cardiovascular disease, or lung cancer, we know that there's a relationship. Do we know what the action item or the exposure would be for testicular cancer? Are there known exposures?

There's not equipped organisms. So if the testicle doesn't descend, that's a risk factor, right? But the, the, I can't give you a percentage on the smoking or if there's a correlation with the smoking and the test.

No, I don't think there's no data. There's no data on that. But I can tell you this for infertility, men who are having trouble with sperm production, a huge area is environmental toxins. And there's some excellent review articles just out recently talking about all the things in the environment that theoretically can affect sperm production because you're making millions of sperm a day, and with rapidly turning over cells, they're going to be exposed to whatever is in the environment that could come in and halt that cell division. So, you know, the, a lot of the, um, uh, like coal, people who live around coal mining areas, they are breathing in things that can affect their sperm production, uh, tox, uh, thing, uh, soil fumigants, um, pesticides, and alcohol.

What, what is that?

It's got this terrible look.

No, I don't. So I was actually thinking about the veterans and I was thinking about the veteran community and infertility. But taking it one step further, I was thinking about testicular cancer in the veteran population. I was.

But I, you know, that's a very interesting point because we're just starting to look at the burn pit.

Yes.

Patients, I mean, exposures in terms of fertility, because it's, you know, all the other things have been identified, many things have been identified that are health issues, but it's just your husband is starting to look.

Listen, this is what we talk about at night. You know, people are starting to look at this in the veteran population, and I think it's going to be a very important thing.

I, I would agree with you. Gentlemen, thank you so much for coming on. If you would like to leave the listener or the viewer with one, it could be a tip, it could be a statement for their physician, or as physicians, the floor is yours.

I'd say low testosterone and ED are a marker of poor health. And just don't ignore it. If you have low T or ED, look at what the cause is because it could be potentially life-saving.

And you have a wonderful TED talk on sex span. So we'll link it at the bottom.

Thank you. I was there front row popcorn.

Uh, I mean, one thing, uh, and that is we've shown that poor sperm production, infertility is a metric of a man's health. So men who have low sperm production, increased risk of all-cause cancer, earlier mortality, greater incidence of comorbidities, and you know, that can't be overlooked as simply something for reproduction. It's, it's a metric of health.

It's very well said.

You need to be proactive. You need to take agency for your own health.

Don't be anxious, depressed, sitting on the couch. You are the CEO of your own body.

Right. Take care of it.

Well said. Thank you so much.

Thank you.

Thank you.