The Hidden Costs of High-Dose Testosterone: The Line Between Therapy and Enhancement

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4:16Hey everybody, welcome back to The Mailroom. I'm your host, Dr. Jesse Mills. I am honored, thrilled, super excited, maybe even pumped to welcome back Dr. Jasper Bash to our program. Dr. Jasper Basch is an assistant professor of urology at Oregon Health Sciences University in Portland, Oregon. He also did medical school and residency there. I was thrilled and honored for him to spend his fellowship year training with me at David Geffen School of Medicine at UCLA, where he completed his fellowship with honors and high accolades in male reproductive medicine and surgery. and Dr. Bash now serves back at OHSU as the role of assistant professor of virology and soon to be named co-director of the male reproductive medicine and surgery program at OHSU and also little known fact that Dr.

5:10Bash is an acclaimed acapella musician and a tenor for the beautiful voices of the testosterone and their hit album Mendorphins which is still available on iTunes And I'm hoping to see a bump in this from our listenership when you hear the velvet smooth sounds of an acapella group speaking about testosterone. Dr. Bash, welcome. So good to see you and hear you again. What is new? What a pleasure to be back with you. Let's see. Looking forward to those sales rolling in on endorphins. Long time coming, but life is good over here. You get a tenth of a cent per download. Is that what it is per stream?

5:48It's something very good. I'm in it for the emotions more than the money, and I think that really helps with the outcomes. I think you're in it for the wordplay. I could almost say you went into this field just to own up to the name testosterone. It was an early signal of where I would end up in urology and then men's health. That's great. Well, Dr. Bash, I brought you back specifically to talk about the world of testosterone and most specifically super physiologic testosterone. What does that mean? We dig pretty deep into the testosterone world in this show because so many guys are on it. We've had episodes discussing what hypogonadism is, but we haven't really talked about what hypergonadism is.

6:35In other words, if a guy comes into your clinic with normal testosterone and he's like, man, I want to get jacked. I want to look huge. I want to be that guy at the gym. So tee me up. What I want to know, because you've done some work on this, you've spoken about this, you're pretty good command of the literature. I want to know what that means. What does that look like to you? So we're going to get into on this episode, what are normal ranges for testosterone? and where did those ranges come from? In other words, are we just making this up or are there some physiologic parameters by which we know that the window that we think is normal is normal?

7:18And then also what actually happens to a body if somebody decides to go large and then what are the risks to that? So let's jump in. Give us a little background on the normal testosterone level, the range, what you see in your clinic, and just also how often is it? How often does a guy walk in your office and say, dude, make me huge? Well, I'd be happy to. To start off, how things normally work. So usually in a man, the brain sends signals to the testicles and says, make testosterone. And the testicles do that. And in our younger, healthy guys, testosterone is highest in the morning, and then it can drop by as much as 30 % into the afternoon.

8:03And that's totally normal. As we get older, that drop becomes much less, maybe 10%. Nice and high in the morning, which is just when we want to test it. When we think about what is physiologic, physiologic means how are things supposed to naturally work? And we have great data looking at lots of guys of different ages. And that was compiled. And we have American guidelines and we have European guidelines. And so in America, we would say that a normal testosterone drone is above 300 nanograms per deciliter, which is how we measure it. So above 300. In Europe, they'd say 350 is where they want people.

8:37I'm not sure what to make of that culturally, but there is certainly a difference, which shows you there is a difference of opinion. A difference of opinion or difference of culture. Maybe Europeans just need a higher level to feel as good as Americans at 300, or maybe it's just all made up. It certainly could be. We also know that just as we're all different in many ways, everyone probably needs a different amount of testosterone to feel good. And so some people have much higher testosterone. Some people have lower testosterone. And as long as those are in what we'd consider a safe range, and I'm going to go ahead and say maybe 300 to 800, probably nothing dangerous is happening, right?

9:14We know that if we get below 300 and we start getting lower and lower, we start worrying about effects to the bone and low bone density, effects to the cardiac or the heart function, and a host of other things, not feeling good, erections, not working well, bad things that we don't want on this show, I'm sure. As we age, it will come as no surprise to listeners that people's testosterone often decreases as we get older. But as we have talked about before, people's eyesight usually gets worse as they get older, and no one's saying you shouldn't have glasses. That's not natural. And so now is a wonderful time to be talking about testosterone and be a prescriber of testosterone because we're having more and more safety data and we're able to offer testosterone to more and more guys, making them feel good and making them perform well, well into their lives as they age.

10:02I love what you just said there, because that was actually my next question is, what is normal? So if you see an 80-year-old guy with a testosterone of 300, but he's still bench pressing Jordan's level of bench press, he's putting up three wagon wheels and feeling amazing, powerlifting, working down at Venice Beach at hitting the boardwalk hard, his testosterone is normal for his age. But if you see that same guy that's 300 and he's 22 years old, and he's feeling more like an 80-year-old that doesn't bench press 315 pounds, are those the same blood levels, or do you have a different interpretation for those two clinical scenarios?

10:43Absolutely. So we think across the board, 300 is kind of the bottom deck that we shouldn't go under. There was some great work that was done by Andino and colleagues that was looking at younger guys. And we know that younger guys really do need higher testosterone. No surprise there. So if you've got a guy in, he's around 18, let's say, he probably shouldn't be under 400. We call 400 to be his low number. So we take it in context of age, of health. And then we also think about symptoms. So if I've got a guy who's coming in and he's just above 300 and he feels great, like you said, I'm not going to worry about it that much.

11:19The symptoms of low testosterone are very vague. Fatigue, low libido, not having as much drive to the gym, difficulty putting on muscle mass. I often joke with my trainees that these are all the symptoms of being a resident, right, and just training hard. And so that can often overlap with other things like sleep apnea. If you're not sleeping well at night, number one, you'll have low testosterone because it suppresses your brain. But number two, you're just going to feel like crap all day. And if I can fix the sleep apnea with a CPAP machine, they may not need testosterone therapy that might fix their testosterone and make them feel good.

11:54So overlapping symptoms, overlapping causes that can make them confusing. But there are certainly lots of men out there who truly have low testosterone and deserve to be treated in a safe way. So yeah, you've hit safety twice in your discussion. So what does that mean? Because what we're going to get into today is what happens at a supra-physiologic dose. And so say that you're not going to take care of this guy, because if you see a guy that comes in, he has no symptoms of low testosterone, but he's heard about it. He's heard other influencers talking about their journey with testosterone therapy, and he's just got to be on it.

12:34And he wants to be on it with a high level. First of all, what would you consider a super physiologic dose? How do guys get to those levels? In other words, what are they taking? And then what is either good or bad about that? So I would say for the vast majority of guys, above 800 or 900 perhaps is going to be super physiologic. Now, my best friend is an exceptional cyclist, and he measured his testosterone the other day, and I think he was 1 ,100. What? And I thought, well, that fits. I mean, man, you were in good shape. And for him, that's natural and more power to him. But for most guys, we'd say above 800, 900 is going to be high.

13:10If I've got a guy who comes in and says, is 1200 or bust for me, I've got to be up there in those numbers. Some things I would remind him of are number one, if you take testosterone, it tells your brain, we've got plenty of hormone and your brain tells your testicles, you boys can take the week off. They'll stop working. They'll shrink, which many men don't like, not surprisingly. And it can be hard for some people to get off the testosterone. So that's one thing I try to impart upon them. Also, you can't top up testosterone. So if guys say, listen, I made 100. I just need a little boost to get to 1 ,100.

13:44I remind them that if I give you any testosterone, it's probably going to shut your pituitary off. You're going to stop making any of your own testosterone, and your levels are going to drop, which is the last thing they want. People who want really high levels may do it just with testosterone alone. They may also think, I want to do this for gains at the gym. I want to do this for performance. I'm going to mix in some other things. There are many adjunct medications you can use, an aromatase inhibitor to block estrogen production or other estrogen blockers or mixing in anabolic steroids. We know that testosterone is an androgenic steroid mostly, meaning it's doing andro male things, an anabolic steroid is going straight to the muscle and saying, let's get huge, let's make more muscle.

14:30A lot of the literature, when we think about high testosterone, we have to make sure we're not conflating or falsely connecting or overlapping testosterone literature with anabolic steroid literature. Those things are different and those medications work very differently.

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18:36you brought up a lot of amazing points there uh one of the ones that i would react emphasize that i tell people is that that be clear that the r in trt is replacement it's not it's not s as in It's supplementation. It's not TST. And so that actually is a great way for men to understand when they're seeing their doc, if you tell them that, what you said was, look, I want to be at 1 ,200. I'm at 600 now. You just got to bump me up 600. So just give me a little boost. It doesn't work that way at all. What you do is you take them down to zero to bring them back up to 1 ,200 or not maybe zero, but somewhere lower than that.

19:20And along the way, their testicles shrink and they start to have that dependency. So that's number one. Now, number two, I would love for you to dig in a little bit more to the difference of anabolic versus androgenic steroids. And then maybe, you know, we can talk a little bit about the androgen receptor, because I think that's a great thing for people to understand that maybe part of the reason that that 80-year-old guy feels great with a T of 300 is because he has an androgen receptor threshold that's a little bit more sensitive at a lower level. But walk us through that because I think that's what we're trying to get at is what happens when a guy goes large, you know, and he goes from the androgenic wagon to the anabolic wagon.

20:07Absolutely. So, you know, these are all steroid hormones that we're talking about. And then what that means is that this is a signal in your body that goes into the cell, into the nucleus where all the DNA is. And it says, make more of these signals and let's do something on a cellular level. And so that's how these all work. Androgenic, andro, male, androgenic effects are going to be like body hair growth, right? So that is something I don't make a lot of facial hair myself, but my testosterone is normal, I guarantee it. But androgenic effects are those kind of things. When we, if you imagine your bucket and your androgenic bucket is full, meaning that the effects that that can have are maxed out, if you're using just testosterone, you will find that you're tipping over into the anabolic, anabolism meaning building.

20:53And so if you give yourself enough testosterone, you can certainly tip over, fill up that bucket and start being anabolic, fill androgenic, start doing anabolic. Anabolic steroids will just go for the anabolic muscle building qualities. And if you don't take some testosterone with them, you will actually lose out and have lower amounts of androgen, lower kind of male forward effects. Okay. So what I'm hearing you say is that anabolic steroids lead to muscle production, that you can take an androgenic steroid, like let's talk you know let's talk esters here you know sipionate and anthepropionate some of my favorites ask for them by name exactly right ask them by name it's at your local pharmacy or back alley and the androgenic steroids then if say a normal dose i mean for if i see a guy you know most of the men we start off somewhere you know between 100 to 200 milligrams a week testosterone and sometimes on a weekly dosing, sometimes twice a week.

21:58If guys are into giving themselves shots twice a week, it may be a little bit more physiologic. But yeah, we're staying in that 100 to 200 range. What point then, and let me ask you just for fun, who have you seen in your clinic that goes above that? And what's the highest weekly milligram dosing of the androgenic steroids you've seen? Yeah, so in terms of, I would say the patient population in Los Angeles is a touch different than the patient population in Oregon. It'll come as no surprise to you. We do not have the San Monica Boardwalk here in Oregon. It's too cold. There are too many rocks.

22:33I don't find a lot of guys coming in over, let's say, 300 milligrams of testosterone a week. But we have really interesting studies coming out of Los Angeles in the 90s, where they took guys and they said, let's figure this out. We know that the prostate tissue is probably saturated at a pretty low amount of testosterone, meaning if you're a testosterone of 300 and I send you up to 600, the prostate is not going to change differently. Very good evidence for that. What about other tissues in the body? So they took a group of young guys and they gave them low doses of testosterone, 25, 50. They gave them a medium dose, like you said, about 100 to 200, and they went up to 600 milligrams a week, which I think anyone would agree.

23:18That's a hefty dose of testosterone. That's a Monday. I'm sorry. No, I'm kidding. Now, a caveat to the listeners, this data is going to make testosterone sound really appealing. And I'm just going to warn you about that because that's what I thought when I read this. And they found they took these young guys and half of them they said, exercise. And half of them said, don't exercise. Just lay around and see what the testosterone does. Now, no surprise, the guys that were on high T and exercised had the most gains in terms of muscle area and strength. but the guys who just lay around and let the testosterone wash over them also had very impressive gains in muscle strength and area so testosterone like we're saying you can fill up that androgenic male side and it will start doing anabolic things for you at a high enough dose that's critical for people to understand is that it's really almost a spectrum as opposed to a dichotomy and that you can go anabolic at high dose androgenic sort of, you know, go to your local pharmacy steroid without going to get the horse doses, you know, from outside of this country.

24:27So that's huge. Okay. So, all right. So you said that you're going to make it sound really appealing. So, so far I'm, I'm sold. I'm trying to figure out if it's ethical to write my own prescriptions as we're listening here. So, so to otherwise, you know, you might get a call from a 310 number here when this show's over. Oh, I'll be ready. But there's got to be a downside to it, right? Nothing, there is no free lunch. I mean, one thing that I think about as knowing something about this field is the myocardium, the heart, it's a muscle. And do we want our myocardium to be totally jacked as well?

25:01Yeah, I think that's a fine point. Like you said, there's, I think that testosterone is as close to a fountain of youth as we've gotten so far, but certainly it is not truly that, and there are downsides. When we look at testosterone and risks of that really high dosing of testosterone, it's interesting to see it in younger guys and in older guys. Now, younger guys are not going to show as many negative effects probably, and so in those trials I was talking to you about the super high dosing, the main thing young guys got was acne, right, because of the hormone changes. In the guys who are in the older group, and again, we're giving tea to a lot of different people of different ages.

25:38In the older group, they found that with those higher doses, they were having trouble with fluid retention, so maybe holding water, getting puffy in the legs. That's not good. They had trouble with the hematocrit or the amount of red blood cells, and the blood got too high. We worry about blood clots and pulmonary embolisms with that. And so those were the main things that we saw that made us think, maybe there's a kind of safety signal going on here with these super high dosing. Also, there's being on a high dose for a couple of months, and there's being on a high dose for your whole lifetime.

26:10If I may, I'm going to speak to a little bit to anabolic use because there is testosterone in a lab, and there's testosterone in real life. I love this. So there was a wonderful study that was done in the Netherlands where they went around a gym and they said, listen, you're all going to do an anabolic cycle. We can just tell. We want to study this. You provide the drugs, you'll do it your way, but we're going to do measurements on you as you do it. And this is to get a real world field for how people are actually using an anabolic androgenic cycle. What they found was really interesting. First, about half the meds weren't properly labeled.