← The Peter Attia Drive
The Peter Attia Drive
#351 ‒ Male fertility: optimizing reproductive health, diagnosing and treating infertility, and navigating testosterone replacement therapy | Paul Turek, M.D.
02:19:12
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- [00:11]
Peter Attia
Hey everyone. Welcome to the Drive Podcast. I'm your host Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness and we've established a great team of analysts to make this happen. It is extremely important important to me to provide all of this content without relying on paid ads to do this. Our work is made entirely possible by our members and in return we offer exclusive member only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com subscribe My guest this week is Dr. Paul Trek. Paul is a world renowned expert in male fertility and reproductive health and you can think of this as part one of a two part miniseries we're doing on fertility and reproductive health, with this one of course, being on the male system. Next week we'll feature Dr. Paula Amato, who is going to be the female expert on this topic. Paul is the founder and medical Director of the Turek Clinic, specializing in cutting edge treatments for infertility and men's health, and a pioneer in advancing research on sperm biology, genetics and reproductive longevity. He's also the host of the Talk with Trek podcast. In this episode with Paul, we explored the intricate and highly evolved process of conception, discussing the challenges sperm face on their journey to fertilization. This of course, is important to understand all the places where it can go wrong. So it's not just an interesting story, it also explains how challenging it actually is. But Paul shares insights into male fertility, including how sperm function in coordination to navigate the female reproductive tract. We discuss how various factors such as heat exposure, stress and environmental toxins impact sperm quality. We talk about what men can do to optimize their reproductive health. Paul explains the effects of testosterone replacement therapy on fertility, debunking many myths and offering strategies for men looking to preserve their ability to conceive while being on hormone replacement therapy. Talk about the emerging fertility technologies, including advanced sperm sorting techniques, genetic testing and innovative treatments that could redefine reproductive medicine. Also talk about the differences between the risk in the aging male and the aging female. And this was actually one of the most interesting things I learned about in this podcast. So without further delay, please enjoy the first of two parts on a discussion of Fertility and reproductive health. This one with Dr. Paul Trek. Hey Paul, thank you so much for coming out to Austin.
- [03:06]
Dr. Paul Turek
Peter Attia, the man, the myth, the legend. I am so excited to be here.
- [03:09]
Peter Attia
This is in many ways, I guess what's going to be part one of a two part series I hope to do on fertility. And given the complexity of it, I think the most logical way to do it would be to break it down into male fertility, female fertility. And there's obviously going to be things we talk about that'll overlap. But I was trying to think about the best way to start this. The first thing that came to my mind was can we just explain what's involved in conception and maybe do it through the lens of the sperm? But how much of a challenge is this? I mean, obviously there's an enormous evolutionary pressure for this to go as easily as possible, but what is actually involved? So what happens for a sperm to fuse with an egg? What are all the things that are standing in its way, so to speak?
- [03:50]
Dr. Paul Turek
So reproduction is an incredibly highly evolved million year process and remarkably conserved among mammalian species, even among land species and water species of animals. Vaginas, cervixes, uteruses. And the question is, why is it so much work for a sperm to get into the vagina, especially in say, water, and then have to go through a cervix and then the immune system in the uterus is very active because there's a hole in the woman to the peritoneum to the abdomen, so it has to be highly protected. And then you have to go through the uterus. So there's a 10 inch, 12 inch swim, which is equivalent to about a 20 mile swim for a human based.
- [04:30]
Peter Attia
On the size of the swim after.
- [04:31]
Dr. Paul Turek
Ejaculation and how much distance they have to go. And they do that in minutes, which is crazy. So it's an interesting challenge that nature has kept in place for a million years. And I really respect evolution and it is why we're here for, you know, eat, sleep, reproduce. So basically with ejaculation, the penis is shaped to fit into the cervix. Everyone wonders, is it getting to the right spot? It's also interesting that the semen is coagulated and then it liquefies. And that's because there's a lot of species of lower phyla that they have to leave as soon as they have sex, otherwise they'll get killed, like praying mantises and black widow spiders. So you gotta get out of there as a guy. So our ejaculates and humans are sticky, by the way.
- [05:13]
Peter Attia
Is there an evolutionary explanation for that phenomenon?
- [05:16]
Dr. Paul Turek
I have no idea, Peter. I have no idea why you would do that. I don't know why one queen bee and the bees in the hive die after mating. I have no idea why that's an advantage. But I guess females are prioritized in evolution and that makes sense. The anatomy is perfectly defined. So a lot of men think they're having trouble placing things. I usually don't worry about it because the cervix and the penis expands, it forms a seal. Then there's a crypt. Sperm have to go through a crypt, a channel which is only a few sperm make it. So 100 million sperm may start out. Maybe 5 million make it through the first barrier, which is the cervical barrier. The vaginal fluid is acidic.
- [05:53]
Peter Attia
How acidic?
- [05:54]
Dr. Paul Turek
5. Ph of 5. And the semen is a pH of 7. It's all buffered as a hostile environment. So it has to get out of there quickly. As soon as it liquefies, there's sugars in there. And then they go through the cervical path. So 5 million will make it. 1 out of 20 makes it through the cervix. Then 100 make it to the fallopian tube. And then 1 will make it to the egg.
- [06:13]
Peter Attia
Literally only a hundred.
- [06:15]
Dr. Paul Turek
Right. And this cetlage studies in the 50s had Women have sex before hysterectomies. And then he swabbed different parts of the reproductive tract. These are young women for different reasons, not infertility. And found these numbers. And that's the basis for our move to technology from 5 million moving sperm is when we start doing inseminations versus sex, et cetera. So those are based on the numbers of sperm that reach the uterus and reach the thing. What's really interesting is there's some fascinating research. Everyone thought the vanguard sperm wins, Right. So it's the Phelps sperm that's going.
- [06:50]
Peter Attia
To make it right.
- [06:51]
Dr. Paul Turek
And there's a company out of Boston called Eric's Biosciences and I'm consulting with them disclosure. But they've discovered that sperm work in phalanxes. So because the immune system is so vibrant in the uterus, the first round of sperm gets through the cervix and typically absorbs the immune system secretes FCR receptor.
- [07:11]
Peter Attia
And by the way, we've referred to the immune system a couple of times now. What is it? Is it just a bunch of antibodies? Are they B cells? What is the barrier?
- [07:19]
Dr. Paul Turek
There's T cells, B cells and antibodies.
- [07:22]
Peter Attia
It's a full immune response.
- [07:23]
Dr. Paul Turek
Absolutely.
- [07:24]
Peter Attia
So it's a specific immune response.
- [07:26]
Dr. Paul Turek
Anything foreign.
- [07:27]
Peter Attia
Wow.
- [07:27]
Dr. Paul Turek
And there's also a mucus plug that exists for 28 days a month to prevent anything from going through. Cause it's a hole into the woman's body. And peritonitis is severe. Right. And the cervical mucus thins, and that's to let sperm through for two days a month. It's incredibly detailed, perfectly orchestrated system. So looks like the first round of sperm get through the cervix, get into the uterus, and they get demolished. Like a phalanx. Like a Roman phalanx. And maybe a second round goes through and they get demolished. And they're secreting the FCR receptor on the immunoglobulin, because that's what antibodies bind to. So the female antibodies bind to that. And we don't know how many phalanxes go through, but then it's like a run up the middle, and then eventually a couple of sperm or fourth make it, and the immune system's deactivated and they get there. It's wild. And that can be measured now. And there's actually gonna be an assay available to look at whether you're doing this. They're calling it a sperm cycle, almost like ovulation, spermulation. But it's an hour and a half cycle when the phalanx is working, sperm are deactivating the immune system, and then maybe they don't. So there are jaculates, which is a group of sperm, some of which do this well and some of which don't. And that can be a whole reason for infertility. If you're not able to deactivate the system, you're not going to be able to get through because the immune system is active.
- [08:49]
Peter Attia
Let's go through those numbers one more time. About 100 million ejaculated at the cervix. 5 million get through to cervix into the uterus. Yep.
- [08:56]
Dr. Paul Turek
100 to 500 get to the fallopian tube, and one gets to the egg.
- [09:01]
Peter Attia
Wow.
- [09:02]
Dr. Paul Turek
Why do you need so many sperm? The classic answer I used to give is they don't like to ask for directions. Men don't like to ask for directions. But this is probably why.
- [09:11]
Peter Attia
So let's also define what makes up the ejaculate, because we've talked about the sperm. So how are sperm made? Because an important consideration for a sperm is it can only have half the genetic information contained within all the other cells in the man's body. So when does that take place?
- [09:26]
Dr. Paul Turek
So the testicle, baked sperm, it takes about 60 to 70 days. And it's a process called meiosis. So in a car assembly line, the model T assembly, you know, mass produced, you want it all be the same. In meiosis, which is unlike mitosis, you want things to be different and to be a little easy peasy. So you get what's called recombination, and so that's the source of evolution. So the genes, the chromosomes, blend in a different way and separate a different way. And through that process of a couple of those, you get half the number of chromosomes which is required to join the other half.
- [09:57]
Peter Attia
But it's not always the same half.
- [09:59]
Dr. Paul Turek
Correct. It's loosey goosey. It's not the same as when it started.
- [10:02]
Peter Attia
Yeah, a funny story, which I think I've shared on the podcast before, but if not, I'm sure someone will be amused by my stupidity. I had to take the MCAT before doing any of the pre med stuff because I had studied engineering and then decided I wanted to do medicine, but didn't want to spend two years preparing, one year taking the postbac and then the MCAT and then doing it. So I was like, I'm going to just wing it and take this mcat. Having never taken a biology class since high school, I took freshman biology. So I am studying my heart out for this little MCAT test. And the physics and the chemistry are fine, but this biology thing is killing me. And I bought this cheap study guide. I didn't have the money or I didn't want to splurge for the official study guide. There's an official MCAT study guide? The thing was like 60 bucks, but there were these knockoff books for 10 bucks. I was like, they're just as thick. So I buy one of those, and every time I encounter the word meiosis and mitosis, I assume it's a spelling mistake, because I bought the knockoff book. So I'm treating it as the same thing. Every time I see the word meiosis, I'm like, these guys, they just misspelled it. Idiots. It's mitosis. Mitosis, mitosis. Finally, on the night before the examination, which I still remember, August 17th was the day I took the test. I realized they were two totally different things.
- [11:26]
Dr. Paul Turek
Big things.
- [11:27]
Peter Attia
Oh, my God. That realization might have got me into med school, because I think I barely got a 10 on the biology section, which was. It's hard to get into a good med school if you get below that. So anyway, to this day, I get such a chuckle out of the confusion of the nomenclature. But again, just to explain, for people, mitosis is what happens when cells are dividing in our body constantly, where they're trying to create a perfect replica of the entire suite of DNA. So really, to my knowledge, the only time we're undergoing meiosis is in the creation of an egg or a sperm.
- [11:58]
Dr. Paul Turek
That's right.
- [11:58]
Peter Attia
Okay, now remind me, are women born with all of their eggs? I feel like that's something I vaguely remember.
- [12:03]
Dr. Paul Turek
5 million eggs at conception, 1 million eggs at birth, and you basically ovulate a thousand in your lifetime. Okay, so by the time you're 45, you're out of eggs. You actually ovulate one a month, but you.
- [12:17]
Peter Attia
So you lose 10 for every one.
- [12:19]
Dr. Paul Turek
Right. So a lot of waste. But they're stuck in a stage of perpetual space where they're just boom, you know, and they get older and they don't evolve, really. And then they mature when they're asked to at that time. But sperm are constantly renewed.
- [12:33]
Peter Attia
Is that just a mass space problem? Because the testes. If we did the same thing women did, would we just have to have an enormous set of testes?
- [12:40]
Dr. Paul Turek
Why do you think out of the box like that? So, no, I'm not sure. I mean, there's a whole issue of what's the source of human evolution. It's really sperm.
- [12:48]
Peter Attia
Yeah.
- [12:48]
Dr. Paul Turek
Because they're constantly dividing, they're constantly influenced by the environment, and they're throwing off mutations and epigenetic changes. And what's most interesting for me for this talk is that whatever happens in sperm happens to offspring.
- [13:02]
Peter Attia
That's an interesting point.
- [13:03]
Dr. Paul Turek
So it's trans generational.
- [13:05]
Peter Attia
Does that mean that the father is more likely to pass on environmental stressors than the mother?
- [13:11]
Dr. Paul Turek
Probably, yeah. And that's definitely been shown.
- [13:14]
Peter Attia
Okay, so let's go back to it. So the sperm is the actual cell. Where does it get the little tail from? And what is the other part of the cocktail that is?
- [13:22]
Dr. Paul Turek
One of the most magnificent transformations of a cell in the body is the making of a sperm. It starts with a spermatogonial stem cell, which looks like other cells. That spermatogonial stem cell is actually the first and the bottom of a tube. There's 12 stages of spermatogenesis. That cell is remarkable. It's actually the human male embryonic stem cell. So I have a patent on that cell. Because if you take that cell and you put it in a niche environment like an embryonic stem cell, it'll become embryonic, almost like it can Become multipotent, pluripotent, multipotent. We don't know about pluripotent, but you can form tumors and you can form bone, mesoderm, ectoderm and endoderm. You can do all three layers of the body with that adult spermatogonial stem cell.
- [14:03]
Peter Attia
Is there any other cell in the body that is capable of that?
- [14:05]
Dr. Paul Turek
No. I mean there are stem cells in the bone marrow, there might be stem cells in fat, but none of this we showed. The capability of the cell is magnificent. I think it's the source. Women have eggs and embryonic stem cells. That's the male embryonic stem cell. In my opinion. It hasn't been taken advantage of yet with cell based therapy. But it is really incredible what this cell can do.
- [14:26]
Peter Attia
And a man potentially has access to this cell his entire life as long.
- [14:31]
Dr. Paul Turek
As he's making sperm. So that starts out and it usually reproduces mitotically and then at puberty it'll go down the path of meiosis, which is a couple steps more than is mitosis involved with meiosis. But it's the halving and the mixing up of the chromosomes and the newness of the genome introduces mutations and stuff. And most mutations are bad and some are good, but you don't really think about that. But we could have a long talk about genetics versus epigenetics.
- [14:57]
Peter Attia
Actually, let's focus on that for a second. I hadn't considered that. So when the cell that is becoming a sperm undergoes meiosis and it divides, what's the fraction of times when this becomes an aneuploidic sperm? And explain maybe to people what aneuploidy is and what's the process by which that thing gets discarded.
- [15:17]
Dr. Paul Turek
So if you look at healthy human sperm for chromosomal content and what's correct and what's incorrect, probably 2% of them are off. They'll still be made, they're just off because it doesn't really click the system to negate it. We don't know at what level of chromosome abnormalities the system will say, this.
- [15:35]
Peter Attia
Is not, this is absolutely defective.
- [15:36]
Dr. Paul Turek
Yeah, But I would say if you look at making of sperm, it's very logarithmic. You're probably looking at one out of four that are being made go through the epididymis, which is the next 10 days, which is a collecting duck after the testicle, where it matures, gets epigenetically modified. And you'll see these zones, different epididymosomes and things like that happening. And there's A lot of post production modification, not of DNA, essentially. But I think there's a filter going on where a lot of the bad aneuploidy comes out, because if you look at the chromosomal abnormality rate in testicular sperm before it goes through the rest of the system and compared to ejaculate, it's higher, it's two to three fold higher.
- [16:15]
Peter Attia
So something is getting filtered. Yeah. And just so folks know, when we say aneuploidy, we mean you don't have one copy of each chromosome. You either have none or you have two. Or anything that's not one is bad.
- [16:26]
Dr. Paul Turek
Right.
- [16:27]
Peter Attia
When aneuploidy occurs in the fusion of the sperm and the egg, do we know? I guess we can figure out pretty easily if it's maternal or paternal in origin.
- [16:36]
Dr. Paul Turek
If you look at the embryo, it's kind of hard to tell. There are some markers of paternal and maternal origin. It depends on where you're going back in mitosis and meiosis. So they can sort of ascribe it in the embryo, in the sperm, you're really going to have to look at the sperm. And if you see a translocation, some characteristic change in sperm and you see it in the embryo, then you know it's paternal, but not usually. And 98% of sperm are typically normal. In a guy with infertility, it might be 95%. Here's an example. If you have a patient with Klinefelter syndrome, a male with an extra X chromosome in every cell in their body, or a transgenic model with that feature.
- [17:15]
Peter Attia
So this is a man who's xxy instead of XY.
- [17:18]
Dr. Paul Turek
So 47 chromosomes, not 46.
- [17:20]
Peter Attia
Yep. And phenotypically, he kind of has a distinctive look. Right.
- [17:25]
Dr. Paul Turek
10% of the time.
- [17:26]
Peter Attia
Oh, really? 90% of the time. A man with Klinefelters, you'd never know.
- [17:29]
Dr. Paul Turek
Yeah. Okay, so that's the board question.
- [17:31]
Peter Attia
That's the board question.
- [17:32]
Dr. Paul Turek
Right, the MCAT question.
- [17:34]
Peter Attia
Yep. Yep.
- [17:35]
Dr. Paul Turek
All right, so in these men, if you look at their sperm, Aneuploidy. Right. So every cell in their body and in the mice, and the transgenic mice all have an extra X chromosome. Only about 10% will have it in the sperm.
- [17:46]
Peter Attia
Meaning they will produce an X or.
- [17:48]
Dr. Paul Turek
A Y sperm just like everyone else.
- [17:50]
Peter Attia
The only difference is they have a 2/3 chance of producing an X and a 1/3 chance of producing a Y. I'm assuming, instead of 50. 50.
- [17:56]
Dr. Paul Turek
Don't think we know that. That's math, Peter. That's math.
- [17:59]
Peter Attia
Yeah.
- [18:00]
Dr. Paul Turek
Biology's not math, remember? And I had two Klinefelters patients yesterday that I operated on and they're not doing pre implantation genetic diagnosis of the embryos that they're gonna create from their sperm because the chance is not that high. So it goes from in mice, 0.1% chance of normal men having XXY sperm or an aneuploid sperm, an abnormal sperm, to 1% in humans it goes from 1% or so to 10%, but 90%. That's remarkable.
- [18:30]
Peter Attia
That's amazing.
- [18:30]
Dr. Paul Turek
It's remarkable how efficient this is.
- [18:32]
Peter Attia
I interrupted you. You were in the process of explaining how we actually make the sperm where the tail comes from and the.
- [18:38]
Dr. Paul Turek
Yeah, it's all done in the testicle.
- [18:39]
Peter Attia
Yep.
- [18:39]
Dr. Paul Turek
It's an amazing machine. Weird question we should maybe get to is why is it out in the breeze like that?
- [18:44]
Peter Attia
I assumed it was temperature related. Why, why does it need to be a little cooler?
- [18:49]
Dr. Paul Turek
Yeah. Why?
- [18:50]
Peter Attia
I would guess because I like to makes things up that it's so energetically demanding that it's giving off more heat in the process of creating something that is going to be so efficient to be able to swim 20 miles effectively. And that's very glycolytic. I'm assuming the amount of ATP that must be generated.
- [19:07]
Dr. Paul Turek
75 mitochondria for sperm. That's like electric motor on each wheel.
- [19:11]
Peter Attia
Yeah. So that would be my guess is it's an overheating problem if you tried to keep those guys inside.
- [19:16]
Dr. Paul Turek
And I think overheating could be translated to oxidative stress, which is a cause of a lot of infertility.
- [19:21]
Peter Attia
We don't know is the answer.
- [19:22]
Dr. Paul Turek
Right. And it's interesting that ovaries are inside. So men get in hot baths and they're cooked. Women can get in hot baths and they're okay.
- [19:29]
Peter Attia
It's funny, I had a buddy over who shall remain nameless. He does not have kids, but he would like to have kids. And we saunaed the other day. He went up to my freezer beforehand. I didn't really know what he was doing in there. I thought he was getting a drink or something and he came down with ice packs. We were sitting in the sauna and he was in the sauna, but he's got ice packs all over his groin. Immediately understood why he was doing that. But yeah, we'll come back to whether or not that's an important strategy for men in saunas who want to have kids.
- [19:53]
Dr. Paul Turek
So the complete sperm spermatogenesis is the whole process. Spermiogenesis is when you go from the round cell stage and you get half the number of chromosomes and then you have to make a tail and then whole motor assembly. And that is the most profound transformation of a cell in the body. It takes about three weeks to go from that stage and we're learning now. It's a lot of. It's vitamin A driven. Three weeks of the six or seven to make a sperm. Then it's complete and non modal and it's packaged.
- [20:22]
Peter Attia
Give us some size comparison before the tail is on. What is the size of that cell?
- [20:27]
Dr. Paul Turek
Probably similar to a lymphocyte. Half the size of a lymphocyte or half the size of a red blood cell.
- [20:33]
Peter Attia
A couple microns and then the tail.
- [20:35]
Dr. Paul Turek
Makes it 35 micron. Tail, yeah. So really magnificent engineering feat. It's got microtubules in the middle and there's these links to the tail. It's like a kite and the engine runs it and it tail wags. Remarkable 300 genes control movement of sperm alone. There's mitochondrial DNA in there, all that stuff. It's just wildly compact. 10 times more compact than any other cell in the body.
- [20:58]
Peter Attia
From a mitochondrial density standpoint, from a.
- [21:00]
Dr. Paul Turek
Cytoplasmic standpoint, a nuclear standpoint. It goes from histones to protamines. That DNA is condensed a lot more because it's got to go on the road. So it's gotta be packaged really well to survive outside the body and be in good shape because it's transgenerational. So a lot of energy in that. And then during the epididymis, which is a collecting duct.
- [21:20]
Peter Attia
Sorry, one other question. Where is the ATP or carbohydrate or whatever, the glucose stored in the sperm.
- [21:26]
Dr. Paul Turek
Stored probably in the cytoplasm and in the tail.
- [21:29]
Peter Attia
Okay. And it's interesting, you know, when you think about a rocket ship with its payload, it uses a solid fuel obviously as opposed to a liquid fuel. It's packaged for that one shot. I assume it's the same here. There's no transporters to bring glucose in or anything. It has its solid fuel. One shot. Go for broke.
- [21:46]
Dr. Paul Turek
That's right.
- [21:47]
Peter Attia
Yeah. It is a lot like a rocket, isn't it?
- [21:48]
Dr. Paul Turek
It is a lot. So that's going to bring the physics in. So then there's two week period where it stays in the epididymis, which is a 35 foot tubule with estrogen. And there's a lot of post modification of the sperm.
- [22:02]
Peter Attia
The epididymis is 35ft if you stretched it out roughly.
- [22:05]
Dr. Paul Turek
Yeah.
- [22:05]
Peter Attia
And just for folks listening, 700ft of.
- [22:07]
Dr. Paul Turek
Tubules in the testis.
- [22:08]
Peter Attia
The epididymis is on the back of the testes.
- [22:10]
Dr. Paul Turek
It's a comma shaped organ in the back.
- [22:12]
Peter Attia
Yeah, yeah. And we'll come to this, I'm sure, later. This is prone to infection and that'll probably factor into maybe some of the issues that deal with fertility.
- [22:19]
Dr. Paul Turek
Right?
- [22:20]
Peter Attia
Yeah.
- [22:20]
Dr. Paul Turek
Epididymis has been relatively understudied, but it has actually become very important epididymosomes, and there's a lot of modifications we don't really understand. I wrote the chapter for our textbook on reproductive physiology, and it really is a lot of work in the 50s and 60s. But now we're beginning to understand DNA fragmentation. And the quality of sperm is driven by the epididymis. A lot of the quality of sperm, not the shape and stuff like that.
- [22:44]
Peter Attia
Meaning based on its residence time within.
- [22:46]
Dr. Paul Turek
The epididymis and what other environmental influences that occur there. Because the epididymis is not as walled off from the body as the testis is, immunologically and otherwise. It's more susceptible to drugs, exposures, heat, et cetera. Testis is very walled off. Very little happens in the testis because the Sertola cells that line the tubules have a blood brain barrier. Blood testis barrier, same as the brain. It's highly protective.
- [23:11]
Peter Attia
It's as protective, yes.
- [23:12]
Dr. Paul Turek
Harvey Cushing at Yale did that in late 18th century. Took brain dead patients, injected them with dye methylene blue. I think the blood brain barrier came about when nothing went into the brain and nothing went into the testicle. Two areas of the body that were completely immune from normal transport processes. Wow. Blood test is barrier. So the two things that we know happen in the epididymis after production of sperm are motility improves. So sperm begin to learn progressive motility. So they start moving forward as opposed to not moving or moving in circles, which is important. And the most curious thing is they.
- [23:48]
Peter Attia
Learn how to smell, meaning there's basically a chemical signal that they need to be able to track, to which I'm assuming is the egg.
- [23:55]
Dr. Paul Turek
So the follicular fluid. So they actually detect follicular fluid. So if you take testicular sperm and inseminate it into a uterus with insemination technology, it'll just be killed. If you take an epididymal sperm and you do that from the top of the epididymis, it'll maybe run in circles and it'll be killed by the immune system of the female.
- [24:13]
Peter Attia
It has to go through that Whole epididymal cycle.
- [24:15]
Dr. Paul Turek
Once it's at the end of the epididymis, where it's stored, and that's how many weeks? 2. 10 to 14 days. 600 million sperm live in a bucket, a pot of soup, Toccata epididymis. And you ejaculate from that pot, which tells you a lot about sperm quality, because it can get old. But that sperm, if you put it in it, will know exactly where to go and it'll move forward because it's like a shark sensing blood in the water. One part per billion of follicular fluid can be sensed by a sperm. That's incredible. It's literally an olfactory sense. It's a smell sense that sperm have for follicular fluid, so they know exactly.
- [24:50]
Peter Attia
Where to go again. You have to wonder how many years it took to perfect this system. Right.
- [24:57]
Dr. Paul Turek
You do have to wonder.
- [24:58]
Peter Attia
Do we know what the chemoreceptor is?
- [25:02]
Dr. Paul Turek
It was published in Nature recently and stuff like that. So it's really interesting. It's an olfactory type receptor. Yeah.
- [25:07]
Peter Attia
Do we have anything else that we can burn? Smell.
- [25:10]
Dr. Paul Turek
Peter?
- [25:10]
Peter Attia
Yeah. Is there anything like what is the most noxious thing that we can smell with our nose and at what point. Concentration can we detect it?
- [25:19]
Dr. Paul Turek
I have no idea.
- [25:19]
Peter Attia
Yeah. Because I wonder, just for comparison.
- [25:21]
Dr. Paul Turek
Give me a minute.
- [25:22]
Peter Attia
Yeah, yeah, yeah. No, I've always thought about this. I like to hunt. So anyone who's ever bow hunted especially, knows that animals can smell at a level that we can't even fathom. They can smell us literally a mile away if the wind is just blowing their direction. So it's always seemed to me like we have really, really insufficient noses. We were given lots of superpowers in many ways, but smell wasn't really one of them.
- [25:46]
Dr. Paul Turek
I think I would agree with that. And I'd also say that if you block a sensory bank of the five, others increase remarkably, like braille. I'm a microsurgeon. This stuff matters a lot. But I can't do braille or hearing. I think you can crank it up if you lose a sense. And you see that with people who are deaf from, you know, your ability to see. And I don't think seeing better is really the issue. But hearing and smell, I think it can crank up.
- [26:11]
Peter Attia
So one part per billion. This is remarkable. So you mentioned that at the base of the epididymis is basically the launch pad. How many are stored in that?
- [26:20]
Dr. Paul Turek
Half a billion.
- [26:21]
Peter Attia
Half a billion. So five ejaculations?
- [26:25]
Dr. Paul Turek
Yep. Okay, that's A pot.
- [26:28]
Peter Attia
And what's the time to rebuild that? What's the rate at which you fill?
- [26:31]
Dr. Paul Turek
Oh, I don't know.
- [26:33]
Peter Attia
We're going to come to this, I'm sure. But is there a frequency of ejaculation that is too much, that if a guy is, say, ejaculating every single day, is that insufficient to get a complete replenishment? Where if he's having infertility, you would say you gotta move it to every other day or whatever the number is.
- [26:49]
Dr. Paul Turek
So that's a great extrapolation of the pot of soup idea. And so on that note, I would say, typically we recommend two days of abstinence. Sex every other day to optimize. Right. But not for the semen analysis. That's for conception. Depends how old you are in your biology. But most men need a day or two to recharge completely. A day or two. That's why we recommend that. That's sort of a generalization. Some men are fine every day. I had a guy once who had to bank sperm for hepatitis treatment, and he was like Mickey Rourke and he had a wooden leg and he's about 50. And I said, you're going to need to abstain for a couple, three days to do this semen analysis. So we get a good sample. I want it to be optimized. One, he looked at his partner and she looked at me. She grabs him and says, he can't do that. He's. Every day, he can't do that. I don't know what he's going to do. So he's like, he was panicking that he had to hold off. I said, often you have sex. He said, twice a day, every day. I'm like, okay, that was great. Then I had one man, wonderful orthopedic surgeon at Stanford, and I asked him on my questionnaire, I said, how often do you have sex? And he wrote, 0.00001356.
- [27:53]
Peter Attia
He divided once a year 0.00 weekly.
- [27:56]
Dr. Paul Turek
1.0015. Avogadro's number. Right. Which meant he was so frustrated that a beautiful way to say that was the 0.001355. So anyway, for a semen analysis for diagnostics for infertility, when you abstain longer, your sperm count will rise, but your motility will fall because it's older.
- [28:18]
Peter Attia
There's a min max curve that you're optimizing for, which you would say is.
- [28:22]
Dr. Paul Turek
Three days would be about right. When you're not gonna gain that much. You're not Gonna lose that much motility after that. So there's biological variability which we try to minimize when we do the semen analysis. So two to four days of abstinence, that's a different period than what we're recommending for sex, which is every other day. And that's based on New England journal paper where they looked at, I think 700 couples and they had them keep diaries. It was a Boston based paper. Keep diaries of how they had sex, when they ovulated and when they got pregnant. And then they said, do what you normally do and then give us the diaries. And then they evaluated them and they found that having sex, say ovulation is day 15 of the cycle. When they started having sex on 9, 11, 13, there were significant pregnancy rates. And every other day was the optimal interval. But even five days before and three days before, there were substantial pregnancy rates before ovulation. But if you waited to ovulation and then had sex, that's about 20% of conception. So when you get the kit, don't react to it, predict in front of it. So front load the sex. Very important.
- [29:27]
Peter Attia
And why is that?
- [29:28]
Dr. Paul Turek
Is that because there's a reservoir effect in this uterus. It's managed. Sperm survive for a day or two.
- [29:34]
Peter Attia
If ovulation is day 15, how could a day 11 sperm survive four days?
- [29:41]
Dr. Paul Turek
It's nurtured once it's past the vagina.
- [29:44]
Peter Attia
But how many of them are surviving? Is it literally the lone wolf or the last hundred?
- [29:49]
Dr. Paul Turek
Maybe some of the sperm bind to.
- [29:51]
Peter Attia
The oviduct and wait, remind me where the oviduct is.
- [29:53]
Dr. Paul Turek
So the uterus and the fallopian tubes.
- [29:55]
Peter Attia
Fallopian tubes.
- [29:56]
Dr. Paul Turek
And that's the oviduct.
- [29:57]
Peter Attia
The oviduct is right below where the scorpion tube, essentially.
- [30:00]
Dr. Paul Turek
Yeah. They bind to the endothelium and just park is. If there's no egg, they'll just sit there in the.
- [30:05]
Peter Attia
So again, going back to our moon analogy, this is after you've done stage one, stage two, stage three, you're now out of gravity. Right. Like it's actually not an energetics problem anymore.
- [30:15]
Dr. Paul Turek
Right. Or death star problem. Right?
- [30:17]
Peter Attia
That's right. You've escaped the hostile environment in this case of gravity.
- [30:20]
Dr. Paul Turek
So now it's fun place, it's the right ph, it's warm.
- [30:23]
Peter Attia
So do we have a sense, this would be a very interesting experiment of what is the longest duration that a sperm could survive for conception? In other words, to do the experiment, let's just make it as a thought experiment. You had a large Number of women that you knew were going to ovulate on day 15, and then you would have them have intercourse on day 7, 8, 9, 10. And you create a histoplot or a distribution of what's the frequency of pregnancy across those things and ask what's the bottom fifth percentile? Which is the theoretical possibility.
- [30:56]
Dr. Paul Turek
Yeah, that's a good one.
- [30:57]
Peter Attia
And then the same thing after. You want to develop the bell curve of the whole thing.
- [31:01]
Dr. Paul Turek
Well, we know that once the egg is ovulated, about eight hours and then it's over.
- [31:05]
Peter Attia
This is a very important point. It really needs to be front. If it's only eight hours of survival.
- [31:10]
Dr. Paul Turek
After ovulation, but eight hours, it's dead if it's not.
- [31:13]
Peter Attia
This is a very, very left tail curve, correct? Ah, I did not know that.
- [31:18]
Dr. Paul Turek
Okay, so you want the sperm there ahead of time. 80% of conceptions naturally or at home, occur when sex is front loaded as opposed to reacting to ovulation. And most of the apps that are available nowadays will tell you that. Peter, you're drawing a graph.
- [31:32]
Peter Attia
I am.
- [31:33]
Dr. Paul Turek
I have to draw and it looks like it's algebraic.
- [31:37]
Peter Attia
This is incredible. It's easier for me to think about these things graphically than to think that it basically shuts off at about eight hours.
- [31:43]
Dr. Paul Turek
So I give some more physiology. There was a study that showed how long it took to make a sperm and it was published in Science, I think in the 60s. And they gave men tritiated water, they gave men radioactive hydrogen and then they biopsied their testicles, which could never be done nowadays. But I did it a little different. I gave deuterated water with a group at Berkeley and we gave healthy men deuterated water for a week. And then we checked the first.
- [32:10]
Peter Attia
Sorry, dumb question. Why didn't they just measure the ejaculate? Why did they have to biopsy the testes?
- [32:15]
Dr. Paul Turek
Did they just want to know about spermatogenesis? But we didn't want.
- [32:18]
Peter Attia
They actually wanted to torture the guys.
- [32:20]
Dr. Paul Turek
But that's wild. But that was the best data. And we did deuterated water, which is not radioactive, and we could measure that. So we gave them a dose and then we watched their ejaculates weekly and we looked for when deuterated. The hydrogen showed up in the DNA and it was an average of 74 days. So normally say three months to make a sperm. So some went were 42 days. And that's going through the epididymis and getting ejaculated. We talked about maybe two months in the testis and two weeks, a week or two in the epididymis and then maybe a couple of weeks to ejaculate. And this was all the average 74 days. So it actually changed the timeline enormously to a much faster one. So 74 days. So when you do anything to a man, fertility wise, you're not going to expect to see anything change for at least two and a half months. And when you talk about full replacement of that semen, it's probably in the B90 days when it's all replaced, the pot is replaced. That's a limitation in what we do 42 year old women want now. And we have three to six months. When I did a study on fixing varicoceles, which is an infertility problem in men, it's surgery. And I looked at the mean time to conception, it was about seven months after repair, which is two cycles of sperm production.
- [33:30]
Peter Attia
So let's now define infertility. We've been using this term quite a bit. I suspect it actually has a formal definition.
- [33:37]
Dr. Paul Turek
It's one year of inability to conceive after sex, using sex.
- [33:41]
Peter Attia
Okay.
- [33:41]
Dr. Paul Turek
It doesn't have to be timed intercourse, just has to be whatever the couple does when they think they're trying to conceive.
- [33:45]
Peter Attia
When someone shows up in your office, is it usually after they've gone down the rabbit hole of troubleshooting the female partner, or are people doing this in parallel?
- [33:58]
Dr. Paul Turek
There's a large bias in Western worlds about how infertility is evaluated. The reasons are complex, but I would say my practice is not typical. So most of my patients have been through a lot before they come to me. And typically I think Keith Jarvey's data was good at about 23% of men get a formal evaluation for infertility before couples go through IVF in North America.
- [34:23]
Peter Attia
And how does that differ from the rest of the world?
- [34:25]
Dr. Paul Turek
I don't think it's been studied in the rest of the world, but there are countries like Germany and Spain with single insurers and government pays. And it's also recommended by society guidelines like American Society of Reproductive Medicine who, et cetera, that both partners get evaluated simultaneously. But the bias is female, gets very evaluated for lots of money. And the men typically may get a semen analysis, but may not. And it's very complex reasoning there. It's a different beast. They're not part of the problem, they refuse to do it. There's a lot of denial. It does get at your masculinity a little bit to get checked out and things so it does go deep for men. It can be a little bit of a problem. So I would say that lately, with large insurers coming in, Progeny Maven and things like that, you're seeing a lot more men up front, which is fabulous. And we can have long discussions about the biomarker concept, why that's good for the field and good for men's health and good for longevity.
- [35:24]
Peter Attia
Okay, let's talk about your workup. What do you do when a guy comes in and what are the things you want to know about him?
- [35:32]
Dr. Paul Turek
So getting a guy in is great. Usually they're dragged in by their partners. Usually the partners come along to make sure they show up. For me, it's one visit. So we do one visit, and I do everything else where they are where they are. I don't ask them to come in a million times anymore. So it's a very different kind of practice. But I try to get everything done in one visit because when you get them there, it's rare to get them there. And the physical exam. So you do a history, a very thorough history, which is usually preceded by a questionnaire. I give 200 questions, and that has all the hot bath stuff and all the exposures they have. And they have to do that before they see me. That's a really important part of it. If you could pick one in a multiple choice question, what matters the most is probably the history. History of paternity matters, a history of exposures matters, et cetera. Physical exam, very important. 1 to 5% of male infertility can be due to a major medical issue. Testis cancer, diabetes, things like that. So physical exam, varicoceles is very important. You could be missing a vas deferens. One in 500 men have perfectly normal testicles, but they have a natural vasectomy. It's congenital. Absence of the VAs. They're gonna be sterile or infertile.
- [36:37]
Peter Attia
Can you explain what that. We haven't talked about how a vasectomy works and why a guy still ejaculates but is infertile. Explain what the vas deferens, how the whole thing works in the plumbing.
- [36:46]
Dr. Paul Turek
Right. So we didn't answer that question, which was, what's the semen consist of? It's about 10% vasal fluid with sperm. It's about 80% seminal vesicle fluid, which is an accessory sex gland in the back of the prostate, and about 10% prostate. So typically during ejaculation, prostatic fluid, which is clear and sticky, will grease the barrel of the Urethra pre cum. Then, during the ejaculation process, the pellet of sperm gets pumped from the vas deferens into a chamber called the ejaculatory duct. And this happens quickly. And then the seminal vesicle, which is like a bladder, contracts, sends it into the prostatic urethra. Between the bladder and the outdoor world, there's two valves. One is the bladder neck, it closes, and one is the urethral sphincter that we pee through, and that opens and it gets forced out with muscular contractions in seconds.
- [37:35]
Peter Attia
Yeah. So therefore, if the vas deferens is clipped, you're getting essentially 90% of the volume. You're just missing the 10% of the volume that contains the payload.
- [37:44]
Dr. Paul Turek
So in 3,000 men I've done vasectomies on, in 30 years, two men have said, my volume went down. And I said, really? One of them banked sperm, and he had a semen analysis before and after, and he did go down by 15%, and he noticed it. And I said, good for you. What do you want to do now? So it can be noticeable, but not usually. And so the color is the same, the opacity is the same, the whole process of liquefaction's the same viscosity, et cetera.
- [38:10]
Peter Attia
So, physical exam. Do you need an ultrasound? How are you able to detect if a person is congenitally missing a vas deferens?
- [38:17]
Dr. Paul Turek
Pure physical exam.
- [38:18]
Peter Attia
What, you feel it? Interesting.
- [38:20]
Dr. Paul Turek
So my fingers can feel two and a half millimeters. The vast deference is like piano wire. I mean, it is different than anything else on the cord. I did a study. A third of my men with absent vas were only found out having procedures until I saw them. I usually just do the exam, but it is an expertise thing.
- [38:37]
Peter Attia
Yeah. It's not like the PCP can figure this out. You have to be doing this all day, every day, I'm assuming.
- [38:41]
Dr. Paul Turek
Yeah. I think you need to be trained on that. But if you're well trained, it should be purely a physical exam.
- [38:46]
Peter Attia
What percentage of men are congenitally missing their voice?
- [38:48]
Dr. Paul Turek
1 in 500.
- [38:49]
Peter Attia
1 in 500.
- [38:50]
Dr. Paul Turek
The most common genetic disease in America is cystic fibrosis. So the big implication is these men can't conceive naturally. They have a natural vasectomy. We use sperm retrieval techniques in ivf. But they definitely have the chance of passing on cystic fibrosis to a child.
- [39:06]
Peter Attia
Why is that so?
- [39:07]
Dr. Paul Turek
Very interesting biology. But men with cystic fibrosis, the most common genetic disease in America, have no vas deferens.
- [39:14]
Peter Attia
Okay, so what's the Venn diagram of cystic fibrosis and congenital lacking vas deferens?
- [39:19]
Dr. Paul Turek
The genes for that were discovered. It's a chromosome 7. There's 17, 1800 mutations, maybe 2000. So they cloned the genes and got the variants in the late 80s. And then they found there's another group of men who are perfectly healthy, do not have cystic fibrosis, which is a major metabolic disease with a short life expectancy. Better. Now, those men had absent vas deferens in the absence of disease. They took the gene sets and looked at them and they were the same, just not as many. So you have homozygous or heterozygous, so you have a carrier for cystic fibrosis will have an absent vas, but a full blown CF patient, cystic fibrosis patient will have no vas deference too. So it's a form frust of cystic fibrosis, but it doesn't have all the chemical and metabolic side effects.
- [40:03]
Peter Attia
So in other words, when you identify a man who does not have CF with a congenitally absent vas, there's a very probability he's a carrier of cf.
- [40:12]
Dr. Paul Turek
Yes. And you can usually define it, which.
- [40:14]
Peter Attia
We can genetically test easily.
- [40:15]
Dr. Paul Turek
Yeah. And then you have to worry. There's a 4% chance in America anyway that a partner might carry it. They're two carriers. You have a one in four chance of having a very affected child. So that's the big concern in my practice and I'm proud to say in 30 years, we have no CF children. It's all about good engineering and doing it right. So that's the vast difference part.
- [40:34]
Peter Attia
What else on physical exam are you looking for?
- [40:37]
Dr. Paul Turek
Cancers, infections, epididymitis.
- [40:40]
Peter Attia
Yeah, tell me about epididymitis. Obviously, anything that interferes with that section of the journey is going to be critical. Remind me, is it EBV that we typically are Measles, mumps. What's the infection?
- [40:50]
Dr. Paul Turek
Mumps. Yeah. So among viruses in the world, there aren't many that get into the testicle like other things. Very little gets into the testicle similar to the brain, but the mumps virus does it about a third of the time. When you're a child with mumps, the parotid gland infection, it's a glandular disease, so it really only matters when you're pubertal and you get mumps. Then it goes to lots of glands, it go to your pancreas, cause diabetes, it can go to the Salivary glands and go to the testicles. It's some kind of. There's an open time.
- [41:22]
Peter Attia
So just one more reason why everyone should really get the MMR vaccine when they're a child, notwithstanding the tragedy.
- [41:27]
Dr. Paul Turek
That's a big deal.
- [41:28]
Peter Attia
Yeah, of course. Children dying from preventable diseases. But this is another non lethal but significant complication of the muscle.
- [41:34]
Dr. Paul Turek
Absolutely. And it will cause viral necrosis and edema of the testis. And similar to a brain, it's in a calvarium. Right. The brain is in a fixed space, so when it swells, you gotta do something, because it can die if it swells too much. Testicle is a fixed cavity with the tunic albuginea. And so if it swells too much, it necroses, and then you get fibrosis and then you get sterility. I've got techniques where I can find sperm in lots of these men. Very little pockets, but most of it. You're ablating the testis, it's going to scar and die from ischemic necrosis. Zika, Ebola. I mean, the CDC called me when these were coming around. Zika has been transmitted through semen. It causes the anencethephaly issues when these pandemics recurring. Ebola, too. I got a call that there was an Ebola patient who survived, went to the institute, survived hemorrhagic fever, and then a year later transmitted Ebola to a partner who transmitted it to six other men. And it was another outbreak in South.
- [42:32]
Peter Attia
Africa, Meaning the patient that survived Ebola, the virus managed to survive in the.
- [42:39]
Dr. Paul Turek
Testes somewhere, but it was transmitted sexually a year later, when he was.
- [42:44]
Peter Attia
Well, when he was asymptomatic, he'd already developed immunity.
- [42:46]
Dr. Paul Turek
Right. We don't know about testis, but we know that mumps will do that to the testes. But their Zika is also persistent in these.
- [42:52]
Peter Attia
But in that case, you have to think, wherever the virus hung out, it had to be very, very immune privileged.
- [42:59]
Dr. Paul Turek
Yep. Or at low levels, like low viral loads, where there's no disease. I'm not sure, but these are concerning cases.
- [43:05]
Peter Attia
But then it was transmitted at a low viral load, an even lower viral load.
- [43:09]
Dr. Paul Turek
Right. So it's tricky. There may be bulbourethral glands. Maybe it's semovesical. It's hard to know, but, yeah, it's getting away. But most viruses don't go there. So the big one would be Covid. What did Covid? There was a big deal about the AC receptor being in the lung and being in the testicle. And maybe COVID infection would make you sterile. There was one Zika paper in Nature that looked, if you infect mice, or was it rats, with Zika, the testicles shrivel up and they get infertile. And that caused a huge scare in the field. But we really didn't see it. Maybe see it and see if we don't see it in fertility.
- [43:42]
Peter Attia
And what is it about the Zika virus that does this?
- [43:44]
Dr. Paul Turek
We're not sure why it did it in rats. It's a blood testis barrier thing. It's an amazing barrier. And nothing really gets through, including viruses. But mumps does only at puberty than Zika does. Zika does in animals, but we didn't see it in humans.
- [43:58]
Peter Attia
But I thought you said that Zika was leading to anencephaly in cases.
- [44:00]
Dr. Paul Turek
Yeah, but that could be seminal. That could be just in the semen itself, not in the sperm. Like Ebola is probably seminal, not testicular. It's not on sperm. It's around sperm or in the fluid. That's the conclusion so far. So, Covid, the big worry was when this Chinese paper came out, like, oh, my God, it's going to the lung, bind to the AC receptor. Testile has it too. It's going to make men sterile forever. And there were cases of infertility with bad infections. Was that just the fever, which typically does it even after a flu, or was that Covid specific? And we didn't know. A couple of colleagues did some papers. One which impressed me was at out of Cedars was a bunch of men, maybe not reproductive age, died with florid Covid. So they got autopsies and they looked for virus in different locations in the body. And I think out of 10 men, or seven men, one had it in the testicle. So these are the men with the highest viral load you can imagine, and only one of them had it. So I believe that there is a risk of it. But I'd say in the thousand men I've seen since COVID I think there were two cases that I would say were unexplained where men were either fertile or had normal semen quality, had a bad COVID infection, maybe hospitalized and three months later sterile. So I think there's a low profusion rate there.
- [45:15]
Peter Attia
What is the phenotype of their sterility, aside from the presentation that says I can't get someone pregnant?
- [45:21]
Dr. Paul Turek
So sterility means no sperm in the semen. And typically, if you measured the signals to the test.
- [45:25]
Peter Attia
Oh, that's literally what it means. I'M sorry. Okay. So literally no sperm in semen. They stopped. Understood.
- [45:30]
Dr. Paul Turek
It's a primary problem. So the third thing we do, history, physical semen analysis, is a third. Fourth would be hormones. And that's what we check in men, too, because production of sperm is driven by the brain. So nothing happens to sperm being made without the brain telling it what to do. Similarly with eggs and controlling. It's all a homeostatic mechanism with negative feedback. Classically, anabolic steroid users.
- [45:53]
Peter Attia
Yeah. Which I want to talk about in detail. Can we go back to semen analysis? You're looking for, obviously, the count and the motility. What else do you look for?
- [46:02]
Dr. Paul Turek
So in the semen analysis, there's several features. I consider it sort of a poker hand. There's a volume. How much of the semen volume. There's a count, concentration of sperm. That's numbers per mil. And then there's motility, which is percent motion. You do a forward progression. So how good is the quality of motion? And typically, some measure of shape called morphology. There's three liquid liquefaction, agglutination and viscosity. And then you look for other cells that aren't sperm. They're called round cells. And either they're going to be pus cells or immature germ cells that are ejaculated early.
- [46:34]
Peter Attia
And presumably you want to see fewer of those.
- [46:36]
Dr. Paul Turek
There's a number, like less than a million is normal.
- [46:38]
Peter Attia
Okay.
- [46:39]
Dr. Paul Turek
So if you ask me, how do I look at a semen analysis that's a little different? I look at that as a poker hand with each card has a meaning, but they have a look. So if you said, what do you mean by that? So if the volume is low, it's one of five things. You're always going to find something. It's at the collection error. I call it first sample syndrome. Guy's not good at it. You know, it's like, okay, I got to put it in the cup and I got to stop doing what I'm doing. So you do a second sample, and then there's low testosterone can cause it. There's an absent vas deferens, which means you have an absent seminal vesicle. There's ejectory, by the way.
- [47:09]
Peter Attia
Do you ever have that on one side and not the other?
- [47:11]
Dr. Paul Turek
Yeah. No, it's very variable. It's segmental. So there's five real issues. So when I see a low volume semen as a surgeon, I'm going to find something. So that's really good. Other than that, the semen analysis, I think I've been published as saying it's a blunt instrument for fertility. Unless it's zero, you can't really say much about their fertility because people conceive at all levels.
- [47:30]
Peter Attia
Obviously you rattled off a whole bunch of parameters that you can access there. But are there certain null states that don't exist where everything is amazing, but this one thing is horrible? Like do you see scenarios where everything is remarkable, Perfect motility but bad morphology or perfect morphology?
- [47:46]
Dr. Paul Turek
Isolated, Isolated example.
- [47:47]
Peter Attia
You do see isolated things, Right.
- [47:48]
Dr. Paul Turek
So one of them is called, I call it syndromic sperm shape problem. So you can have a perfectly normal semen analysis, count motility, volume progression. And the sperm looked terrible. And so there are rare conditions, 1 in 5,000 where you might have globosospermia or two tailed sperm or pinhead sperm. So if you look at shape, 4% should look normal, which is terrible. We can have a whole discussion about why 4% of human sperm being normal is normal when 99% of animal species in the wild have normal looking sperm. But it's all a construct. It's all a construct of someone decided what normal is. But in men who have large abnormal forms, like 4%'s normal, if they're 1% normal and you look at the abnormalities.
- [48:31]
Peter Attia
I'm sorry, I'm still confused on that point. Are you saying that you would consider it perfectly normal if only 4% of the sperm are morphologically perfect and 96% are not? And that means the 96% that are not could be pinhead, could be double.
- [48:46]
Dr. Paul Turek
Tail, amorphous or tapering. As a mathematician, that's not a great number, is it?
- [48:51]
Peter Attia
No.
- [48:51]
Dr. Paul Turek
If you look at marine species, 99.9 look perfect in the wild.
- [48:56]
Peter Attia
Yeah. And presumably that's because their environment is so much more hostile. They're doing this all in the ocean.
- [49:01]
Dr. Paul Turek
I don't know. But it's amazing that we're that good with the sperm. But again, it's a construct. It's like putting stars ordering stars in the universe. Cassiopeia. Someone named Kruger said this is what a normal sperm looks like. But we know that two tailed sperm have double.
- [49:14]
Peter Attia
I mean it might be the two tail, might not be the worst thing in the world. It's just extra rocket boosters. But what about the pinhead? What does the pinhead imply?
- [49:21]
Dr. Paul Turek
Pin means there's no nucleus, it's a tail.
- [49:22]
Peter Attia
So that's a true problem.
- [49:24]
Dr. Paul Turek
Yeah, it's like a little tiny head and moving along.
- [49:27]
Peter Attia
If you give somebody credit for their two tails. What does your normal go up to from 4%?
- [49:31]
Dr. Paul Turek
Oh, it depends. But maybe 20. But most of them are going to be amorphous. Head's a little rounder, head's a little narrower. Those are called stress patterns. And things like hot baths and varicoceles and smoking will do that, which isn't that bad. In the case of 1% normal, you got to look at the 99%, because that's not the story. The story's in the other chunk. And if they're all looking the same, then it's syndromic and then you have a problem.
- [49:56]
Peter Attia
I see. So the more homogeneous the failures are, the more likely that you have a clear etiology.
- [50:04]
Dr. Paul Turek
And that's hard to fix. I mean, they'll fail with sex, they'll fail with inseminations, they'll fail with ivf.
- [50:09]
Peter Attia
They'll fail with ivf.
- [50:10]
Dr. Paul Turek
Yeah, they'll fail with IVF and icsi, sometimes with globulusospermia, where they're called lollipop sperm. They just have a big round head with no acrosome. There's all nucleus and there's some of the components they'll just bounce off an egg. They'll never work. They'll never work naturally. And to get them to work with ivf, you have to single sperm, inject them into the egg, and then shock the egg with calcium. Do a calcium or piezoelectrics to get it to start to actually fertilize. Because the sperm is important with fertilization. Not only has to bind, but the calcium channels are regulated by sperm. And what shuts the doors to polyspermy in an egg is calcium activation.
- [50:45]
Peter Attia
This is the reason why even if you launch a hundred sperm at an egg, it's only one that can get in. Because the first guy that breaches sets off the calcium channel that shuts the. I mean, the Star wars space analogies here are. They're just phenomenal.
- [51:01]
Dr. Paul Turek
Million years, Peter. Just a million years.
- [51:04]
Peter Attia
No more breaches in the hull.
- [51:05]
Dr. Paul Turek
So morphology can matter a lot, but it's very rare. So I'd say twice a year in my practice I'll see this, because everything's failing and everything looks normal. And they ask me what's going on, and I'll look at it really closely and say, you have this issue and there's not much we can do to treat it now. We're going to try sperm sorting technologies, which are out new on the market, microfluidics and things like that. And I've been throwing that at them. Sometimes it works, sometimes it doesn't.
- [51:27]
Peter Attia
Is that something that we know the genetic underpinning of?
- [51:32]
Dr. Paul Turek
We're getting there. PLZ zeta deficiency is one of them. Recently discovered that runs the calcium channel, which tends to be associated with a certain look like Global's spermia. So it's coming around.
- [51:41]
Peter Attia
Think about that for a second. From an evolutionary perspective, that's possible. That is the single least desirable genetic mutation you could acquire.
- [51:51]
Dr. Paul Turek
Yeah, unless you're not making sperm.
- [51:53]
Peter Attia
Yeah, but this is a dead end to the genome, Right?
- [51:56]
Dr. Paul Turek
Right.
- [51:57]
Peter Attia
So does that mean it is only an acquired mutation, never inherited? I mean, it can't be inherited, presumably, unless it's homozygous. But Even still, that's one of the.
- [52:06]
Dr. Paul Turek
50 we throw off each generation. 50 mutations.
- [52:09]
Peter Attia
God, that's just incredible.
- [52:10]
Dr. Paul Turek
I think what I would like to emphasize in this podcast is how fluid evolution actually is. And it's sperm driven and it's transgenerational. So if you ask me what's the theme for today, I'd say sperm matter a lot. A lot. A lot more than we've given them credit for.
- [52:30]
Peter Attia
All right, so basically, just rounding out the semen analysis, physical semen analysis. On the semen analysis, what if motility is the problem?
- [52:37]
Dr. Paul Turek
So I look at, in my poker analogy of the hand, if everything looks good but the motility is low, I think of short term toxins, severity. So things like exposures, so medications. I would think about habits, pot smoking, hot baths. I think about behaviors, lifestyle. So I look for an exposure in that individual. Basically picked up on the history, varicoceles and exposure, things like that. And if the count's down and the motility's down, I think of a more severe exposure. There's royal flushes and there's four of a kind. My goal when I see that semen analysis and see that patient is to figure out if he's not normal.
- [53:17]
Peter Attia
Why, by the way, do you get that analysis the day he's in the clinic with you? Or is that something you follow up on an appointment with?
- [53:24]
Dr. Paul Turek
Pretty much have it in my hand when I see them. Either they give it to me or I get one. I want that there because when I look at them, I'd like to have that in front of me to say, what kind of poker hand are you playing?
- [53:34]
Peter Attia
And this is something that's standardized and automated through microfluidics. How is the assay actually done? So the guy ejaculates in a cup, takes it to a lab.
- [53:41]
Dr. Paul Turek
Oh, I mean, used to be done manually.
- [53:43]
Peter Attia
Okay.
- [53:44]
Dr. Paul Turek
And now it's done with hemocytometers, it's done with machines. Computer assisted semen analysis does most of them in IVF groups.
- [53:51]
Peter Attia
It's really standardized.
- [53:52]
Dr. Paul Turek
Oh, yeah. I like the bespoke suit. So when I have mine repeated, I usually have someone do it by hand because there's observations I like, which is, hey, you know what? 1% morphology, but all the others look like this. Those comments are incredibly valuable that you don't really get from a computer assisted semen analysis, but it's faster and you don't have a lot of human effort involved with the computer.
- [54:15]
Peter Attia
Are they using AI for this yet?
- [54:16]
Dr. Paul Turek
Yeah, I mean, some people are for sperm selection a little bit, but yeah, there's a lot of stuff to help out and that will be really helpful for morphology to standardize it because one man named Kruger in South Africa correlated bad sperm shape with IVF outcomes and did not find that they were good when the sperm looked bad. That's where the 4% came from. But it's really hard to do that every time and do it well because it's so hard to do well. Hoping AI machine learning can help standardize the look because sperm is hard.
- [54:45]
Peter Attia
Yeah. Given how good AI is at image recognition, this should be a one foot putt. Yeah. Okay, you mentioned hormones. You were obviously alluding to LH and fsh. What else are you looking at? Testosterone.
- [54:57]
Dr. Paul Turek
Right. So to make normal amounts of sperm, you need proper amounts of testosterone and fsh. Think of it as flowering a plant. You need the water and you need the sunlight. So testosterone and FSH are key. To get normal amounts of T testosterone, you're going to need lh, which drives it. Same in women. These are all named in women in females, so that signaling is really important. So there are cases of genetic infertility like Kalman syndrome or men aren't making any sperm, but they're just not sending the signals down and you can just give them the signals with injections.
- [55:26]
Peter Attia
Sorry. These men are not making FSH and lh, so they have virtually no testosterone.
- [55:31]
Dr. Paul Turek
Right. Nor sperm. But you can give them synthetic signals. Yeah. So hcg, FSH injections, and they will be fertile.
- [55:38]
Peter Attia
So is the problem in the pituitary, not the hypothalamus?
- [55:40]
Dr. Paul Turek
No, it's the olfactory node in the hypothalamus. So they don't smell either.
- [55:45]
Peter Attia
So could you give them Clomid and would they make.
- [55:47]
Dr. Paul Turek
No, no. Pituitary is not working. Yeah, the GNRH is not.
- [55:52]
Peter Attia
The GNRH is not pituitary okay, got it. What about estradiol? Does it play a role?
- [55:55]
Dr. Paul Turek
Yeah. So estradiol is sort of a mild poison for male infertility. So everyone needs an estradiol level. Female hormone levels, testosterone gets converted to estradiol. So that's a byproduct of it, along with dht. And then estradiol goes back to the brain and is a feedback. So if it's there, the brain knows how much testosterone it's making. So if there's too much estradiol, the brain senses it's a negative feedback, senses, hey, there's too much of this. So let's make less testosterone. So it will lower your testosterone to have high estradiol. When estradiol is made, it gets metabolized differently than testosterone. It goes to the liver or to fat and aromatases. Convert it to something else, or testosterone gets converted to female hormone and aromatases. So you can get high levels being obese or having liver dysfunction. So alcohol, alcoholic cirrhosis, hepatitis, it'll rev it up, and it'll make a lot more estradiol level. And there's some medications that do it, too, and that will act and lower your testosterone, which will lower sperm production because you're not watering the plant.
- [56:53]
Peter Attia
But if you correct for testosterone. So in other words, if a guy has normal fsh, lh, and testosterone, is there an estradiol level by itself that is problematic?
- [57:02]
Dr. Paul Turek
Not usually.
- [57:02]
Peter Attia
Okay, so it's really only high estradiol in the context of suppressed testosterone.
- [57:07]
Dr. Paul Turek
So that's when you would act on it. If you see that there's a low count and the testosterone's low, and you could say you need to lose 100 pounds, which is the key secret for everything. Right. But you can also give aromatase inhibitors like weightlifters use to keep their levels down.
- [57:22]
Peter Attia
Okay, so those are four big pillars. Anything else besides the history, the exam, the analysis, and the hormones?
- [57:28]
Dr. Paul Turek
So you usually do two semen analyses three weeks apart or more to get a sense of things, because it varies quite a bit. So a very important point is that the semen analysis, any feature of that semen analysis, vary by 50 to 100%.
- [57:41]
Peter Attia
So never make a decision on one semen analysis.
- [57:43]
Dr. Paul Turek
It's really hard.
- [57:43]
Peter Attia
Yeah. Especially if it's the first one, as you said, for all the potential.
- [57:47]
Dr. Paul Turek
So I do a lot of consulting for the fda, and they do medications in reproductive age, men, and they're trying to show the semen analysis. They're going to the FDA and they're saying, can you Help us interpret this data for the fda. I said garbage in, garbage out. I mean, there's so much variability you really can't say anything. So you have to do at least two samples and it still varies quite a bit. There's inter observer variability. Who does the seam analysis. There's biological variability on what your system's like. So that's the big problem with studies.
- [58:12]
Peter Attia
So what percentage of drugs that are going through an FDA approval process are having a semen analysis as part of the evaluation?
- [58:20]
Dr. Paul Turek
I don't think many.
- [58:21]
Peter Attia
Why is that?
- [58:22]
Dr. Paul Turek
Because usually the indications aren't reproductive age. Men and women, for some of them, if they do, they'll do animal models. They won't do human studies, they'll do animal models, they'll do beagles, mice and beagles. There's no fertility effects. They don't really look at semen analyses in those. They'll look at fertility effects in animals. If there's nothing there, then they'll probably not require human studies. If there's any suggestion of a problem in the animal models, which is a million dollars of work. So if you ask me why I patented the somaticonial stem cell, I want an in vitro test for human infertility that we could use instead of animal models. Save the animals, save a million dollars. Do an in vitro spermatogenesis model and see if there's an effect at all.
- [59:04]
Peter Attia
It just seems to me that in this day and age, with people reproducing at older and older ages, we shouldn't just assume that because we've developed a drug for blood pressure or diabetes, that it's not going to be used by people with fertility. I'll give you a silly example. Have GLP1 agonists been tested for fertility?
- [59:22]
Dr. Paul Turek
No, because it's sort of an off label use of a diabetic medication.
- [59:25]
Peter Attia
But it's no longer off label. I know it's an on label use.
- [59:27]
Dr. Paul Turek
Today, but it looks like it might be helping with fertility.
- [59:30]
Peter Attia
But even if it was on label, I mean, I'm just using that as one example of a drug that was initially approved when we thought, ah, this is going to be for people who are not having kids. But the truth of it is you're going to have lots of people that are trying to reproduce on many of these drugs.
- [59:43]
Dr. Paul Turek
Absolutely, absolutely. And you know, there are 80,000 chemicals out there that are not been studied reproductively that are commonly used in industry. European commissions are a little better off. They've screened them and they've warned about them. But America, why Is that. I don't know, it's attention to detail. It's one of those things that just doesn't. I don't know.
- [60:02]
Peter Attia
Is it under the purview of the fda?
- [60:04]
Dr. Paul Turek
Yeah.
- [60:04]
Peter Attia
Or the epa?
- [60:05]
Dr. Paul Turek
Probably a combination. Or maybe everyone's thinking it's the other person's job. I'm not sure. But they're untested and they're out there.
- [60:12]
Peter Attia
Why don't we just talk about some of those things then now? So this is, I'm sure, a contentious topic, but as you know, lots of discussion around microplastics. So I don't know how far we want to go down that rabbit hole. I recently did a podcast on this topic. I didn't really touch on fertility because I just didn't see any great evidence. I talked more about things where I thought there was a little bit more evidence. Obviously with the microplastic story, there's quite a bit of smoke, but there's no real fire. My conclusion from the analysis was there is enough smoke that take steps where they are reasonable and reduce your exposure to these things. So everything from microplastics to PFAS chemicals to phthalates and even the PM2.5s. Like, there's no reason to expose yourself unnecessarily to this. If you can take relatively straightforward steps, eliminate 60 to 80% of it in your life, do it. Tell me what your impression is of the effect of any or all of the above on fertility.
- [61:06]
Dr. Paul Turek
So although sperm are made constantly and are susceptible to that, we know the testicles are pretty good place, excuse me, and insulated from exposures. I also think there's a lot of smoke there and it needs to be sorted out. But especially with the 80, 60 to 80,000 chemicals that are being used that aren't really tested at all. I think the only way to know is to do stem cell in vitro testing as much as you can before you put it on at the ID investigational drug stage, not at the final stages for clinical trials, but early on, do it. So you're screening them way in advance of getting into clinical trials and where the money gets big. But I think that there are windows of susceptibility in men, unlike maybe with women whose eggs are constantly exposed to toxins. Men have windows. And one of those windows is birth and early development, the first 12 weeks of life. Bad early when all organ systems are developing, including testicles. I mean, Shauna Swan did this one with maternal beef consumption, estrogenized beef consumption. Their sons had lower sperm counts when they were 20 years later or something. So I think that's a window of susceptibility. I also think puberty is a window of susceptibility when things turn on. So I think if exposures in those moments are probably going to matter the most to men. I don't know about other times.
- [62:23]
Peter Attia
And what is your advice to a guy when you're giving him counsel on everything he can do? We're going to talk about everything. But on this particular domain, if he says, hey, should I stop drinking Starbucks coffees in those plastic cups with the plastic lids and should I get a reverse osmosis filter in the house? Where are you telling him to draw that line?
- [62:44]
Dr. Paul Turek
I'm not great at that because the stress level goes up so much.
- [62:47]
Peter Attia
And I think the stress counterbalances any amount of microplastics you save.
- [62:51]
Dr. Paul Turek
If you double the stress in a man and his testosterone level will fall and then the sperm production falls for a whole different reason.
- [62:57]
Peter Attia
My testosterone level when I left residency.
- [63:00]
Dr. Paul Turek
Oh, I bet.
- [63:01]
Peter Attia
So how old was I? 33. Should have had a pretty good total t. 220 nanograms per deciliter.
- [63:07]
Dr. Paul Turek
Did you measure LH? It was probably low.
- [63:10]
Peter Attia
Yeah, I'm sure FSH and LH were totally low.
- [63:12]
Dr. Paul Turek
I don't remember what they were.
- [63:13]
Peter Attia
Secondary free testosterone of like 3 to 4. Well, the sleep deprivation, the stress.
- [63:18]
Dr. Paul Turek
So what does stress do? Stress is the sympathetic nervous system. It's fight or flight. You're running from a woolly mammoth, it doesn't know what you're running from. Know whether it's sleep or travel or financial or emotional, it's just the body. We are cats and dogs. We have the same binary nervous system. Either you're on or you're off. And when you're on, do you want testosterone? No, you want cortisol. You're running for your life. And do you want fertility? When you're running for your life in any species, no. You're trying to save your life. So cortisol goes on. Testosterone is nowhere to be found. Fertility is nowhere. You turn off all that stuff. Then when you outrun the woolly mammoth and you're behind a rock and you grab the berries and you catch a nap, Boom. Testosterone shoots up because it's rest and restore and you have to rebuild for the next run.
- [64:02]
Peter Attia
How quickly do you think that occurs in humans?
- [64:05]
Dr. Paul Turek
Days, easily. Chronic stress, is it. We love acute stress. All species love acute stress. We love that. Starvation, intermittent fasting. It's really healthy. But not low level chronic stress. Not connected to your computer. Not your emails, not the workday that never ends. Terrible for us. And the best manifestation is erections, because erections will fall if you're under stress, too. Penis has a mind of its own, according to Da Vinci. I had a guy come in, 25, in San Francisco, a startup guy, and he comes in and says, I got to see you. I said, why? He said, I lost my erection yesterday. He's 25. He said, first time? He said, yes. I said, all right, come on in. So he comes in and he's got his act together. He looks good. And I said, what happened? He said, I just lost my erection. It's never happened to me before. I think something's wrong. I said, okay, tell me about yourself. He's just getting his A round of funding. He's traveling half a million miles a year. He sleeps three to four hours a night, if any, and he's constantly running. And I said, congratulations, welcome to the human race. And he's like, what are you talking about? You're not impervious. Stress has its effects. So clearly the fertility. Oh, the great study was a moderate exercise, moderate exercise men. I wrote a blog on this called can youn Be Too Fit to Be Fertile? Moderate exercise went to extreme exercise, measured as two hours a day of VIO2, 80% maximum capacity. So pretty heavy workouts for 12 week periods. So moderate to extreme and then back to moderate. Sperm counts fell by 40%, went moderate to extreme, and testosterone fell by 50% and then went back up. And there's also military studies of men under acute stress during hell weeks in training, where they were taking their testosterone and LHS, and they were dropping by about 50% with severe stress. And that's okay for a day or two or a week, but when you're doing it chronically, we're not built for that, Peter. We're not built for chronic stress. That's a longevity issue.
- [66:04]
Peter Attia
Yeah. Let's talk about the use of anabolic steroids. Let's talk about it more broadly with the three most commonly used approaches to testosterone replacement. The way I see it is the three most common approaches are using either clomiphene or enclomiphene, using hcg, or using exogenous testosterone in one of its derivatives. Would you agree that those are kind of the big three? Okay, we'll just briefly highlight for everybody why each is a little bit different. Exogenous testosterone, you're just giving testosterone, the body senses it and immediately shuts down the hypothalamus.
- [66:40]
Dr. Paul Turek
All natural production.
- [66:41]
Peter Attia
Yep, Yep. So lh and FSH will go to zero. Testosterone will be as high as you want it to be. There's no limit to how high it goes. I've had a couple of people on this podcast who have blown my mind with how much testosterone they've talked about taking. Not clear how that's possible, but nevertheless, they're doing it. HCG is synthetic luteinizing hormone. So you give a person hcg, they will make testosterone. So it's endogenously produced, but they're making so much of it that they'll also suppress LH and fsh. So LH and FSH will come down, testosterone will go up, and then clomiphene or enclomiphene block the signal of estrogen at the level of the hypothalamus. So the hypothalamus thinks doesn't see any. Oh, my gosh, we need more testosterone. It ramps up FSH and LH production, which has the same effect as making more testosterone. But you'll now see high normal FSH and lh.
- [67:38]
Dr. Paul Turek
And the two different classes are the LH and Clomid versus testosterone. So unlike testosterone, shutting off the natural production, the lh, the hcg, and the clomiphene. And clomiphene will stimulate natural production. So you keep your testicular size, you maintain your fertility, whereas the others, you're gonna shrivel up your testicles and not maintain your fertility. And you can't generate levels that you can with the exogenous testosterone. With these, you'll never get to 3,000. You can't do that. It's tightly regulated.
- [68:08]
Peter Attia
So question one. If a guy is taking exogenous testosterone, and let's just say he's been on it now for a few months, is he able to create sperm?
- [68:20]
Dr. Paul Turek
95% chance he's not.
- [68:21]
Peter Attia
Wow.
- [68:22]
Dr. Paul Turek
While he's on it, Yep, understood. But can he create it once he stops?
- [68:25]
Peter Attia
And we'll definitely address that. But just to be clear, even a couple of months on exogenous testosterone in any form, injection, topical, oral, whatever, you basically have shut off the ability to make sperm because your testes themselves have shut down.
- [68:43]
Dr. Paul Turek
Right? No signals, no gas to the engine. It's nuanced. There are formulations that are topical, that are less potent that way, less inhibitory than injectables. So there are variations in the spectrum of exogenous testosterone that will maintain some of your fertility.
- [68:59]
Peter Attia
I don't want to go so far as to call it the marketing material, but for lack of a better term, the marketing material is suggestive that the more frequently delivered variants. So for example, the intranasal variant, which is delivered three times a day, the oral variant delivered twice a day have less of a negative impact because they're producing far lower surges than if you did a weekly injection. Is that what you're referring to?
- [69:25]
Dr. Paul Turek
Yeah. So they do more physiologic. They're in the normal range. More. What gives you side effects from testosterone, including sterility is too much.
- [69:33]
Peter Attia
Yeah. So in your experience, has that borne out?
- [69:36]
Dr. Paul Turek
Yeah.
- [69:37]
Peter Attia
You've seen men taking natesto three times a day. Doing a nasal.
- [69:41]
Dr. Paul Turek
Keeping their sperm count.
- [69:42]
Peter Attia
Keeping their sperm counts. Okay, that's interesting to note. What about the oral testosterone? The twice a day.
- [69:47]
Dr. Paul Turek
Love it. Testosterone 08 and it was not available in America for 50 years. It was available in Europe and a couple of researchers at ucla, a husband wife team. Beautiful. What happened was we were worried when we took oral testosterone.
- [70:02]
Peter Attia
Yeah. And go to the liver.
- [70:03]
Dr. Paul Turek
Right. So the biliary system and go to the liver caused liver cancer. So it was always verboten.
- [70:08]
Peter Attia
Even though there was no evidence this was happening in Europe for 50 years.
- [70:11]
Dr. Paul Turek
Yeah, not much. It's FDA approved, the EEA approved it. So this group came up with a way to get it metabolized through the lymphatics. So it could absorb through lymphatics and never hits the liver. And it's really good. I mean there is a non response rate of around 10%. So it's 10% of men, some like gels too. 15% won't respond. There's groups that won't respond that well. But it is really good.
- [70:32]
Peter Attia
Do you prescribe it?
- [70:33]
Dr. Paul Turek
Oh yeah.
- [70:34]
Peter Attia
I'd be interested to hear your experience with it. We have prescribed it now to maybe a half a dozen patients. One of the silly challenges we have with it is we actually have no idea if they're therapeutic because trying to get their blood drawn to figure out when to draw their blood to actually see the level. For example, if a guy takes the drug at 8 o' clock in the morning and then at 1 o' clock in the afternoon, which is sort of what we're told is a great window to take it so that you get that mid dose. Mid dose. Right. If he does his blood draw at 7 o' clock the next morning, he's been 18 hours off drug, he has unmeasurable testosterone, he's going to show up at 200, he's going to look like I did 50, 20 years ago. His LSH and FSH are still completely suppressed because that doesn't go away over 18 hours. But I don't know how to interpret what is he walking around at during the day, which is what I care about.
- [71:24]
Dr. Paul Turek
It's hard to know. But usually you don't want to do it right away too. So you want to give them a couple weeks to stabilize hemostatically. Right. But usually you can get pretty good levels because the half life isn't that short.
- [71:34]
Peter Attia
They say it peaks in five hours. So I don't know what the half life is.
- [71:38]
Dr. Paul Turek
A half life would be more like 12. More like 12? You wouldn't dose it at 100% decay, you would dose it at 50%. So he's probably not responding. We can check it at different times, but it's probably not much of a response.
- [71:49]
Peter Attia
And what are you dosing it at? It comes in 100 and 200.
- [71:53]
Dr. Paul Turek
Depends. I usually go to the mid dose 298 twice a day. And then you can double it or whatever. I usually start out at not the lowest dose. And it depends what you're trying to solve too. The problem. Right. If you want them, you're not gonna get em to 800 or a thousand very easily. You can get em 400 to 600, 600, 700 pretty well. But no side effects. I haven't seen anything. Maybe a couple dozen men really well tolerated.
- [72:17]
Peter Attia
Interesting. So this is not something you used when you're trying to get a guy from 300 to 1,000.
- [72:23]
Dr. Paul Turek
You could, but probably not the first choice. Yeah.
- [72:25]
Peter Attia
And now you're taking 500 twice a day or something crazy like that.
- [72:29]
Dr. Paul Turek
Yeah. And twice a day is a big deal for men it is.
- [72:31]
Peter Attia
What about Natesto? How are you? Are you using?
- [72:33]
Dr. Paul Turek
I've never.
- [72:34]
Peter Attia
You've never prescribed?
- [72:35]
Dr. Paul Turek
No one tolerates that.
- [72:36]
Peter Attia
What's the experience like? We've never used it.
- [72:39]
Dr. Paul Turek
Well, have a flu and try to get your testosterone level up. You can't do it. You have to spray it in your nostril. Each nostril three times a day. And it's gooey and it's gel like. And men within a week will call and say, can't do this.
- [72:50]
Peter Attia
Yeah, we've had more luck getting women to use this.
- [72:53]
Dr. Paul Turek
So the other big differences between the two types of testosterone replacement or supplements. One is, we'll call it the natural ones versus the exogenous ones is side effect. Profiles differ widely. It's very difficult to get polycythemic or thickening in your blood with the physiologic levels. It just doesn't happen very often. I've seen it once or twice. But if you take testosterone exogenously, you're at risk for polycythemia or blood thickening. So testosterone stimulates epipotent in the kidney, you make more blood, Athletes love it. But if you went a long flight and you're dehydrated, you're gonna throw a clot. And people look at it for longevity and it's like, be careful because I've seen 70 year old men want longevity in taking this stuff and then they have a clot and they have a stroke and now they're 71. And.
- [73:38]
Peter Attia
And do you find that the clot risk is proportional to hemoglobin, hematocrit simply? At what level are you saying?
- [73:44]
Dr. Paul Turek
So I mean, the studies aren't broad, but Ramasamy just did another paper on it. The most significant event occurring with testosterone replacement or supplementation is polycythemia and events. The high level for hemoglobin 17, Matocrit 50, you start seeing events happen about 18, definitely at 19.
- [74:04]
Peter Attia
One of the things we do with patients who are injecting testosterone, cypionate, and we have some patients who love doing this, I think it would drive me nuts if I were trying to do this. They inject it every day, so they'll do 10 to 15 milligrams every single day. And it actually produces the same effect, which is they don't have the polycycthemia.
- [74:21]
Dr. Paul Turek
Right. Because they don't hit these peaks.
- [74:22]
Peter Attia
They never hit these crazy peaks. Ten years ago, everyone I saw that was prescribing, this was prescribing. The standard was 200 milligrams every two weeks, which was crazy.
- [74:32]
Dr. Paul Turek
Highest risk.
- [74:32]
Peter Attia
Yeah, yeah. So what is your typical injection schedule?
- [74:36]
Dr. Paul Turek
So once a week, and I think twice a week you can have the dose. Right. So that is a little safer. But then it becomes the intensity and just I can't do it like that or whatever. I want a pellet instead.
- [74:47]
Peter Attia
Do you put pellets in?
- [74:48]
Dr. Paul Turek
Oh yeah, yeah, I do them all.
- [74:50]
Peter Attia
The pellet also, I don't know the kinetics of it, but I would imagine you're pretty supra physiologic for a month or so maybe.
- [74:55]
Dr. Paul Turek
Yep. So pellets are like the long term contraceptives for women. You know, in the arm they put it subcutaneously, we put it in the butt and it's a couple minute procedure in the office. You don't have to worry about anything. There's no compliance issues, we don't have a lot of side effects or consequences. From it, it's done with a chokar and a thick needle and pretty quickly, within a couple days, you'll get a level and then it'll slowly decay. Pretty much half of it by three months or so and then the rest by four to six. Supposed to be a six month physiologic level, but normally it's four, four or five. And men feel great for a while and they can feel it because it's slow, but it is even. And you do have this risk of polycythemia and things like that, but there's a three month periodic risk. And then usually when you're in the normal range, it kind of goes away. So I don't see a lot of consequences with that if it's six months, I really don't.
- [75:42]
Peter Attia
So let's go back to the Clomid HCG route. What is the extent to which fertility is preserved when a man is on one of those agents?
- [75:49]
Dr. Paul Turek
So Clomid is. We give it for fertility all the time, so it's very good, might even improve it. HCG depends on the dose. So, like you said, high doses suppresses normally fertile. You want LH and FSH going to the testicle, you want the water and the sunlight, you want the testosterone. If you've got the testosterone. But your FSH is, if you don't have any sunlight, you're not going to bloom. So I usually add Clomid to HCG if the dose is above 1500 units, three times a week, because that's going to start suppressing the FSH and Clomid will keep it going and then your fertility is preserved.
- [76:19]
Peter Attia
1500 three times a week of HCG is a whopping dose. You're saying beneath that, you typically don't have issues with FSH and LH suppression.
- [76:29]
Dr. Paul Turek
Right? LH you will because it's LH, but not FSH. No. Maybe 1,000 to 1,500, you start seeing it. So that's why you protect the fertility.
- [76:38]
Peter Attia
And what dose of Clomid will you give on top of that regimen?
- [76:42]
Dr. Paul Turek
Depends. I mean, usually half a pill a.
- [76:44]
Peter Attia
Day, half of 25, half a 50.
- [76:46]
Dr. Paul Turek
50 milligram pills? Yes, usually half.
- [76:48]
Peter Attia
You'd give 25 every day. These are staggering doses. How high are these guys? Testosterone.
- [76:56]
Dr. Paul Turek
Getting the testosterone is driven mainly by the HCG. I shoot for the normal range of 500 to 1000. I'm not an anabolic guy. I'll nail it today.
- [77:03]
Peter Attia
Yeah, yeah. It's interesting. I mean, we don't like Clomiphene at all. Just because. Well, there are a whole bunch of reasons, but they have to do with kind of lipid stuff. Even when we would use it, we would probably use 53 times a week. So that's about the same, right?
- [77:16]
Dr. Paul Turek
25 a day.
- [77:17]
Peter Attia
25 a day. But for most guys that would be sufficient alone, even without hcg.
- [77:22]
Dr. Paul Turek
Well, HCG is, that's driving the T. We're just trying to protect it. If you said, what do you give on isolation as monotherapy?
- [77:28]
Peter Attia
Yeah. What would you Give for clomidography?
- [77:30]
Dr. Paul Turek
12 and a half to 25 typically, depending on how sensitive.
- [77:32]
Peter Attia
And do you prefer Clomid and Clomiphene?
- [77:35]
Dr. Paul Turek
So it's very interesting. Clomiphene is really good. It's an interesting FDA story. So Clomid is not approved for men and Clomiphene isn't either. Clomid's approved for women and Clomiphene is not approved for either. Clomiphene is compounded. Clomid is available for 50 years. So a lot more data. And one's a cis isomer and one's a trans isomer. So they're different and the estrogenic effects are slightly different. So I have enormous experience. I have 560 men on Clomid and I have fewer in Clomiphene. But it was developed for older men to preserve their testosterone levels as they age because the signaling tends to get weaker, the pituitary tends to get lazier. And this is to keep your testosterone levels up more physiologically than taking testosterone. So it went through some very good randomized trials that were published.
- [78:21]
Peter Attia
This was Clomiphene, Clomiphene citrate.
- [78:23]
Dr. Paul Turek
And they were done by reputable people in the field and published. And then it went to the FDA for approval for secondary hypogonadism, sort of age related changes, not primary testicular failure in age related androgen deficiency of the aging male or adam. FDA sat on it for a couple years and said, nope.
- [78:40]
Peter Attia
Why?
- [78:41]
Dr. Paul Turek
Good question. So it's published, they're good trials, it's safe, it's as good as Clomid. And they didn't approve it. And I think it's hard to know, but I think the reason was that there's such an uproar about testosterone in America right now. And the FDA doesn't like what's happening. What happened is you can advertise your drug to the consumer now. So you know all the biological response modifiers for psoriasis, all those drugs go on and they give you five seconds on the benefits and the lesions go away. And then 25 seconds on side effects. Right? So you can do that. If you do that with testosterone, what you hear is, do you fall asleep after dinner? Are you not as athletic as you used to be? Are your erections not as good as they used to be? There's 10 questions in the Adam questionnaire.
- [79:22]
Peter Attia
And every guy's gonna be like, yeah.
- [79:24]
Dr. Paul Turek
Everyone who ages has those issues, right? So it's a no brainer. If they go on tv, they're gonna want this stuff. So the cat's out of the bag. They're stuck. And so now when any testosterone trial comes back, they're gonna point out, the FDA makes sure that we point out the dangers of testosterone replacement. So this is part of that energy, which is we don't want another testosterone.
- [79:46]
Peter Attia
So I think there's another reason, Paul, and it's everything you just said. But HCG and testosterone are Schedule 4.
- [79:55]
Dr. Paul Turek
True.
- [79:56]
Peter Attia
Which means you cannot prescribe them through these testosterone clinics that don't even see patients and are literally just not being doctors. They're just sort of giving it to anybody who shows up and pays. It's a coin operated testosterone dispensary. But Clomid and I assume by extension and Clomiphene are not scheduled, which means you can coin operate those. And my guess is that's probably why the FDA is saying what it's saying. It's already bad enough that the Clomid cat is out of the bag, but we don't want to put another one of these unscheduled drugs out there in the land of shady medicine.
- [80:36]
Dr. Paul Turek
The indications are pretty clear. And they're really safe. They're really safe drugs. My effect is someone comes in who's young, who maybe wants kids, hasn't had them, and they have a low testosterone of 220. You measure their LH, which no one does, it's low secondary hypogonism. So it's not a testicle failing, it's a signaling issue. And that's probably stress. So I say, get rid of your stress. And they say, how do I do that? It's like, okay, so exercise, acupuncture, massage, or yoga. I mean, for men, I say physical activity is the best thing for sex. So as an aside, during COVID I had two groups of men. They said, what do I do? My life's a mess. You know, everyone's life's a mess. So half of them had drinks at five o' clock, started drinking a lot, and the other half went out for runs or got a Peloton, which most of the country did. That's a great story. The peloton story. And then about six months later, these guys realized it's not working and they started doing, shifting over to exercise. I was very proud of them. These guys I was really happy with. Like, nice. Because that's the best way to handle stress is when you have no control over things. Go for a run, go for a walk, get out there. So good for you. It's just decompressing. Hold. Get your mind off something, anything, surfing, whatever. They don't do that. So I said, well, let's do this. I think what's happening is this. I think it's your stress. Maybe try traveling less or whatever. And then I'll give them Clomid. I'll say let's try this for three to six months and let's see how you feel. Sometimes it's sexual health issues. Erections aren't typically that dependent on testosterone. Typically it's other things. I'll give you the benefit of the doubt. Maybe you were higher before and we don't know that. But let's do something pretty safe and easy and I'll double your testosterone or triple it. Let's see how you do and then I'll check in with them at three and six months. How are you feeling? I feel great. Or hey, it's not working. I feel the same. It's like. Well, it's not testosterone related. Whatever the symptom is you're having, you wouldn't have it with a testosterone. We know levels of testosterone above which you should not have symptoms. We know libido, we know erections, we know fertility, things like that.
- [82:35]
Peter Attia
And what are the approximate levels for each of those?
- [82:37]
Dr. Paul Turek
I don't know. Erections. I would say the best study is about 290.
- [82:40]
Peter Attia
Yeah. So most guys that are having difficulty with erections are above 290. There's some other issue usually, but you.
- [82:46]
Dr. Paul Turek
Have to prove it to them and I'm fine with that as long as it's safe. You're convincing them.
- [82:51]
Peter Attia
And then what about libido?
- [82:52]
Dr. Paul Turek
Libido, I'd say 350 is sort of a range. It's pretty sensitive and it's harder to call. Libido's driven by so many different things. Fertility, I'd say 300 is a good one.
- [83:02]
Peter Attia
You start seeing issues with how much FSH and lh.
- [83:04]
Dr. Paul Turek
I don't know.
- [83:05]
Peter Attia
Okay. Obviously the other thresholds would be anabolic capacity, like muscle mass and things of that nature. And mood tends to be a lot more variable in my mind.
- [83:13]
Dr. Paul Turek
Absolutely. I think there's myths around testosterone and those are some of them, but is sort of a Morgan Taylor and equilibrium story, where if you're low, you have symptoms and you're low, those symptoms will get better when you go up, but then there's a point where it flattens out. There's no increase or improvement in symptoms. Sexual health symptoms are classically ascribed to that. There also is a linear relationship between testosterone and that would be blood and muscle. So more is better for making blood doping and also blood doping and also for muscle absolutely linear.
- [83:44]
Peter Attia
Yeah. I'll tell you why I find that interesting, Paul. And I only learned that, really, in talking to bodybuilders who were taking 500 to 2,500 milligrams of testosterone a week, because my initial reaction to that was, you've already saturated the androgen receptor. Probably five logs. I mean, not five logs, but like at least one or two logs earlier. But they convinced me. No, no, no. There's a real difference between 510, 20, 500 in terms of muscle mass, which it sounds like you agree with. And I don't understand the physiology of how that's possible. I mean, how many androgen receptors would you need? You'd have to upregulate them, when in fact you'd be downregulating them.
- [84:22]
Dr. Paul Turek
So I'm not sure. But the effect is indirect. The effect of testosterone, muscle mass, is indirect. It's not that you're going to do it and create mass. You don't just create mass. What it allows you to do is recover from injury. So if you push the system and you need two days to recover, you can go to one day, you can push it again harder. So that's what testosterone does in the primitive world.
- [84:41]
Peter Attia
There's even studies that show, by the way, that high enough doses of testosterone will increase muscle protein synthesis absent the stimulus, absent the lifting stimulus.
- [84:49]
Dr. Paul Turek
So it's the potential to recover that is improved. And I'm not sure that's receptor driven at all. Like, it might be several pathways going on that are logarithmically better, but it allows you to push the system and go back and then push it again. And that's how you build muscle.
- [85:03]
Peter Attia
All right, so now let's talk about the guy who comes to see you. He's been on exogenous testosterone for three years. So he was given poor advice three years ago. He went to some shady back alley website. He was 27 years old at the time. I mean, this is tragically a very common story, by the way. Right. So this Guy's been on 200 milligrams of testosterone a week for the past three years. He's now 30 years old, he's met the love of his life. Lo and behold, they can't seem to get pregnant. So he's in your office during the history. You find out pretty quickly he's been on 200 milligrams of testosterone for three years. Tell me what his sperm analysis looks like. Presumably there are no sperm.
- [85:42]
Dr. Paul Turek
I would bet 95% confidence that he would have no sperm or semen.
- [85:46]
Peter Attia
Okay, so what are you telling him now? How are you going to solve this problem?
- [85:50]
Dr. Paul Turek
So it's funny because a lot of guys come in and they look good. When I examine, I'll say, are you taking anything? Because they never put it on their medications, Right. You never write it out on the history. You always have to get it out of the.
- [86:02]
Peter Attia
If they're super jacked, but then they have of shriveled testes.
- [86:05]
Dr. Paul Turek
Yeah. And they're zero. And they're wondering what you know. Right? So I will look them in the eye and say, are you taking testosterone? And I'll look them in the eye until they answer. And if they look down and they don't say anything, I know they're on it. If they look me in the eye and say no, then I know they're not, but they'll always look away. It's this verboten thing.
- [86:23]
Peter Attia
This is the same, by the way, as I'm sure you experienced as a resident in the er, the people that come in with foreign rectal bodies and abdominal pain, that's the one thing they emit from their history. They tell you, this is the last time I ate. This is this, this is this. But then you get the X ray back and there's like a candlestick in their colon. And then you say, yeah, yeah, what about this candlestick? And they're like, oh, I totally forgot to mention that. Yes, yes, it was lit when it went in. Yeah, yeah, yeah, yeah.
- [86:50]
Dr. Paul Turek
So my theories about this is why is he taking it? So if he's taking it for anabolics, then he probably has a pretty good idea. I want to give you a little research we're doing on the lifespan of anabolic steroid users. So remind me at the end of the story, give you a little brief about what I know about that. So how he takes it matters. So if he's been in constant use injectables, that's the most Suppressive of fertility. And if you turn a gland, like a testicle off long enough, it's off. So I gave a lecture to the Enneagraine Society on recovering men from hypogonadism in young men. And I asked them a question at the end. My whole procedure comes from steroid users. I take notes when the anabolic guys come see me because they're really smart and they know a lot about reactions. Biology, yeah, it's incredible, but it's a science. Some of them are PhDs. I took notes for years and then came up my approach along with what I know. So it's very much in concert with concert with them. So everything I say is built on a large experience. And it's called Getting off the Juice, the blog. And I have people read that blog, do it and say, get about 80% of the way, and then call me and say, I need help here. Now I'm here.
- [87:58]
Peter Attia
We'll link to this in the show. Notes for sure.
- [87:59]
Dr. Paul Turek
It's for sure getting off the Juice. And there's a PowerPoint in it. So the recovery is usually possible in young men, but it depends on how much they took, how long they took it and how they took it. If they do it like a cycling effort, that's the best. So if you cycle steroids, you recover the pituitary, you get back to normal, and then you hit it again. That's actually quite smart. Constant use is not. Constant use for longevity or whatever is not a good idea for fertility. So that's going to be much more. Suppressive injections are worse than orals or any gels. So the next thing is, how long? So I asked the endocrine society, since I answered all their questions, I said, I have a question for you. Can you turn a testicle off like in a thyroid or an adrenal gland? If you suppress it enough, can you turn it off for good? And they said, yeah, that's a board question of ours. We can do that. And I said, because we believe it's always reversible in the field of infertility in men. And so that got me a little worried. And so now I kind of worry about 5 to 10 years of use. After 5 or 10 years of use, you may not get it back either the ability to make sperm or the ability to make testosterone.
- [88:59]
Peter Attia
We typically tell men in our practice, two years would be the absolute ceiling. Are we too conservative?
- [89:05]
Dr. Paul Turek
Maybe.
- [89:06]
Peter Attia
Okay.
- [89:06]
Dr. Paul Turek
Depends on dose they get everything right if they're taking 250 a week.
- [89:09]
Peter Attia
No, I mean in our practice it.
- [89:11]
Dr. Paul Turek
Would be 50 twice a week.
- [89:12]
Peter Attia
Yeah.
- [89:12]
Dr. Paul Turek
I published a study when I was a fellow in Houston of a guy who took it for 25 years. And we drove at him with gonadotropins, that's HCG and fsh. And we didn't get anything, but we got a low number of sperm back. And I just had a guy from Louisiana come in, 25 years of chronic use. I did a mapping procedure to find sperm in his testicle. And he's going to be having a kid, but he made a couple of sperm.
- [89:36]
Peter Attia
But you pump him full of HCG.
- [89:38]
Dr. Paul Turek
And synthetic FSH and get nothing. And then you have to look in the testicle because production can be low enough to be there but not coming out.
- [89:44]
Peter Attia
But this is the rescue protocol. It's lhfsh.
- [89:47]
Dr. Paul Turek
Basically, there's three ways to do it. One is never stop the testosterone suddenly. Interesting because men will hit the doldrums and go. And they'll flop over like they have the flu. They'll feel like shit and they'll get right back on it. They'll feel terrible because they have nothing going on. If you take the testosterone away, their system's turned off, they're not making their own. It takes time to get the system to reactivate, so that's the hardest. So I always taper testosterone over what period of time? Six weeks. Typically you halve the dose for two, have the dose for two and then off for two, and then you measure and that's getting out of the white water into the green wall a little bit. So that's a little smoother. So taper and then I offer em two options. One option is taper alone, taper with Clomid or. And Clomiphene, which is a little quicker, getting the pituitary to turn back on. So that will soften the blow of the feeling of feeling completely fatigued. Or more aggressively HCG and Clomid. And then I usually check them at about six weeks.
- [90:44]
Peter Attia
It's interesting. If you give Clomid, the pituitary will make FSH and lh.
- [90:49]
Dr. Paul Turek
Yeah, it takes a while.
- [90:51]
Peter Attia
Well, that's a way more cost effective approach than giving because synthetic FSH is pricey.
- [90:55]
Dr. Paul Turek
Yes. Couple thousand a month in America. Yeah.
- [90:58]
Peter Attia
So is there any reason to do that over the Clomid approach or is it just that it's faster?
- [91:01]
Dr. Paul Turek
I think you might gain a couple of weeks of time.
- [91:05]
Peter Attia
So for most people that's not a.
- [91:07]
Dr. Paul Turek
Price worth paying that taper over a month or two. I usually check their T levels at around two weeks off of the last testosterone, and that's the lowest they'll be. And if they're in a good range there, you can use that as a predictor of their response. What would be good if they're in a normal range.
- [91:22]
Peter Attia
Oh, really? Okay. We want within a couple months to see them back to 600, 300 would be okay.
- [91:28]
Dr. Paul Turek
To make sperm.
- [91:29]
Peter Attia
Okay. All right.
- [91:30]
Dr. Paul Turek
But then to get them to where they want to be depends on their symptoms and what they're happy with. You won't know until you wait longer to see how high you can get them. That's the lowest they'll be, but they'll be off of testosterone. And if they go along that taper and they're not tolerating, I try to tell them, don't go back. Just stay there, because time will help you. You are not going to feel maybe that great. But try to do this, because if you don't, if you go back, then we have to start over. But if you can just maintain it for a while, you'll feel better. And some of them dip a little bit. But remarkably, most men do really well with that taper.
- [92:00]
Peter Attia
Now, I want to get onto some of the other topics here, but just to close the loop on this, do you ever advocate crazy ideas for guys that are using testosterone to use lower doses and then combine it with hcg? Just as we were talking about the Clomid plus HCG approach. Okay, not an unreasonable approach to combine Clomid with testosterone at low doses to preserve testicular function.
- [92:24]
Dr. Paul Turek
Yesterday I operated on a man testicular sperm retrieval on a man who was asospermic for genetic issues. And he was on testosterone for 10 years because he needed it. His testicles are failing. And I said, you're not going to make sperm on this. So we put him on hcg, which didn't do anything for him. Felt terrible and did that for a year. And he said, I can't do this anymore. I said, okay, or maybe it was six months. And I said, I need a little more time for you to be off testosterone. But since you've been on HCG for six months.
- [92:54]
Peter Attia
And what dose did you have him on?
- [92:56]
Dr. Paul Turek
3,000. Three times a week.
- [92:58]
Peter Attia
That's a whole vial a week?
- [92:59]
Dr. Paul Turek
Yeah. Wow. Then I said, okay, let's add in a low dose T gel testosterone gel, get your testosterone up, and we're Gonna Lower the HCG to 500. Three times a week? Twice a week. And I did a sperm retrieval yesterday. Boom. Plenty of sperm.
- [93:13]
Peter Attia
How old was he?
- [93:14]
Dr. Paul Turek
35.
- [93:16]
Peter Attia
Interesting.
- [93:17]
Dr. Paul Turek
You can maintain whatever's going on in the testicle with HCG and take any testosterone you want to.
- [93:24]
Peter Attia
That's an important lesson. Yeah.
- [93:26]
Dr. Paul Turek
Here's the catch, though. The caveat is it was done in, I think, Finnish bodybuilders. They were doing a cycle of steroids, huge amounts. They took Lotus HCG, 500 twice a week. And John Amory has worked out in Washington, has worked out all the exact doses. But 250 to 500 twice a week is a good dose for that. It keeps your intratesticular testosterone high, keeps your sperm production going. And they went on both concurrently for 12 weeks, and their sperm counts were normal the whole time at any dose of tea. Now, what happened after that is people start saying you can preserve your fertility on testosterone replacement, which is possible.
- [94:02]
Peter Attia
They missed half the story, but it.
- [94:03]
Dr. Paul Turek
Was only 12 weeks. And if you're doing it for three years and you miss your dose of HCG, boom, you're done, you're cooked. You're gonna go to zero. So unopposed testosterone without. So you have to be 95% compliant.
- [94:16]
Peter Attia
Do you think that there's a difference between HCG and Clomid in that effect as the adjunct?
- [94:20]
Dr. Paul Turek
The Clomid doesn't work.
- [94:21]
Peter Attia
HCG is the one.
- [94:22]
Dr. Paul Turek
Yeah. Clomid doesn't improve intertesticular testosterone levels like HCD does. It's ineffective.
- [94:27]
Peter Attia
Got it.
- [94:28]
Dr. Paul Turek
It will potentially make you more recoverable. If you do it 80%, you'll be zero, even though you thought you might have a sperb count, but your recovery will be faster because it's done something. But the only way to maintain your current fertility is you have to be 100% compliant with dual therapy. You can't go on monotherapy with testosterone outside of fertility.
- [94:49]
Peter Attia
Given the popularity of testosterone replacement therapy today, is there another advantage to just doing dual therapy? Obviously, for fertility, we wouldn't be talking about it, but can you think of any other reason why it might be advantageous if a guy can deal with the hassle and the cost?
- [95:05]
Dr. Paul Turek
Yes. Depends on the indication, though.
- [95:07]
Peter Attia
Everything but fertility. Like any other health benefit.
- [95:10]
Dr. Paul Turek
Well, I think muscle mass. So with aging, it's a great one. I mean, used to be, like, growth hormone with age wasting syndrome, things like that. I mean, muscle mass is a key.
- [95:19]
Peter Attia
For men, but I'm saying, as opposed to just being on testosterone injectable, to do the dual therapy versus just monotherapy.
- [95:26]
Dr. Paul Turek
You mean if you're going to do some kind of therapy?
- [95:28]
Peter Attia
Yes, if you've committed to doing therapy.
- [95:29]
Dr. Paul Turek
No, I think the only reason Would be if you want testicles to be big.
- [95:33]
Peter Attia
Okay, so just volume.
- [95:34]
Dr. Paul Turek
I just created a new procedure to make testicles larger naturally by putting a fat injection in the hydrostele space in men on testosterone because they don't like their small testicles.
- [95:42]
Peter Attia
So it's the equivalent of the Brazilian butt procedure for the testes.
- [95:46]
Dr. Paul Turek
Yeah. So it's all natural and there's no prosthetics and you can't tell. And it makes them nice and big. And test is fat grafting. And it's fabulous.
- [95:53]
Peter Attia
Medicare improved.
- [95:54]
Dr. Paul Turek
No. Yeah. Creatively approved.
- [95:58]
Peter Attia
So let's shift gears and talk about other modifiable factors. Let's talk about heat. We've talked about it a little bit.
- [96:04]
Dr. Paul Turek
So for fertility.
- [96:04]
Peter Attia
Yes, for fertility. So tell me about the impact of cold plunging and sauna and hot tubbing on fertility for men.
- [96:13]
Dr. Paul Turek
Okay, so the test, it says outside the body, it's 3 degrees cooler than the rest of the body. So 95 versus 98 degrees Fahrenheit. And then there's a reason for that. Unknown. We had that conversation. Don't really know why, but it may be that it's an immunologic sanctuary and that's the only way to do it and that God or Darwin could figure out. But if you heat up the testicle, it's also close to the skin, so it's a radiator. So when the heat comes down, the arterial blood, it has to cool, so it raises and lowers. And there was an article in the Journal of irreproducible results. About 20 years ago, a man went to Big Sur and wore nothing. And he measured ambient temperature. And then he marked on this leg with a marker where his scrotum hung, how low it hung. And he could tell the ambient temperature by how high or low his scrotum hung. He became a thermometer. So it does go up and down. Is that Peter Ortia laughing? Journal of Irreproducible Results.
- [97:07]
Peter Attia
Oh, God.
- [97:08]
Dr. Paul Turek
Really cool. But it showed that it's very temperature sensitive and it goes up and down to regulate it closer to the body. When you want it warmer, et cetera, you go into a cold shower or a plunge. Where are your testicles?
- [97:18]
Peter Attia
They're way up there in my abdomen. Yeah.
- [97:20]
Dr. Paul Turek
And that's all the cremasteric muscle, and it's all temperature driven. So it spends all of its time regulating its temperature to stay at 95. Now, saunas, baths, hot tubs, Jacuzzis, steam rooms change that. The worst one of those is anything underwater submerging underwater because you're 1cm away, you're a liquid, it's a liquid. You are going to turn that temperature. Maybe not the inner part of your body, but little kids going into hot tubs, right, they overheat.
- [97:47]
Peter Attia
So you get into a 105 degree hot tub, which is a very typical temperature for a hot tub is 105 to 110. You're saying within a relatively short period of time, your testes will assume that temperature?
- [97:57]
Dr. Paul Turek
Absolutely. You're 70% liquid. This is right at the surface. So I did a study, published it in the Brazilian Journal of urology. I published 200 studies. This was the hardest one to get in. Everyone said, we know that it affects fertility, so we're not going to publish it. So American went to the Brazilian Journal of Urology. It then went to the New York Times as a press release. That's how popular it was. It's probably my most cited paper ever and it's certainly not my best. It's very interesting. I took infertile men with low sperm counts and stopped the tubs. They were in hot baths because I used the word Jacuzzi. Jacuzzi called me up and said, stop, don't use that word. So I don't use that word. So hot baths or tubs, and I told them out and they went up 300%. Semen quality went up 300%. Total mold count in three months or four months and 600% in six months. You have to give us some time. And that's that curve, the recovery curve. And we didn't look at fertility, we just looked at that recovery and some in more zero and went up to close to normal.
- [98:53]
Peter Attia
What was the age range of these men?
- [98:55]
Dr. Paul Turek
35.
- [98:57]
Peter Attia
So fertile men.
- [98:57]
Dr. Paul Turek
Yep. Trying to conceive.
- [98:59]
Peter Attia
Yeah. These are men who are not able to conceive. You're making the diagnosis, I think it's your hot tub, let's get you out of there. And they have a six fold increase in sperm count, total motor sperm count.
- [99:09]
Dr. Paul Turek
Meaning count motility, mainly driven by motility.
- [99:12]
Peter Attia
Interesting. So it's motility that the price, the biggest one.
- [99:15]
Dr. Paul Turek
But also count might have doubled. Chilly may have gone up threefold kind of thing. So six fold increase overall. Then I calculated, after that I calculated a lethal dose of tubbing. So what's the lethal dose?
- [99:26]
Peter Attia
Yeah, what's the LD? 50. Yeah.
- [99:27]
Dr. Paul Turek
So lethal dose to me means you're zero. You do it enough, you have no sperm. And it came out to be 20 minutes of a hot bath or tub. 20 minutes 104 degrees three times a week would probably make you zero.
- [99:41]
Peter Attia
There have to be a lot of guys out there who are spending at least three times 20 minute sessions in a hot tub that's at least 104 degrees a week.
- [99:52]
Dr. Paul Turek
Interesting. The largest group of people in tubs in Northern California, we did the study, were environmental lawyers. Is your job that stressful? It's like, yeah, it is. I mean, it probably is in California. All right, so the only study ever done prior to that was a PhD thesis at Vassar College where someone had a guy dip their testicles into a bucket for 20 minutes at really hot and looked at their sperm counts or their fertility and they went, that was the only. And I couldn't even find it. It wasn't published. You had to figure out this thesis thing, but that's how little was written about it. And they gave me so much flack for publishing this. It was really funny. And the New York Times had an article said, drew a condom and it drew birth control pills and it drew a guy in the tub. It's like, pick your contraceptive. So it's huge. I'd say 10% of my population's in it. Then the next question is, what about saunas? So saunas is not underwater. It's not submersion, but saunas are. You're in a hot room, it's going to affect it. And I would say the effect is 1/4 to 1/3 as profound as a hot bath or submersion.
- [100:50]
Peter Attia
So my friend was absolutely right to have those ice packs on his scrotum.
- [100:55]
Dr. Paul Turek
I think he's reading.
- [100:56]
Peter Attia
Yeah, he's listening to. He's a smart guy. Yeah.
- [101:00]
Dr. Paul Turek
And then I would say steam rooms, showers are probably fine. You're in an ambient, temperature's normal. And I think steam rooms are probably between saunas. And it depends how much time you spend, but it's probably not normal. But not a hot bath. Hot baths are terrible.
- [101:15]
Peter Attia
Okay, and then what about the cold?
- [101:17]
Dr. Paul Turek
I don't worry about cold. I remember Surfer magazine called me and said, I'm a Northern California surfer. Right. An LA surfer. The editor of Surfer magazine called me and said, are surfers infertile? I said, is that water bad for them? Because California water is 60 degrees. I said, no, I've never met an infertile surfer. So I don't think it's bad at all.
- [101:34]
Peter Attia
All right. So the cold is okay.
- [101:36]
Dr. Paul Turek
Especially plunge where you're talking seconds.
- [101:38]
Peter Attia
Yeah, yeah.
- [101:38]
Dr. Paul Turek
You know, your tests are going to go up, you're going to be able to maintain that heat. I think if you did it all the time, it would probably be bad. Yeah, because enzymes work in the testicle at that one temperature. They work optimally.
- [101:52]
Peter Attia
Okay, let's talk about exercise. You mentioned one example of exercise that can be problematic, which was, I believe you said in a study where men were ramped up to two hours a day of exercise, it was above 80% of VO2 max, which is pretty strenuous. That was enough to put a dent in their fertility. Tell me about riding a bicycle.
- [102:14]
Dr. Paul Turek
I'm a biker. I have old vintage bikes that I used to race in Connecticut and I had them rehabbed and they're all Italian and they're all steel and they weigh a ton and the seats are from Britain and they've got 10,000 miles on them and they weigh four pounds.
- [102:28]
Peter Attia
As much as just like a Brooks.
- [102:29]
Dr. Paul Turek
Saddle, these Brooks leather saddles and all worked out. And it's like that saddle nowadays is about half the weight of a carbon bike. But I love it. And I was thinking of maybe going senior league and doing this gorgeous steel frames and trying to keep up with those guys. Because it's not about the bike really. It's like when you get golf clubs and I got $150 set of golf clubs, I'm going to be as bad a golfer with thousand dollar clubs as 100. So it's really about the biker. But there are some differences in terms of momentum in the wheel force and all that. But I love my old steel bikes. And they see this. It's like hanging at my office when I come to work in the morning and I bike in San Francisco and then I have this seat and it's like, that's a bad saddle. And so the issue really is it got started that biking was bad for reproductive health with a Spanish competitive cycling study. Competitive Spanish cyclists, Tour de France caliber cyclists. Their sperm counts were examined.
- [103:20]
Peter Attia
But what was the control group? Did they have a control group of runners?
- [103:23]
Dr. Paul Turek
I don't remember. I don't think so.
- [103:24]
Peter Attia
So in other words, it could have been the exercise, it could have been the intensity of their exercise.
- [103:27]
Dr. Paul Turek
Not a good group to study.
- [103:28]
Peter Attia
Yeah.
- [103:28]
Dr. Paul Turek
So their sperm counts were low, their morphologies were off, and they're extreme athletes. So we know that and we know maybe they were on drugs. Maybe they were. You know, it's a big industry. They're super fit. They're certainly exercising two hours. And so they said, look at these guys who are really healthy and look at their sperm counts. But this other data didn't come out. So I did a blog called Cycling into Childlessness, and I looked at a more comparable study, which was British commuting, cyclists, everyday people bicycling to work in Britain on different saddles. And I looked at their fertility, and their fertility was far better than the average Brit.
- [104:03]
Peter Attia
So even if they were taking some hit off the bike, it was probably more than compensated for by their healthy lifestyle, which included probably riding the bike. But obviously there's a healthy user bias because anybody who's riding their bike to work is probably consuming less Guinness, fewer fish and chips, smoking less. In other words, riding a bike is a proxy for being healthy. But in spite of that, it didn't offset that health risk. Unless we found people who were equally healthy who didn't ride a bike.
- [104:33]
Dr. Paul Turek
I don't remember what they controlled for, but I think they did a lot of the socioeconomics. It may just been activity, but the bicycle.
- [104:38]
Peter Attia
So is this a myth?
- [104:40]
Dr. Paul Turek
Yes. Now, if you said, am I worried about bicycles? Yes. So I worry about sexual health, I worry about the pudendal nerve, and I worry about seed anatomy. So the best seat for a bicycle. So if you're biking a lot, that's good. If you're biking and you're getting pelvic numbness, that's bad. So you need to get a better seat. The best seat was studied by the nach. The NA. I forgot it was Dr. Schrader at the NIH. The best seat is the saddles that are shaped like this are bad for your sit bones because they come into the middle where the arteries and nerves are to the penis. So it's an erection issue. Those aren't good saddles. The saddles with the two little tongs that hold your iliac crestbones with no nose, perfect. So it's pressure, where the pressure is outside, facing, leaning in. So he gave those to police in Washington, the bicycling police down in National Cathedral area in the parks, and they all gave the seats back a week later. Said, you're not doing this. He said, what's going on? He said, we don't know where the seat is. We go sit down and it lands somewhere. You have to have the nose for bicyclists because they use it to guide when they sit down. They use it to guide where they sit. So the best saddle is flat or gel in the back, cut out in the middle, and some kind of lean in like this. So cut out saddles and then you should get your bones fit. You can do this online. You can ask Them to send you a pressure pad and you sit on it and then you send it back and they measure the distance and there's only a couple of different saddles, maybe 12 widths that you could do and you get it done. Or like me, you use a saddle use for 30 years and it's perfect. But it weighs four pounds.
- [106:11]
Peter Attia
That's because it's a leather saddle and it fit too. Yeah, yeah, yeah, Iconic. Okay, let's talk about alcohol specifically and let's talk about any other recreational drugs.
- [106:22]
Dr. Paul Turek
So fertility wise, I'd say the government wants men. I'm gonna talk about men to less than two glasses of alcohol a day is okay. They consider for binging. Now, alcohol is a small molecule, goes right into the brain, goes right into the testicle. It's definitely a poison. It goes everywhere. The testicle, doesn't limit it. So I worry about it a lot. The effects I see are direct when it's abused. So I would say you see morphology, motility and count issues. So that's a direct effect. As a direct toxin, it's one of the few things that gets into the testicle. Second would be a hormonal effect. So alcohol use tends to cause the liver to rev up, tends to cause more estrogenization. So you tend to get low testosterone from that. So it's a hormonal effect and a direct effect.
- [107:09]
Peter Attia
Any evidence that it's having an epigenetic effect?
- [107:11]
Dr. Paul Turek
Probably. I don't know about evidence, but I'm sure it does.
- [107:14]
Peter Attia
Let's talk about common recreational drugs. Let's start with marijuana.
- [107:17]
Dr. Paul Turek
That's the worst player for me. So thc, same thing. Count, motility, morphology. And it probably has an effect. We know it has an effect on fragmentation, which is a quality measure of sperm. Not only the way it looks descriptively, but quality and also probably an epigenetic effect. Some of the early studies on epigenetics showed alterations with nicotine and with pot. What I don't like about pot is you ingest it. And however you ingest it, you get a peak, you feel it, it goes away, you feel it's out of your system like nicotine. But it sits in two weeks for a month or three weeks and it's a depot effect and it keeps coming back. So you get a low level toxicity, which I don't like at all. So I am not a fan of pot. The other thing that really concerns me about pot in reproductive age men is I wrote a couple blogs on this called the Weed Worries. And there's some compelling evidence from epidemiology in two studies 10 years apart validating each other that chronic pot use is associated with testis cancer.
- [108:14]
Peter Attia
And we think that that's causal.
- [108:16]
Dr. Paul Turek
I don't know, it just worries me. Weed worries me.
- [108:19]
Peter Attia
Interesting. Given that it otherwise seems kind of benign. I personally can't stand this stuff, but I know so many people that use it so frequently that seem to have relatively few effects.
- [108:30]
Dr. Paul Turek
It's a interesting phenomenon. It's medical marijuana.
- [108:32]
Peter Attia
Right.
- [108:32]
Dr. Paul Turek
So medical means safe. But I asked someone, I have a lot of pot growers in the Emerald City up in Northern California and they have the artisanal stuff that wins awards and stuff. And it's like, which is worse for driving, being stoned or being drunk?
- [108:45]
Peter Attia
Undoubtedly being drunk.
- [108:46]
Dr. Paul Turek
Yeah. So it looks like reflexes. But you know, he said to me, well, we tend to stop at stoplights and wait for them to turn when we're stoned.
- [108:55]
Peter Attia
Yeah. I'm not saying that one is driving stoned is good, but there are probably far fewer people that die at the hands of a stoned driver than a drunk driver.
- [109:03]
Dr. Paul Turek
Probably. And I think the signs, the LA Story signs and they have the lit up signs about open season traffic. Remember the movie LA Story? They do say, now drunk or stoned, watch out, we're going to get you.
- [109:14]
Peter Attia
What do you think is the mechanism of action by which THC is having these negative fertility impacts?
- [109:20]
Dr. Paul Turek
Not sure. I don't think it's the mechanism. I don't think it's the root. So I don't think it's toking or edibles. But it might just be the chronic exposure. And I don't see there's some evidence that THC acts like LH and binds the receptor and blocks it, but blocks it from lh so you can get low testosterone, but it's not been that profound.
- [109:39]
Peter Attia
What about nicotine, either synthetically or in the form of tobacco?
- [109:44]
Dr. Paul Turek
Bad actor at high doses, I think too, either one. Yep. It's nicotine is the issue.
- [109:49]
Peter Attia
Nicotine per se is the issue.
- [109:52]
Dr. Paul Turek
And it doesn't last as long as thc. It does have count motility effects and fertility effects. We think probably both of these are oxidants. It's the oxidants that do it. It's oxidizing things.
- [110:03]
Peter Attia
You mentioned diabetes earlier as part of your history and physical. What is it about diabetes? Is it the high levels of glucose? Is it the microvascular damage? Is it the inflammation that typically travels in parallel with it? Why is type 2 diabetes a risk factor for infertility?
- [110:20]
Dr. Paul Turek
Probably all of them, I don't think we know exactly, but I'd say that I diagnose diabetes in a lot of infertile men. I make the diagnosis.
- [110:28]
Peter Attia
What's the physical finding you're seeing in the testes that tells you, like, you know, how an ophthalmologist will often make the diagnosis because they're looking into the eye.
- [110:35]
Dr. Paul Turek
So for me, it's usually their weight and their count motility are low. I'm looking for a chronic exposure. And then they have polyuria or polydipsia or something like that where they're drinking a lot and they're peeing a lot because the sugar is dragging it out. And you check their UA and it's full of sugar. And then some of them have an A1C that's a little pre diabetic, but I think a lot of it is neurogenic too. They can develop ED. A third of type 2 diabetics have low testosterone, so that's a clue, and that's secondary. So you give them Clomid. You can bet them right back. But that's probably the common one, is the look, the sugars and then the low T and the low sperm count. Just kind of a picture.
- [111:15]
Peter Attia
And then we've kind of talked about sleep and stress, obviously, metabolic health in general. What are some of the other modifiable things that you see?
- [111:23]
Dr. Paul Turek
The most common is a varicocele.
- [111:25]
Peter Attia
Okay, tell people what a varicocele is.
- [111:27]
Dr. Paul Turek
You develop varicose veins in your leg and need treatment. And this is the same thing in the scrotum, but it's not related. And it happens typically at puberty. You'll develop this. You won't know it sometimes, unless it hurts. It's a reflux of blood in the wrong direction. So the testicle drains to the kidney, which is uphill, and it wants to drain back down. The reason why it drains back down is because as a species, we stood up a half a million years ago, maybe three quarters of a million years ago. And when you're an animal, your kidney and your testicle drains this way. There's no gravity. But when you stand up, you're now draining uphill. The system was never made for valves. And if you said to me, what's the reason our sperm counts are falling? I would say we stood up as a species. Probably not a good idea for male fertility, because that budget that's supposed to be staying up there comes back down to the testicle, pulls around it like a hot bath is warmer. And usually the first Sign is a testicle on that side, which is the left, usually is smaller than the right. So the physical exam will be a testicular discrepancy in size. That's the first thing you see. And then you feel above it and you feel a bag of worms.
- [112:28]
Peter Attia
But sorry, there are no valves in that vein.
- [112:30]
Dr. Paul Turek
Correct.
- [112:31]
Peter Attia
So what's the head? It has to climb. That's got to be 30cm. So how is it doing that without a valve?
- [112:38]
Dr. Paul Turek
Oh, no.
- [112:38]
Peter Attia
That's a pretty big distance to travel without.
- [112:41]
Dr. Paul Turek
I don't know.
- [112:42]
Peter Attia
Yeah, interesting. Okay.
- [112:43]
Dr. Paul Turek
But there might be a few during puberty. But the growth spurt, those blow the angle of the renal vein and there's a right angle. The right side has a natural valve off the vena cava. So it's kind of has to go around 270 degrees. So you don't reflux on the right. Left sided lesion in most men. You can be perfectly fertile with it. If you look at statistically, 85% of men conceive naturally without varicoseals. 80% will conceive naturally about a year. So the curves are very similar. Clinically, maybe insignificant, but there is a difference. And it's statistical. But if you multiply that by millions of people, it becomes important.
- [113:15]
Peter Attia
And you'll figure that out easily on a physical exam.
- [113:17]
Dr. Paul Turek
The best way is easy physics. I don't order ultrasounds. If I can palpate it, then it's clinical.
- [113:22]
Peter Attia
That's an office repair.
- [113:24]
Dr. Paul Turek
It's an outpatient surgery. Takes an hour. We do micro surgery.
- [113:26]
Peter Attia
Oh, it is. Okay.
- [113:26]
Dr. Paul Turek
Yeah.
- [113:27]
Peter Attia
So it's more involved than a vasectomy.
- [113:29]
Dr. Paul Turek
Yes, it is. And you're doing it at microsurgery, at the level where you don't cut muscle. You want him to recover quicker. It's an involved area with lots of veins.
- [113:36]
Peter Attia
But he's not under general.
- [113:38]
Dr. Paul Turek
I use twilighty twilighty sedation.
- [113:40]
Peter Attia
Yep.
- [113:40]
Dr. Paul Turek
So that's the most common thing.
- [113:41]
Peter Attia
That's the most common thing. Wow.
- [113:43]
Dr. Paul Turek
And most men are fertile. But so again, you look at the semen analysis as a poker hand and you see count and motility being down, nothing else going on. And you see a varicocele and it's implicated.
- [113:53]
Peter Attia
All right, have we missed any other of the major.
- [113:55]
Dr. Paul Turek
Yeah, I'd say the major ones are varicocele. And then I would look for hormonal issues. So alvaricosils may be 40 hormonal, maybe 10 or 15. Genetics.
- [114:03]
Peter Attia
So they're non modifiable now.
- [114:05]
Dr. Paul Turek
Right.
- [114:05]
Peter Attia
Okay. So you talked about a few of those already, what are some other ones? On the genetic side?
- [114:11]
Dr. Paul Turek
The most common one is for zero sperm is Klinefelter is extrax chromosome. The most common one for low sperm count is Y chromosome deletions. This is an interesting area.
- [114:20]
Peter Attia
What does that phenotype look like?
- [114:22]
Dr. Paul Turek
No phenotype in general. Yeah, no phenotype. Normal.
- [114:26]
Peter Attia
A Y chromosome deletion male.
- [114:28]
Dr. Paul Turek
Yeah. Because it's only the long arm and it's only a couple of floors on the building, there's regions that are missing.
- [114:34]
Peter Attia
I see. Okay. I'm sorry, I thought you meant a complete deletion of the Y chromosome. Yeah, yeah, got it.
- [114:38]
Dr. Paul Turek
So it's the long arm and deletions regions. Yeah, Rhym deletion. You're right. So Rene riopera, found at MIT 20, 30 years ago. Now that the Y chromosome is a hall of mirrors. And in meiosis every chromosome has a partner except the Y and the X and a man. The Y plays with itself, it combines with itself. Instead of finding a partner, it has to do the dance too. And so it changes a lot. So it's very adaptable. It actually comes from the X through evolution. So there's a lot of X genes that are on the Y and the Y. We thought it was sort of a wasteland, maybe hairy ears and tooth decay and things like that, but now it's probably more important. So there are regions on the long arm of the Y. The short arm, Y is very important. Has a gene called sry, which makes you male. The SRY is the male sex determining gene. If you have that gene, your phenotype will be male. If you don't have that gene, you're probably going to be female. It's complicated now, but that's sort of what it is. But the long arm has these genes that control fertility and some of them. So typically we ordered in men with a low sperm count of below 5 million. So that would be a pretty common cause of a sperm count lower than 5 million. And I published a study that if you have a Y chromosome deletion and you have a varicocele and they both cause low sperm counts and you fix the varicocele, you're not going to improve because it's non modifiable in all ways. It's who you are. But if you didn't have the bichromosome deletion and you fixed the varicose, you'll expect a good response. Two thirds will improve, one third or more will conceive naturally. So you could take guys with low sperm counts. And you can fix them or not, but the driver's genetics and the phenotype in offspring is simply inherited as a Y chromosome deletion. It'll either be, I just had a couple from Texas actually. He had a Y chromosome deletion. He conceived with help of technology with low sperm count. Sons have it, they have no sperm. So you can inherit the deletion, but it might increase. So you're gonna get what your dad had. Or it might be worse because mutations tend to get larger and until they.
- [116:36]
Peter Attia
Try to conceive, they would never know this. Everything else is normal, Right?
- [116:40]
Dr. Paul Turek
So then there's environmental lifestyle things. So I think obesity is a big one.
- [116:44]
Peter Attia
And do you think that that's mostly propagated through the endocrine system then?
- [116:47]
Dr. Paul Turek
Yeah, that's a big one in terms of the percent of sperm with the lifestyle issues. And then lousy diet is probably something that. So obesity and diet, lifestyle, recreational drugs, what else do I review with them? Toxic exposures at work. So any smelly solvents? I'm really worried. Some airport fuels, airline stuff, machine shop oils, anything. Benzene derivatives used to be pesticides and stuff like that, but they're pretty well controlled. So environmental exposures are kind of an unknown. I think viruses have a role. Saw you recently wrote about hpv, and I've been thinking about that for years because there are men. It used to be half the men who came in. When I entered the field 30 years ago, we didn't know what was going on with them. But now it's probably like 10 or 20% with lifestyle issues and stuff like that, you can pretty much sort it out. It's not that unknown. But there are men who are like, what is going on here? He's a perfectly healthy guy. Practicing in California is incredible because everyone's so healthy. You have to look elsewhere, you have to ask other questions. And when there's obesity, it's always the elephant in the room. But everyone is so healthy and eating. So I get to poke around places where no one else goes because I have to explain it and there's nowhere to go. But I did a study. So HPV is the most common. You wrote about that. Is that. What's the link? It's hard to know. There's herpes, very common. The STDs that we know about, like the 11 common beasts, chlamydia and gonorrhea and syphilis, those we know a little more about, and they're pretty obvious. But some of these trichomonas and stuff are pretty subtle. I was really concerned about this because one guy 20 years ago now is a professor at UCSF. He sent me a picture of electron photograph of a sperm with a. A hexagonal herpes virus in it. And I don't even know if it's photoshopped, but there's this virus in a sperm. Like, yeah, it looks like there's a virus in that sperm. You think that's what's causing it? I said, I don't know. I don't know. But normally when you see infections as a cause, viral or bacterial, as a cause of semen analysis, you'll see pus cells. So you'll see what's called pylospermia, leukocytospermia, the round cells we talked about. And the semen analysis will show up in higher numbers. They tend to be destructive and they tend to lower motility. So you tend to see a certain look to the semen analysis. Volume, normal count, motility is really low. A lot of the sperm are dead because they've been wiped out by these cytokines and all the white cells. And then maybe you'll find the pathogen somewhere, maybe not. But culturing mycoplasma, CMV, all these viruses. So Joe Derisi, really bright guy at UCSF, won a MacArthur Award. He took my patient semen. This is back when microwaves were popular in the 2000s, and he had like 2000 all mammalian viruses on his chip, everything. And we ran fertile guys and we ran infertile guys and looked at semen, not sperm. And 99% of the infertiles were positive for something, and 98% of the normals were positive for something. So ubiquitous was the word. And so it left us high and dry because you can't really do much with that. So it's out there. But I do agree with your assessment that the pathologic phenotypes, the worst ones, are probably doing something. The question is, how do we measure it? What do we look for? And with semen analysis, as I said early on, it's a blunt instrument. It varies a lot. It's tough to do it. But I love whether we do genotyping on is it in sperm? Probably not. I don't know. And when you look at hpv, it's probably one of those things that might be in the ejaculate after ejaculation might be coming from another fluid source and not in the sperm itself. So its effect would be post ejaculation, which could still have a fertility effect, but it won't be probably as deep.
- [120:16]
Peter Attia
And what if, for example, a guy has prostatitis and the prostatic fluid has pus in it? Pus in it. Then that could sabotage the whole thing.
- [120:24]
Dr. Paul Turek
Right? I mean, the problem with the male system is it's all through the same tube. So urine comes through that tube and semen comes through that tube. So you have to look for infections in the urinary tract and anything like that when you're doing fertility. Because pus cells kill whatever they see.
- [120:37]
Peter Attia
Yep.
- [120:38]
Dr. Paul Turek
So if your urine's infected, that's a big deal.
- [120:41]
Peter Attia
Have you done work with intra testicular PRP and stem cells?
- [120:45]
Dr. Paul Turek
Just stem cells, but not prp. Not a big fan. As a trained stem cell biologist and someone trying to make sperm from skin and working with some of the best stem cell scientists in the world, I have a lot of respect for them, but it's not that simple. There's 560 offshore stem cell companies in the world that will take your money and do things like stick PRP in there. They'll stick bone marrow aspirates fat in your testicle. And I'd say my experience has not been favorable. Some of the toughest cases in the world and they come to me after that and I do my techniques and I don't find anything. And the trials aren't really real. Come here, we're going to do this and then we're going to do a microdissection on your testicle. But they didn't have one beforehand. So the chance of it finding it even without that is X and they're finding X. So it's just not well done. And I have my patients investigate all that. And I say you do the work, you tell me who you found, let me call them, let them be the workers. And then I'll call them and I'll say, hi, I was just wondering about do you have any papers or what's the science behind it? And they usually hang up or it's really interesting, but so far I'd say it's unfounded.
- [121:51]
Peter Attia
Yeah, I've had a very similar experience with a few of my friends and patients who have wanted me to talk with some of their stem cell docs.
- [121:59]
Dr. Paul Turek
You're pretty evidence based, Peter.
- [122:01]
Peter Attia
Well, yeah. And so I accept the fact that they're not going to have remarkable peer reviewed data, but it is amazing at how few individuals can provide even one cell layer of scientific reasoning. It's a topic I'd like to explore more deeply on the podcast My guess is there are some indications for where it makes sense.
- [122:22]
Dr. Paul Turek
I agree with that.
- [122:23]
Peter Attia
But, boy, I'd like to figure it out without people wasting so much money.
- [122:27]
Dr. Paul Turek
There's a there there, but it's just not that easy.
- [122:30]
Peter Attia
Yeah. Let's just say for every hundred guys that walk in your office who are struggling with infertility, what percentage of them will be able to conceive? Assuming they are able to fully comply with the prescriptions that you provide, be it lifestyle or pharmaceutical, for example, hormone modulation, et cetera, without requiring. And let's exclude the 40% varicoceles. Cause you're gonna fix those guys, and they're fine. So a hundred people who don't have a varicocele, who don't have a genetic condition. I'm going to really simplify this. Okay, so these are a hundred guys that presumably have showed up with some iatrogenic reason for infertility. How many of those guys are going to be able to conceive without resorting to ivf?
- [123:18]
Dr. Paul Turek
I would say that's the goal of my practice. And I would say the answer is most.
- [123:22]
Peter Attia
Wow.
- [123:23]
Dr. Paul Turek
But the caveat is, you got to tell me about the woman, because I will defer. This is the only data I can give you. So I did a paper where I saw men for their infertility evaluation, got it done, and I thought they were fine. They had varicoceles and stuff, but their semen analysis was normal. And my investigation of their risks, lifestyle, everything was good. And I said, you're fine, you're cleared. No one's ever said that before. And they went home and they said, Turek couldn't figure out what was wrong with us. I said, that's not what I said. I don't do women, my expertise. I'm saying something positive here. Most people would say, I'm not sure why you're not conceiving. I said, I'm pretty sure you're not the problem. Didn't get interpreted like that. That got me a little angry. So I did a study with usc and I took these men that I cleared, and I called them up a year later. And I said, what happened last year after Turek cleared? You had a resident do this? And the answer was 65% had conceived naturally. Another 15 to 20% conceived with IUI or IVF. These women were 35 years old, year and a half, infertility. They weren't going to wait around. Most conceptions occurred within six months. I didn't do anything for them. I didn't fix Their varicoceles. I didn't touch them any medication. I just said, you're fine. So I published it as a lifestyle study. Not that I was right. And the idea was they probably made changes. They probably took a nutritional supplement. They probably timed their sex better. They probably got out of hot tubs and all that stuff and they were taking pills. I have a list of what they did. I had a table in that paper that said that 65% natural pregnancy rate that is higher than anything I can offer as a treatment that we have published on. So if you fix their varicocele or you rarely get a 65% natural conception rate. So I had a table of all the published conception rates for the technologies that work. And I'm saying this is even better. So if that addresses your question, that's the only data I have. Okay.
- [125:12]
Peter Attia
What advice do you give a guy who comes in your practice? Maybe you don't see a lot of these guys, but let's say you get a guy who comes in and says, hey, look, I want to bank my sperm. I want to freeze my sperm. Now presumably you'll get a lot of that if a guy's undergoing therapy for cancer or something like that. Is there anything a guy needs to know? And would you recommend a guy do that if he's 40, doesn't have a partner, but says, look, I want to have kids? And isn't there something to the idea that my sperm are better today than they will be in a decade?
- [125:38]
Dr. Paul Turek
It's a huge issue. Paternal age, paternal age and fertility. Paternal age. So we can go there. But I don't place value judgments. I say, good idea. A disclosure. I'm on a board of legacy. I love their mission driven. I like the fact they're going for military and exposed patients and this and that and va. I'm for that. I think it's the lowest hanging fruit in the field, obviously for cancer survivors and things. I don't care what you think might happen with your cancer. I would still bank it. I started a nonprofit called Banking on the future. 16 year olds to 21 year olds with cancer. We'll do it for you, we'll pay for it. Five years, Just give us a sample because it's so much harder afterwards or not.
- [126:17]
Peter Attia
So you would advise any male that hasn't reproduced and who might want to, who's undergoing any chemotherapy for any cancer, just play it safe.
- [126:25]
Dr. Paul Turek
Bank for cancer. Yes. Now, should anyone do it for any reason? Probably not. But again, I don't pass the judgment if they're worried about something, then they should.
- [126:34]
Peter Attia
What paternal age do you worry about?
- [126:36]
Dr. Paul Turek
You look at national guidelines for sperm donation. 40 is considered older paternal age. 50 for sure. If you look at risks to offspring, miscarriages, stillborns, autism, birth defects, things immediately related to conception, prematurity, those go up with paternal age. Then you look at birth defects when they're born, those go up, up one to twofold. And then the worrisome ones are the single gene defects and the epigenetics, like psychiatric morbidity. So the autism, schizophrenia, dyslexia, bipolar disorder, potentially Alzheimer's in offspring. And they're not detectable young. So big issues. I've written a lot about that, published on it. I was actually having my second child at 50 when I was writing this thing. Should I be doing this, writing a paper on all these risks and with Alan Duchenko from University of Pittsburgh. But I think it's a hockey stick curve for wrist to offspring.
- [127:32]
Peter Attia
And you think the inflection is 40 or 50?
- [127:35]
Dr. Paul Turek
I think it's more like 60. I think there's a slow linear increase in risk to offspring from 25 to 50 or 60. And then there's an inflection and then there's the blade of the stick. And I think that's logarithmic. Same curve as women with chromosomal.
- [127:51]
Peter Attia
Yeah, but they're shifted 20 years earlier or something like that.
- [127:54]
Dr. Paul Turek
Yeah. So it's a shorter curve, but the same thing. 40, 38 to 40. It's kind of a point where things really ramp up with chromosomes. The men's stuff is not chromosomal. If you take the curves together, they're different spans, same shape. But I think the female curve is on top of the male curve. This is not the same relative risk. So women, you go from 25 to 40, your chance of a miscarriage. Oh, it's chromosomal. It goes up quite significantly after that. Very significantly. And the consequence of women's issues with offspring related health is basically miscarriage in many ways.
- [128:31]
Peter Attia
It's almost easier to detect.
- [128:32]
Dr. Paul Turek
Very. They've been doing it for years.
- [128:34]
Peter Attia
It can be more dramatic and now.
- [128:36]
Dr. Paul Turek
Prevented with pre amputation genetic testing. Men are different. You can't detect these things. They're single gene mutations. The machinery is constantly working. It's getting old. The quality control of the process goes down and little gene mutations get in there that are always being spun off in the heat of the engine. They're not getting vetted, so the machinery is not doing a good job. So they're getting through and they're not going to be lethal, they're going to be deleterious. So that's where you get things. And autism's a classic one, paternal age related. Looks like that's the biggest risk factor for it. And that worries me a lot. So the facts are that human evolution is entirely driven by sperm, because eggs are just sitting there correcting the problem. It's entirely driven by sperm. And so 50 mutations a year a generation usually gets spit out based on a nature paper, probably between generations. And there's always mutations occurring in 14 year old fathers, but it goes way up with 60 year old fathers. So the rate of mutations goes way up with age, but it averages 50 over a reproductive life. And most of them, half of the mutations that we are throwing off as a species are not ears or hands or feet or height. It's all neurodevelopmental. It's like half neurodevelopmental. So when you think about what we're seeing, you know, the Martians from the fifties and the movies with big heads, that's kind of where we're headed. It's autism, dyslexia, bipolar disorder. These are neural developmental neurodegenerative issues. And why is that? Well, that's what's going on. I mean, that's where we're being stimulated. That's where we're being asked to evolve. Look at the last 30 years. Funny, one of the biggest investors in Salesforce said to me, I realized I was dyslexic when my son was born. And I said, really? He said, yeah, but you know what? It helped me be the man I am to realize that Salesforce is going to fly. Gave him the first 500,000, gave him the first million, they never took any more money. And he said, it let me focus. So autism is one of those where you put out, you ignore a lot of input and you find the gift. And it's amazing if you go down the rabbit hole of what they're good at. It's like their whole brain trust is there. So is that a disease or is that where we're headed?
- [130:43]
Peter Attia
I mean, I think it exists on a spectrum. I think anyone who's probably spent time with kids using ASD as an example, boy, mild versions of it, the way it can be defined because it really has three categories now in the DSM 5. I think the mildest version probably comes with more superpowers than limitations or maybe equal amount. But clearly the more severe it gets. That's pretty debilitating. This idea of Paternal aids.
- [131:07]
Dr. Paul Turek
We're calling it disease though. Yeah, but maybe it's not disease. Maybe it's where we're headed. Maybe it's the future. Maybe the non sequiturs that come out of those brains look at who's changing the world right now, at least in Silicon Valley.
- [131:18]
Peter Attia
Yeah, but again, I would argue most of those people would be in category class one, not class three.
- [131:23]
Dr. Paul Turek
Anyway, something's like that.
- [131:24]
Peter Attia
What's the thaw success rate? So if a guy is 40, he goes ahead, he freezes and banks his sperm, assuming they were good to go in, are they? Very high probability of thawing correctly.
- [131:36]
Dr. Paul Turek
So when you freeze sperm, it's about a 200 year old process, regularly used for about 75. I forgot who the Italian scientist was who froze sperm in snow and then thawed it and it was alive a couple hundred years later after Leeuwenhoek came up with a microscope, they found it was moving and it was possible. So egg thawing is very new. Egg freezing and thawing is very new. This is very old. So everyone is thinking about sperm now because eggs are being frozen left and right. But this is much older technology and the cell is much hardier than an egg, so it does a lot better. Typically when you freeze it, it's the freezing process that kills sperm, be from icicles on the inside. And then while it's frozen, there's usually no issue. And then there's another problem. When you thaw, rapid to temperature shift. So that's where the kill rate comes from. In a good sample, half of it should survive.
- [132:21]
Peter Attia
Okay, so how much sperm would you tell a guy to bank if he has to do it? If it's the definitive samples for his life. So, meaning he's 40 or he's about to undergo chemotherapy or some other exposure where he should just assume he will not have normal sperm. Again, what do you tell him?
- [132:41]
Dr. Paul Turek
So I usually say, depending on what technology you're going to use, but if your sperm counts normal, three ejaculates is one kid's worth of sperm with insemination technology where you would thaw it and then Turkey based it.
- [132:53]
Peter Attia
So 10 ejaculates for three shots on goal for three kids, potentially for three.
- [132:56]
Dr. Paul Turek
Kids with low technology. But 10 ejaculates will give you most of China with IVF.
- [133:01]
Peter Attia
Got it. Oh, when you say low technology, you mean IUI or something like that.
- [133:04]
Dr. Paul Turek
So there's three levels, sex, no tech. High tech is ivf and in the middle is iui. That's the stuff that's turkey Basting, it's relatively straightforward, relatively cheap. I see three kids for that. But plenty of sperm for ivf.
- [133:16]
Peter Attia
So three ejaculates would be more than enough if they're normal for ivf.
- [133:20]
Dr. Paul Turek
Yeah. So the population you're talking about, maybe cancer survivors, half of those will not be normal. They're really looking at ivf.
- [133:26]
Peter Attia
Yep.
- [133:26]
Dr. Paul Turek
So they don't need that many, but I'd say three is a good number. But it's an insurance policy.
- [133:30]
Peter Attia
Yeah.
- [133:30]
Dr. Paul Turek
Right.
- [133:30]
Peter Attia
Okay. Well, Paul, this has been a super interesting tour through the world of male fertility. I can honestly say I knew very little about this coming in. Some of this stuff I understood pretty well, the hormone stuff, but boy, a lot of this stuff I had no idea. So I will be studying my notes from this. We're going to link to a lot of the stuff you've created. You've got a lot of great content out there, so we'll make sure people know where to find you.
- [133:55]
Dr. Paul Turek
Yeah, a podcast, too.
- [133:55]
Peter Attia
Tell me about that.
- [133:56]
Dr. Paul Turek
Well, we started a podcast last year because of the blog of 15 years. And we're just doing timely topics. And it's me and my associate Rob Clyde, who's a director in Hollywood, and we're going to be the Anthea Bourdain of Men's Health. We're going to just take on the topics testosterone, et cetera, penis myths, and just talk about stuff that everyone is asking questions about but no one's talking about. And like you, data driven answers.
- [134:18]
Peter Attia
Okay. And what's it called?
- [134:19]
Dr. Paul Turek
Talk with Turek on all channels.
- [134:21]
Peter Attia
Got it. Okay. We'll make sure folks know that you have a clinic that you run up and down the coast of California. So obviously we'll make sure folks know how to find you there. But presumably, I think we've given folks a roadmap for their local urologist as well, if they're getting the workup. Basically, it sounds like if you're being worked up for fertility with your urologist and they're not going through the steps that we've described, maybe you should find somebody else.
- [134:46]
Dr. Paul Turek
Yes, I think it should be done. That's the first step. There's a lot going on now that the biomarker concept relates a lot to your views on Medicine 3.0. The paper came out two days ago looking at longevity based on the semen analysis in Danish den the Regulhasspartlatten in Copenhagen. They looked at 74,000 men over 50 years and found that those guys with, say, normal semen quality lived three years longer. All causes than men with low sperm counts when they were younger. This was a single payer system, so they have all the data on it. It's very much a landmark study. So if you ask me what excites me about the field, I would say as the author of the biomarker concept, early in my career, I would say I'm really happy that we're scaring couples to realize that their fertility is a measure of their health. And now we have our foot in the door. If we can get a sperm count and get them in the office, we can actually tell them a little bit about their trajectory. And that's getting more and more every day. And we've never had a chance to do preventative medicine with young men. So it's a men's health play in a big way because their partners are bringing them in, but who cares? They're in the office. Your father had prostate cancer when he was 50. Someone had colon cancer in the VA. So I have now an NP Molly Jessup, who is medical. And it's like, okay, there's metabolic stuff and you can pick up diabetes. And we have an opportunity here we've never had ever, is to get men at younger ages. And I was a professor at UCSF for 15 years in Dow chair. I left and I went to Yosan University, Traditional Chinese medicine. I lecture there now. We had a conference last week and I lectured and I liked it because I thought Western medicine, maybe your view too is too reactive. They're always trying to get men out of trouble or get patients out of trouble. But we're not thinking about getting them from unhealthy to healthy, which is the preventative aspect. We're just not very good at it. Your general surgery, every example you give is a guy did something bad, you get him back, whatever. But you got to think, next step. Like kidney stones. Great urologists, we treat them all day. It's fun. It's endoscopic, it's lasers, it's shockwaves. But what are we doing about that stone? I mean, how come we're not preventing these more? It's not on the radar. I go to Yosan University in traditional Chinese medicine. Fabulous place, and it's all holistic. So I see patients who get referred by acupuncturists, and they come in, their diet's under control, their stress is under control, they're doing acupuncture, they're sorted out, and what do I find? Varicoceles, because they don't find those. But the phenotype is totally different than the Western referral. I've loved that because that's 3.0. That's medicine 3.0, which they're doing. They've been doing it for 4,000 years. And it's interesting how we don't give a lot of street cred to it, but in my view, much of we don't understand about fertility. Certainly men, possibly women, is epigenetic. And the drivers of epigenetics, which are marks on the DNA, not DNA mutations. 50 DNA mutations a generation doesn't explain it. There's other stuff going on. Epigenetics is all lifestyle and diet driven. It's all lifestyle and diet driven. It's everything in your book.
- [137:45]
Peter Attia
Well, Paul, very interesting stuff. Thank you again for making the trip out here. Thanks for sharing your insights.
- [137:51]
Dr. Paul Turek
It's been great. Yeah. All right. Thanks, Peter.
- [137:54]
Peter Attia
Thank you for listening to this week's episode of the Drive. Head over to Peteratti md.com shownotes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram and Twitter, all with the handle PeterAttiaMD. You can also leave us review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional healthcare services, including the giving of medical advice. No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or Advise, please visit PeterAttiamD.com about where I keep an up to date and active list of all disclosures.