Welcome to the Huberman Lab Podcast where we discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Shana Swann.
Dr. Shana Swann is a professor of environmental medicine and public health at the Mount Sinai School of Medicine. She is a world expert in how exposure to various toxins and compounds in the food and environment impact our reproductive health. She focuses on how these compounds in our air, in our food supply, in our water supply, in cosmetics, even in household items impact the developing fetus, children and adults at the level of their reproductive biology, so things like testosterone and estrogen and the pathways within the brain and body that are impacted by testosterone and estrogen.
But also how all those things in our environment and that we put into our body impact our health on a daily basis and our long-term health. So during today's discussion you will learn why fertility rates are indeed dramatically dropping from year to year and have been for quite some time now. You'll also learn why testosterone levels are dropping, why sperm counts are dropping, why things like polycystic ovarian syndrome are increasing in women and what we can do about it. In fact, during much of today's discussion, Dr.
Swann emphasizes the things that you can do every single day and that in fact turn out to be very simple. They involve certain things to do and certain things to avoid in order to limit your exposure to these environmental toxins and their impact. So by the end of today's episode, you will be highly informed by the world expert on endocrine disruptors and environmental toxins. And you will also be highly informed in terms of how you can have agency, how you can take control of your health in relation to these various compounds.
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Element.
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Shana Swan. Dr. Shana Swan. Welcome.
Dr. Andrew Huberman, thank you. I'm super excited for today's conversation. I've followed your work for a number of years.
I've seen some of your appearances on other podcasts, and I got to see you speak while we were both in Copenhagen. I was in the audience, you didn't know I was there. But incredible stuff that you've been doing as a researcher, as a public educator, as a writer. Let's kick off by just asking the basic question.
Are there things in our environment, including our food, that are diminishing our reproductive and overall health? And if so, which are the ones that you think about? And perhaps if you could just mention a few of the more salient, maybe even shocking, but salient results that you've observed over the years. What was the kind of like, whoa, result or results that have really steered your attention in the last couple of decades?
And I'll just say what we were talking about before we were on the microphone, which is that you are a skeptic. You are not somebody who walks out into the world and looks for things that could be messing up our biology, messing up our health. And yet, you've found some. So if you could just share with us what you've observed and what you find really compelling and important for people to know about, we can dive in.
That was a lot of questions. I could probably talk for a long time. Feel free? I won't speak until you're done.
No, but I want to break it up. Let's break it up. So I think the first question about was, are there forces, chemicals, agents in the environment that can affect our reproductive health? Yes.
Okay. So my answer to that is yes. I think there's no question about that. The question comes down to when and in whom and what dose and so on and so forth.
But whether there are, let's just say broadly things. Yes, of course. The category that I focus on are manmade primarily manmade chemicals, although I do also include the influence of other factors, factors of choice. For example, sleep exercise, that kind of thing.
We can talk about that. But let's just focus here on the chemicals, because I think that's what led me to do a lot of my research and to write the book that I wrote. And so my thesis is that chemicals in the environment, that's a very broad class. So we'll have to say some chemicals in the environment at the right time to the right organism effect fertility.
Okay. So, and let me just say fertility is one area that I focused on, but actually this class of chemicals that I'm primarily interested in are those that affect the body's hormones. So those are known as hormone disrupting chemicals or endocrine disrupting chemicals, hormone altering chemicals, whatever, you know, there's a lot of names. But that helps you focus on where to look for the effects, because if it's hormone altering, you can now have something to really ask.
Okay, here's the chemical. Does it affect a hormone? Which hormone, when, how? And then you start, that's almost a laying out an experiment right there, right?
So, so focusing in on hormone disrupting chemicals, I think is useful. Absolutely. Yeah. And I think much of what we'll talk about today probably centers on the estrogen and testosterone pathways as they relate to masculinization or feminization of the brain and body and sperm and egg quality.
Right. So, I'm a reproductive epidemiologist. I got there in an indirect path. I think probably my work on oral contraceptives led me there most directly.
And oral contraceptives are endocrine disrupting chemicals. So, what's the desire to do? Right. That's what they're designed to do.
Change your body's hormones. You're reproductive hormones. So, it's interesting, you know, way back when when I work on the study at Kaiser on oral contraceptives, which is the largest study of its kind in the world, actually trying to figure out where their adverse effects of oral contraceptives, if so, you know, for whom and when and how much and so on. And so, there's a very great study.
And coming forward in time, I, you know, I studied environmental chemicals, not so much pharmaceuticals for quite a while in when I was at the California Department of Health Services. And then I had an aha moment. I was flying to Japan with my friend John Brock, who's a chemist at CDC, wonderful chemist. And you have long flights, we were talking about this.
And he says, Shauna, you should look at phallates. And I'm going, why should you look at phallates? I never heard of phallates. Right.
And he said, well, we can now measure them at the CDC. And we see there in everybody. They're in women of reproductive age, fact one, fact two. Colleagues at the NTP have shown something they are calling the phallate syndrome.
And so he explained. What is NTP? National Toxicology Program. I'm sorry for using alphabet.
National Toxicology Program, a governmental research center. And their job is to look at chemicals and see what is the toxicity. So it could be reproductive. It could be carcinogenicity.
It could be neurotoxicity. That's what they do. And so they had signaled out these phallates as being reproductively toxic and specifically to males and specifically when exposure is in utero. Pregnant mom is exposed to phallates.
And somehow the fetus is disrupted. Yes. If you don't mind, I'd like to know, is mom ingesting phallates in the form of food? Is she inhaling phallates?
Are they landing on her skin? What are the modes of entry into the body of the mom that? Let's just assume it goes through the placental barrier into the fetus and is impacting fetal development. Right.
So in those experiments, it was through food. But we are exposed in all those ways you mentioned every way that something can get into our body. Thallates get in there. But let's come back to that.
Let me go to the experiment at NTP. So if they did it at NTP, National Toxicology Program, they fed mother rats, various doses of these various phallates. And what they found was no changes in the females or not that they found at that time. The female offspring?
The female offspring. Sorry. But in the male offspring, they found that the genitals were summarized by saying incompletely masculinized. So I'll explain what that is.
So for that, I have to back up and say something you know probably know very well, but I'll just explain it. The general tract initially is a ridge. So single ridge, it's the same in males and females. It's not sexually demorphic at the beginning.
And then under the influence of testosterone in a very specific window called the male programming window in rats, it stays, I think, nine to 12 of gestation. So a very short window. To orient people, I think rat mouse gestation is about 21 days or so. Yeah.
So it's for us, it'll be early first trimester. Okay. But that comes later. So, so at that time, if they feed their mother that chemical in her food, then her male offspring are born with changes in his genitals, or more likely to.
Right. And so what they tend to have is a smaller penis. Less descent of the testes, more likely to have under center testicles. There are internal changes that we didn't get into in our human study because we can't look there, but the epidemis, there are changes and so on there.
The whole general tract is altered. And the most important measure for me, as it turned out, and for humans, and perhaps animals, is something that the scientists, animal scientists had studied for a long time for actually 90 plus years, but had never been studied in humans. And that is the distance from the anus to the genitals. This collection of changes in the male genitals was given the name the phthalate syndrome.
Now, you're a physician, and you challenge you to think of any syndrome aside from alcohol. There's a syndrome, but what syndrome is attached to a chemical class? Just for technical purposes, I'm a PhD, not a clinician. But I worked on neural development for years, and then prior to that, some endocrine stuff.
So I'm facile with the general terms. One that comes to mind would be, for instance, the thalidomide babies, right? Anti-miscarriage drug that changed limb development. That's a very extreme example.
I would say for human normal development, what I'm most familiar with are the early organizing effects. The early organizing effects of androgens that convert to estrogen on external phenotype, which is basically nerd speak for during development. The Y chromosome produces at least the production of a number of genes and eventually proteins, through RNA, etc. That are including testosterone and dihydrotestosterone that in the brain organizes the brain male and causes the growth of the penis, or organizes, meaning it sets up the penis to then during puberty when the penis is exposed to testosterone and estrogen, and ADHD, it's a bunch of things, not just testosterone.
The penis grows. And lots of other things. So the word soup that I just put forward is basically saying that there are a lot of things in development where hormones set up a potential to respond to other hormones later. It's not that testosterone grows the penis during development.
It does that, but more so it establishes a potential for the penis to grow when exposed to things later during puberty. As far as the name goes, which is the phthalate syndrome, there is the lytomide. It's not usually called the phyllamide syndrome, but it's extremely rare. And there's no environmentally chemical in the environment opposed to a pharmaceutical.
That is given the syndrome. This is very, very unique. And so I thought, wow, John's telling me this on the plane, right? Something in the environment that is basically having an endocrine and body disruptive effect, at least on par with alcohol, fetal alcohol syndrome and phyllamide syndrome.
So at this point, it was only animals, right? Because John was telling me about the NTP study, which was in rats. And so I thought, wow, I like puzzles. So my first question was, is this happening in humans?
You might ask that. That's a natural thing to ask. And then I thought, how would we find out? And answering that question took me 10 years.
And so if you think about, okay, phthalate in the mother changes in the genitals of the offspring, connect them. How do we do that? Right? So we have to start with phthalates in the mother.
How do we know that? Well, fortunately or not, I had stored a lot of urine from pregnant women from a study that I was doing on sperm count. I just got the women's urine coincidentally, if you realize, well, save it, you know, it's not expensive. And not hard.
Mine is 80 degree freezers. It doesn't take a lot of room. Put it in there. So I had this urine save from pregnant women.
And then I knew from John that we could look in the urine for phthalate metabolites. So these are products at the body forms when they're exposed to phthalates and you can measure them in urine. So I thought, okay, I could get that urine. I could look at the phthalate metabolites.
And then I'd know what the mother was exposed to. And based on the animal data, we have good evidence that it actually makes its way to the fetus. So then I thought, okay, then maybe there's a change in the babies. So then I had to get the babies.
So fortunately, I had done this study on pregnant couples, pregnant women and their partners, and I was able to call them and say, would you come in and let us measure your babies' genitals? Right? How willing were parents to let you do that? They were okay.
Most of them were with that. Yeah. Well, they trusted us. They didn't have to study with us.
And, you know, we were right. Those babies were still young, but not newborn. So this was a while later. The babies that we actually got were on average to think about a month, 12 months old.
So not ideal maybe because the rats have been measured at birth. The rat genitals have been, but that's what we could do with that. Yeah. The reason I ask is there's always the potential for ongoing thalate exposure to the newborn system.
But I suppose in either case, you're able to draw some potential link between, or potentially draw a link. You have to be careful with my language there between thalate exposure in utero and ex utero and these external biomarkers. Yeah. I mean, given that the critical window is quite short and quite early, by the way, let me just say, when the rats, they did a lot of work on this critical window.
And when the rat moms were exposed before day nine, it did nothing. And when they were exposed after day 12, it did nothing. So it was only the exposure during that critical window is very delicate. And by the way, true of the brain as well.
So they're teasing out what is the critical window is of one of the challenges that we have when we work with these chemicals. So I wasn't so much worried about exposure in the delivery room and, you know, in their feed as in the first year of life, because I knew it was unlikely to change these measures. Do other things, but maybe but not these measures. So then the question became kind of what you're asking is what do we measure?
What do we actually measure? And if you think about a newborn rat or mouse, their generals are pretty small. And there's not, there's, it's very difficult to know exactly how that corresponds to the human general system and what you see at birth, you know, when you spread a voice like a squirt. And so I got a pediatrician in Los Angeles who worked with me on how to make that translation and how to do do this exam.
And that took us quite a while because we really wanted to come as close as we could. What was clear was that the anus part of it was easy. Go to the center of the anus. So that was easy.
Then what's the other landmark? What's the general landmark? So it turns out there are in males to and in females there are to as well. So, but let's just talk about meals.
So for males, the best place to measure actually closest to the rat measurement is the place where the tissue changes where the scrotum. Inserts and that goes from rugator to smooth. Tissue and that point is pretty clear. Pretty easy to measure.
The other measure and that was the inner scrotal distance and the other measurement we took was the, you know, penal distance and that was the insertion, the anterior insertion of the penis. The part closest to the body. That closest to the head. Yeah.
And, and that was not so obvious because you don't have a change in tissue there. So where exactly do you put your caliber and we had a lot of discussion about do you press down? You know, how where exactly do you make that mark? And actually the inner scrotal is the measurement with the least variance because you can measure most precisely, but the anal penal is another measurement.
And, and then you can do something similar in females and we did that, but that's we maybe don't have to go into that now. So we designed this exam and we did a lot of work to make sure it was repeatable across examiners. And what we finally did was bring them others and bring the babies in and got three measurements. And then on every tenth baby, we got an independent examiner to get three measurements.
So we could look at within and between examiners variation. You understand this is the first time this had done this way in humans. There was a Mexican study that tried to do this and I never learned very much about it and I was excited that they had done this, but I'm not sure how it relates to this. I just mentioned that out of honesty, you know, there's somebody who makes go do this, but to my knowledge, this is the first time it was used as a toxicological measure in humans.
Right. So we were we did that study. We related those measurements to what CDC had measured in the urine of our women collected while they were pregnant. And we found this out at Valley Center.
Could you explain what the correlation was between phthalate metabolite levels, which is not not by number because I don't remember it anymore, but but there was a significant. Let's just take the AGD. The AGD of mothers who had higher levels of three, the most anti antigenic valides. I'll tell you what those are in a minute had significantly shorter.
And then I have to say that which I haven't said and should have that. And your business is actually demographic. So it tends to be 50 to 100% longer in males and females. That makes sense.
If you think about what's going in that space. There's a lot of real estate in males between the anus and, you know, the penis, the penis, the penis insertion much more than in females. So it's natural that that will be longer. But that's that's an error.
And that I began doing some work in other looking at other species and it turns out that that's true in all mammalian species except to. And when is the hyena? All right. And when is the elephant?
So in the hyena, I'm just saying this because you might be amused by that. I do. I know more about hyena genitalia than I'd like to admit. And I can tell you why after you educate us.
But I'll keep my explanation brief. But I'm very familiar with hyena genitalia. So I know Stephen Glickman who works with a, you might know him too. He works in Berkeley.
He was my instructor when I was a graduate student at Cal. And I used to run in Tilden Park. I suppose I'll tell it now. And there was a colony of wild hyenas.
But they were behind Chainlink. Actually a favorite hike of mine up the Strawberry Canyon Trail. And a good friend of mine, Brian Prennergas, who's now a professor at the University of Chicago, worked on the Prairie Divles. And the Prairie Divles that were also housed at that facility.
And a fun thing to do was to go see the hyenas with Steve. They're brutally dangerous animals. And Steve has tons of stories about them. We should probably resist our temptation to spiral into that.
Maybe sometime I'll do a little like evening chat podcast where I tell Steve Glickman stories. He's a delightful person. And yeah, those let's just say this. The female hyenas have clitoris is larger than some of the male hyenapenas.
And those females give birth through those clitoris as we both know. So you will not be surprised to know that the female HD is longer than the male. Right, because they're heavily androgenized. As I recall by Andristine Dion.
Actually I don't know that. It became popular during the era of steroids in professional baseball because Andristine Dion was being used pretty frequently in baseball at that time. Anyway, we could go down the spiral of a... But also in terms of behavior, the female is the alpha.
They eat first. They're physically and hierarchically dominant. So it's really interesting, isn't it, that they would have a longer, more masculine, androgenetic analysis. Elephants, we won't go into now, but they're kind of midway in many things.
So including their about equal, androgenetic analysis and males and females. Other than that, humans and others, maybe male, androgenetic analysis is 50 to 100 percent longer. However, so three phthalates, diethylhexylthylthylate, DEHP, diethylthylthylate, DBP, and butylbenzylthylthylate, BBZP are the most anti-androgenetic testosterone lowering phthalates. And those are the ones that were associated with a shorter individual distance.
In males. In human males. Human males and animal. So we replicated that animal study in humans.
And then, because you know this is how it is in science, I had to do it all again, right? So I started a whole new study, and that study is still going on. The children are still being followed. I think we started in 2012.
The first paper on In the function, we don't know that kids are only 12 years old. So we would like to know that and we will know that. Okay, but I have another answer for you about that. So we started the second study, and the second study, which is called TIDES, which is the infant development and environment study.
By the way, these are both in four cities in the United States. And there we did it right. So we got the urine in the first, you know, early urine because we knew that could be important. We didn't have that option in the first one.
Remember those urine samples were accidental? We got them when we could, right? And we got repeated urine, one in each trimester to look at the effects in different trimesters. And then we examined the baby's at birth, which is what the rats said.
So we came much closer to replicating their rodent study, and we saw it again. I'd like to take a quick break and thank our sponsor, AG1. AG1 is an all-in-one vitamin mineral probiotic drink with adaptogens. I've been taking AG1 daily since 2012, so I'm delighted that they're sponsoring this podcast.
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It sounds like the distributions moved more closely together. Yes. Although it wasn't the females that moved. Sorry.
The male distribution became more likely to say feminized, but more female-like in it. But these boys also had smaller penises, less descent of the testes, smaller scrotums. They were smaller. Everything was in their general lyrics.
Are all the secondary sex characteristics of puberty in males, atoms, apple, facial, or growth, thickening of the vocal cords, therefore lowering the voice, etc. Are those all later activating effects of hormones, or are there precursors to those that are present in males? Because in mice, as I recall, I couldn't tell you, we call it in the laboratory people. I was chucked like this, but it's like sexing the animals when you look to determine if it's a male or female.
When they're really young, you have to look carefully at first, right? And then you get pretty good at it. As they get older, it gets easier. But when the mice are, you know, feet down, back up, you know, you can't really tell.
As the mice get older, their testicles become visible in males, even from above. But, you know, as far as I know, there aren't really external markers. So you may have found the one truly external biomarker of maleness. And so I do want to say one thing about females, because then that will lead me to my conclusion about the role of this measure.
So if the mother is exposed to more testosterone than expected, you might expect that her female offspring would have a more male in a general distance. Is that the case? Yes. Can we also presume that if the mother either secretes or is exposed to more androgen, then the males can become hyper male?
No, we never, I don't know what that would be. We never saw anything that would be hyper male. So the, the guess I said to you was the result of a study where we looked at the girls born to women with PCOS. So women with PCOS is, you know, have access to testosterone.
Always just, always just go various things. We've talked about it a little bit before in the podcast. It's a, it's associated with my understanding is it's associated with elevated levels of androgens. So that's right.
And these women often have facial hair and, you know, they're not just the moms, but the, the people, the women with PCOS. Yes. Have elevated androgens. Yes.
Not just, we're not talking about pregnant moms. Exactly. And so in our study population, we did a search for women who had diagnosis of PCOS and took that as a marker of higher testosterone exposure and then looked at the girls. And yes, those girls had a longer quote, more masculine in a general distance.
What age group were you looking at? In the infants. Oh, the PCOS was at, was that pregnancy at the time they were pregnant. Or people between, they're like somewhere in their twenties out to their forties.
Yeah. Yeah. So adult human females who have PCOS tend to, we know they have higher levels of androgens, but they also have more male like, you know, genital distance. They do not.
Their daughters do. Their daughters do. Thank you for that clarification. Their daughters.
And so put this together. This measure is a look inside the womb at the androgen level that the fetus is exposed to at that time, which is amazing because you can't go in there without disturbing, you know, you can't. And so this is very early for a strumester. You can't even get, you know, fluid and so on.
So this tells you, this is like a readout of what was in, you know, in the fluid at the time. So then your next question was, what does this mean for later fertility? Yes. Yeah.
What, what is the impact of this early androgen exposure to female offspring or let's just say reduction in functional androgen exposure to male offspring. The reason I'm using these, you know, loop-de-loop languages, as you probably know, but for the audience, not trying to complicate things here, but a lot of the masculinizing effects of hormones in fetal development is actually testosterone that's converted into estrogen. So it can get pretty tricky. Right.
And, but maybe for sake of simplicity today, we'll just stick with androgen effects on masculineization with the understanding that some of those effects are the consequence of testosterone being converted into estrogen. Right. It's just that people form such strong associations falsely that testosterone is male, male-ness and that's not true. And estrogen is female-ness and it just gets really murky.
But for the time being, you identified an external biomarker of fetal androgen, aka masculinization via the mother. That's right. Got it. Okay.
So then we asked the question you've asked and many people asked, who cares? What, why would we worry about a boy having a slightly smaller and a gentle distance? Well, I can tell you, there are many boys that are probably worried about it right now. Right.
I've probably got the ruler and the caliper's out right now, which is, you know, but I'm going to answer that question. Right. So I told you that our kids are too young. They're not producing sperm right now.
Right. So we had to go to a developed population. Right. And so we went to a population of college students in Rochester, New York.
And what we did there was make an assumption, which is based on animal data. It's true in animals. We've been following the animal path here all along. So in the animals, my colleague, Earl Gray, who did these studies said...
His name is Earl Gray. Yeah. That's cool. Yeah.
He said, A.G.D. is forever. The inner general distances forever. Now, what that means is it's not like your inner general distance today is what it was when you were born.
Of course, you're a bigger person. But that means adjusted for body size. Right. So if you assume that A.G.D.
is forever, if you're born with a short for your size, A.G.D., then when you're 20, you'll have a short for your size, A.G.D. Okay. Can we use in that? Okay.
So if we assume that, then if we get these college students to come in and we can measure their inner general distance, we're getting a reflection of what it was when they were born. Okay. And then we can get their sperm count. And then we can see if they're related.
And that's what we did. So we got this population of volunteers paid them $75. And one of the guys said, for $75, you can do anything. And so what we did was we measured their inner general distance, and then we got them to give us a statement sample and complete a questionnaire and things you do in a study.
We'll link to that study, but I have a couple questions about the controls in that study. Just for sake of people understanding how a study like this would be done. I don't expect you to recall all the details, but you're adjusting for body size and body weight, height, weight. What are the factors that would scale here that would allow you to normalize?
In other words, what you're trying to do is backtrack to what it likely was at. No, we didn't actually try to go back. Let me just tell you what the results were. In this group of men, if they had a longer inner general distance, they had a higher sperm count.
Got it. So you record those two measures. Right. And then if we wanted to say something about, we didn't try to say anything about how it was when they were born.
We just said, okay, we'll take that assumption that this reflects their early AGD. If we want to say something about early AGD and sperm count. So it's easy to say AGD is related to sperm count because we measured that. We saw that a correlation.
That's published. Okay. If we want to say their early AGD at birth and their sperm count, that's a leap of faith in some sense because we don't have their early for these guys in Rochester. We didn't measure their AGD.
Were there any conditions of being a participant in the study such as refraining from alcohol, cannabis, et cetera, in the 90 days prior, 90 days being the duration of a spermatic. I don't remember that. Is there college students? So presumably some of them are drinking.
Okay. So, but in the end, it was a robust link. And then I'm like, I just heard who you might know. Yeah, I probably get to know.
He's been on this podcast. Yeah. Good. Good.
So he's a colleague of mine too. And he looked at men in a fertility clinic and those who had born children and those who had not born children and the men who had born children had a longer, in a general distance than men who had never born a child. Never born, but we're trying. Yes.
Right. These were not people who opted out. Exactly. These were people who were having challenges with fertility versus success with with.
By the way, you know, the question of how you measure AGD in an adult man is a different question than how you measure it in the newborn. And we did a lot of work on that and Michael helped with that too. So it sounds like, oh, and they ask were the sperm counts that were on the, let's just say the lower, like the lower quartile with the quote unquote lower sperm counts functionally lower because I always wonder about this. Like it's come up in a number of discussions like with Robert Sapolsky with Mike Eisenberg and now I'm asking you, you know, when we hear that sperm counts are going down, are they going down to the point where fertility is impacted.
That's really the one of the functional questions. So I'm going to, let's lay aside the question of AGD, right? That's really interesting. But let's talk about sperm count.
Okay, so, um, if you there's a beautiful study among pregnancy planners out of Denmark quite a long time ago. And in that study, what they did was take couples that were trying to conceive that had never, or not recently I can't remember used oral contraceptives. And then they saw what the sperm count was and how long it took them to conceive right time to pregnancy in relation to you. And what they showed is a really interesting curve which has never been corrected to my knowledge is what I use and what I think people use, which is that if you, I wish I could draw here, we should have a board and what.
The problem is a lot of people are listening, but maybe we can talk people through it. So, so just think about a curve where you go all the way down to zero that would be no sperm. And then as the probability of conceiving is zero, you're looking at sperm count along, you know, is X axis and months to conception. And what you see is that if you have no sperm, you don't have no conception.
If you go up to around 40, 45, there's a steep increase. So the more sperm you have 40, 45 million million per million per million. And this is million per million just so just pure concentration, not number of motile sperm. This is just how many we're not talking about quality.
No, no, no, no, no. And when you have 45 to 50 million per million per million a liter. And below, it matters a lot what your sperm count is. You know, people say it doesn't matter.
Yeah, if you get in this range where the probability of conception is dropping off really rapidly, it matters a lot. And then there around 45 to 50 starts to level off. And then after that, after certainly after hundreds, probably 75, it doesn't matter at all. So 100 million sperm per milliliter of semen.
Yes. So can you see this? Okay. So it, so when people say does sperm count matter for Tilly?
Yes, it matters a lot if it's low. And no, it doesn't matter at all if it's high. So you did we just have too many sperm. I mean, I don't.
And there's nature runs a probability game over produce sperm. Right. Some of those will be high quality. Some will be low quality depending on their age when they were that is when they were generated or their conditions or their conditions.
How much heat exposure, et cetera. So nature runs a probability game. That's right. Hoping that the best quality sperm will fertilize the egg.
So below 45,000, excuse me, below 45 million below 45 million sperm per milliliter of semen. The sperm count really matters. It drops off precipitously. Once you get up to 75, 100 million per milliliter of sperm, then you're good to go.
Right. And sperm counts range anywhere from, you know, it could be low, eight, nine, 10 million per milliliter in the very low situation. It could be zero and some people right all the way up to 400 million. There's a huge range.
And that's a function of age. It's a function of genetics. It's a function of presumably thalate exposure. Yeah.
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Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman lab listeners. Again, that's FunctionHealth.com slash Huberman to get early access to Function. We were on to the fact that sperm counts are dropping. There's a relationship to ano-general distance, and there's a relationship between ano-general distance and thalate exposure.
And then I asked the question, okay, we're hearing about sperm counts dropping, but is it functionally relevant? Is that one of the reasons why fertility is dropping? And we've also got the female side where we've got women with elevated androgens, so we can talk about that a little bit later. And then of course we have the sociobiology piece where people are opting out, or it's also economics in some cases, opting out of having kids.
So let's go back to sperm count because we haven't really talked about that. It's a kind of a different path. And my introduction into thalates was not through sperm count. It was through this question of my colleague asking me, you should look at this on the challenge, and I looked at it, and that was really, really interesting journey that I went on.
But there was a separate for a while journey that I was on, and that started in the late 1990s when I was asked to join a committee of the National Academy of Sciences. And that committee was assembled to look at the question of whether formerly active chemicals, endocrine disrupting chemicals in the environment posed a threat to human health. Because at that time it was like, well, yeah, we hear about this, but should we care, right? And so that committee wanted to consider a study that had come out of Denmark a few years earlier, which claimed that sperm count had dropped 50% in 50 years.
That's a huge drop. That's what we're seeing worse than that, by the way, now. So, okay, they said to me, I was the only statistician on that panel, would you look at this and see if we need to consider this in our deliberations. And as I mentioned, I'm skeptical and I looked at it and I thought, I don't think so.
That was my initial reaction. And that was because, first of all, I didn't know who had written this, I just saw it in a journal and it was never big, and not for many figures, not very much data. And I thought of it and I thought, that's a big claim for a little paper. But I'll look at it, because it's important.
And so what I did then was to think about all the factors that we epidemiologists call confounders, things that might have caused that decline, if it wasn't real biologically. And so we could think of some of them together. Maybe the method of counting sperm had changed, so that later methods counted fewer sperm in the same sample. That's certainly possible.
But it turned out that wasn't the case because they actually had all used the same method. And maybe the man had changed. So maybe you can't get a sperm count at random. You have to get somebody to volunteer.
So who were these men? Are they very different in the early part of the study, in the late part of the study, in a way that maybe in the late part of the study, they were men with lower sperm count. And they were more concerned. Maybe they were more obese.
That's pretty plausible. Obesity is related to sperm count, fertility. And maybe they smoked more. And so on and so forth.
And so what I did was to get the 61 studies, go through them, and try to extract information on all the factors that could explain the decline. So I created a multivariable model and ran that model into my astonishment when I was done. The slope of the decline was exactly the same to the first decimal place. It had not explained anything.
I was like, Oh my God, this looks like it might be real. And for those listening, what Dr. Swan is describing is being the excellent scientist that she is, she went and looked for all the things that could impact the result that were not related to what the main conclusion seemed to be, which is that sperm counts were going down over time. Right.
And this is really important to, because I think what we're talking about here in parallel to the main conversation is how to do really great science, especially in human populations that are out there, living, you know, some of these men probably, you know, smoked some cannabis. I'm not saying that reduces sperm count. It might reduce sperm motality. However, we covered that in the podcast.
Now that all the cannabis folks go, well, you know, so and so got so and so pregnant. When they were doing so many a lot of we, and I always say, okay, well, there are a number of other factors, right? But alcohol, there's frequency of ejaculation, right? The requirements abstain for 48 to 72 hours to up to five days prior, you know, et cetera.
All these factors that men may or may not faithfully report, but you assume that if some are telling the truth and some aren't, that there's an equal distribution. That's all the different things. Right. This is so very different than looking at, for instance, ovarian reserve, like the number of eggs where you use ultrasound and you use AMH levels and sure things can impact that, but it's a little different than when you're doing it.
It's a little different than when taking sperm counts. So thank you for doing the studies so carefully and for repeating them so many times. I mean, many of the studies that you've done are, you've done follow up on these sperm count studies across multiple years. You know, as you said, the first study was in 1992, then you did one in 2017, then there was one again, and it was an update I noticed online.
So you are extremely thorough. And it probably reflects your early training in math and statistics and probability theory. You're not somebody to just kind of go in and go, oh, yeah, like, and these people that eat a few too much of this, then there's a little less of that. So I just wanted to, today's discussion feels like we're really, we're laving through this.
That's intentional. And it's important for people to hear these kinds of claims are not the sort of thing that you could people make them all over the board, but work like this needs to be done with an extremely meticulous eye and consideration of all the variables. Well, it's scientific method. Yeah.
Yeah. And I would say especially with human epidemiological work because of the number of potential confounding variables. Right. So, so when I saw that and actually did another study to select my own studies and not accept her 61 studies that had been published that Elizabeth Carlson published some new studies came up to more recent times went back further.
Did it again found exactly the same thing. Okay. So there were three, you know, three looks at that and I thought, okay, I'm going to accept this now. This is firm count is declining.
And why that turn to the why? Okay, because up and down now we hadn't said anything about why we just said is it doing that yes. Okay, if it now we believe it is declining why. And so then I thought quite a lot and talk to people and ruled out genetics because it was too fast.
It's two generations is too fast. 50 years to generation. So if it's not genetics, then it's environment. And so what is it about the environment that could do this.
So I asked, okay, in the environment, there could be things that are making sperm decline. So if you think about how you might look at that, you might design the study that I designed next, which is another study. And by the way, this preceded the AGD. So it just so we had four cities in the United States that we picked with different environments.
And then we got men to come in and we used the same equipment at each place. We used the same method of selection, selecting the man. The technicians were trained centrally at UC Davis. We had very good quality control.
So samples were sent around every quarter to make sure that everybody was measuring things the same way we didn't want drift, right? And then we got their urine. And that's how I had those urine samples. So if you wanted to do this study and you wanted to get a representative sample of men, where would you go?
Because I can't ask a guy in the street to give me a semen sample right now. It's not something you get very, you know, so I thought, how can I get a representative sample and which would teach me something about a larger population called the parent population. So here's a sample it should represent the parent. So how do I ensure that?
And what I decided was to sample partners of pregnant women. Because pregnant women all come to medical care, almost all. And if their partners will give a same example, then we have a representative sample. And we know what we're looking at.
So that's what we did. So this is a, the semen study is the study of partners of pregnant women. And, and of course they'll have slightly higher semen quality because they got their partner pregnant. And so we had their urine, we had their blood, and we looked at their semen quality, and then we decided to look at pesticides.
And the reason we looked at pesticides was because there was a lot of gradation across our four centers and pesticide use. And what we found was really extraordinary that men who were living in Central Missouri, where I was living at the time, who were in the middle of an agricultural belt where there was spraying all the time for soybeans and so on. Those men had half as many moving sperm as men in Minneapolis. Whoa, whoa, huge.
Right. And then we went one step further. And within Missouri, we looked at a sample of men who had very high sperm parameters and very low sperm parameters and showed that five pesticides were significantly higher in the men with the low sperm parameters that include motility and morphology, you know, all of them. So these are pesticides that are being sprayed in the air on crops.
You mentioned soybeans. What other types of crops? I don't know. I don't remember.
So plant and fruit crops. Yeah, whatever they were growing in Columbia, Missouri. And just to make sure I understand it, it's not that many corn and soybeans. But we're not talking about eating corn and soybeans.
We're talking about living in an area where pesticides are being used by, I guess, a call. This is still called dust crop. Yeah, we didn't go into how they got these. We just looked in their urine and there were the metabolites.
The metabolites don't get in their urine unless they were exposed. Expose through the air, exposed by eating corn and soybeans. We don't know. We don't know.
We don't know. But this was not particularly, we didn't sample farmers only or anything like that. So whoever came in to the, remember how we got these men? Their wives were pregnant.
They were having prenatal care at the University of Missouri. So that's where we got them. Whoever happened to come in to the prenatal clinic and agree to be in our study, they're the male. You know, your, males urine was measured for these pesticides.
I'm sure a number of people, including myself, are wondering in what other products are these five pesticides present? Are these commonly used pesticides or is it something about? They were, they're called the triasine pesticides. The aftersane is the most widely used and it's a huge use around the world.
I mean, it's highly, you know, one of the largest commercial pesticides. So these were very big players in the pesticide field. A relevant theme there would be, maybe we could take a moment and talk about atrozide and its effect on male sexual behavior in amphibia. And we'll come back to the sperm size because when I was a graduate student at UC Berkeley, I had the wonderful experience of taking a course from the now, I think you mentioned he's 18.
There are multiple deans on campus. Tyrone Hayes is a wonderful researcher who established a link through his research between atrozine exposure and male sexual behavior of amphibia. Yes. Could you elaborate on that result?
Yeah. So Tyrone first caught frogs in the wild and environments that were more or less exposed to atrozine and showed effects on development and sexual behavior. Then he, in his lab, he actually exposed them. So he knew exactly who was exposed and how much.
And he showed that, I can tell you what percent or what, you know, but a significant number of frogs exposed to this pesticide atrozine shows to mate with other male frogs. Tried to make with other male frogs presumably unsuccessful. Well, they clap. They mounted them.
He has photos of the male males mounting males. And so presumably this is a neural change that occurred, neuroendocrine change, but ultimately neural since mounting behavior is controlled by, actually we now know the, the hypothalamic nucleotics. Hypotallamic nucleotics control that David Anderson has been on this podcast has people in his laboratory that, including a former graduate student of mine, working on this specific issue of what the circuitry is. That's a remarkable result.
It's been kind of, you know, used and misused out there in the media and in popular culture. But if nothing else, it suggests that the organization of the neural circuits and neuroendocrine pathways that control sexual, I don't want to say partner because he's a meeting, the frogs aren't monogamous, but sexual preference. Are significantly impacted by this by this atrozine. Yes.