The Peter Attia Drive
#351 ‒ Male fertility: optimizing reproductive health, diagnosing and treating infertility, and navigating testosterone replacement therapy | Paul Turek, M.D.
Mon, 02 Jun 2025
View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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, Instagram, Facebook and YouTube
Chapter 1: What is the main topic of this episode?
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.
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If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peteratiamd.com forward slash subscribe. 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 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 how various factors such as heat exposure, stress, and environmental toxins impact sperm quality. We talk about what men can do to optimize their reproductive health.
Paul explains the effects of testosterone replacement therapy on fertility, debunking many myths and offering strategies for men looking to preserve their ability to conceive while being on hormone replacement therapy. Talk about the emerging fertility technologies, including advanced sperm sorting techniques, genetic testing, and innovative treatments that could redefine reproductive medicine.
Also talk about the differences between the risk in the aging male and the aging female. And this was actually one of the most interesting things I learned about in this podcast. So without further delay, please enjoy the first of two parts on a discussion of fertility and reproductive health. This one with Dr. Paul Turek. Hey, Paul. Thank you so much for coming out to Austin.
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Chapter 2: How do sperm navigate the female reproductive tract?
And this Settlage studies in the 50s had women have sex before hysterectomies. And then he swabbed different parts of the reproductive tract. These are young women for different reasons, not infertility, and found these numbers. And that's the basis for our move to technology from 5 million moving sperm is when we start doing inseminations versus sex, et cetera.
So those are based on numbers of sperm that reach the uterus and reach the thing. What's really interesting is there's some fascinating research. Everyone thought the Vanguard sperm wins, right? So it's the Phelps sperm that's going to make it. And there's a company out of Boston called Eric's Biosciences, and I'm consulting with them, disclosure.
But they've discovered that sperm work in phalanxes. So because the immune system is so vibrant in the uterus, the first round of sperm gets through the cervix
And typically absorbs the immune system, secretes FCR receptor. 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? There's T cells, B cells, and antibodies. It's a full immune response. Absolutely. So it's a specific immune response. Anything for it.
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 on the immunoglobulin because that's what antibodies bind to. So the female antibodies bind to that.
And we don't know how many phalanxes go through, but then it's like a run up the middle. And then eventually a couple of sperm or fourth make it and the immune system's deactivated and they get there. It's wild. And that can be measured now. And there's actually 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 jaculates, which is a group of sperm, some of which do this well and some of which don't. And that can be a whole reason for infertility.
If you're not able to deactivate the system, you're not going to be able to get through because the immune system is active. Let's go through those numbers one more time. About 100 million ejaculated. At the cervix. 5 million get through. To cervix, into the uterus.
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Chapter 3: What factors affect sperm quality and fertility?
So anyway, to this day, I get such a chuckle out of The confusion of the nomenclature. But again, just to explain for people, mitosis is what happens when cells are dividing in our body constantly where they're trying to create a perfect replica of the entire suite of DNA. So really, to my knowledge, the only time we're undergoing meiosis is in the creation of an egg or a sperm. That's right.
Okay. Now, remind me, are women born with all of their eggs? I feel like that's something I vaguely remember.
Five million eggs at conception, one million eggs at birth, and you basically ovulate a thousand in your lifetime. Okay. So by the time you're 45, you're out of eggs. You actually ovulate one a month, but you actually produce 10 a month. So you lose 10. For every one. Right. So a lot of waste.
But they're stuck in a stage of perpetual space where they're just, 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. 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? Why do you think out of the box like that? No, I'm not sure. I mean...
There's a whole issue of what's the source of human evolution. It's really sperm. Yeah. Because they're constantly dividing. They're constantly influenced by the environment. And they're throwing off mutations and epigenetic changes. And what's most interesting for me for this talk is that whatever happens in sperm happens to offspring.
That's an interesting point. So it's transgenerational. Does that mean that the father is more likely to pass on environmental stressors than the mother? Probably, yeah. And that's definitely been shown. 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...
That spermatogonial stem cell is actually the first and the bottom of a tube. There's 12 stages of spermatogenesis. That cell is remarkable. It's actually the human male embryonic stem cell. So I have a patent on that cell. Because if you take that cell and you put it in a niche environment like an embryonic stem cell, it'll become embryonic almost like it can become multipotent. It's pluripotent?
Multipotent. We don't know about pluripotent, but you can form tumors and you can form bone, mesoderm, ectoderm, and endoderm. You can do all three layers of the body. with that adult spermatogonial stem cell.
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Chapter 4: How does testosterone replacement therapy influence fertility?
There are some markers of paternal and maternal origin. It depends on where you're going back in mitosis and meiosis. So they can sort of ascribe it in the embryo. In the sperm, you're really going to have to look at the sperm. And if you see a translocation, some characteristic change in sperm, and you see it in the embryo, then you know it's paternal. But not usually.
And 98% of sperm are typically normal. In a guy with infertility, it might be 95%. Here's an example. If you have a patient with Klinefelter syndrome, a male with an extra X chromosome in every cell in their body, or a transgenic model with that feature.
So this is a man who's XXY instead of XY. So 47 chromosomes, not 46. Yep. And phenotypically, he kind of has a distinctive look, right? 10% of the time. Oh, really? 90% of the time, a man with Klinefelter's, you'd never know. Yeah.
Okay.
So that's the board question. That's the board question, right?
That's the MCAT question. Yep, yep. 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 extra X chromosome. Only about 10% will have it in the sperm.
Meaning they will produce an X or a Y sperm. Just like everyone else. The only difference is they have a two-thirds chance of producing an X and a one-third chance of producing a Y, I'm assuming, instead of 50-50. Don't think we know that.
That's math, Peter. That's math. Biology is not math, remember? And I had two Kleinfeldt patients yesterday that I operated on, and they're not doing pre-implantation 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 XXY sperm or an aneuploid sperm, an abnormal sperm, to 1%.
In humans, it goes from 1% or so to 10%. But 90%, that's remarkable. That's amazing. It's remarkable how efficient this is.
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Chapter 5: What are the challenges of diagnosing male infertility?
It's just wildly compact, 10 times more compact than any other cell in the body. From a mitochondrial density standpoint? From a cytoplasmic standpoint and nuclear standpoint, it goes from histones, the 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.
Sorry, one other question. Where is the ATP or carbohydrates, whatever the glucose stored in the sperm? Stored probably in the cytoplasm and in the tail. Okay. And it's interesting, 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. That's right. Yeah, it is a lot like a rocket, isn't it? It is a lot.
So that's going to bring the physics in. So then there's a two-week period where it stays in the epididymis, which is a 35-foot tubule with estrogen, and there's a lot of post-modification of the sperm.
The epididymis is 35 feet if you stretched it out? Roughly, yeah. And just for folks listening- 700 feet of tubules in the testis. The epididymis is on the back of the testis. It's a comma-shaped organ in the back, yeah. Yeah. And we'll come to this, I'm sure, later. This is prone to infection, and that'll probably factor into maybe some of the issues that deal with fertility. Infertility, right.
Yeah.
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 50s and 60s, but now we're beginning to understand epididymis.
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. Meaning based on its residence time within the epididymis? And what other environmental influences that occur there? Because the epididymis is not as walled off from the body as the testis is. immunologically and otherwise.
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Chapter 6: How can lifestyle choices impact male fertility?
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? I have no idea. Yeah, because I wonder, just for comparison- Give me a minute. Yeah, yeah, yeah. No, I've always thought about this. I like to hunt. So anyone who's ever bow hunted especially knows that animals can smell at a level that we can't even fathom.
They can smell us literally a mile away if the wind is just blowing their direction. So it's always seemed to me like we have really, really insufficient noses. We were given lots of superpowers in many ways, but smell wasn't really one of them. I think- I would agree with that.
And I'd also say that if you block a sensory bank of the five, others increase remarkably like braille. I'm a microsurgeon. This stuff matters a lot, but I can't do braille or hearing. I think you can crank it up if you lose a sense and you see that with people who are deaf. 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.
So one part per billion, this is remarkable. So you mentioned that at the base of the epididymis is basically the launchpad. How many are stored in that? Half a billion. Half a billion. So five ejaculations. Yep. Okay. That's a pot. And what's the time to rebuild that? What's the rate at which you fill? Oh, I don't know. 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 got to move it to every other day or whatever the number is?
So that's a great extrapolation of the pot of soup idea. And so on that note, I would say... Typically, we recommend two days of abstinence, sex every other day.
To optimize. Right.
But not for the semen analysis. That's for conception. Depends how old you are in your biology, but most men need a day or two to recharge completely, a day or two. That's why we recommend that. That's sort of a generalization. Some men are fine every day. I had a guy once who had to bank sperm for hepatitis treatment. And he was like Mickey Rourke, and he had a wooden leg, and he was about 50.
And I said, you're going to need to abstain for a couple, three days to do this semen analysis so we get a good sample. I want it to be an optimized one. And he looked at his partner, and she looked at me, and she grabs him and says... he can't do that. He's every day. He can't do that. I'm always going to do. So he's like, he was panicking that he had to hold off for a day.
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Chapter 7: What are the latest advancements in reproductive medicine?
The fallopian tube, essentially. Yeah.
They bind to the endothelium and just park.
Because if there's no egg, they'll just sit there. 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. Right. Or a death star problem, right? That's right. You've escaped the hostile environment, in this case of gravity. So now it's a fun place.
It's the right pH. It's warm. 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 yeah that's a good one and then the same thing after you want to develop the bell curve of the whole thing well we know that once the egg is ovulated about eight hours and then it's over this is a very important point it really needs to be front if it's only eight hours of survival after ovulation about eight hours it's dead if it's not this is a very very left tail curve correct ah i did not know that so you want the sperm there ahead of time
80% of conceptions naturally or at home occur when sex is front-loaded as opposed to reacting to ovulation. And most of the apps that are available nowadays will tell you that. Peter, you're drawing a graph. I am. I have to draw.
And it looks like it's algebraic. 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. So I'll 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.
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Chapter 8: How important is genetic testing in fertility treatments?
For men, it can be a little bit of a problem. So I would say that lately with... large insurers coming in, Progeny, Maven, and things like that, you're seeing a lot more men up front, which is fabulous. And we can have long discussions about the biomarker concept, why that's good for the field and good for men's health and good for longevity.
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? So getting a guy in is great.
Usually they're dragged in by their partners. Usually the partners come along to make sure they show up. For me, it's one visit. So we do one visit and I do everything else where they are, where they are. I don't ask them to come in a million times anymore. So it's a very different kind of practice.
But I try to get everything done in one visit because when you get them there, it's rare to get them there. And the physical exam, so you do a history, a very thorough history, which is usually preceded by a questionnaire. I give 200 questions and that has all the hot bath stuff and all the exposures they have. And they have to do that before they see me. That's a really important part of it.
If you could pick one in a multiple choice question, what matters the most is probably the history. History of paternity matters, a history of exposures matters, et cetera. Physical exam, very important. One to 5% of male infertility can be due to a major medical issue, testis cancer, diabetes, things like that. So physical exam, varicoceles, is very important.
You could be missing a vas deferens. One in 500 men have perfectly normal testicles, but they have a natural vasectomy. It's congenital absence of the vas. They're going to be sterile or infertile.
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. Right. So we didn't answer that question, which was what's the semen consist of?
It's about 10% vasofluid with sperm. It's about 80% seminal vesicle fluid, which is an accessory sex gland in the back of the prostate, and about 10% prostate. So typically during ejaculation, prostatic fluid, which is clear and sticky, will grease the barrel of the urethra pre-cum.
Then during the ejaculation process, the pellet of sperm gets pumped from the vas deferens into a chamber called the ejaculatory duct. And this happens quickly. And then the seminal vesicle, which is like a bladder, contracts, sends it into the prostatic urethra between the bladder and the outer world. There's two valves. One is the bladder neck. It closes.
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