#351 ‒ Male fertility: optimizing reproductive health, diagnosing and treating infertility, and navigating testosterone replacement therapy | Paul Turek, M.D.

View the Show Notes Page for This Episode https://peterattiamd.com/paulturek/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250602-pod-paulturek&utm_content=250602-pod-paulturek-podfeed Become a Member to Receive Exclusive Content https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250602-pod-paulturek&utm_content=250602-pod-paulturek-podfeed Sign Up to Receive Peter's Weekly Newsletter https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=250602-pod-paulturek&utm_content=250602-pod-paulturek-podfeed This is part one of a two-part mini-series on fertility and reproductive health, with next week's guest, Dr. Paula Amato, focusing on the female side of the equation. Paul Turek is a world-renowned expert in male fertility and reproductive health, the founder and medical director of the Turek Clinic, and host of the Talk with Turek podcast. In this episode, Paul explores the topic of male fertility, offering a detailed look at the complex and highly coordinated process of conception and the many challenges sperm face on their journey to fertilizing an egg. He shares fascinating insights into how sperm work together to navigate the female reproductive tract, how environmental factors like heat, stress, and toxins impact sperm quality, and what men can do to improve their reproductive health. Paul also dispels common myths about testosterone replacement therapy and its effects on fertility, providing strategies for preserving fertility while on TRT. The episode also highlights cutting-edge advances in reproductive medicine, from genetic testing and sperm sorting to emerging treatments for infertility. We discuss: The incredibly complex and hostile journey sperm must take to fertilize an egg [3:00]; How sperm are made: meiosis, genetic variation, and the continuous renewal influenced by environmental factors [9:00]; The built-in filter that weeds out genetically abnormal sperm [14:45]; How sperm are finalized in form and function: tail formation, energy storage, and chemical sensing abilities [18:30]; How to optimize conception through the timing of sex, ejaculation frequency, and understanding the sperm lifecycle [26:30]; Male infertility and Paul's diagnostic approach: detailed history, a physical exam, and identifying red flags [33:30]; Viral infections that can affect the testes and potentially lead to sterility [40:30]; Semen analysis: morphology, motility, and hormonal clues to male fertility [45:45]; Effects of medication, microplastics, stress, and exercise on fertility [57:15]; Testosterone replacement therapy (TRT) and male fertility [1:06:00]; Restoring fertility after prolonged use of exogenous testosterone [1:25:00]; Effects of heat and cold exposure on fertility and sperm quality [1:36:00]; How different levels of exercise—especially cycling—affect male fertility [1:41:45]; How alcohol, marijuana, and nicotine affect male fertility [1:46:00]; Why type 2 diabetes is a risk factor for male infertility [1:50:00]; How varicoceles—a common cause of male infertility—are diagnosed and treated [1:51:15]; Genetic factors that affect fertility [1:54:00]; The impact of lifestyle and environmental exposures on fertility [1:56:30]; The evidence (or lack thereof) behind stem cell and PRP therapies for male infertility, and how lifestyle and non-invasive interventions often lead to successful conception [2:00:30]; Considerations for sperm banking, and how paternal age impacts fertility planning and offspring health [2:05:00]; Semen quality as a biomarker: linking male fertility, longevity, and preventative health through Medicine 3.0 and epigenetics [2:14:45]; and More. Connect With Peter on Twitter https://twitter.com/PeterAttiaMD, Instagram https://www.instagram.com/peterattiamd/, Facebook https://www.facebook.com/peterattiamd/ and YouTube https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:11Dr. 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 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 the subscription.

• 0:54Dr. Peter Attia?

  If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe.

• 1:04Dr. Peter Attia?

  My guest this week is Dr. Paul Turek. 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 mini-series 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 Turek podcast. In this episode with Paul, we explore the intricate

• 1:47Dr. Peter Attia?

  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. Paul shares insights into male fertility, including how sperm function in coordination to navigate the female reproductive tract. We discuss-

• 2:10Dr. Peter Attia?

  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

• 2:54Dr. Peter Attia?

  and reproductive health, this one with Dr. Paul Turek.

• 3:03Dr. Peter Attia?

  Hey, Paul. Thank you so much for coming out to Austin.

• 3:05Speaker 01

  Peter Attia, the man, the myth, the legend. I am so excited to be here.

• 3:09Dr. 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?

• 3:50Speaker 01

  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.

• 4:30Dr. Peter Attia?

  Based on the size of the sperm.

• 4:30Speaker 01

  After 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 in humans are sticky.

• 5:12Dr. Peter Attia?

  By the way, is there an evolutionary explanation for that phenomenon?

• 5:15Speaker 01

  I have no idea.

• 5:17Dr. Peter Attia?

  Yeah.

• 5:17Speaker 01

  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 a hundred million sperm may start out, maybe five million make it through the first barrier, which is the cervical barrier. The vaginal fluid is acidic.

• 5:52Dr. Peter Attia?

  How acidic?

• 5:53Speaker 01

  Five, pH of five and the semen is a pH of seven. 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 five million will make it. One out of 20 makes it through the cervix, then a hundred make it to the fallopian tube and then one will make it to the egg.

• 6:12Dr. Peter Attia?

  Literally only a hundred?

• 6:14Speaker 01

  Right. And the Setlaj 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. Technology from five 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.

• 6:48Dr. Peter Attia?

  Yeah.

• 6:48Speaker 01

  So it's the Phelps sperm that's going to make it.

• 6:50Dr. Peter Attia?

  Right.

• 6:51Speaker 01

  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 phalanges. 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.

• 7:11Dr. 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?

• 7:19Speaker 01

  There's T cells, B cells and antibodies.

• 7:21Dr. Peter Attia?

  It's a full immune response.

• 7:23Speaker 01

  Absolutely.

• 7:23Dr. Peter Attia?

  So it's a specific immune response.

• 7:25Speaker 01

  Anything foreign.

• 7:26Dr. Peter Attia?

  Wow.

• 7:27Speaker 01

  And there's also a mucus plug that exists for 28 days a month to prevent anything from going through because 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 it 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 and the immunoglobulin because that's what antibodies bind to. So the female antibodies bind to that and we don't know how many phalanges go through, but then it's like a run up the middle and then eventually a couple of sperm are forth, make it.

• 8:11Speaker 01

  And the immune system's deactivated and they get there. It's wild. And that can be measured now and there's actually going to 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 ejaculates, 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.

• 8:48Dr. Peter Attia?

  Let's go through those numbers one more time. About 100 million ejaculated.

• 8:52Speaker 01

  At the cervix.

• 8:53Dr. Peter Attia?

  5 million get through.

• 8:54Speaker 01

  To cervix, into the uterus.

• 8:55Dr. Peter Attia?

  Yep.

• 8:56Speaker 01

  100 to 500 get to the fallopian tube and one gets to the egg.

• 9:01Dr. Peter Attia?

  Wow.

• 9:02Speaker 01

  Why do you need so many sperm? The classic answer 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.

• 9:10Dr. 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?

• 9:25Speaker 01

  So the testicle makes 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 produce, you want it all to 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.

• 9:56Dr. Peter Attia?

  But it's not always the same half.

• 9:58Speaker 01

  Correct. It's loosey goosey. It's not the same as when it started.

• 10:02Dr. 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 post-bac 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.

• 10:47Dr. Peter Attia?

  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 myosis 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 myosis, I'm like, these guys, they just misspelled it idiots. It's mitosis, mitosis, mitosis. Finally, on the night before the exam, which I still remember, August 17th was the day I took the test. I realized they were two totally different things.

• 11:25Speaker 01

  Big things.

• 11:26Dr. 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 myosis is in the creation of an egg or a sperm.

• 11:57Speaker 01

  That's right.

• 11:58Dr. Peter Attia?

  Okay. Now, remind me, are women born with all of their eggs? I feel like that's something I vaguely remember.

• 12:03Speaker 01

  Five million eggs at conception, one million eggs at birth, and you basically ovulate a thousand in your lifetime.

• 12:09Dr. Peter Attia?

  Okay.

• 12:10Speaker 01

  So by the time you're 45, you're out of eggs. You actually ovulate one a month, but you actually produce 10 a month. So you lose 10.

• 12:17Dr. Peter Attia?

  For every one.

• 12:18Speaker 01

  Right. So a lot of waste, but they're stuck in a stage of perpetual space where they're just bong. 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.

• 12:33Dr. 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?

• 12:40Speaker 01

  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.

• 12:47Dr. Peter Attia?

  Yeah.

• 12:48Speaker 01

  Cause 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.

• 13:02Dr. Peter Attia?

  That's an interesting point.

• 13:03Speaker 01

  So it's transgenerational.

• 13:05Dr. Peter Attia?

  Does that mean that the father is more likely to pass on environmental stressors than the mother?

• 13:10Speaker 01

  Probably, yeah. And that's definitely been shown.

• 13:13Dr. Peter Attia?

  Hmm. 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?

• 13:21Speaker 01

  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 in 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.

• 13:50Dr. Peter Attia?

  It's pluripotent?

• 13:51Speaker 01

  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.

• 14:03Dr. Peter Attia?

  Is there any other cell in the body that is capable of that?

• 14:05Speaker 01

  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.

• 14:26Dr. Peter Attia?

  And a man potentially has access to this cell his entire life?

• 14:29Speaker 01

  Mm-hmm. Yep. As long as he's making sperm. So that starts out and it usually reproduces mitotically and then puberty, it'll go down the path of meiosis, which is a couple of steps more than, is mitosis involved with meiosis? But it's the having 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. You don't really think about that. But we could have a long talk about genetics versus epigenetics.

• 14:56Dr. 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 anaploidic sperm? And explain maybe to people what anaploidia is and what's the process by which that thing gets discarded?

• 15:16Speaker 01

  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're still being made. They're just off because it doesn't really click the system to negate it. We don't know at what level of chromosomal abnormalities the system will say this is not.

• 15:35Dr. Peter Attia?

  This is absolutely defective. Yeah.

• 15:37Speaker 01

  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 duct 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 threefold higher.

• 16:15Dr. Peter Attia?

  So something is getting filtered.

• 16:16Speaker 01

  So there's a filter.

• 16:16Dr. Peter Attia?

  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.

• 16:25Speaker 01

  Right.

• 16:26Dr. 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.

• 16:36Speaker 01

  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. And a guy with infertility, it might be 95%. Here's an example. If you have a patient with Kleinfelter syndrome, a male with an XX chromosome in every cell in their body, or a transgenic model with that feature.

• 17:14Dr. Peter Attia?

  So this is a man who's XXY instead of XY.

• 17:18Speaker 01

  So 47 chromosomes, not 46.

• 17:19Dr. Peter Attia?

  Yep. And phenotypically, he kind of has a distinctive look, right?

• 17:24Speaker 01

  10% of the time.

• 17:25Dr. Peter Attia?

  Oh, really? 90% of the time, a man with Kleinfelter's, you'd never know?

• 17:29Speaker 01

  Yeah.

• 17:29Dr. Peter Attia?

  Okay.

• 17:30Speaker 01

  So that's the board question.

• 17:31Dr. Peter Attia?

  That's the board question, right.

• 17:32Speaker 01

  The MCAT question.

• 17:33Dr. Peter Attia?

  Yep, yep.

• 17:34Speaker 01

  All right. So in these men, if you look at their sperm aneuploidy, right? So every cell in their body, and in the mice, in the transgenic mice, all have an XX chromosome. Only about 10% will have it in the sperm.

• 17:46Dr. Peter Attia?

  Meaning they will produce an X or a Y sperm.

• 17:49Speaker 01

  Just like everyone else.

• 17:49Dr. 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?

• 17:56Speaker 01

  Don't think we know that. That's math.

• 17:58Dr. Peter Attia?

  Yeah.

• 17:58Speaker 01

  That's math, yeah. Biology is not math, remember? And I had two client fentanyl patients yesterday that I operated on and they're not doing preamputational genetic diagnosis of the embryos that they're going to create from their sperm because the chance is not that high. So it goes from, in mice, 0.1% chance of normal men having an XXY sperm, or an aneuploid sperm, an abnormal sperm, to 1%. In humans, it goes from 1% or so to 10%.

• 18:27Dr. Peter Attia?

  Hmm.

• 18:28Speaker 01

  But 90%, that's remarkable.

• 18:29Dr. Peter Attia?

  That's amazing.

• 18:30Speaker 01

  It's remarkable how efficient this is.

• 18:32Dr. 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 whole process.

• 18:37Speaker 01

  It's all done in the testicle.

• 18:38Dr. Peter Attia?

  Yep.

• 18:39Speaker 01

  It's an amazing machine. Weird question we should maybe get to is why is it out in the breeze like that?

• 18:44Dr. Peter Attia?

  I assumed it was temperature related.

• 18:46Speaker 01

  Why?

• 18:46Dr. Peter Attia?

  Why does it need to be a little cooler?

• 18:48Speaker 01

  Yeah, why?

• 18:50Dr. Peter Attia?

  I would guess, because I like to make 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.

• 19:06Speaker 01

  75 mitochondria per sperm. That's like, it's like an electric motor on each wheel.

• 19:11Dr. Peter Attia?

  Yeah, so that would be my guess is it's an overheating problem if you tried to keep those guys inside.

• 19:16Speaker 01

  And I think overheating could be translated to oxidative stress, which is a cause of a lot of infertility.

• 19:20Dr. Peter Attia?

  We don't know, is the answer.

• 19:21Speaker 01

  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.

• 19:28Dr. 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 sauna'd 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.

• 19:53Speaker 01

  So the complete sperm, spermatogenesis is the whole process. Spermogenesis 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 a 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.

• 20:14Dr. Peter Attia?

  Three weeks?

• 20:16Speaker 01

  Of the six or seven to make a sperm. Then it's complete and non-modal and it's packaged.

• 20:22Dr. Peter Attia?

  Give us some size comparison. Before the tail is on, what is the size of that cell?

• 20:26Speaker 01

  Probably similar to a lymphous, half the size of a lymphocyte or half the size of a red blood cell, a couple of microns.

• 20:33Dr. Peter Attia?

  And then the tail makes it now?

• 20:35Speaker 01

  Thirty-five 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 the tail wags. Remarkable. Three hundred genes control movement of sperm alone. There's mitochondrial DNA in there, all that stuff. It's just wildly compact, ten times more compact than any other cell in the body.

• 20:57Dr. Peter Attia?

  From a mitochondrial density standpoint?

• 20:59Speaker 01

  From a cytoplasmic standpoint and nuclear standpoint, it goes from histones to protamines. The DNA is condensed a lot more because it's got to go on the road. So it's got to 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.

• 21:20Dr. Peter Attia?

  Sorry, one other question. Where is the ATP or carbohydrate or whatever, the glucose stored in the sperm?

• 21:26Speaker 01

  Stored probably in the cytoplasm and in the tail.

• 21:29Dr. 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.

• 21:45Speaker 01

  That's right.

• 21:46Dr. Peter Attia?

  Yeah, it is a lot like a rocket, isn't it?

• 21:48Speaker 01

  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 thirty-five foot tubule with estrogen. And there's a lot of post-modification of the sperm.

• 22:01Dr. Peter Attia?

  The epididymis is thirty-five feet if you stretched it out.

• 22:04Speaker 01

  Roughly, yeah.

• 22:05Dr. Peter Attia?

  And just for folks listening.

• 22:06Speaker 01

  Seven hundred feet of tubules in the testes.

• 22:08Dr. Peter Attia?

  The epididymis is on the back of the testes.

• 22:10Speaker 01

  It's a comma shaped organ in the back.

• 22:11Dr. Peter Attia?

  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.

• 22:19Speaker 01

  Right.

• 22:19Dr. Peter Attia?

  Yeah.

• 22:20Speaker 01

  Epididymis has been relatively understudied, but it has actually become very important, epididymisomes. 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 fifties and sixties, 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.

• 22:43Dr. Peter Attia?

  Meaning based on its residence time within the epididymis?

• 22:46Speaker 01

  And what other environmental influences that occur there? Because the epididymis is not as walled off from the body as the testes is immunologically and otherwise. It's more susceptible to drugs, exposures, heat, et cetera. Testes is very walled off. Very little happens in the testes because the sertolos cells that line the tubules have a blood-brain barrier, blood-testis barrier, same as the brain. It's highly protected.

• 23:10Dr. Peter Attia?

  It's as protective?

• 23:11Speaker 01

  Yes. Harvey Cushing at Yale did that in the late 18th century, took brain-dead patients, injected them with dye, methylene blue, I think. The blood-brain barrier came about when it, nothing went into the brain and nothing went into the testicle. Two areas of the body that were completely immune from normal transport processes.

• 23:29Dr. Peter Attia?

  Wow.

• 23:30Speaker 01

  Blood-testis 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 learn how to smell.

• 23:49Dr. Peter Attia?

  Meaning there's basically a chemical signal that they need to be able to track to, which I'm assuming is the egg?

• 23:54Speaker 01

  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.

• 24:13Dr. Peter Attia?

  It has to go through that whole epididymal cycle?

• 24:15Speaker 01

  Once it's at the end of the epididymis where it's stored.

• 24:17Dr. Peter Attia?

  And that's how many weeks?

• 24:18Speaker 01

  Two, 10 to 14 days. 600 million sperm live in a bucket, a pot of soup to call an 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 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 the follicular fluid. So they know exactly where to go.

• 24:51Dr. Peter Attia?

  Again, it's, you have to wonder how many years it took to perfect this system, right?

• 24:56Speaker 01

  You do have to wonder.

• 24:58Dr. Peter Attia?

  Do we know what the chemoreceptor is?

• 25:01Speaker 01

  It was published in Nature recently and stuff like that. So it's really interesting. It's an olfactory type receptor. Yeah.

• 25:07Dr. Peter Attia?

  Do we have anything else that we can?

• 25:09Speaker 01

  Is there any smell, Peter?

• 25:10Dr. Peter Attia?

  Yeah. Is there anything like, what is the most noxious thing that we can smell with our nose? And at what concentration can we detect it?

• 25:18Speaker 01

  I have no idea.

• 25:19Dr. Peter Attia?

  Yeah. Cause I wonder, just for comparison.

• 25:21Speaker 01

  Give me a minute.

• 25:22Dr. Peter Attia?

  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.

• 25:46Speaker 01

  I think I would agree with that. And it also say that if you block a sensory bank of the five, you know, there's increased remarkably like braille. I'm a micro surgeon. 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. 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.

• 26:10Dr. 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?

• 26:20Speaker 01

  Half a billion.

• 26:21Dr. Peter Attia?

  Half a billion. So five ejaculations.

• 26:25Speaker 01

  Yep.

• 26:25Dr. Peter Attia?

  Okay.

• 26:26Speaker 01

  That's a pot.

• 26:27Dr. Peter Attia?

  And what's the time to rebuild that? What's the rate at which you fill?

• 26:31Speaker 01

  I don't know.

• 26:32Dr. 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've got to move it to every other day or whatever the number is.

• 26:48Speaker 01

  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.

• 26:57Dr. Peter Attia?

  To optimize.

• 26:58Speaker 01

  Right, but not for the semen analysis. That's for conception. Depends how old you are and 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. 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 the semen analysis. So we get a good stamp. I want it to be optimized one. And he looked at his partner. And she looked at me, she grabs him and says, you can't do that. He's every day. You 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 do you have sex? He said, twice a day, every day. I'm like, okay, that was great.

• 27:42Speaker 01

  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 point zero zero zero zero one three five six.

• 27:53Dr. Peter Attia?

  He divided once a year?

• 27:54Speaker 01

  Point zero zero weekly, one point zero zero one five five. Avogadro's number, right? Which meant he was so frustrated that.

• 28:02Speaker 01

  A beautiful way to say that was the point zero zero one three five five. 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.

• 28:17Dr. Peter Attia?

  There's a min-max curve that you're optimizing for.

• 28:20Speaker 01

  Right.

• 28:20Dr. Peter Attia?

  Which you would say is.

• 28:21Speaker 01

  Three days would be about right. When you're not going to gain that much, you're not going to 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 a 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 nine, 11, 13, there were significant pregnancy

• 29:06Speaker 01

  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 kid, don't react to it, predict in front of it. So front load the sex. Very important.

• 29:26Dr. Peter Attia?

  And why is that? Is that because?

• 29:29Speaker 01

  There's a reservoir effect in this uterus. It's managed sperm will survive for a day or two.

• 29:33Dr. Peter Attia?

  If ovulation is day 15, how could a day 11 sperm survive four days?

• 29:41Speaker 01

  It's nurtured once it's past the vagina.

• 29:43Dr. Peter Attia?

  But how many of them are surviving? Is it literally the lone wolf or is it the last 100?

• 29:48Speaker 01

  Maybe. Some of the sperm bind to the oviduct and wait.

• 29:52Dr. Peter Attia?

  Remind me where the oviduct is?

• 29:53Speaker 01

  So the uterus and the fallopian tubes.

• 29:55Dr. Peter Attia?

  Fallopian tubes?

• 29:56Speaker 01

  And that's the oviduct.

• 29:57Dr. Peter Attia?

  The oviduct is right below where the ovaries sit.

• 29:59Speaker 01

  Essentially, yeah. They bind to the endothelium and just park. As if there's no egg, they'll just sit there and they'll bind.

• 30:05Dr. 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.

• 30:14Speaker 01

  Right. Or a death star problem, right?

• 30:16Dr. Peter Attia?

  That's right. You've escaped the hostile environment, in this case of gravity.

• 30:20Speaker 01

  So now it's fun place. It's the right pH. It's warm.

• 30:22Dr. 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 seven, eight, nine, 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?

• 30:56Speaker 01

  Yeah, that's a good one.

• 30:57Dr. Peter Attia?

  And then the same thing after. You want to develop the bell curve of the whole thing.

• 31:01Speaker 01

  Well, we know that once the egg is ovulated, about eight hours and then it's over.

• 31:05Dr. Peter Attia?

  This is a very important point. It really needs to be front. If it's only eight hours of survival.

• 31:10Speaker 01

  After ovulation, about eight hours, it's dead. If it's not.

• 31:12Dr. Peter Attia?

  This is a very, very left tail curve.

• 31:15Speaker 01

  Correct.

• 31:16Dr. Peter Attia?

  Ah, I did not know that.

• 31:18Speaker 01

  So you want the sperm there ahead of time. Eighty percent 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.

• 31:31Dr. Peter Attia?

  I am. I have to draw.

• 31:33Speaker 01

  And it looks like it's algebraic.

• 31:36Dr. 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.

• 31:43Speaker 01

  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 all 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.

• 32:09Dr. Peter Attia?

  Sorry, dumb question. Why didn't they just measure the ejaculate? Why did they have to biopsy the testes?

• 32:15Speaker 01

  Did they just want to know about spermatogenesis? But we didn't want to biopsy the testes.

• 32:18Dr. Peter Attia?

  They actually wanted to torture the guys, but.

• 32:20Speaker 01

  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 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 someone were 42 days. And that's going through the epididymis and getting ejaculated. We talked about maybe two months in the testes 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.

• 33:05Speaker 01

  And when you talk about full replacement of that semen, it's probably in the being 90 days, when it's all replaced, the pot is replaced. That's a limitation of what we do. Forty-two-year-old women want now, and we have three to six months. When I did a study on fixing varicose seals, 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.

• 33:29Dr. 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.

• 33:37Speaker 01

  It's one year of inability to conceive after sex, using sex.

• 33:40Dr. Peter Attia?

  Okay.

• 33:41Speaker 01

  Doesn't have to be timed in a course. Just has to be whatever the couple does when they think they're trying to conceive.

• 33:45Dr. 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?

• 33:58Speaker 01

  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. About 23% of men get a formal evaluation for infertility before couples go through IVF in North America.

• 34:23Dr. Peter Attia?

  And how does that differ from the rest of the world?

• 34:25Speaker 01

  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 there's a 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

• 35:11Speaker 01

  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.

• 35:24Dr. 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?

• 35:31Speaker 01

  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 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.

• 36:15Speaker 01

  Physical exam, very important. One to 5% of male infertility can be due to a major medical issue, testis cancer, diabetes, things like that. So physical exam, varicose seals 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. It's they're going to be sterile or infertile.

• 36:37Dr. 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.

• 36:45Speaker 01

  Right, so we didn't answer that question, which was what's the semen consist of? It's about 10% basal fluid with sperm. It's about 80% seminal vesical 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 vesical, which is like a bladder, contracts, sends it into the prostate. Static urethra between the bladder and the the out there world. There's two valves. One is the bladder neck. It closes and one is the urethral sphincter that we pee through.

• 37:30Speaker 01

  And that opens and it gets forced out with muscular contractions in seconds.

• 37:34Dr. Peter Attia?

  Yep. 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.

• 37:43Speaker 01

  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 is the same, viscosity, et cetera.

• 38:09Dr. 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?

• 38:16Speaker 01

  Pure physical exam.

• 38:17Dr. Peter Attia?

  What, you feel it? Interesting.

• 38:19Speaker 01

  So my fingers can feel two and a half millimeters. The vast deferens is like piano wire. I mean, it is different than anything else in the chord. I did a study, a third of my men with absent vass were only found out having procedures until I saw them. I usually just do the exam, but it is an expertise thing.

• 38:37Dr. Peter Attia?

  Yeah, it's not like the PCP can figure this out. You have to be doing this all day, every day.

• 38:41Speaker 01

  Yeah, I think you need to be trained on that. But if you're well trained, it should be purely a physical exam.

• 38:45Dr. Peter Attia?

  What percentage of men are congenitally missing their vass?

• 38:48Speaker 01

  One in 500.

• 38:49Dr. Peter Attia?

  One in 500.

• 38:49Speaker 01

  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 and IVF, but they have definitely have the chance of passing on cystic fibrosis to a child.

• 39:06Dr. Peter Attia?

  Why is that?

• 39:06Speaker 01

  It's a very interesting biology, but men with cystic fibrosis, the most common genetic disease in America, have no vast deferens.

• 39:14Dr. Peter Attia?

  Okay, so what's the Venn diagram of cystic fibrosis and congenital lacking vast deferens?

• 39:19Speaker 01

  The genes for that were discovered, it's a chromosome seven, there's 17, 1800 mutations, maybe 2000. So they cloned the genes and got the variants in the late 80s. And then they found that 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 vast deference 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 vast deference too. So it's a form frust of cystic fibrosis, but it doesn't have all the chemical and metabolic side effects.

• 40:03Dr. 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 good probability he's a carrier of CF.

• 40:11Speaker 01

  Yes, and you can usually define it.

• 40:13Dr. Peter Attia?

  Which we can genetically test easily.

• 40:15Speaker 01

  Yeah, and then you have to worry if there's a 4% chance in America anyway, that a partner might carry it. There are two carriers, you have a 1 in 4 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 deference part.

• 40:34Dr. Peter Attia?

  What else on physical exam are you looking for?

• 40:37Speaker 01

  Cancers, infections, epididymitis.

• 40:40Dr. 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, or measles, mumps? What's the infection?

• 40:50Speaker 01

  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 goes to your pancreas, cause diabetes, it can go to the salivary glands, it can go to the testicles. It's some kind of, there's an open time.

• 41:21Dr. Peter Attia?

  So just one more reason why everyone should really get the MMR vaccine when they're a child, notwithstanding the tragedy of children dying from preventable diseases. But this is another non-lethal but significant complication of the mumps.

• 41:34Speaker 01

  Absolutely, and it will cause viral necrosis and edema of the testis. And then, similar to a brain, it's in a calvarium, right? The brain is in a fixed space, so when it swells, you've got to do something because it can die if it swells. Swells too much, testicle is a fixed cavity with the tunic alvegina. And so if it swells too much, it necrosis and then you get fibrosis and then you get sterility. I've got techniques where I can find sperm in lots of these men, real little pockets, but most of it, you're blading the testes. 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 that causes the anastaphyly issues. When these pandemics recurring Ebola too.

• 42:16Speaker 01

  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 to six other men. And it was another outbreak in South Africa.

• 42:32Dr. Peter Attia?

  Meaning the patient that survived Ebola, the virus managed to survive in the testes?

• 42:40Speaker 01

  Somewhere, but it was transmitted sexually a year later when he was well.

• 42:44Dr. Peter Attia?

  When he was asymptomatic, he'd already developed immunity.

• 42:46Speaker 01

  Right. We don't know about testes, but we know that mumps will do that to the testes, but there Zika is also persistent in the semen.

• 42:52Dr. Peter Attia?

  But in that case, you have to think wherever the virus hung out, it had to be very, very immune privileged.

• 42:59Speaker 01

  Yep. Or at low levels, like low viral loads where there's no disease. I'm not sure. But these are concerning cases.

• 43:05Dr. Peter Attia?

  But then it was transmitted at a low viral load and even lower viral load.

• 43:09Speaker 01

  Right. So it's tricky. There may be bulbous urethral glands, maybe it's some vesical, 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 ACE 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 at 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, we don't see it in fertility.

• 43:42Dr. Peter Attia?

  And what is it about the Zika virus that does this?

• 43:44Speaker 01

  We're not sure. Why did it in rats? It's a blood testis barrier thing. It's amazing barrier and nothing really gets through, including viruses, but mumps does only at puberty.

• 43:54Dr. Peter Attia?

  And Zika does.

• 43:55Speaker 01

  Zika does in animals, but we didn't see it in humans.

• 43:57Dr. Peter Attia?

  But I thought you said that Zika was leading to anencephaly in cases.

• 44:00Speaker 01

  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. It's testicle 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. Couple of colleagues did some papers. One which impressed me was 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.

• 44:45Speaker 01

  And I think out of 10 men or seven men, one had it in the testicle. So these are 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 perfusion rate there.

• 45:15Dr. Peter Attia?

  What is the phenotype of their sterility? Aside from the presentation that says I can't get someone pregnant.

• 45:20Speaker 01

  So sterility means no sperm in the semen. And typically if you measure the signals to the testicle.

• 45:25Dr. Peter Attia?

  That's literally what it means. I'm sorry. Okay. So literally no sperm in semen. They stopped, understood.

• 45:30Speaker 01

  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. Similar with eggs and controlling it's all a homeostatic mechanism with negative feedback. Classically anabolic steroid users.

• 45:53Dr. 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?

• 46:02Speaker 01

  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 issues: 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.

• 46:34Dr. Peter Attia?

  And presumably, you want to see fewer of those.

• 46:36Speaker 01

  There's a number, like, less than a million is normal.

• 46:38Dr. Peter Attia?

  Okay.

• 46:39Speaker 01

  So if you ask me, well, 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 gotta put it in the cup and I gotta 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 somatovesical. There's ejaculatory.

• 47:08Dr. Peter Attia?

  And by the way, do you ever have that on one side and not the other?

• 47:10Speaker 01

  No, no, it's very, very segmented. 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.

• 47:29Dr. 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?

• 47:45Speaker 01

  Isolated, isolated.

• 47:46Dr. Peter Attia?

  You do see isolated things?

• 47:48Speaker 01

  Right. 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 look terrible. And so there are rare conditions, one in 5,000, where you might have globospermia, or two-tailed sperm, or pinhead sperm. So if you look at shape, 4% should look normal, just terrible. We can have all discussion about why. 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% is normal if they're 1% normal and you look at the abnormalities.

• 48:30Dr. 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 tail.

• 48:47Speaker 01

  Amorphous or tapering in it. As a mathematician, that's not a great number, is it?

• 48:51Dr. Peter Attia?

  No.

• 48:51Speaker 01

  If you look at marine species, 99.9 look perfect in the wild.

• 48:55Dr. Peter Attia?

  Yeah, and presumably that's because their environment is so much more hostile. They're doing this all in the ocean.

• 49:00Speaker 01

  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.

• 49:14Dr. Peter Attia?

  Yeah, 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?

• 49:20Speaker 01

  Pinhead means there's no nucleus. It's a tail.

• 49:22Dr. Peter Attia?

  So that's a true problem.

• 49:23Speaker 01

  Yeah, it's like a little tiny head and moving along.

• 49:26Dr. Peter Attia?

  So if you give somebody credit for their two tails, what does your normal go up to from 4%?

• 49:31Speaker 01

  Oh, it depends, but maybe 20. But most of them are going to be amorphous, heads a little rounder, heads a little narrower. Those are called stress patterns. And things like hot baths and varicose seals and smoking will do that, which isn't that bad. In the case of 1% normal, you've 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.

• 49:55Dr. Peter Attia?

  I see. So the more homogeneous the failures are, the more likely that you have a clear etiology.

• 50:03Speaker 01

  And that's hard to fix. I mean, they'll fail with sex, they'll fail with inseminations, they'll fail with IVF.

• 50:08Dr. Peter Attia?

  They'll fail with IVF.

• 50:09Speaker 01

  Yeah, they'll fail with IVF nixie. Sometimes with globosa spermia where they're called lollipop sperm, they just have a big round head with no acrozone. 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 do 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 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 polyspermia in an egg is calcium activation.

• 50:44Dr. Peter Attia?

  This is the reason why even if you launch 100 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.

• 51:01Speaker 01

  Million years, a million years.

• 51:03Dr. Peter Attia?

  No more breaches in the hull.

• 51:05Speaker 01

  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, if we can try sperm sorting technologies, which are new on the market, microfluidics and things like that. And I've been throwing that at them. Sometimes it works, sometimes it doesn't.

• 51:27Dr. Peter Attia?

  Is that something that we know the genetic underpinning of?

• 51:32Speaker 01

  We're getting there. PLZ's, ADA deficiencies, one of them, recently discovered that runs the calcium channel, which tends to be associated with a certain look like globus ospermia. So it's coming around.

• 51:41Dr. Peter Attia?

  Think about that for a second, from an evolutionary perspective.

• 51:44Speaker 01

  That's probably.

• 51:45Dr. Peter Attia?

  That is the single least desirable genetic mutation you could acquire.

• 51:50Speaker 01

  Yeah, unless you're not making sperm.

• 51:52Dr. Peter Attia?

  Yeah, but this is a dead end to the genome.

• 51:55Speaker 01

  Right, right.

• 51:56Dr. 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.

• 52:04Speaker 01

  That's one of the 50 we throw off each generation, 50 mutations.

• 52:09Dr. Peter Attia?

  God, that's just incredible.

• 52:10Speaker 01

  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? It's a sperm matter a lot, a lot, a lot more than we've given them credit for.

• 52:29Dr. Peter Attia?

  All right. So basically just rounding out the semen analysis.

• 52:32Speaker 01

  History, physical semen analysis.

• 52:33Dr. Peter Attia?

  On the semen analysis, what if motility is the problem?

• 52:37Speaker 01

  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, varicose seals and exposure, things like that. And if the count's down and the motility is 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, see that patient is to figure out if he's not normal, why?

• 53:18Dr. Peter Attia?

  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?

• 53:23Speaker 01

  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 that's 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?

• 53:33Dr. 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?

• 53:41Speaker 01

  Oh, I mean, it used to be done manually.

• 53:43Dr. Peter Attia?

  Okay.

• 53:43Speaker 01

  And now it's done with the hemocytometers. It's done with machines. Computer assisted semen analysis does most of them in IVF groups.

• 53:50Dr. Peter Attia?

  It's really standardized.

• 53:52Speaker 01

  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 a computer.

• 54:14Dr. Peter Attia?

  Are they using AI for this yet?

• 54:16Speaker 01

  Yeah, I mean, some people are for sperm selection a little bit. But yeah, there's a lot of stuff to help out. And now it'll 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. Hoping AI, machine learning can help standardize the look because sperm is hard.

• 54:44Dr. 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?

• 54:56Speaker 01

  Right, so to make normal amounts of sperm, you need a proper amounts of testosterone and FSH. Think of it as flowering a plant. You need the water, 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 Coleman syndrome where 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.

• 55:26Dr. Peter Attia?

  Sorry, these men are not making FSH and LH?

• 55:28Speaker 01

  No.

• 55:28Dr. Peter Attia?

  So they have virtually no testosterone?

• 55:30Speaker 01

  Right, nor sperm. But you can give them those signals. Yeah, so HCG, FSH injections, and they will be fertile.

• 55:37Dr. Peter Attia?

  So is the problem in the pituitary, not the hypothalamus?

• 55:40Speaker 01

  No, it's the olfactory node in the hypothalamus. So they don't smell either.

• 55:44Dr. Peter Attia?

  So could you give them Clomid and would they make?

• 55:47Speaker 01

  No.

• 55:47Dr. Peter Attia?

  No.

• 55:48Speaker 01

  Pituitary is not working, yeah. The GnRH is the incentive.

• 55:52Dr. Peter Attia?

  The GnRH is not, okay, got it. What about estradiol? Does it play a role?

• 55:55Speaker 01

  Yeah, so estradiol is sort of a mild poison for male infertility. So everyone needs 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 if high estradiol. When estradiol is made, it gets metabolized differently than testosterone. It goes to the liver or to fat. And aromatase is converted to something else, or testosterone gets converted to female hormone aromatase.

• 56:35Speaker 01

  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.

• 56:52Dr. 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?

• 57:01Speaker 01

  Not usually.

• 57:02Dr. Peter Attia?

  Okay. So it's really only high estradiol in the context of suppressed testosterone.

• 57:06Speaker 01

  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 a hundred pounds, which is the key secret for everything, right? But you can also give aromatase inhibitors like weightlifters use to keep their levels down.

• 57:21Dr. Peter Attia?

  Okay. So those are four big pillars. Anything else besides the history, the exam, the analysis and the hormones?

• 57:27Speaker 01

  So 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 varies by 50 to 100%.

• 57:40Dr. Peter Attia?

  So never make a decision on one semen analysis.

• 57:42Speaker 01

  It's really hard.

• 57:43Dr. Peter Attia?

  Yeah, especially if it's the first one, as you said, for all the potential.

• 57:46Speaker 01

  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 here, they 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 semen analysis? There's biological variability on what your system's like. So that's the big problem with studies.

• 58:11Dr. 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?

• 58:19Speaker 01

  I don't think many.

• 58:20Dr. Peter Attia?

  Why is that?

• 58:21Speaker 01

  Because usually the indications aren't reproductive age men or women for some of them. If they do, they'll do animal models. They won't do human studies, do animal models. They'll do beagles, mice and beagles. And if there's no fertility effects, they don't really look at semen analyses in those. They'll look at fertility effects in the 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, in animal models, which is a million dollars of work. So if you ask me why I patented this hematopoietic 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 hematogenesis model and see if there's an effect at all.

• 59:03Dr. 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 GLP-1 agonists been tested for fertility?

• 59:21Speaker 01

  No, because it's sort of an off-label use of a diabetic medication.

• 59:24Dr. Peter Attia?

  But it's no longer off-label.

• 59:26Speaker 01

  I know.

• 59:26Dr. Peter Attia?

  It's an on-label use today.

• 59:27Speaker 01

  But it looks like it might be helping with fertility.

• 59:30Dr. 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.

• 59:43Speaker 01

  Absolutely, absolutely. And, you know, there are 80,000 chemicals out there that are not been studied reproductive that are commonly in used in industry. European commissions are a little better off. They've screened them and they've warned about them, but America, mm-mm.

• 59:56Dr. Peter Attia?

  Why is that?

• 59:57Speaker 01

  I don't know. It's attention to detail. It's one of those things that just doesn't, I don't know.

• 1:00:02Dr. Peter Attia?

  Is it under the purview of the FDA?

• 1:00:03Speaker 01

  Yeah.

• 1:00:04Dr. Peter Attia?

  Or the EPA?

• 1:00:05Speaker 01

  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.

• 1:00:12Dr. 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 takes steps where they are reasonable and reduce your exposure to these things. So everything from microplastics to PFAS chemicals to phthalates and even the PM 2.5s. Like, there's no reason to expose yourself unnecessarily to this.

• 1:00:54Dr. Peter Attia?

  If you can take relatively straightforward steps, eliminate 60 to 80% of your life, do it. Tell me what your impression is of the effect of any or all of the above on fertility.

• 1:01:05Speaker 01

  So although sperm are made constantly and are susceptible to that, we know the testicle is a 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, 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 and 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 way in advance of getting into clinical trials and when 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.

• 1:01:50Speaker 01

  Men have windows, and one of those windows is birth and early development, the first 12 weeks of life.

• 1:01:55Dr. Peter Attia?

  That early.

• 1:01:56Speaker 01

  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.

• 1:02:23Dr. 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? Like, where are you telling him to draw that line?

• 1:02:44Speaker 01

  I'm not great at that because the stress level goes up so much. And I think the stress

• 1:02:48Dr. Peter Attia?

  counterbalances any amount of microplastics you save.

• 1:02:50Speaker 01

  You double the stress in a man and testosterone level will fall. And then the sperm production falls for a whole different reason.

• 1:02:56Dr. Peter Attia?

  My testosterone level when I left residency.

• 1:03:00Speaker 01

  Oh, I bet.

• 1:03:01Dr. Peter Attia?

  So how old was I? Thirty-three, should have had a pretty good total T, 220 nanograms per deciliter.

• 1:03:07Speaker 01

  Did you measure LH? That's probably low.

• 1:03:09Dr. Peter Attia?

  Yeah, I'm sure FSH and LH were totally low. I don't remember what they were. Free testosterone of like three to four. Well, the sleep deprivation, the stress.

• 1:03:18Speaker 01

  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. It doesn't 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.

• 1:04:02Dr. Peter Attia?

  How quickly do you think that occurs in humans?

• 1:04:04Speaker 01

  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 the erections will fall a few 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 gotta see you. I said, why? He said, I lost my erection yesterday. He's 25. I said, first time? He said, yes. So I come on in. So he comes in and he's got his act together, looks good.

• 1:04:49Speaker 01

  And I said, what happened? He said, I just, 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 or 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 fertility. Oh, the great study was a moderate exercise, moderate exercise. Man, I wrote a blog on this called, can you 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.

• 1:05:34Speaker 01

  So moderate to extreme and then back to moderate. Sperm counts fell by 40% when 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 testosterones 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.

• 1:06:04Dr. 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 Nclomiphene, 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.

• 1:06:39Speaker 01

  All natural production.

• 1:06:40Dr. Peter Attia?

  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.

• 1:07:25Dr. Peter Attia?

  So the hypothalamus thinks,

• 1:07:26Speaker 01

  Doesn't see any.

• 1:07:27Dr. Peter Attia?

  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.

• 1:07:38Speaker 01

  And the two different classes are the LH enclomid 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 going to shrivel up your testicles and not maintain your fertility. And you can't generate levels that you can with exogenous testosterone. With these, it'll never get to 3,000. You can't do that. It's tightly regulated.

• 1:08:07Dr. 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?

• 1:08:19Speaker 01

  95% chance he's not.

• 1:08:21Dr. Peter Attia?

  Wow.

• 1:08:21Speaker 01

  While he's on it.

• 1:08:22Dr. Peter Attia?

  Yep, understood.

• 1:08:23Speaker 01

  But can he create it once he stops?

• 1:08:24Dr. 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.

• 1:08:43Speaker 01

  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.

• 1:08:59Dr. 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?

• 1:09:24Speaker 01

  Yeah, so they do more physiologic. They're in the normal range more, but gives you side effects from testosterone, including sterility is too much.

• 1:09:33Dr. Peter Attia?

  Yeah. So in your experience, has that borne out?

• 1:09:36Speaker 01

  Yeah.

• 1:09:36Dr. Peter Attia?

  You've seen men taking Natesto three times a day, doing a nasal-

• 1:09:41Speaker 01

  Keeping their sperm count.

• 1:09:42Dr. Peter Attia?

  Keeping their sperm counts. Okay. That's interesting to note. What about the oral testosterone, the twice a day?

• 1:09:47Speaker 01

  Love it. Testosterone that can that can noate. 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-

• 1:10:02Dr. Peter Attia?

  Yeah, we go to the liver.

• 1:10:03Speaker 01

  Right to the biliary system and go to the liver, cause liver cancer. So it was always verboten.

• 1:10:07Dr. Peter Attia?

  Even though there was no evidence this was happening in Europe for 50 years?

• 1:10:10Speaker 01

  Yeah, not much. It's FDA approved, EEA approved it. So this group came up with a way to get it metabolized through lymphatics. So it can 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 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.

• 1:10:32Dr. Peter Attia?

  Do you prescribe it?

• 1:10:33Speaker 01

  Oh, yeah.

• 1:10:33Dr. 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 eight o'clock in the morning and then at one 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-

• 1:10:58Speaker 01

  Mid-dose.

• 1:10:59Dr. Peter Attia?

  Mid-dose, right? If he does his blood draw at seven 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.

• 1:11:23Speaker 01

  It's hard to know. Usually you don't want to do it right away too. So you want to give him a couple of weeks to stabilize hemostatically, right? But usually you can get pretty good levels because the half-life isn't that short.

• 1:11:34Dr. Peter Attia?

  They say it peaks in five hours. So I don't know what the half-life is. The half-life would be-

• 1:11:38Speaker 01

  Probably 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. You can check it at different times, but it's probably not much of a response.

• 1:11:49Dr. Peter Attia?

  And what are you dosing it at? It comes in 100 and 200.

• 1:11:52Speaker 01

  It 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 going to get them to 800 or 1,000 very easily. You can get them 400 to 600, 600, 700 pretty well, but no side effects. I haven't seen anything, maybe a couple dozen men, really well tolerated.

• 1:12:17Dr. Peter Attia?

  Interesting. So this is not something you used when you're trying to get a guy from 300 to 1,000?

• 1:12:23Speaker 01

  You could, but probably not the first twice, yeah.

• 1:12:25Dr. Peter Attia?

  And now you're taking 500 twice a day or something crazy like that?

• 1:12:28Speaker 01

  Yeah, and twice a day is a big deal for men.

• 1:12:30Dr. Peter Attia?

  It is. What about Natesto? How are you, are you using-

• 1:12:33Speaker 01

  I've never, no one tolerates that.

• 1:12:36Dr. Peter Attia?

  What's the experience like? We've never used it.

• 1:12:38Speaker 01

  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 then within a week, we'll call and say, can't do this.

• 1:12:50Dr. Peter Attia?

  Yeah, we've had more luck getting women to use this.

• 1:12:53Speaker 01

  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 going to 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 and taking this stuff and then they have a clot and they have a stroke and now they're 71 and.

• 1:13:38Dr. Peter Attia?

  And do you find that the clot risk is proportional to hemoglobin hematocrit?

• 1:13:42Speaker 01

  Absolutely.

• 1:13:42Dr. Peter Attia?

  Simply, at what level are you saying?

• 1:13:44Speaker 01

  So, I mean, the studies aren't broad, but Ramaswamy 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, hematocrit 50, you start seeing events happen about 18, definitely at 19.

• 1:14:03Dr. 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 polycythemia.

• 1:14:21Speaker 01

  Right, because they don't hit the peaks.

• 1:14:22Dr. Peter Attia?

  They never hit these crazy peaks. 10 years ago, everyone I saw that was prescribing this was prescribing, the standard was 200 milligrams every two weeks, which was crazy.

• 1:14:31Speaker 01

  Highest risk, yeah.

• 1:14:32Dr. Peter Attia?

  Yeah. So what is your typical injection schedule?

• 1:14:36Speaker 01

  So once a week and I think twice a week where you can have the dose, right? So that is a little safer, but then it becomes the intensity and just a bit, I can't do it like that or whatever. I want a pellet instead.

• 1:14:47Dr. Peter Attia?

  Do you put pellets in?

• 1:14:48Speaker 01

  Oh yeah, I do them all.

• 1:14:49Dr. Peter Attia?

  The pellet also, I don't know the kinetics of it, but I would imagine you're pretty super physiologic for a month or so, maybe?

• 1:14:55Speaker 01

  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. You don't have a lot of side effects or consequences from it. It's done with a trocar and a thick needle. And pretty quickly, within a couple of 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 per year 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.

• 1:15:40Speaker 01

  I really don't.

• 1:15:41Dr. 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?

• 1:15:49Speaker 01

  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 for all 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.

• 1:16:19Dr. 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?

• 1:16:29Speaker 01

  Right. LH you will, because it's LH. But not FSH. Maybe a thousand to 1500, you start seeing it. So that's why you protect the fertility.

• 1:16:38Dr. Peter Attia?

  And what dose of Clomid will you give on top of that regimen?

• 1:16:41Speaker 01

  Depends. I mean, usually half a pill a day.

• 1:16:44Dr. Peter Attia?

  Half a 25, half a 50?

• 1:16:46Speaker 01

  50 milligram pills, yes, usually half.

• 1:16:48Dr. Peter Attia?

  You'd give 25 every day? These are staggering doses. How high are these guys testosterone getting?

• 1:16:56Speaker 01

  The testosterone is driven mainly by the HCG. I shoot for the normal range of 500 to 1,000. I'm not an anabolic guy all night.

• 1:17:02Dr. Peter Attia?

  Yeah, yeah, yeah. No, 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. W's 53 times a week. So that's about the same.

• 1:17:15Speaker 01

  Yeah.

• 1:17:16Dr. Peter Attia?

  Right?

• 1:17:16Speaker 01

  Twenty five a day.

• 1:17:16Dr. Peter Attia?

  Twenty five a day. But for most guys, that would be sufficient alone, even without HCG.

• 1:17:22Speaker 01

  Well, it's HCG that's driving the T.

• 1:17:24Dr. Peter Attia?

  The T.

• 1:17:24Speaker 01

  We're just trying to protect it. If you said, what do you give on isolation as monotherapy?

• 1:17:28Dr. Peter Attia?

  Yeah. What would you give for Clomid?

• 1:17:29Speaker 01

  Twelve and a half to 25 typically, depending on how sensitive the system is.

• 1:17:33Dr. Peter Attia?

  Do you prefer Clomid and Clomiphene?

• 1:17:35Speaker 01

  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's not approved for either. Clomiphene's compounded, Clomid is available for 50 years. So a lot more data. And once a cis isomer was a trans isomer.

• 1:17:53Dr. Peter Attia?

  Yep.

• 1:17:53Speaker 01

  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.

• 1:18:20Dr. Peter Attia?

  This was Clomiphene?

• 1:18:21Speaker 01

  And Clomiphene citrate. 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 of years and said, nope.

• 1:18:39Dr. Peter Attia?

  Why?

• 1:18:40Speaker 01

  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 and everyone who ages-

• 1:19:23Dr. Peter Attia?

  Guys are gonna be like, yeah.

• 1:19:24Speaker 01

  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 going to 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.

• 1:19:46Dr. Peter Attia?

  So I think there's another reason, Paul, and it's everything you just said, but HCG and testosterone are schedule four.

• 1:19:55Speaker 01

  True.

• 1:19:55Dr. 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

• 1:20:34Speaker 01

  That's right.

• 1:20:34Dr. Peter Attia?

  shady medicine.

• 1:20:35Speaker 01

  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.

• 1:20:55Dr. Peter Attia?

  Right.

• 1:20:55Speaker 01

  It's a signaling issue. And that's probably stress. So I said, 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 shifting over to exercise. So 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.

• 1:21:40Speaker 01

  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 just 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. I say, well, it's not testosterone related. Whatever your, the symptom is you're having, you wouldn't have it with a testosterone.

• 1:22:25Speaker 01

  We know levels of testosterone above which you should not have symptoms. We know libido, we know erections, we know fertility, things like that.

• 1:22:34Dr. Peter Attia?

  And what are the approximate levels for each of those?

• 1:22:36Speaker 01

  I don't know, erections, I would say the best study is about 290.

• 1:22:39Dr. Peter Attia?

  Yeah, so most guys that are having difficulty with erections are above 290. There's some other issue.

• 1:22:45Speaker 01

  Usually.

• 1:22:45Dr. Peter Attia?

  Yeah.

• 1:22:46Speaker 01

  But you have to prove it to them.

• 1:22:47Dr. Peter Attia?

  Yep, sure.

• 1:22:47Speaker 01

  And I'm fine with that, as long as it's safe. You're convincing them.

• 1:22:50Dr. Peter Attia?

  And then what about libido?

• 1:22:52Speaker 01

  Libido, I'd say 350 is sort of a range. It's pretty sensitive and it's harder to call. Libido is driven by so many different things. Fertility, I'd say 300 is a good one. You start seeing issues.

• 1:23:02Dr. Peter Attia?

  With how much FSH and LH?

• 1:23:04Speaker 01

  I don't know.

• 1:23:04Dr. 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.

• 1:23:13Speaker 01

  Absolutely. I think there's myths around testosterone and those are some of them, but it's 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 are also, it's a linear relationship between testosterone and that would be blood and muscle.

• 1:23:36Dr. Peter Attia?

  Yep.

• 1:23:37Speaker 01

  So more is better for making blood doping and also blood doping and also for muscle. Absolutely linear.

• 1:23:43Dr. 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.

• 1:23:54Dr. Peter Attia?

  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 500 and 1,000 and 2,500 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 don't, I mean, how many androgen receptors would you need? You'd have to upregulate them when in fact you'd be down regulating them.

• 1:24:21Speaker 01

  So I'm not sure, but the effect is indirect. Effective 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.

• 1:24:41Dr. 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.

• 1:24:48Speaker 01

  So it's the potential to recover that is improving. 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.

• 1:25:02Dr. 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.

• 1:25:42Speaker 01

  I would bet 95% confidence that he would have no sperm in his semen.

• 1:25:46Dr. Peter Attia?

  Okay. So what are you telling him now? How are you going to solve this problem?

• 1:25:49Speaker 01

  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? They never write it out on the history. You always have to get it out of them.

• 1:26:01Dr. Peter Attia?

  If they're super jacked, but then they have shriveled testes.

• 1:26:05Speaker 01

  Yeah, and they're zero. And they're wondering, what? You know, right? So I will look them in the eye. So 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.

• 1:26:23Dr. 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, you know, 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.

• 1:26:47Speaker 01

  It was lit when it went in.

• 1:26:48Dr. Peter Attia?

  Yeah, yeah, yeah.

• 1:26:49Speaker 01

  So my theories about this is why is he taking it? So if he's taking it for anabolic, then, you know, 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, it's 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 Antigen 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.

• 1:27:34Dr. Peter Attia?

  Yeah, it's incredible.

• 1:27:35Speaker 01

  But not everything.

• 1:27:36Dr. Peter Attia?

  Yeah.

• 1:27:36Speaker 01

  But it's a science. Some of them are PhDs. I took notes for years and it 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.

• 1:27:57Dr. Peter Attia?

  We'll link to this in the show notes.

• 1:27:58Speaker 01

  It's for people 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 an important question of ours. We can do that.

• 1:28:43Speaker 01

  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 five to 10 years of use. After five or 10 years of use, you may not get it back. Either the ability to make sperm or the ability to make testosterone.

• 1:28:58Dr. Peter Attia?

  We typically tell men in our practice, two years would be the absolute ceiling. Are we too conservative?

• 1:29:05Speaker 01

  Maybe.

• 1:29:06Dr. Peter Attia?

  Okay.

• 1:29:06Speaker 01

  Depends on dosing and everything, right? If they're taking 250 a week.

• 1:29:09Dr. Peter Attia?

  No, I mean, in our practice, it would be 50 twice a week.

• 1:29:11Speaker 01

  It takes a while. 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 as 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.

• 1:29:36Dr. Peter Attia?

  But you pump him full of HCG and synthetic FSH.

• 1:29:39Speaker 01

  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.

• 1:29:44Dr. Peter Attia?

  But this is the rescue protocol. It's LHFSH.

• 1:29:47Speaker 01

  Basically, there's three ways to do it. One is never stop the testosterone suddenly.

• 1:29:51Dr. Peter Attia?

  Hmm, interesting.

• 1:29:52Speaker 01

  Because men will hit the doldrums and go boom, 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.

• 1:30:11Dr. Peter Attia?

  Over what period of time?

• 1:30:12Speaker 01

  Six weeks typically. You have 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 them two options. One option is taper alone, taper with Clomid or enclomiphene. 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.

• 1:30:43Dr. Peter Attia?

  It's interesting, if you give Clomid, the pituitary will make FSH and LH?

• 1:30:49Speaker 01

  Yeah, it takes a while.

• 1:30:50Dr. Peter Attia?

  Well, that's a way more cost effective approach than giving synthetic. Cause synthetic FSH is pricey.

• 1:30:55Speaker 01

  Yes, a couple thousand a month.

• 1:30:57Dr. Peter Attia?

  Yeah.

• 1:30:57Speaker 01

  In America, yeah.

• 1:30:58Dr. Peter Attia?

  So is there any reason to do that over the Clomid approach? Or is it just that it's faster?

• 1:31:01Speaker 01

  I think you might gain a couple of weeks of time.

• 1:31:05Dr. Peter Attia?

  So for most people, that's not a price worth paying.

• 1:31:07Speaker 01

  With 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.

• 1:31:19Dr. Peter Attia?

  What would be good?

• 1:31:20Speaker 01

  If they're in a normal range.

• 1:31:21Dr. Peter Attia?

  Oh, really? Okay. We want within a couple of months to see them back to 600.

• 1:31:26Speaker 01

  300 would be okay to make sperm.

• 1:31:29Dr. Peter Attia?

  Okay.

• 1:31:29Speaker 01

  All right. 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're 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.

• 1:32:00Dr. 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.

• 1:32:24Speaker 01

  Yesterday, I operated on a man, testicular sperm retrieval on a man who says he's a spermic 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.

• 1:32:54Dr. Peter Attia?

  And what dose did you have him on?

• 1:32:55Speaker 01

  3,000, three times a week.

• 1:32:57Dr. Peter Attia?

  That's a whole vial a week.

• 1:32:58Speaker 01

  Yeah.

• 1:32:59Dr. Peter Attia?

  Wow.

• 1:33:00Speaker 01

  Then I said, okay, let's add in a low dose T gel, testosterone gel, get your testosterone up, and we're going to lower the HCG to 500 three times a week, twice a week. And I did a sperm retrieval yesterday. Boom, plenty of sperm.

• 1:33:13Dr. Peter Attia?

  How old was he?

• 1:33:13Speaker 01

  35.

• 1:33:15Dr. Peter Attia?

  Interesting.

• 1:33:16Speaker 01

  You can maintain whatever's going on on the testicle with HCG and take any testosterone you want.

• 1:33:24Dr. Peter Attia?

  That's an important lesson, yeah.

• 1:33:26Speaker 01

  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 low dose HCG 500 twice a week. And John Amory has worked out, and Washington has worked out, all the exact doses, but 250 to 500 twice a week is a good dose for that. It keeps your intra-testicular 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 T. Now, what happened after that is people start saying, you can preserve your fertility on testosterone replacement, which is possible.

• 1:34:01Dr. Peter Attia?

  They missed half the story.

• 1:34:03Speaker 01

  But it 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 going to go to zero. So unopposed testosterone without it, so you have to be 95% compliant.

• 1:34:15Dr. Peter Attia?

  Do you think that there's a difference between HCG and Clomid in that effect as the adjunct?

• 1:34:19Speaker 01

  The Clomid doesn't work.

• 1:34:20Dr. Peter Attia?

  HCG is the one.

• 1:34:21Speaker 01

  Yeah. Clomid doesn't improve intra-testicular testosterone levels like HCG does. It's ineffective.

• 1:34:27Dr. Peter Attia?

  Got it.

• 1:34:27Speaker 01

  It will potentially make you more recoverable. If you do it 80%, you'll be zero, even though you thought you might have a sperm 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.

• 1:34:47Dr. Peter Attia?

  Outside of fertility, given the popularity of testosterone replacement therapy today...

• 1:34:53Dr. Peter Attia?

  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?

• 1:35:04Speaker 01

  Yes, depends on the indication, though.

• 1:35:06Dr. Peter Attia?

  Everything but fertility, like any other health benefit?

• 1:35:09Speaker 01

  Well, I think muscle mass. So with aging, it's a great one. I mean, it used to be like growth hormone with age wasting syndrome, things like that. Then I mean, muscle mass is a key for men.

• 1:35:19Dr. Peter Attia?

  But I'm saying as opposed to just being on testosterone injectable to do the dual therapy versus just monotherapy.

• 1:35:25Speaker 01

  Oh, you mean if you're going to do some kind of therapy?

• 1:35:27Dr. Peter Attia?

  Yes, if you've committed to doing therapy.

• 1:35:29Speaker 01

  No, I think the only reason would be if you want testicles to be big.

• 1:35:32Dr. Peter Attia?

  Okay, so just volume.

• 1:35:33Speaker 01

  I just created a new procedure to make testicles larger naturally by putting a fat injection in the hydrocele space in men on testosterone because they don't like their small testicles.

• 1:35:42Dr. Peter Attia?

  So it's the equivalent of the Brazilian butt procedure for the testes?

• 1:35:45Speaker 01

  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.

• 1:35:52Dr. Peter Attia?

  Medicare approved?

• 1:35:53Speaker 01

  No.

• 1:35:56Speaker 01

  Creatively approved.

• 1:35:57Dr. 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.

• 1:36:03Speaker 01

  So for fertility?

• 1:36:04Dr. Peter Attia?

  Yes, for fertility. So tell me about the impact of cold plunging and sauna and hot tubbing on fertility for men.

• 1:36:13Speaker 01

  Okay, so the test is outside the body. It's three 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 his 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.

• 1:36:58Speaker 01

  He became a thermometer. So it does go up and down. Is that P D R T A Laffick?

• 1:37:05Speaker 01

  Journal of irreproducible results.

• 1:37:07Dr. Peter Attia?

  Oh, God.

• 1:37:07Speaker 01

  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 plunge, where are your testicles? They're way up there.

• 1:37:18Dr. Peter Attia?

  In my abdomen, yeah.

• 1:37:20Speaker 01

  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 one centimeter away, you're a liquid, it's a liquid, you're going to turn that temperature, maybe not the inner part of your body, but little kids going at the hot tubs, right? They overheat.

• 1:37:46Dr. 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.

• 1:37:57Speaker 01

  Absolutely. You're 70% liquid. This is right at the surface. So I did a study, published it in the Brazilian Journal of Virology. 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 Americans, I went to Brazilian Journal of Virology. 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 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%.

• 1:38:39Speaker 01

  Total mold count in three months or four months and 600% in six months. You have to give it some time. And that's that curve, the recovery curve. And we didn't look at fertility, we just looked at that recovery. And someone was zero and went up to close to normal.

• 1:38:54Dr. Peter Attia?

  Age range of these men?

• 1:38:55Speaker 01

  35.

• 1:38:56Dr. Peter Attia?

  So fertile men?

• 1:38:57Speaker 01

  Yep, trying to conceive.

• 1:38:58Dr. 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 sixfold increase in sperm count.

• 1:39:08Speaker 01

  Total mold of sperm count, I mean, count motility, mainly driven by motility.

• 1:39:12Dr. Peter Attia?

  Interesting. So it's motility that the price.

• 1:39:13Speaker 01

  The biggest one, but also count might have doubled. Chilli may have gone up threefold kind of thing. So sixfold increase overall. Then I calculated after that, I calculated a lethal dose of tubbing. So what's the lethal dose?

• 1:39:25Dr. Peter Attia?

  Yeah, what's the LD50? Yeah.

• 1:39:27Speaker 01

  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 on 104 degrees, three times a week would probably make you zero.

• 1:39:40Dr. 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.

• 1:39:50Speaker 01

  Yes.

• 1:39:51Dr. Peter Attia?

  A week.

• 1:39:52Speaker 01

  Interesting. The largest group of people in tubs in Northern California, we did this study, were environmental lawyers. Is your job that stressful as a kid? It is. I mean, it probably is in California.

• 1:40:01Dr. Peter Attia?

  All right.

• 1:40:01Speaker 01

  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, that 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 a tub. It's like, pick your contraceptive. So it's huge. I'd say 10% of my population's in it. And 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.

• 1:40:44Speaker 01

  And I would say the effect is one quarter to one third as profound as a hot bath or submersion.

• 1:40:49Dr. Peter Attia?

  So my friend was absolutely right to have those ice packs on his scrotum.

• 1:40:55Speaker 01

  I think he's reading.

• 1:40:56Dr. Peter Attia?

  Yeah.

• 1:40:57Speaker 01

  He's listening to.

• 1:40:57Dr. Peter Attia?

  He's a smart guy.

• 1:40:58Speaker 01

  The Turk Protocol.

• 1:40:59Dr. Peter Attia?

  Yeah.

• 1:41:00Speaker 01

  And then I would say steam rooms, showers are probably fine. You're in an ambient temperature is 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.

• 1:41:14Dr. Peter Attia?

  Okay. And then what about the cold?

• 1:41:16Speaker 01

  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 says, are surfers infertile? I said, is that water bad for them? Cause 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.

• 1:41:34Dr. Peter Attia?

  All right. So the cold is okay.

• 1:41:35Speaker 01

  Especially plunge, where you're talking seconds.

• 1:41:37Dr. Peter Attia?

  Yeah, yeah.

• 1:41:38Speaker 01

  You know, your testicles are gonna go up.

• 1:41:39Dr. Peter Attia?

  Yeah.

• 1:41:40Speaker 01

  And you're gonna be able to maintain that heat. I think if you did it. All the time, it would probably be bad. Yeah. Cause enzymes work in the testicle at that one temperature. They work optimally.

• 1:41:52Dr. 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 rammed up to two hours a day of exercise that was above eighty percent of VO2 max, which is pretty strenuous.

• 1:42:09Speaker 01

  That's right.

• 1:42:10Dr. Peter Attia?

  That was enough to put a dent in their fertility. Tell me about riding a bicycle.

• 1:42:14Speaker 01

  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 as much as like-

• 1:42:28Dr. Peter Attia?

  Just like a Brooks saddle, these Brooks leather saddles?

• 1:42:30Speaker 01

  And you know, 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'm, I was thinking of maybe going senior league and doing this gorgeous steel frames and trying to keep up with those guys, cause it's not about the bike really. It's like when you get golf clubs and I got a hundred fifty dollars set of golf clubs. I'm going to be as bad a golfer with thousand dollar clubs as I ever been. So it's really about the biker, but there are some differences. I'm, you know, in terms of momentum and the wheel force and all that. But I love my old steel bikes and they see this. It's like I hang at my office when I come to work in the morning and I bike in in San Francisco. And then I have the 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.

• 1:43:15Speaker 01

  Competitive Spanish cyclists, Tour de France caliber cyclists, their sperm counts were examined.

• 1:43:19Dr. Peter Attia?

  But what was the control group? Did they have a control group of runners?

• 1:43:22Speaker 01

  I don't remember. I don't think so.

• 1:43:23Dr. Peter Attia?

  So in other words, it could have been the exercise. It could have been the intensity of their exercise.

• 1:43:26Speaker 01

  Not a good group to study.

• 1:43:27Dr. Peter Attia?

  Yeah.

• 1:43:28Speaker 01

  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're, you know, it's a big industry. They're super fit. They're certainly exercising two hours of- 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.

• 1:44:02Dr. 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.

• 1:44:32Speaker 01

  Yeah, 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 didn't appear to.

• 1:44:38Dr. Peter Attia?

  So is this a myth?

• 1:44:39Speaker 01

  Yes. Now, if you said, am I worried about bicycling? Yes. So I worry about sexual health. I worry about the pudendal nerve and I worry about seat anatomy. So the best seat for a bicyclist, 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 N A, I've forgotten, it was Dr. Schrader at 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 crest bones with no nose, perfect. So it's pressure, where the pressure is outside facing, leaning

• 1:45:24Speaker 01

  in. So we 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 and 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 then measure the distance. And there's only a couple of different saddles, maybe 12 widths that you could do and you get it done.

• 1:46:06Speaker 01

  Or like me, you use a saddle used for 30 years and it's perfect, but it weighs four pounds.

• 1:46:11Dr. Peter Attia?

  That's because it's a leather saddle and it fit you.

• 1:46:13Speaker 01

  Yeah.

• 1:46:13Dr. Peter Attia?

  Yeah, yeah. Iconic. Okay, let's talk about alcohol specifically and let's talk about any other recreational drugs.

• 1:46:22Speaker 01

  So fertility wise, I'd say the government wants men, I'm going to 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.

• 1:47:05Speaker 01

  So it's a hormonal effect and a direct effect.

• 1:47:08Dr. Peter Attia?

  Any evidence that it's having an epigenetic effect?

• 1:47:11Speaker 01

  Probably. I don't know about evidence, but I'm sure it does.

• 1:47:14Dr. Peter Attia?

  Let's talk about common recreational drugs. Let's start with marijuana.

• 1:47:17Speaker 01

  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 sperm epigenetics showed alterations with nicotine and with pot. What I don't like about pot is you ingest it and however. 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 your fat 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 and reproductive

• 1:47:59Speaker 01

  age men is I wrote a couple of 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 uses associated with testis cancer.

• 1:48:13Dr. Peter Attia?

  And we think that that's causal?

• 1:48:15Speaker 01

  I don't know. It just worries me. Weed worries me.

• 1:48:19Dr. Peter Attia?

  Interesting, given that it otherwise seems kind of benign. I personally can't stand the stuff, but I know so many people that use it so frequently that seem to have relatively few

• 1:48:29Speaker 01

  I mean, it's a distinct phenomenon. It's medical marijuana, right? 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 I said, which is worse for driving, being stoned or being drunk?

• 1:48:44Dr. Peter Attia?

  Undoubtedly being drunk.

• 1:48:46Speaker 01

  Yeah. So it looks like reflexes, but you know, like he said to me, well, we tend to stop at stoplights and wait for them to turn when we're stoned. It's like.

• 1:48:54Dr. Peter Attia?

  Yeah, I'm not saying, 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.

• 1:49:02Speaker 01

  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.

• 1:49:14Dr. Peter Attia?

  What do you think is the mechanism of action by which THC is having these negative fertility impacts?

• 1:49:19Speaker 01

  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.

• 1:49:34Dr. Peter Attia?

  But blocks it from LH.

• 1:49:35Speaker 01

  So you can get low testosterone, but it's not been that profound.

• 1:49:39Dr. Peter Attia?

  What about nicotine, either synthetically or in the form of tobacco?

• 1:49:44Speaker 01

  Bad actor at high doses, I think, too.

• 1:49:46Dr. Peter Attia?

  Either one?

• 1:49:47Speaker 01

  Yep. It's nicotine is the

• 1:49:49Dr. Peter Attia?

  Nicotine per se.

• 1:49:50Speaker 01

  Is the issue. 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.

• 1:50:02Dr. 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?

• 1:50:19Speaker 01

  Probably all of them. I don't think we know exactly, but I'd say that I diagnose diabetes in a lot of infertilemen. I make the diagnosis.

• 1:50:27Dr. 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?

• 1:50:34Speaker 01

  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 prediabetic. But I think a lot of it is neurogenic, too. They can develop an ED. A third of type 2 diabetics have low testosterone, so that's a clue. And that's secondary, so you can clomot, you can betam right back. But that's probably the common one is the look, the sugars, and then the low T and the low sperm count. It's kind of a picture.

• 1:51:15Dr. 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?

• 1:51:23Speaker 01

  The most common is a varicose hill.

• 1:51:25Dr. Peter Attia?

  Okay, tell people what a varicose hill is.

• 1:51:27Speaker 01

  You could 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 bud that's supposed to be staying

• 1:52:10Speaker 01

  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.

• 1:52:28Dr. Peter Attia?

  But sorry, there are no valves in that vein?

• 1:52:30Speaker 01

  Correct.

• 1:52:30Dr. Peter Attia?

  So what's the head it has to climb? That's got to be this.

• 1:52:33Speaker 01

  Thirty centimeters.

• 1:52:34Dr. Peter Attia?

  So how is it doing that without a valve?

• 1:52:37Speaker 01

  I don't know.

• 1:52:38Dr. Peter Attia?

  That's a pretty big distance to travel without a valve.

• 1:52:40Speaker 01

  It does it at night. I don't know.

• 1:52:41Dr. Peter Attia?

  Yeah, interesting. Okay.

• 1:52:42Speaker 01

  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 varicose. 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.

• 1:53:15Dr. Peter Attia?

  And you'll figure that out easily on a physical exam?

• 1:53:17Speaker 01

  The best way is easy. If I don't order ultrasound, if I can palpate it, then it's clinical.

• 1:53:22Dr. Peter Attia?

  That's an office repair?

• 1:53:23Speaker 01

  It's an outpatient surgery. Takes an hour. We do microsurgery.

• 1:53:26Dr. Peter Attia?

  Oh, it is?

• 1:53:26Speaker 01

  Yeah.

• 1:53:26Dr. Peter Attia?

  So it's more involved than a vasectomy?

• 1:53:28Speaker 01

  Yes, it is. And you're doing it at microsurgery at the level where you don't cut muscle. You want it to recover quicker. It's an involved area with lots of veins.

• 1:53:36Dr. Peter Attia?

  But he's not under general?

• 1:53:37Speaker 01

  I use twilight, twilight sedation.

• 1:53:39Dr. Peter Attia?

  Yeah.

• 1:53:40Speaker 01

  So that's the most common.

• 1:53:40Dr. Peter Attia?

  That's the most common thing. Wow.

• 1:53:42Speaker 01

  And most men are fertile, but so again, you look at the semen analysis as a poker hand and you see count motility being down, nothing else going on. And you see a varicose seal and it's implicated.

• 1:53:52Dr. Peter Attia?

  All right. Have we missed any other of the major?

• 1:53:55Speaker 01

  I'd say the major ones are varicose seal. And then I would look for hormonal issues. So varicose cells may be 40, hormonal maybe 10 or 15 genetics.

• 1:54:03Dr. Peter Attia?

  So they're non-modifiable now?

• 1:54:04Speaker 01

  Right.

• 1:54:05Dr. Peter Attia?

  Okay, so you talked about a few of those already. What are some other ones on the genetic side?

• 1:54:10Speaker 01

  The most common one is for zero sperm is Kline filter is X, X chromosome. The most common one for low sperm count is Y chromosome deletions. This is an interesting area.

• 1:54:20Dr. Peter Attia?

  What does that phenotype look like?

• 1:54:21Speaker 01

  No phenotype in general?

• 1:54:23Dr. Peter Attia?

  Yeah.

• 1:54:24Speaker 01

  No phenotype, normal.

• 1:54:25Dr. Peter Attia?

  A Y chromosome deletion male?

• 1:54:27Speaker 01

  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.

• 1:54:33Dr. Peter Attia?

  I see, okay. I'm sorry, I thought you meant a complete deletion of the Y chromosome. Yeah, yeah, yeah, got it.

• 1:54:37Speaker 01

  So it's the long arm and it's deletions, regions. Yeah, rhyme of deletion, you're right. So Randy Ropera 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 in 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 of Y is very important, has a gene called SRY, which makes you male.

• 1:55:22Speaker 01

  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 order it in men with a low sperm count of below 5 million. So that would be a pretty common cause of a sperm count low than 5 million. And I published a study that if you have a Y chromosome deletion and you have a varicose seal and they both cause low sperm counts and you fix the varicose seal, 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 B chromosome deletion and you fix the varicose, you'll expect a good response. Two thirds will improve, one third or more will conceive naturally.

• 1:56:06Speaker 01

  So you could take guys at 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 a low sperm count. Sons have it. They have no sperm. So you can inherit the deletion, but it might increase. So you're going to get what your dad had, or it might be worse because mutations tend to get larger.

• 1:56:35Dr. Peter Attia?

  And until they try to conceive, they would never know this.

• 1:56:37Speaker 01

  Right.

• 1:56:38Dr. Peter Attia?

  Everything else is normal.

• 1:56:39Speaker 01

  Right. So then there's environmental lifestyle things. So I think obesity is a big one.

• 1:56:44Dr. Peter Attia?

  And do you think that that's mostly propagated through the endocrine system then?

• 1:56:47Speaker 01

  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 wary. Some airport fuels, airline stuff, machine shop oils, anything benzene derivatives. It 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 a 10 or 20% with

• 1:57:30Speaker 01

  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

• 1:58:13Speaker 01

  more about and they're pretty obvious. But some of these trichomonas and stuff are pretty subtle. I was really concerned. Concerned about this because one guy 20 years ago, now it's professor UCSF. He sent me a picture of electron photograph of a sperm with a hexagonal herpes virus in it. And I don't even know it was photoshopped, but there's this virus in the sperm like, yeah, it looks like there's a virus in this 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 pilospermia, 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.

• 1:58:56Speaker 01

  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, UCSF, one of MacArthur Ward. He took my patient's semen, it's back when microwaves were popular in the 2000s. And he had like 2,000, 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.

• 1:59:39Speaker 01

  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 semen analysis, as I said earlier, is 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.

• 2:00:16Dr. Peter Attia?

  And what if, for example, a guy has prostatitis and the prostatic fluid has

• 2:00:20Speaker 01

  PUS in it.

• 2:00:21Dr. Peter Attia?

  PUS in it, then that could sabotage the whole thing and

• 2:00:24Speaker 01

  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.

• 2:00:37Dr. Peter Attia?

  Yep.

• 2:00:38Speaker 01

  So if your urine's infected, that's a big deal.

• 2:00:41Dr. Peter Attia?

  Have you done work with intra-tisticular PRP and stem cells?

• 2:00:45Speaker 01

  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 cells 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. I, 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 finding it even without that is X and they're finding X. So

• 2:01:31Speaker 01

  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. I'll 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.

• 2:01:50Dr. 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.

• 2:01:59Speaker 01

  You're pretty evidence-based, Peter.

• 2:02:00Dr. 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.

• 2:02:15Dr. Peter Attia?

  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.

• 2:02:22Speaker 01

  I agree with that.

• 2:02:22Dr. Peter Attia?

  But boy, I'd like to figure it out without people wasting so much money.

• 2:02:27Speaker 01

  There's a there there, but it's just not that easy.

• 2:02:29Dr. 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% varicose seals because you're going to fix those guys and they're fine. So 100 people who don't have a varicose seal, who don't have a genetic condition, I'm going to really simplify this. Okay. So these are 100 guys that presumably have showed up with some iatrogenic reason for infertility.

• 2:03:11Dr. Peter Attia?

  How many of those guys are going to be able to conceive without resorting to IVF?

• 2:03:17Speaker 01

  I would say that's the goal of my practice and I would say the answer is most.

• 2:03:22Dr. Peter Attia?

  Wow.

• 2:03:22Speaker 01

  But the caveat is you gotta 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 varicose seals and stuff, but their semen levels is 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 Turk couldn't figure out what's wrong with us. And I said, it'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.

• 2:04:08Speaker 01

  And I said, what happened last year after Turk cleared you had a resident do this? And the answer was 65% had conceived naturally. Another 15 to 20% conceived with IOI 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 varicose seals. I didn't touch them and 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.

• 2:04:50Speaker 01

  That is higher than anything I can offer as a treatment that we have published on. So if you fix their varicose seal 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.

• 2:05:10Dr. Peter Attia?

  Okay. 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?

• 2:05:38Speaker 01

  It's a huge issue, paternal age, paternal age and fertility, paternity. So we can go there, but I don't place value judgments. I say, good idea. My disclosure, I'm on a board of legacy. I love their mission driven. I like the fact they're going from 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 have happened 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 will do it for you. We'll pay for it for five years. Just give us a sample because it's so much harder afterwards or not.

• 2:06:16Dr. 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, bank.

• 2:06:25Speaker 01

  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.

• 2:06:33Dr. Peter Attia?

  What paternal age do you worry about?

• 2:06:35Speaker 01

  And you look at national guidelines for sperm donation, 40 is considered older paternal age. A 50 for sure. If you look at risks to offspring, miscarriages, stillborns.

• 2:06:48Dr. Peter Attia?

  Autism.

• 2:06:49Speaker 01

  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 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 Danchenko from University of Pittsburgh. But I think it's a hockey stick curve for risk to offspring.

• 2:07:32Dr. Peter Attia?

  And you think the inflection is 40 or 50?

• 2:07:35Speaker 01

  I think it's more like 60.

• 2:07:36Dr. Peter Attia?

  Okay.

• 2:07:36Speaker 01

  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.

• 2:07:51Dr. Peter Attia?

  Yeah, but they're shifted 20 years earlier or something.

• 2:07:53Speaker 01

  Yeah, so it's a shorter curve, but the same thing. 40, 38 to 40 is 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 a, the same relative risk. So women, you go from 25 to 40, your chance of a miscarriage, though 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.

• 2:08:30Dr. Peter Attia?

  In many ways, it's almost easier to detect.

• 2:08:32Speaker 01

  Very. They've been doing it for years.

• 2:08:33Dr. Peter Attia?

  It can be more dramatic.

• 2:08:35Speaker 01

  And now prevented with pre-implication genetic testing. Men are different. You can't detect these things. There's 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 is 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.

• 2:09:17Speaker 01

  And so 50 mutations a year, a generation usually gets spit out, for instance, in 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 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 marshals from the 50s in the movies with big heads. That's kind of where we're headed. It's autism, dyslexia, bipolar disorder. These are neurodevelopmental, neurodegenerative issues.

• 2:10:00Speaker 01

  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 these 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?

• 2:10:42Dr. 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 five. I think the mildest version probably comes with more superpowers than limitations, or maybe equal amount, but clearly the more severe it gets, it's pretty debilitating.

• 2:11:06Speaker 01

  But that's what we're calling it disease, though.

• 2:11:08Dr. Peter Attia?

  Yeah.

• 2:11:09Speaker 01

  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.

• 2:11:18Dr. Peter Attia?

  Yeah. But again, I would argue most of those people would be in category, class one, not class three.

• 2:11:23Speaker 01

  Anyway, something to think about.

• 2:11:24Dr. 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?

• 2:11:36Speaker 01

  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 Lewinho came up with the 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 or temperature shift. So that's where the kill rate comes from. In a good sample, half of it should survive.

• 2:12:21Dr. 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?

• 2:12:40Speaker 01

  So I usually say, depending on what technology you're going to use, but if your sperm count's normal, three ejaculates is one kid's worth of sperm with insemination technology where you would thaw it and then turkey baste it.

• 2:12:52Dr. Peter Attia?

  So 10 ejaculates for three shots on goal for three kids?

• 2:12:55Speaker 01

  For three kids with low technology, but 10 ejaculates will give you most of China with IVF.

• 2:13:00Dr. Peter Attia?

  Got it. Oh, when you say low technology, you mean I U I. Or something like that?

• 2:13:04Speaker 01

  So there's three levels, sex, no tech, high tech is IVF and in the middle is I U I. That's the stuff that's turkey basting. It's relatively straightforward, relatively cheap.

• 2:13:12Dr. Peter Attia?

  I see.

• 2:13:13Speaker 01

  Three kids for that, but plenty of sperm for IVF.

• 2:13:15Dr. Peter Attia?

  So three ejaculates would be more than enough?

• 2:13:18Speaker 01

  If they're normal.

• 2:13:19Dr. Peter Attia?

  For IVF?

• 2:13:20Speaker 01

  Yeah. So the population you're talking about may be cancer survivors. Half of those will not be normal. They're really looking at IVF.

• 2:13:25Dr. Peter Attia?

  Yep.

• 2:13:25Speaker 01

  So they don't need that many, but I'd say three is a good number, but it's an insurance policy.

• 2:13:29Dr. Peter Attia?

  Yeah. 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.

• 2:13:54Speaker 01

  Podcast, too.

• 2:13:55Dr. Peter Attia?

  Tell me about that.

• 2:13:56Speaker 01

  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 anti-burden of men's health. We're going to just take on the topics, testosterone, et cetera, penis mitts, and just talk about stuff that everyone is asking questions about, but no one's talking about. And like you, data-driven answers.

• 2:14:18Dr. Peter Attia?

  Okay. And what's it called?

• 2:14:19Speaker 01

  Talk with Turek on all channels.

• 2:14:20Dr. 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 work up. 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.

• 2:14:45Speaker 01

  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, in the Riggel Hospital in Copenhagen, they looked at 74,000 men over 50 years and found that those guys with, say, normal semen quality live 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

• 2:15:25Speaker 01

  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 it'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... 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.

• 2:16:06Speaker 01

  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 and Dow chair. I left and I went to Yoson 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, you know, did something bad, you get him back, whatever. But you have to think next step, like kidney stones, great urologist, we treat them all day. It's fun, it's endoscopic, it's lasers, it's shockwaves, but what are we doing about that

• 2:16:51Speaker 01

  stone? I mean, how come we're not preventing these more? It's not on the radar. I go to Yoson University, 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 is under control, their stress is under control, they're doing acupuncture, they're sorted out. And what do I find? Varicose seals 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. It's interesting how we don't give a lot of street cred to it, but in my view, a 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

• 2:17:34Speaker 01

  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.

• 2:17:45Dr. Peter Attia?

  Well, Paul, very interesting stuff. Thank you again for making the trip out here. Thanks for sharing your insights.

• 2:17:51Speaker 01

  It's been great, yeah.

• 2:17:51Dr. Peter Attia?

  All right.

• 2:17:52Speaker 01

  Thanks, Peter.

• 2:17:53Dr. Peter Attia?

  Thank you for listening to this week's episode of The Drive. Head over to peterattiamd.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 PeterAtiaMD. You can also leave us a 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

• 2:18:38Dr. Peter Attia?

  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.