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

24:30But that sperm, if you put it in it, will know exactly where to go and it'll move forward. Because it's like a shark sensing blood in the water, one part per billion of follicular fluid can be sensed by a sperm. That's incredible. Is literally an olfactory sense. It's a smell sense that sperm have for follicular fluid. So they know exactly where to go. Again, it's, you have to wonder how many years it took to perfect the system, right? You do have to wonder. Do we know what the chemoreceptor is? It was published in Nature recently and something like that. So it's really interesting. It's an olfactory type receptor.

25:06Do we have anything else that we can, is there any smellpator? 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? No idea. Yeah, because I wonder just for comparison, like minute, yeah, yeah, yeah. No, I've always thought about this. I like to hunt. So anyone who's ever oh 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.

25:41We were given lots of superpowers in many ways, but smell wasn't really one of them. 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 microsurgeon, this stuff matters a lot, but I can't do braille or hearing. I think you can crank it up if you lose a sense and you see that with people who are deaf from you. And there's 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 epididimus is basically the launch pad.

26:18How 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? 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? Yeah, 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 absinus sex every other day to optimize right but not for the cemen alphas That's for conception depends on what you are in your biology, but most men need a day or two to recharge completely a day or two.

27:08That's what I recommend. That's sort of a generalization. Some men are fine every day. I had a guy once who had the bank's firm for hepatitis treatment. And he was like Mickey Rork and had a wooden leg and he was about 50. And I said, you're going to need to abstain for a couple of three days to do this seamen also. So we get a good standup. I want it to be optimized when 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'm always He's gonna do something, he's like he was panicking that he had to hold off or take it. I said, often he have sex.

27:39He said, twice a day, every day, like, okay, that was great. And then I had one man, wonderful orthopedic surgeon, it's Dan Ferdinand, I asked him on my questionnaire, I said, often he have sex and he wrote, point, zero, zero, zero, zero, zero, one, three, five, six, I bet. Which means he divided once a year, point zero, zero, weekly, and point zero, zero, zero, one, five, avogadros number, right? Which means he was so frustrated that he had a beautiful way to say that. It was the 0 .001355. So anyway, for a cement analysis, for diagnostics, for infertility, when you abstain longer, your sperm count will rise, but your motility will fall because it's older.

28:17There's a min -max curve that you're optimizing for, which you would say is 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 cement analysis. us. 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 the 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 got regulated and when they got pregnant.

28:52And then they said, do what you normally do and then give us the diaries. And then they evaluated they've been waiting for them and they found that having sex, say, ovulation is day 15 of the cycle. When they started having sex on 9, 11, 13, there were significant pregnancy rates and every other day was the optimal interval. But even five days before and three days before, there were substantial pregnancy rates before ovulation. But if you waited to ovulation and then had sex, that's about 20 % of conception. So when you get the kit, don't react to it, predict in front of it. So, front load to sex.

29:26Very important. And why is that? Is that because... Does a reservoir effect in this uterus? It's managed sperm survive for a day or two. If ovulation is day 15, how could a day 11 sperm survive four days? It's nurtured once it's passed the vagina. But how many of them are surviving? Is it literally the lone wolf or is it the last hundred? Maybe. Some of the sperm bind to the oviduct and wait. Remind me where the oviduct is. So there's the uterus and the fallopian tubes. Fallopian tubes. And that's the avid duct. The avid duct is right below where the O3 is. The fallopian tubes, essentially. They bind to the endothelium and just park.

30:03Is it there's no egg? They'll just sit there and they'll buy. 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 desktop problem, right? That's right. You've escaped the hostile environment. In this case of gravity. So now it's 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 we're gonna ovulate on day 15 and then you would have them have intercourse on day seven, eight, nine, 10, and you create a histoplatte 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.

30:56That's a good one. And then the same thing after you want to develop the whole curve of the whole thing. But 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, but 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 to sperm their head at time. 80 % of conceptions, naturally, who are 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 them.

31:30Peter, 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 it gives 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 trudyated water. They gave men radioactive hydrogen. And then they biopsy 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.

32:06And then we checked with the first... Sorry, dumb question. Why didn't they just measure the ejaculate? Why did they have to biopsy the testes? Did they just want to know about spermatogenesis? But we didn't have biopsyces. We had the exact same... We wanted to torture the guys, but... That's wild, but that was the best data. And we did deuterated water, which is not radioactive, and we could measure that. So we gave them a dose, and then we watched their ejaculates weekly. And we looked for when deuterated the hydrogen showed up in the DNA. And it was an average of 74 days. So normally, say, three months to make a sperm.

32:38So someone were 42 days. And that's going through the epidermis and getting ejaculated. We talked about maybe two months in the testis and two weeks a week or two in the epidermis and then maybe a couple of weeks to ejaculate. And this was all the average 74 days. So actually changed the timeline enormously to a much faster one. So 74 days, so when you do anything to a man fertility wise, you're not going to expect to see anything change for at least two and a half months. And when you talk about full replacement of that seam, and it's probably in the being 90 days when it's all replaced. The pot is replaced.

33:12That's a limitation of what we do. 42 -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. So let's now define infertility. We've been using this term quite a bit. I suspect it actually has a formal definition. So, one year of inability to conceive after sex, using sex. Okay. Doesn't have to be timed in, of course, just has to be whatever the couple does when they think they're trying to conceive.

33:45When 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? 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 Jarvis' data was good, and about 23 % of men get a formal evaluation for infertility before couples go through IVF in North America. And how does that differ from the rest of the world? I don't think it's been studying the rest of the world.

34:27But there are countries like Germany and Spain, with its single insurers and government pays and it's also recommended by society guidelines like American Society of Reproductive Medicine, WHO, etc. 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 seam analysis but may not and there's very complex reasoning there. It's a different beast. They're not part of the problem. They refuse used 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.

35:04It 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.

35:40So 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 baths, 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.

36:11History of paternity matters, a history of exposures matters, et cetera. Physical exam, very important. One to five percent of male infertility can be due to a major medical issue, testis cancer, diabetes, things like that. So physical exam, varicoseal is very important. You could be missing a vast deference. One in 500 men have perfectly normal testicles, but they have a natural vasectomy. It's congenital absence of the vast. 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 vast deference, how the whole thing works in the plumbing.

36:45Right. So we didn't answer that question, which was what's the semen consist of. It's about 10 % vasophluid with sperm. It's about 80 % semolovascular fluid, which is an accessory sex gland in the back with a prostate, and about 10 % prostate. So typically during ejaculation, prostatic fluid, which is clear and sticky, will grease the barrel of the urethra, pre -com. Then during the ejaculation process, the pellet of sperm gets pumped from the vast difference into a chamber called the ejectory duct, and this happens quickly. And then the cellulovestical is just like a bladder contract, sends it into the prosthetic re -throw between the bladder and the out -divered world.

37:24There's two valves. One is the bladder neck. It closes, and one is the re -throw sphincter that we pee through, and that opens, and it gets forced out with muscular contractions. The seconds. Yep. So therefore, if the vas devrens is clipped, you're getting essentially 90 % of the volume. You're just missing the 10 % of the volume that contains the payload. So in 3 ,000 man I've done vasectomies on it 30 years. Two men have said, my volume went down and I said, really? One of them banks 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?

38:00So 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, etc. So physical exam, do you need an ultrasound? How are you able to detect if a person is congenitally missing of asdevrens? Pure physical exam. What you feel it? Interesting. So my fingers can feel two and a half millimeters. The vast difference is like a piano wire. I mean, it is different than anything else in the chord. I did a study a third of my men with abs and vass were only found out having procedures until I saw them. I usually just do the exam, but it is an expertise thing.

38:37Yeah, it's not like the PCP can figure this out. You have to be doing this all day every day I'm saying. Yeah, I think you need to be trained on that. But if you're well trained It should be purely a physical exam. What percentage of men are congenitally missing their class? 1 in 500. 1 in 500. Those common genetics, these 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. Why is that? It's a very interesting biology, but men with cystic fibrosis, most common gen X -E's in America, have no vast difference.

39:14Okay, so what's the Venn diagram of cystic fibrosis and congenital lacking vast difference? The genes for that were discovered. It's a chromosome 7, there's 17, 1800 mutations, maybe 2000. So they clone 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 Epidemic cystic fibrosis, which is a major metabolic disease with a short life expectancy better now. Those men had abs and vass difference in the absence of disease. They took the gene sets and looked at them and they were the same. That's not as many. So you have homozygous or heterozygous.

39:49So you have a carrier for cystic fibrosis. We'll have an abs and vass, but a full -blown CF patient, cystic fibrosis patient, will have no vass difference too. So it's a form of a fruest of cystic fibrosis, but it doesn't have all the chemical and metabolic side effects. So in other words, when you identify a man who does not have CF with a congenitally absent vast, there's a very good probability he's a carrier of CF. Yes. And you can usually define it, which we can generally process easily. Yeah. And then you have to worry if there's a 4 % chance in America anyway that a partner might carry it.

40:19There are two carriers. You have a one in four chance of having a very affected child. So that's a big concern in my practice. And I'm proud to say in 30 years we have no CF children. It's all about good and jeering and doing it right. So that's the vast difference part. What else on physical exam? Are you looking for cancers, infections, epidemitis? Yeah, tell me about epidemitis. Obviously anything that interferes with that section of the journey is going to be critical. Remind me, is it EBV that we typically are measles, mumps, what's the infection? Mumps. Yeah, so among viruses in the world, there aren't many that get into the testicle like other things.

40:56Very 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 paraded 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 to go to your pancreas, caused diabetes. It can go to the salivary glands and then go to the testicles. It's some kind of, there's an open time. 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.

41:31But this is another non -lethal, but significant complication of the mops. Absolutely. And it will cause viral necrosis and a deem of the testis. And similar to a brain, it's in a calvarium, right? The brain is in a fixed space. So when it swells, you've got to do something. Because it can die if it swells too much. Testicles of fixed cavity with the tunic albogenia. 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 and lots of these men, really pockets, but most of it you're blading the testis. It's going to scar and die from a schemic macrosis.

42:05Zika Ebola, I mean the CDC called me when these were coming around. Zika's been transmitted to semen that causes the antinstefeli issues when these pandemics recurring Ebola too. I got a call that there was an Ebola patient who survived when did the Institute survive 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. Meaning the patient that survived Ebola, the virus managed to survive in the testies? Somewhere. But it was transmitted sexually a year later when he was well. When he was asymptomatic, he had already developed immunity.

42:46Right. We don't know about testes, but we know that mumps will do that to the testes, but their Zika is also persistent in the scene. But in that case, you have to think, wherever the virus hung out, it had to be very, very immune privileged. Yep. Or at low levels, like low viral loads where there's no disease. I'm not sure. But these are concerning cases. But then it was transmitted at a low viral load, and even lower viral load. Right. So it's tricky. There may be bubble youth or glands. Maybe it's some ravasco. It's hard to know. But yeah, it's getting away. But most viruses don't go there.

43:17So the big one would be COVID. What did COVID, there was a big deal about the AC receptor being in the lung and being in the testicle? And maybe COVID infection would make you sterile. There was one Zika paper in nature that looked at you infect mice, or was it rats with Zika that testicles shrivel up and they get infertile. And that caused a huge scare in the field, but we really didn't see it. We maybe see it and see if we don't see it in fertility. And what is it about the Zika virus that does this? We're not sure. Why did it in rats? It's a blood testous barrier thing. It's amazing barrier and nothing really gets through including viruses, but mumps does only at puberty.

43:54And Zika does. Zika doesn't have animals, but we didn't see it in humans. But I thought you said that Zika was leading to anencephaly in cases. Yeah, but that could be seminal. That could be just in the semen itself, not in the sperm. Leikibull 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 buying to the AC receptor. It's, Tessile has it too. It's going to make men sterile forever. And there were cases of infertility with bad infections.

44:25Was that just the fever, which duplicate 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 at out of seaters, was a bunch of men maybe not reproductive age died with fluorid COVID. So they got autopsies and they looked for virus in different locations in the body. and I think out of 10 men or seven men, one had it in the testicle. So these are 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 at 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 seeming quality, had a bad COVID infection maybe hospitalized and three months later sterile.

45:11So I think there's a low profusion rate there. What is the phenotype of their sterility? Aside from the presentation that says I can't get someone pregnant. So sterile means no sperm in the semen and typically if you measure the signal so the test is literally what it means. I'm sorry. Okay. So literally no sperm in semen. They stopped understood. 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 to because production of sperm is driven by the brain. So nothing happens to sperm being made without the brain telling you what to do.

45:46Same with eggs and control. It's all a homeostatic mechanism with negative feedback. Classically, anabolic storage users. 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? So in the semen analysis, there's several features I considered sort of a poker hand. There's a volume. How much of the semen volume? There's account 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 liquid fraction a glute nation in 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 and And presumably you want to see fewer of those.

46:36There's a number like less than a million is normal. Okay. So if you ask me, well, how do I look at a seam analysis? That's a little different. I look at that as a poker hand with each card as a meaning, but they have a look. So if you said, what do you mean by that? So if the volume is low, that's one of five things. You're always going to find something. It's at the collection error. I call it first sample syndrome. Guys, not good at it. You know, it's like, okay, I've got to put it in the cup. I've got to stop doing what I'm doing. So you do a second sample. And then there's low testosterone can cause it.

47:04There's an abs and vast deference, which means you have an abs and some of us ago There's a jack toy that you ever have that on one side and not the other. Mm -hmm. No, it's very very but segmental So there's five real issues. So when I see a low volume semen as a surgeon, I'm gonna find something So that's really good other than that the semen else is a I think I've been published is saying it's a blood instrument for fertility unless it's zero You can't really say much about their fertility because people can see that all levels Obviously, you rattled off a whole bunch of parameters that you can access there.

47:33But 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 and - isolated, exactly. You do see isolated things. Right. So one of them is called, I call it syndromic sperm -shaped 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 globosospermia or two -tailed sperm or pinheads sperm.

48:07So if you look at shape, 4 % should look normal, just terrible. We can have all discussion about why 4 % of human sperm being normal is normal when 99 % of animal species in the wild have normal looking sperm, but it's all a construct. It's all a construct of someone decided what normal is. But in men who have large abnormal forms, like 4 % normal, if they're 1 % normal, and you look at the abnormalities. 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 more philogically perfect and 96 % or not? And that means the 96 % that are not could be pinhead, could be double tail, a morphus of tapering into it.

48:48That's a mathematician, that's not a great number, is it? No, if you look at marine species 99, nine look perfect in the wild. Yeah, and presumably that's because their environment is so much more hostile. They're doing this all in the ocean. 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, Cassiopia. Someone named Kruger said, this is what a normal sperm looks like. But we know that two -tailed sperm have double. Yeah, I mean, that might be the two -tail. It might not be the worst thing in the world.

49:16It's just extra rocket boosters. But what about the pinhead? What is the pinhead? And there's no nucleus. It's a tail. That's a true problem. Yeah. Yeah. It's like a little tiny head and moving along. So if you give somebody credit for their two tails, what does your normal go up to from 4 % 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 pads and varicoseleons 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.

49:49The story's in the other chunk. And if they're all looking the same, then it's syndromic. And then you have a problem. I see. So the more homogeneous the... Have an amalgam. The failures are the more likely that you have a clear ideology. And that's hard to fix. I mean, they'll fail with sex. They'll fail with inseminations. They'll fail with IVF. They'll fail with IVF. Yeah, they'll fail with IVF and X -E. Sometimes with global Suspermia where they're called lollipop sperm, they just have a big round head with no acrosome. And there's all nucleus and there's some of the components they'll just bounce off an egg.

50:21They'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 to a calcium or piezoelectric to get it to actually fertilize. Because the sperm is important with fertilization, not only has the bind, but the calcium channels are regulated by sperm. And what shuts the doors to polyspermine and an egg is calcium activation. This is the reason why even if you launch a hundred sperm at an egg, it's only one that can get in because the first guy that breaches sets off the calcium channel that shuts the...

50:56I mean, the Star Wars space analogies here are just phenomenal. Million years. Yeah. There's some million years. No more breaches in the hole. 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 and everything looks normal and they ask me, what's going on? And I'll look at it really closely and say, you have this issue and there's not much we can do to treat it. Now, we're gonna try sperm sorting technologies which are out new in the market, microfluidics and things like that. And I've been throwing that at them.

51:25Sometimes it works, sometimes it doesn't. Is that something that we know the genetic underpinning of? We're getting there. PLZ data deficiencies, one of them recently discovered that runs the calcium channel, which tends to be so -so able to certain look like lopos of spermia. So it's coming around. Think about that for a second from an evolutionary perspective. That's probably the single least desirable genetic mutation you could acquire. Yeah, unless you're not making sperm. Yeah, but this is a dead end to the genome. Right. Right. So does that mean it is only an acquired mutation never inherited?

52:01I mean, it can't be inherited presumably unless it's homozygous, but even still. That's one of the 50 we throw off each generation, 50 mutations. That's just incredible. 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 more than we've given them credit for. All right. So basically just rounding out the semen analysis. Physical semen analysis. On the semen analysis, what if motility is the problem? So I look at in my poker analogy of the hand, if everything looks good but the motility's low, I think of short -term toxins, severity.

52:47So things like exposures, so medications, might 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, Verica seals and exposure, things like that. And if the count down and the motilities down, I think of a longer severe exposure. There's royal flushes and there's four -fackein. My goal when I see that seam analysis and see that patient is to figure out if he's not normal, why? By the way, do you get that analysis the day he's in the clinic with you or is that something you follow up on an appointment with?

53:23Pretty much have it in my hand when I see them. Either they admit 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 putting? 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 allow. Oh, I mean, used to be done manually. Okay. And now it's done with the hemocytometers. It's done with machines. Computers that seem analysis does most of them in IVF groups. It's really standardized. Oh, yeah. I like the bespoke suit.

53:54So 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 us, computer -sistered team analysis. But it's faster and you don't have a lot of human effort involved with the computer. Are they using AI for this yet? 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 we'll be really helpful for morphology to standardize it because one man in and Kruger in South Africa, correlated bad sperm shape with IVF outcomes and did not find that they were good when the sperm looked bad.

54:32That'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. While hoping AI and machine learning can help standardize the look, because sperm is hard. Yeah, given how good AI is, it 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? Right, so to make normal amounts of sperm, you need a proper amounts of testosterone and FSH. Think of it as a flowering a plant. You need the water, you need the sunlight. So testosterone, FSH are key.

55:06To get normal amounts of tea, testosterone, you're gonna 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 calm and 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. Sorry, these men are not making FSH and LH. No. So they have virtually no testosterone. Right. No whisper. But you can give them synthetic signals. So HCG, FSH injections, and they will be fertile. So is the problem in the pituitary, not the hypothalamus?

55:40No, it's the olfactory node in the hypothalamus, so they don't smell either. So could you give them clomid, and would they make? No. No. Tuitary is not working. Yeah. The GNRH is the GSH is not Tuitary. Okay, got it. What about estradiol? Does it play a role? Yes, estradiol is sort of a mild poison for male and fertility. So, everyone needs a 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.

56:14So, 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 at high estradiol. When estradiol is made, it gets metabolized differently than testosterone. It goes to the liver or to fat. And aromatases convert it to something else. Or testosterone gets converted to female hormone and aromatases. So you can get high levels being obese or having liver dysfunction, so alcohol, alcohol, 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.

56:47And that will act in lower testosterone, which will lower sperm production. because you're not watering the plant. 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? Not usually. Okay. So it's really only high estradiol in the context of suppressed testosterone. Right, so that's when you would act on it. If you see that there's a low count and that testosterone's low, and you could say you need to lose 100 pounds, which is the key secret for everything, right? But you can also give a romanticism inhibitors like weightlifters use to keep their levels down.

57:21Okay. So those are four big pillars, anything else besides the history, the exam, the analysis and the hormones. So you usually do two seam 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 seam analysis, any feature of that seam analysis vary by 50 to 100%. So never make a decision on one seam analysis. It's really hard. Yeah, especially if it's the first one, as you said, for for all the potential. So I do a lot of consulting for the FDA and they do medications and reproductive age men and they're trying to show the seamenilece that they're going to the FDA and they're saying, can you help us interpret this data for the FDA?

57:56I said garbage in, garbage out. I mean, there's so much variability. You really can't say anything. So you have to do at least two samples and it's still very quiet, but there's inter -observer variability who does the seamenilece. There's biological variability on what your system's like. So that's the big problem with studies. So what percentage of drugs that are going through an FDA approval process are having a seem an analysis as part of the evaluation? I don't think many. So why is that? Because usually the indications aren't reproductive age metawomen, for some of them. If they do, they'll do animal models.

58:28They want to human studies to do animal models. They'll do beagles, mice and beagles. Right. There's no fertility effects. They don't really look at seem 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 models, which is a million dollars of work. So if you ask me why I patented this Madagoglical 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's management as this model and see if there's an effect at all.

59:03It just seems to me that in this day and age with people reproducing at older and older ages, we shouldn't just assume that because we've developed a drug for blood pressure or diabetes, that it's not going to be used by people with fertility. I'll give you a silly example. Have GLP1 agonists been tested for fertility? No, because it's sort of an off -label use of a diabetic medication. But it's no longer off -label. I know. It's an on -label use today. No, but it looks like it might be helping with fertility. But even if it was on -label, I mean, I'm just using that as one example of a drug 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.

59:43Absolutely. Absolutely. And, you know, there are 80 ,000 chemicals out there that are not been studied reproductively that are commonly used in industry. European commissions are a little better off. They've screened them and they've warned about them, but America. Why isn't? I don't know. It's attention to detail. It's one of those things that It just doesn't, I don't know. Is it under the purview of the FDA or the EPA? Probably a combination of maybe everyone's thinking it's the other person's job. I'm not sure, but they're untested and they're out there. Why don't we just talk about some of those things then now?

1:00:14So, 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.

1:00:45So everything from microplastics to PFAS chemicals to phallates and even the PM2 .5. There's no reason to expose yourself unnecessarily. this, 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. So although sperm are made constantly and are susceptible to that, we know the testicles are a pretty good place to be insulated from exposures, I also think there's a lot of smoke there and it needs to be sorted out. But such, but the 80, 60 to 80 ,000 chemicals that are being used that aren't really tested at all.

1:01:22I 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 away in advance of getting it to clinical trials and where the money gets big. But I think that there are windows of susceptibility in men, unlike maybe with women whose eggs are constantly exposed to toxins. Men have windows, and one of those windows is birth and early development, the first 12 weeks of life. Bad early. When all organ systems are developing, including testicles, I mean, Sean Aswanda, this one, with maternal beef consumption, estrogenized beef consumption, their sons had lower sperm counts when they were 20 years later or something.

1:02:10So 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. 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.

1:02:44I'm not great at that because the stress level goes up so much and I think the stress counter balances any amount of microplastics you save. Double the stress in a man and testosterone level will fall. And then the production falls for a whole different reason. My testosterone level when I left residency. Oh, I bet. So how old was I? 33 should have had a pretty good total T 220 nanograms per desoleter. Did you measure LH? It's probably low. Yeah, I'm sure FSH and LH were totally low. I don't remember what they were. That'd be said secondary. Free testosterone of like, so think of me to four. Well, the sleep deprivation, the stress.

1:03:18So 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 to turn off all that stuff.

1:03:52Then when you outrun the woolly mammoth, then you're behind a rock and you grab the berries and you catch a nap. Boom, testosterone shoots up because it's rest in restore and you have to rebuild for the next run. How quickly do you think that occurs in humans? 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 if you under stress too, penis out of the mind of its own according to DaVinci.

1:04:31I had a guy come in 25 in San Francisco, go, it was startup kind, it comes in, it says, I got to see you. I said, why? I lost my erection yesterday. It's 25. I said, first time? He said, yes. I said, all right, come on in. So he comes in. And he's got his act together. It looks good. And I said, what have he said? You know, I just thought, 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 a 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 This is like we're talking about it.

1:05:10You're not impervious stress has a defect so clearly the fertility or the great study was a Moderate exercise moderate exercise man. I wrote blog on this called can you be too fit to be fertile? So moderate exercise went to extreme exercise measured as two hours a day of VIO to 80 % maximum capacity. So pretty heavy workouts for 12 week periods. So moderate to extreme and then back to moderate. Spurm 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 and training where they were taking their testosterone and LHNs and they were dropping by about 50%.

1:05:53with 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. 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 clomathena and clomathene, 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.

1:06:33Exogenous testosterone, you're just giving testosterone. The body senses it and immediately shuts down the hypothalamus. All natural production. 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 LHNFSH.

1:07:13So LH and FSH will come down, testosterone will go up. And then clomophine or inclomophine block the signal of estrogen at the level of the hypothalamus. So the hypothalamus thinks. This is the thing. 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. And the two different classes are the LH and clomid versus testosterone. So unlike testosterone, shutting off the natural production, the LH, the ACG and the comaphyne and clomaphyne 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 the exogenous testosterone, but these will never get to three thousand, you can't do that.

1:08:06It's tightly regulated. 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? 95 % chance he's not. Wow. While he's on it. Yep. Understood. Like, can he create it once he stops? 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. 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.

1:08:53So there are variations in the spectrum of exogenous testosterone that will maintain some of your fertility. 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? Yeah, so they do more physiologic. They're in the normal range more.

1:09:28What gives you side effects from testosterone, including sterility is too much. Yeah. So in your experience has that borne out? Yeah. You've seen men taking nautesto three times a day doing a nasal keeping their sperm counts, keeping their sperm counts. Okay. That's interesting to note. What about the oral testosterone the twice a day? I love it. Tests are not going to get in the way. And it was not available in America for 50 years. It was available in Europe. And a couple of researchers at UCLA has been a wife team. Beautiful. What happened was we were worried when we took oral testosterone to go to the liver, right, to the biliary system and go to the liver, cause liver cancer.

1:10:06So it was always verboten. Even though there was no evidence this was happening in Europe for 50 years. Yeah, not much. It's FDA approved. EA approved it. So this group came up with a way to get it metabolized through lymphatics. So it can absorb through lymphatic 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. Do you prescribe it? Oh yeah. I'd be interested to hear your experience with it. We have prescribed it now to maybe a half a dozen patients.

1:10:40One of the silly challenges we have with it is we actually have no idea if they're therapeutic because trying to get their blood drawn to figure out when to draw their blood to actually see the level. For example, if a guy takes the drug at 8 o 'clock in the morning and then at 1 o 'clock in the afternoon, which is sort of what we're told is a great window to take it so that you get that mid -dose, mid -dose, right? If he does his blood draw at 7 o 'clock the next morning, he's been 18 hours off drug. He has unmeasurable testosterone. He's going to show up at 200. He's going to look like I did 50, 20 years ago.

1:11:13His 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. 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 he and statically, right? But usually you can get pretty good levels because the half -life isn't that short. They say it peaks in five hours. So I don't know what the half -life is. The half -life would be a - I don't really like 12. More like 12. You wouldn't dose it at 100 % decay.

1:11:42a dose at 50%. So he's probably not responding. We can check it at different times, but it's probably not much of a response. And what are you dozing it at? It comes in 100 and 200. 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 in the problem, right? If you want them, you're not going to get them to 800 or 1000 very easily. You can get them 400 to 600, 600, 700 pretty well, but no side effects. I haven't seen anything that maybe a couple dozen men really well tolerated.

1:12:17Interesting. So this is not something you used when you're trying to get a guy from 300 to 1000. You could, but probably at the first twice. Yeah. And now you're taking 500 twice a day or something crazy like that. Yeah. Twice a day is a big deal for men. It is. What about in the test? How are you? Are you using? I've never, you've never been tolerated What's the experience like? We've never used it. Well, have a flu and try to get your testosterone level off. 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 within a week we'll call and say, can't do this.

1:12:50Yeah, we've had more luck getting women to use this. 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 different widely. It's very difficult to get polycytemic or thickening 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 asodinously, you're at risk for polycytemia or blood thickening. So testosterone simulates epipotent. And the kidney, you make more blood, athletes love it. But if you went a long flight and you're dehydrated, you're gonna throw a clot.

1:13:27And people look at it for longevity and it's like, be careful. Because I've seen seven -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 And do you find that the clot risk is proportional to hemoglobin hematocrystalline? Absolutely. What level are you saying? So I mean the studies aren't broad but Rama Sami 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, 18, Maddicate 50, you start seeing events happen about 18, definitely 19.

1:14:03One of the things we do with patients who are injecting testosterone sipionate, and we have some patients who love doing this, I think it would drive me nuts if I were trying to do this, they injected 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 polysychemia. Right, because they don't hit their... 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. Highest risk, yeah. So, what is your typical injection schedule?

1:14:36So, once a week, and I think twice a week, you can have the dose, right? So that is a little safer, but then it becomes the intensity and just a bit more, I can't do it like that or whatever I want to pellet instead. Do you put pellets in? Oh, yeah, I do them all. 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? Yep. So palettes 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 of minute procedure in the office. You don't have to worry about anything.

1:15:06There's no compliance issues. You don't have a lot of side effects or consequences from it. It's done with a choke -ar and a thick needle. And pretty quickly, within a couple days, you'll get a level and then it'll slowly decay pretty much half of it by three a month or so and then the rest by four to six. It's 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 period of risk, and then usually when you're in the normal range, it kind of goes away.

1:15:37So I don't see a lot of consequences with that if it's six months. I really don't. So let's go back to the Clomet HCG route. What is the extent to which fertility is preserved when a man is on one of those agents? So, clomet 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, what your FSH is, you don't have any sunlight, you're not going to bloom.

1:16:09So, I usually add clomet to HCG if the dose is above 1500 units three times a week, because that's going to start suppressing the FSH. And clomet will keep it going, and then your fertility's preserved. 1510 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? Right. LH will, because it's LH, but not FSH. No. Maybe 1 ,000 to 1 ,500 you start seeing it. So that's why you protect the fertility. And what dose of clomid will you give on top of that regimen? Depends, I mean, usually half a pill, they... Half a 25, half a 50.

1:16:4650 milligram pills, yes, usually half. You'd give 25 every day. These are staggering doses. How high are these guys testosterone getting? That testosterone is driven mainly by the HCG. I shoot for the normal range of 500 to 1000. I'm not an antibiotic guy, I'll know. Yeah, yeah. No, it's interesting. I mean, we don't like clomaphine at all just because, well, there are a bunch of reasons, but they have to do with kind of lipid stuff. Even when we would use it, we would probably use 53 times a week. So that's about the same, right? 25 a day, but for most guys, that would be sufficient alone, even without HCG.

1:17:22Well, HCG is at striving the tea, which is trying to protect it. If you said, what do you give on isolation as monotherapy? Yeah. What would you give for Clomathine? 12 .5 to 25, typically depending on how sensitive it is. And do you prefer Clomathine and Clomathine? So it's very interesting. Clomathine is really good. It's an interesting FDA story. So Clomathine is not approved for men. And Clomathine isn't either. Clomathine is approved for women. and clomophines are not approved for either. Clomophines compounded, clomophine is available for 50 years, so a lot more data. And once a cis isomer, it was a trans isomer, so they're different.

1:17:54And the estrogenic effects are slightly different. So I have enormous experience. I have 560 men on clomophine, and I have fewer in clomophine. 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. This was clomaphine. And clomaphine citrate. And they were done by reputable people in the field and published. And then it went to the FDA for approval for secondary hypogonidism, sort of age -related changes, not primary testicular failure in age -related androgen deficiency of the aging male or atom.

1:18:37FDA sat on her for a couple of years and said, Nope. What? Good question. So it's published. They're good trials. It's safe. It's as good as Clomid and that 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?

1:19:11So 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 the used to be? There's 10 questions in the adult questionnaire and everyone who ages... Everyone who ages... Everyone who ages has those issues, right? So it's like no brainer if they go on TV, they're gonna want this stuff. So the cats out of the bag, they're stuck. And so now when any testosterone trial comes back, they're going to point out the FD make sure that we point out the dangers of testosterone replacement.

1:19:42So this is part of that energy, which is, we don't want another testosterone. So I think there's another reason, Paul. And it's everything you just said, but HCG and testosterone are scheduled for, 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 clomaphine 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?

1:20:24It's already bad enough that the clomid cat is out of the bag, but we don't want to put another one of these unscheduled drugs out there in the land of shady medicine. The indications are pretty clear and they're really safe. They're really safe drugs. My effect is someone comes in who's young, who maybe wants kids, hasn't had them. and they have a low testosterone of 220. You measure their LH, which no one does. It's low, secondary hypogonism. So it's not a testicle failing. It's a signaling issue. And that's probably stress. So I say, get rid of your stress and they say, how do I do that? I go, okay.

1:21:01So 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 in 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 really, it's not working. And they started shifting over to exercise. I was very proud of them. These guys I was really happy with, like, nice, because that's the best way to handle stresses.

1:21:35When you have no control over things, go for a run. Go for a walk. Get out there. So good for you. It's the compressing hole to 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 a clone. And 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. Arrections aren't typically that dependent on testosterone. Typically it's other things. I'll give you the benefit of the doubt.

1:22:07Maybe 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 you with them at three and six months. How are you feeling? I feel great or, hey, it's not working. I feel the same. It's like, well, it's not testosterone related. Whatever your, this symptom is you're having, you wouldn't have it with a testosterone. We know levels of testosterone above which you should not have symptoms. We know libido, we know erections, we know fertility, things like that. And what are the approximate levels for each of those.

1:22:36I don't know. A erections, I would say, the best studies about 290. Yeah. So most guys that are having difficulty with erections are above 290. There's some other issue. Usually. Yeah. But you have to prove it to them. Yeah. And I find with that, it's almost as safe. You're convincing them. And then what about libido? 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. For tility, I'd say 300 is a good one. These start seeing issues. With how much FSH and LH? I don't know. Okay. Obviously, the other thresholds would be anabolic capacity like muscle mass and things of that nature.

1:23:10And mood tends to be a lot more variable in my mind. 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 in your 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 into testosterone, that would be blood and muscle. So more is better for making blood, doping, and also blood doping, and also for muscle, absolutely linear.

1:23:44I'll tell you why I find that interesting, Paul, and I only learned that really in talking to body builders who were taking 500 to 2500 milligrams of testosterone a week. Because my initial reaction to that was you've already saturated the endogen receptor, probably five logs, I mean, not five logs, but at least one or two logs earlier. But they convince me, no, no, no, there is 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 mean, how many energy receptors would you need?

1:24:18You'd have to up -regulate them when, in fact, you'd be down -regulating them. 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. If you push the system and you need two days to recover, you can go to one day, you can push it again harder. That's what testosterone does in the primitive world. There's even studies that show, by the way, that high enough doses of testosterone will increase muscle protein synthesis, absent the stimulus.

1:24:47Absent the lifting stimulus. 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 push it again and that's how you build muscle. 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.

1:25:20So 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. Loan 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. I would bet 95 % confidence that he would have no sperm in his semen. Okay. So what are you telling him now? How are you going to solve this problem? So it's funny because a lot of guys come in and they look good.

1:25:53I want to 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 it. If they're super jacked, but then they have shriveled testes. Yeah, and they're zero. And they're wondering, what? You know what I mean? So I will look them in the eye. So you're 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.

1:26:21It's this verboten thing. 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 candle stick and they're colon. And then you say, yeah, yeah, what about this candle stick? And they're like, oh, I totally forgot to mention that. Yes, yes, that was lit. What I went in, yeah, yeah, yeah. So my theory is about this is why is he taking it?

1:26:52So if he's taking it for antibiotics, and you know, he probably has a pretty good idea. I want to give you a little research we're doing on the lifespan of antibiotics storage users. So remind me at the end of the story, it's give you a little brief on 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 Antiquant Society on covering men from hypogonism and young men. And I asked them a question at the end. My whole procedure comes from steroid users.

1:27:29I take notes when the antabolic guys come see me because they're really smart and they know a lot about reactions, biology. It's incredible. 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. We'll link to this in the show now. It's for sure. Getting off the juice.

1:28:00And 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 betoe terri, you get back to normal and then you hit it again. That's actually quite smart. Constant use is not. Constant use for longevity, 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 under -concestiety since I answered all their questions.

1:28:34I said, I have a question for you. Can you turn a testicle off like in a thyroid or in a adrenal gland, if you suppress it enough, can you turn it off for good?" And they said, yeah, that's a part question of ours. We can do that. And I said, because we believe it's always reversible in the field of infertility in men. And so that got me a little worried. And so now I kind of worry about five to ten years of use. After five or ten years of use, you may not get it back. Either the ability to make sperm or the ability to make testosterone. We typically tell men in our practice, two years would be the absolute ceiling.

1:29:04Are we too conservative? Maybe. Okay. Depends on dosing and everything, right? If they're 250 a week, that's in our practice. It would be 50 to 20. Published a study on as a fellow in Houston of a guy who took it for 25 years and we drove at him with his 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 and his testicle and he's going to be having a kid but he made a couple of sperm. But you pump him full of HCG and synthetic FSH. And get nothing and then you have to look in the testicle because production can be low enough to be there, but not coming out.

1:29:44But this is the rescue protocol. It's LHFSH. Basically, there's three ways to do. One is never stop the testosterone suddenly. Hmm, interesting. Because men all hit the doldrums like a poop 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 systems 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 to testosterone over what we've heard it done. Six weeks, typically you have the dose for two, you have the dose for two, and then off for two.

1:30:16And 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 clomet or clomaphein, which is a little quicker, getting the pituitary to turn back on. So that will soften the below of the feeling of feeling completely fatigued or more aggressively HCG and Cllomid. And then I usually check them at about six weeks. It's interesting. If you give Cllomid the pituitary will make FSH and LH, it takes a while. Well, that's a way more cost -effective approach than giving since, because synthetic FSH is pricey.

1:30:55Yes, a couple thousand a month in America. So is there any reason to do that over the climate approach? Or is it just that it's faster? I think you might gain a couple of weeks of time. So for most people, that's not a price worth. 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. What would be good if they're in a normal range? Oh, really? Okay. We want within a couple months to see them back to 600. 300 would be okay to make sperm.

1:31:29Okay, 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 so you wait longer to see how how 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 start over. But if you 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.

1:32:00Now, I want to get onto some 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? All the time. Okay. Not an unreasonable approach to combine Clomid with testosterone at low doses to preserve to stickular function. Yesterday, I operated on a man, testicular sperm retrieval on a man who's a sparmic for genetic issues, and he was on testosterone for 10 years because he needed it. His testicles were failing, and I said, you're not gonna make sperm on this.

1:32:38So 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 8 CG for six months. And what dose did you have on? 3000, three times a week. That's a whole vial a week. Yeah. Wow. 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 or trivially yesterday, boom, plenty of sperm.

1:33:13How old was he? 35. Interesting. You can maintain whatever's going on in a testicle with HCG and take any testosterone you want. That's an important lesson. Here's the catch though. The caveat is it was done in, I think, Finnish bodybuilders. They were doing a cycle of steroids huge amounts. They took Lotus HCG 500 twice a week. And John Aimer, he has worked out in Washington, has worked out all the exact doses, but 250 to 500 twice a week is a good dose for that. It keeps your inter -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.

1:33:54At any dose of tea, now what happened after that is people start saying you can preserve your fertility on testosterone replacement, which is possible. They missed half the story. 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'd have to be 95 % compliant. Do you think that there's a difference between HCG and Clomad in that effect? Oh yeah. Yeah, the Clomad doesn't work. HCG is the one. Yeah. Clomad doesn't improve intertesticular testosterone levels like HCD does.

1:34:26It's ineffective. Got it. 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 out of percent compliant with dual therapy. You can't go on monotherapy with testosterone. Outside of fertility, given the popularity of testosterone replacement therapy today, is there another advantage to just doing dual therapy? Obviously for fertility, we wouldn't be talking about it. But can you think of any other reason why it might be advantageous if a guy can deal with the hassle and the cost.

1:35:04Yes, depends on the indication though. Everything but fertility, like any other health benefit. I think muscle mass. So with aging, it's a great one. I mean, used to be like growth hormone with eight wasting syndrome, things like that. I mean, muscle mass is a key for men. But I'm saying as opposed to just being on testosterone injectable, to do the dual therapy versus just monotherapy. I mean, if you're going to do some kind of therapy, if you've committed to doing therapy. No, I think the only reason would be if you want Testicles to be big. Okay, so just volume. I just created a new procedure to make testicles larger naturally by putting a fat injection in the hydrosylle space in men on testosterone because they don't like their small testicles.

1:35:42So it's the equivalent of the Brazilian butt procedure for the testies? Yeah, so it's all natural and there's no prosthetics and you can't tell and it makes some nice and big and test is fat grafting and it's fabulous. Medicare improved? No. Yeah. Creatively approved. So let's shift gears and talk about other modifiable factors. Let's talk about heat. We've talked about it a little bit. So fertility. Yes, for fertility. So tell me about the impact of cold plunging and sauna and hot tubbing on fertility for men. Okay, so the test says outside the body. It's three degrees cooler than the rest of the body, so 95 versus 98 degrees Fahrenheit.

1:36:21And then there's a reason for that unknown. We had that conversation. and 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 don't we could figure out. But if you heat up the testicles, it's also close to the skin. So it's a radiator. So when the heat comes down to our terroblood, it has to cool. So it raises and lowers and there was an article in the journal of irreproducible results about 20 years ago. A man went to Big Sur and wore nothing and he measured ambient temperature and then he marked on this leg with a marker where I scrolled them hung, how low it hung, and he could tell the ambient temperature by how high or low his scrolled them hung.

1:36:58He became a thermometer. So it does go up and down. Is that p -dirt ill -haffing? Journal of irreproducible results. Oh, 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, etc. You go into a cold shower or a plunge where your testicles, they're way up in my abdomen. And that's all the cremastoric muscle and it's all temperature driven. So it spends all of its time regulating its temperature to state 95. Now, sauna's baths, hot tub secusis, steam rooms change that. The worst one of those is anything underwater, submerging underwater, because you're one centimeter away, you're liquid, it's a liquid, you're going to turn that temperature, maybe not the inner part of your body, but little kids going into hot tubs, right?

1:37:46they overheat. 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 testies will assume that temperature. Absolutely. You're 70 % liquid. This is right at the surface. So I did a study, published it in the Brazilian Gerogirology. 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 Eurology. It then went to the New York times as a press release. That's how popular it was.

1:38:18It'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 to wear jacuzzi. Jacuzzi called mebs at stop. Don't use that word. So I don't use that word. So hot baths are tubs. And I told them out and they went up 300 percent. Seam in quality went up 300 % total more count in three months or four months and 600 % in six months. They have to give us some time and that's that curve, the recovery curve. And we didn't look at fertility, we just looked at that recovery and someone was zero and went up to close to zero.

1:38:54What was the age range of these men? 35. So fertile men. Yep. Trying to conceive. 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 total motor sperm count I mean count motility mainly driven by motility interesting so it's motility that the price the biggest one But also count might have doubled chili may have gone up threefold kind of thing so sixfold increase overall Then I calculated after that I calculate a lethal dose of tuffing so what's the lethal dose? Yeah, which the only 50 yeah, so lethal dose to me means you're zero You do it enough, you have no sperm.

1:39:32And it came out to eat 20 minutes of a hot bath or a tub, 20 minutes on 104 degrees, three times a week would probably make you zero. There have to be a lot of guys out there who are spending at least three times 20 minute sessions in a hot tub that's at least 104 degrees a week. Interesting. The largest group of people in Tubbs at Northern California would do the study where environmental lawyers. It's your job that stressful? It's a kid. It is. I mean, it probably isn't California. All right. So the only study ever done prior to that was a PhD thesis at Vastor College, where someone had a guy dip their test skills into a bucket for 20 minutes.

1:40:12That 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 the steasest 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, Jewa Condom and it drew birth control pills and it drew a guy into the tub. It's like pick your contraceptive. So it's huge. I'd say 10 % of my populations in it. And then the next question is, what about Saunas? So Saunas is not underwater, it's not some immersion.

1:40:41But Saunas are you're in a hot room, it's going to affect it. And I would say the effect is one quarter to one third. It's profound as a hot bath or some immersion. So my friend was absolutely right to have those ice packs on his scrotum. I think he's reading. Yeah. He's a smart guy. A terrific protocol. Yeah. And then I would say steam rooms showers are probably fine. You're in an ambient temperatures normal. And I think steam rooms are probably between solnism. It depends on how much time you spend, but it's probably not normal, but not a hot bath. Hot baths are terrible. Okay. And then what about the cold?

1:41:16I don't worry about cold. I remember surf from magazine called me and said, I'm on the water, California surfer, right? Not at least surfer. The editor of surfer magazine column he says, are surfer from fertile? I said, is that water bad for them? Cause California water is six degrees. I said, no, I've never met an infertile surfer. So I don't think it's bad at all. All right, so the cold is okay. So that you've especially plungery talking seconds. Yeah, you know, your testicles are gonna go up. Yeah. 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.

1:41:46Cause enzymes work in the testicle at that one temperature. They work optimally. 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... We ran it up to two hours a day of exercise. Five days a week. ...that was above 80 % of VO2 max, which is pretty strenuous. That's right. ...that was enough to put a dent in their fertility. Tell me about riding a bicycle. I'm a biker. I have old vintage bikes that I used to race and 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 a Brooks saddle, the Brooks Brothers saddle and you know all worked out and it's like that saddle nowadays is about half the weight of carbon bike but I love it and I'm I was thinking of maybe going seeing your league and doing this gorgeous steel frames and trying to keep up with those guys because Is it not about the bike really?

1:42:45It's like when you get golf clubs and I got $150 that are golf clubs. I'm going to be it's bad at golf or with $1 ,000 club is on it. So it's really about the bike. But there are some differences. I'm in terms of momentum in the wheel force and all that. But I love my old steel bikes. And they see this and it's like, hang it in my office when it comes to work in the morning and I bike in in San Francisco. And then I have this seat and it's like, that's a bad saddle. And so the issue really is, it got started that biking was bad for reproductive health with a Spanish competitive cycling study. Competitive Spanish cyclist, Tour de France caliber cyclist, their sperm counts for example.

1:43:19But what was the control group? Do they have a control group or runners? I don't remember, I don't think so. So in other words, it could have been the exercise. It could have been the intensity of their exercise. Not a good group study. Yeah. So their sperm counts were low, their morphologies were off, and their 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. It was certainly exercising two hours. And so they said, look at these guys who are really healthy and look at their sperm counts. But this other day did come out.

1:43:46So I did a blog called cycling into childlessness. And I looked at a more comparable study, which was British commuting cyclists. Every day people basically knew work in Britain on different saddles. And I looked at their fertility and their fertility was far better than the average Brit. 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.

1:44:21In 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 even remember what they controlled but I think they did a lot of the socioeconomics. It may just been activity, but the bicycle... So is this a myth? Yes. Now, if you said, are my worried about bicycles, yes. So I worry about sexual health. I worry about the pedendal nerve, and I worry about seed anatomy. So the best seat for a bicycle. So if you're biking a lot, that's good. If you're biking and you're getting pelvic numbness, that's bad.

1:44:57Okay. So you need to get a better seat. The best seat was studied by the NACH, the N .A. I forgot it was just Dr. Schrader at the NIH. The best seat is the saddles that are shaped like this are bad for your sit phones 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 in. So we gave those to police in Washington, the bicycling police, then in the national cathedral area in the parks.

1:45:31And they all gave the seats back a week later, said, you know, not doing this. They 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.

1:46:02And there's only a couple of different saddles, maybe 12 widths that you could do and you get it done. Or like me, you use a saddle, use for 30 years, and it's perfect, but it weighs four pounds. That's because it's a leather saddle and it fit to you. Yeah. Yeah. Iconic. Okay, let's talk about alcohol specifically, and let's talk about any other recreational drugs. 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.

1:46:41So I worry about it a lot, the effects IC 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's into the testicle. Second would be a hormonal effect. So alcohol use tends to cause the liver to rev up tends to cause more estrogenization So you tend to get low testosterone from that. So it's a hormonal effect and a direct effect any evidence that it's having an epigenetic effect Probably I don't know if it's but I'm sure it does. Let's talk about common recreational drugs. Let's start with marijuana That's the worst player for me.

1:47:19So 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 epigenetic showed alterations with nicotine and with pot. What I don't like about pot is you ingest it and however you ingest it, you get a peak, you feel it, it goes away, you feel it's out of your system like nicotine, but it's due to the fact that for months or three weeks and it's It's a depot effect and it keeps coming back.

1:47:51So we get a low level toxicity, which I don't like at all. So I am not a phenopathy. The other thing that really concerns me about pot and reproductive age men is I wrote a couple of blogs and this is called The Weed Waries. And there's some compelling evidence from epidemiology and two studies, 10 years apart validating each other that chronic pot uses a sociable testous cancer. And we think that that's causal. I don't know, it just worries me. Weed worries me. 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 effects.

1:48:30I mean, it's a decent phenomenon. It's medical marijuana, right? So medical means safe. But 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 say, which is worse for driving? Being stoned or being drunk? Undoubtedly being drunk. 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 We're still in this thing. I'm not saying that one is driving stone is good, but there are probably far fewer people that die at the hands of a stone driver than a drunk driver Probably, and I think the signs the LA story signs and they have the lit up signs about open season traffic The movie LA story they knew say now drunk or stone to watch out we're gonna get you What do you think is the mechanism of action by which THC is having these negative fertility impacts?

1:49:19Not sure. I don't think it's the mechanism. I don't think it's the root. So I don't think it's talking 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 in blocks it. But blocks it from LH. So you can get low testosterone, but it's not been that profound. What about nicotine either synthetically or in the form of tobacco? Bad actor at high doses, I think, to either one. Yeah, it's nicotine. It's nicotine per se. Yeah. It's the issue. And it doesn't last as long as THC. It does have count motility effects and fertility effects.

1:49:56We think probably both of these are accidents. It's the accidents that do it. It's oxidizing things. 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? Probably all of them. I don't think we know exactly, but I'd say that eye diagnosed diabetes and a lot of infertal men. I make the doubts. What's the physical finding you're seeing in the testies that tells you, like, you know, how an ophthalmologist will often make the diagnosis because they're looking into the eye?

1:50:34So for me, it's usually their weight and their count motorior low. I'm looking for a chronic exposure. And then they have polyureia or polydipsia or something like that where they're drinking a lot and they're peeing a lot because the sugar is dragging it out and you check their UA and it's full of sugar. And then some of them have an A1C that's a little pre -diabetic. But I think a lot of it is neurogenic too. They can develop an ED. A third of type 2 diabetics have low testosterone, so that's a clue. And that's secondary, so you can clone it, you can bend it right back. But that's probably the common one is the look, the sugars, and then the low T and the low sperm count, to kind of a picture.

1:51:15And 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? The most common is a vericoseal. Okay. Tell people what a vericoseal is. You can develop varicose veins in your leg and knee 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 the drain back down. The reason why it drains back down is because there's a species we stood up half a million years ago, maybe three -quarters of a million years ago.

1:51:51And 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 up hill, 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 mud that's supposed to be staying up there, comes back down to the testicle, pulls around it like a hot bath is warmer. And usually the first sign is a testicle on that side, which is the left usually is smaller than the right. So the physical exam will be a testicular discrepancy in size.

1:52:24That's the first thing you see. And then you feel above it and you feel a bag of worms. But sorry, there are no valves in that vein. Correct. So what's the head it has to climb? That's gotta be the centimeters. There's seven meters. So how is it doing that without a valve? I don't know. That's a pretty big distance to travel about. They build a dozen at night, I don't know. Yeah, interesting, okay. But there might be a few. During puberty with 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 K. of a so it's kind of has to go around 270 degrees.

1:52:54So you don't reflux on the right. Left side delusion in most men, you can be perfectly fertile with it. If you look at statistically, 85 % of men conceive naturally without varic seals, 80 % will conceive naturally about a year. So the curves are very similar clinically, maybe insignificant, but there's a difference in its statistical. But if you multiply that by millions of people, it becomes important. And you'll figure that out easily on a physical exam. The best way is easy if I don't order all the sounds. If I can palpate it, then it's clinical. That's an office repair. It's an outpatient surgery takes a now we do my.

1:53:25Oh, it is. Yeah. So it's more involved than a vasectomy. Yes, it is. And you're doing it at the microsurgery at the level where you don't cut muscle. You want to recover quicker. It's an involved area with lots of veins. But he's not under general. I use a toilet. I try to lie to sitation. Yeah. So that's the most common. That's the most common sense. Wow. And most men are fertile. But so again, you look at the semen analysis as a poker hand. And you see count and motility being down. nothing else going on and you see a varic seal and it's implicated. All right. Have we missed any other of the major ones?

1:53:55I'd say the major ones are varic seal and then I would look for hormonal issues. So varic seals may be 40, hormonal may be 10 or 15 genetics. So they're non -modifiable now. Right. Okay. So you talked about a few of those already. What are some other ones on the genetic side? The most common one is for zero sperm is client filter. This extracts chromosome. The most common one for low sperm count is Y chromosome deletions. This is an interesting area. What does that phenotype look like? Now phenotype. In general? Yeah. No phenotype. Normal. A Y chromosome deletion male? Yeah. Because it's only the long arm, and it's only a couple of floors on the building.

1:54:32There's regions that are missing. I see. Okay. I'm sorry. I thought you meant a complete deletion of the Y chromosome. Right now. Yeah, yeah, yeah. Yeah, yeah. Partial. It's the long arm. It's deletion's regions. Yeah. Rhymovolution, you're right. So Rany Raiopera found at MIT 20, 30 years ago now that the Y chromosome is a hall of mirrors. And in meiosis, every chromosome has a partner, except the Y and the X and the 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.

1:55:06So 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 the Y is very important. It has a gene called SRI, which makes you male. The SRI is the male sex determining gene. If you have that gene, your phenotype will be male. If you don't have that gene, you're probably going to be female. It's complicated now, but that's sort of what it is. But the long arm has these genes that control fertility, and some of them so typically we ordered it in man with a low sperm count of a low 5 million.

1:55:40So 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 and always. It's who you are. But if you didn't have the Y chromosome deletion and you fix the varicose, so you'll expect a good response. Two thirds will improve. One third or more will conceive naturally. So you could take guys with low sperm counts and you can fix them or not, but the driver's genetics.

1:56:11And the phenotype in offspring is simply inherited as a Y chromosome deletion. It'll either be, I just had a couple of contexts. Actually, he had a Y chromosome deletion. He conceived with a help of a 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. And until they try to conceive, they would never know this. Everything else is normal. So then there's environmental lifestyle things. So I think obesity is a big one. And do you think that that's mostly propagated through the endocrine system then?

1:56:47Yeah, that's a big one. In terms of the percent of sperm with the lifestyle issues and then lousy diet is probably something that's obesity and diet lifestyle recreational drugs. What else do I review with them? Toxic exposures at work. So any smelly solvents, I'm really aware of some airport fuels, airline stuff, machine shop, oils, anything benzene, derivatives. Used to be pesticides and stuff like that, but they're pretty well controlled. So environmental exposures are kind of an unknown. I think viruses have a role. That's how you recently wrote about HPV. And I've been thinking about that for years because there are men.

1:57:24They 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 at 10 or 20 % with lifestyle issues and stuff like that. You can pretty much sort it out. It's not that unknown. But there are men who are like, what is going on here? He's a perfectly healthy guy practicing in California is incredible because everyone's so healthy. You have to look elsewhere. You have to ask other questions. And when there's obesity, it's always the elephant in the room, but everyone's so healthy in eating. So I get to poke around places where no one else goes because I have to explain it.

1:57:57and there's nowhere to go. But I did study, so HPV's the most common, rewrote about that, is that what's the link? It's hard to know. There's herpes, very common. The STDs that we know about, like the 11 common beasts, chlamydia and gonorrhea and syphilis, those we know a little more about, and they're pretty obvious. But some of these trick -a -monus and stuff are pretty subtle. I was really concerned about this, because one guy, 20 years ago, and now it's professor, you see a staff, he sent me a picture of an electron photograph of a sperm with a hexagonal herpes virus in it. I don't even know what's photoshopped it.

1:58:28It's this virus and a sperm like, yeah, it looks like this. Where's the 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 semenin, you'll see puss cells. So you'll see what's called pylspermia, leukocyte -spirmia, the round cells we talked about. When the semeninels is, we'll 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 semeninels as the volume normal count. Well, Tilties really loved a lot of the sperm or dead because they've been wiped out by these cytokines and all the white cells.

1:59:01And then maybe you'll find the pathogen somewhere, right? But culturing, Michael Plasma, CMV, all these viruses. So Joe D 'Risi, really bright guy, UCSF, one of MacArthur Ward, he took my patient, Seaman, it's back when Microwave is popular in the 2000s. And he had like 2000 all mammalian viruses on his chip, everything. And we ran fertile guys and we ran infertile guys and looked at seam and nuts per arm. And 99 % of the infertiles are positive for something and 98 % of the normals are 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.

1:59:39So 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 we'll see an analysis as a Theta -Ralions, a blunt instrument? It varies a lot, it's tough to do it, but I'd love whether we do genotyping on a recent 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 it's effect would be post -ajaculation, which could still have a fertility effect, but it won't be probably as deep.

2:00:16And what if, for example, a guy has prostitutitis and the prostatic fluid has... Puss in it. ...puss in it, then that could sabotage the whole thing. 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. Yep. So if your urine's infected, that's a big deal. Have you done work with intratusicular PRP and stem cells? Just stem cells, but not PRP. Not a big fan as a trained stem cell biologist and someone trying to make sperm from skin.

2:00:53And working with some of the best stem cells, times 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 bull 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 gonna do this, and then we're gonna do a microdisection 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.

2:01:30So 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'm 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 it's unfounded. 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. You're forgiving space, Peter. 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 reason.

2:02:15It'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. I agree with that. But boy, I'd like to figure it out without people wasting. I think there's a bear there. There's a bear there, but it's just not that easy. Yeah, let's just say for every hundred guys that walk in your office who are struggling within fertility 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 etc Without requiring and let's exclude the 40 % varicoseals because you're gonna fix those guys in their find So, 100 people who don't have a varicoseal, who don't have a genetic condition, I'm going to really simplify this.

2:03:05Okay, so these are a hundred guys that presumably have showed up with some eye atrogenic reason for infertility. How many of those guys are going to be able to conceive without resorting to IVF? I would say it's the goal of my practice, and I would say the answer is most. Wow. But the caveat is we've got to tell you about the woman because I will defer. This is the only date I can give you. So I did a paper where I saw men for their infertility that I was you got it done and I thought they were fine. They had varicoseeals and stuff, but their seamen else was as normal and my investigation of their admiss lifestyle, everything was good.

2:03:40And I said, you're fine. You're cleared. No one's ever said that before. And they went home and they said, Turquan figure I was wrong with us. 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. I didn't get interpreted like that. I got me a little angry. So I did a study with USC, and I took these men that I cleared, and I called them up a year later. And I said, what happened last year after TURT? Clear do at a resident do this. And the answer was 65 % to conceive naturally.

2:04:15Another 15 to 20 % conceive of the IOUI or IVF. These women were 35 years old, year and a half in fertility. They weren't going to wait around. Most conceptions occurred within six months. I didn't do anything for them. I didn't fix the rarex seals. I didn't touch them in any medication. I just said you're fine. So I published it as a lifestyle study, not that I was right. And the idea was they probably made changes. They probably took a nutritional supplement. They probably timed their sex better. They probably got out of hot tubs and all that stuff. And they were taking pills. I have a list of what they did.

2:04:45I had a table in that paper that said that 65 % natural pregnancy rate. That is higher than anything I can offer as a treatment that we have published on. So if you fix their varicoseal 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 a better. So if that addresses your question, that's the only data I have. 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.

2:05:19I want to freeze my sperm. Now presumably you'll get a lot of that if a guys 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? So huge issue, paternal age, paternal age, and fertility, paternal age. So we can go there, but I don't pace value judgments. I say good idea. My disclosure, I'm on a board of legacy. I love their mission driven. I like the fact that going from military and exposed patients and this and that and VA.

2:05:54I'm for that. I think it's the lowest hanging fruit in the field. Obviously for cancer survivors and things. I don't care what you think might happen with your cancer. I would still bank it. I started a non -profit called banking on the future. Sixteen year olds to 21 year olds with cancer will do it for you. We'll pay for it five years. Just do this a sample because it's so much harder afterwards or not. 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 for cancer. Yes. Now who 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 What paternal age do you worry about and you look at national guidelines for sperm donation 40 is considered older paternal age A 50 for sure.

2:06:43If you look at risks to offspring, miscarriages, still borings, autism, birth defects, things immediately related to conception, prematureity. Those go up with paternal age. Then you look at birth defects. And 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 between this Writing a paper on all these risks and with Alan DeCenco from University of Pittsburgh But I think it's a hockey stick curve for risk to offspring and you think the inflection is 40 or 50 I think it's more like 60.

2:07:36I 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 magnetmic. Same curve as women with chromosomal. Yeah, but they're shifted 20 years earlier or something. 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 the same relative risk.

2:08:12So women, you go from 25 to 40, your chance of a miscarriage, so it's chromosomal. It goes up quite significantly after that, very significantly. And the consequence of women's issues with offspring -related health is basically miscarriage. In many ways, it's almost easier to detect. Very. They've been doing it for years. They can be more dramatic. And now prevented with pre -ambitation genetic testing. Man 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.

2:08:51They're not getting vetted. So the machinery's not doing a good job. So they're getting through and they're not going to be lethal. They're going to be deleterious. So that's where you get things. And autism's a classic one, paternal age related. Looks like that's the biggest risk factor for it. And that worries me a lot. So the facts are that human evolution is entirely driven by sperm. Because eggs are just sitting there correcting the problem. It's entirely driven by sperm. And so 50 mutations a year, a generation usually gets spit out for each of their nature paper. Probably between generations.

2:09:24and 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 average is 50 over a year of productive 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 neural developmental. It's a half -neural developmental. So when you think about what we're seeing, you know the Martians from the 50s and the movies with big heads? That's kind of where we're headed. It's autism, dyslexia, bipolar disorder. These are neural development and neurodegenerative issues.

2:10:00And 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 that 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, given the first 500 ,000, given the first million they ever took any more money and he said, it let me focus. So autism is one of these is where you put out, you ignore a lot of input and you find the gift and it's amazing.

2:10:34If 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? I mean, I think it exists on a spectrum. I think anyone who's probably spent time with the kids using ASD as an example, boy, mild versions of it, the way it can be defined, because it really has three categories now in the DSM -5. I think the mildest version probably comes with more superpowers than limitations or maybe equal amount, but clearly the more severe it gets, it's pretty debilitating. But that's what we're calling it disease, though.

2:11:08Yeah. But maybe it's not disease. Maybe it's where we're headed. Maybe it's the future. Maybe the non -sequiters that come out of those brains, look at who's changing the world right now, at least in Silicon Valley. Yeah. But again, I would argue most of those people would be in category class one, class three. Anyway, something to think about. What's the thought 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? So when you freeze sperm, it's about a 200 year old process. Readability used for about 75.

2:11:42I forgot who the Italian scientist was who froze sperm and snow and then thought it and it was alive a couple hundred years later after Leigh went home 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 harder than an egg. So it does a lot better typically. When you freeze it, it's the freezing process that kills sperm. Be firm, icicles on the inside.

2:12:12And then while it's frozen, there's usually no issue. And then there's another problem when you thought rapid or temperature shifts. So that's where the kill rate comes from. In a good sample, half of it should survive. 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 are you telling? So I usually say, depending on what technology you're going to use, but if your sperm counts normal, three ejaculates is one kid's worth of sperm with insemination technology where you would thought and then turkey based it.

2:12:52So 10 ejaculates for three shots on goal for three kids. But three kids with low technology. But 10 ejaculates will give you most of China with IVF. Got it. Oh, when you say low technology, you mean IUI or something like that. There's three levels, sex, no tech, high tech is IVF, and then the middle is IEY. That's the stuff that's turkey -based, and it's relatively straightforward, relatively cheap. I see. Three kids for that, but plenty is burn for IVF. So three ejaculates would be more than enough if they're normal for IVF. Yeah, so the population you're talking about or maybe cancer survivors, half of those will not be normal.

2:13:24They're really looking at IVF. Yep. So they don't need that many. But I'd say three is a good number, but it's an insurance policy. Yep. 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 gonna link to a lot of this 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. And podcast, too.

2:13:55Tell me about that. 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 gonna be the anti -bordane immense health we're gonna just take on the topics testosterone etc penis myths and just talk about stuff that everyone is asking questions about but no one's talking about and like you dated driven answers okay what's it called talk with Turek on all channels 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.

2:14:30But 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. 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 to the Riggles hospitalatin in the 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 and then with low sperm counts in the where they were younger.

2:15:14This was a single payer system so they have all the data on it is very much a landmark study. So if you ask me what excites me about the field, I would say as the author of the biomarker concept early in my career, I would say I'm really happy that we're scaring couples to realize that their fertility is a measure of their health. And now we have our foot in the door. If we can get a sperm count, get them in the office, we can actually tell them a little bit about their trajectory. And that's giving more and more of a day. And we've never had a chance to do preventative medicine with young men.

2:15:48So it's a men's health play in a big way because their partners are bringing him in, but who cares? They're in the office. Your father had prostate cancer when he's 50, someone had colon cancer in the back. So I have now an NP Molly Jessup, who is medical. And it's like, okay, there's metabolic stuff and you can pick up diabetes. And we have an opportunity we've never had ever is to get men at younger ages. And I was a professor at UCSF for 15 years in doubt chair. I left. And I went to Yosan University, Twitch, Chinese medicine, I lectured there now, we had a conference last week. And I lectured and I liked it because I thought Western medicine, maybe your view to, is too reactive.

2:16:28They'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 never good at it. Your general surgery, every example you give is a guy, you know, dissonally bad, you get them back, whatever. But you have to think, next step, like kidney stones, great, urologists, we treat them all day. It's fun, it's endoscopic, it's allasers, it's shock waves. But what are we doing about that stone? I mean, how come we're not preventing these more? It's not on the radar. I go to the Osan University in Tricilchines Medicine, fabulous place, and it's all holistic.

2:17:00So I see patients who get referred by acupuncturists and they come in their diets under control, their stresses under control, they're doing acupuncture, they're sorted out, and what do I find varicoseeals? Because they don't find those. But the phenotype is totally different than the Western referral. I love that because that's 3 .0. That's medicine 3 .0. What's 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 DNA mutations a generation doesn't explain it There's other stuff going on epigenetics is all lifestyle and diatron.

2:17:41It's all lifestyle and diatron It's everything in your book. Well Paul, very interesting stuff. Thank you again for making the trip out here. Thanks for sharing your insights. And great yeah alright. Thanks Peter. Thank you for listening to this week's episode of the drive. Head over to peteratiamd .com forward slash show notes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram and Twitter all with the handle peteratia md. 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.

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