Dr. Michael Eisenberg: Improving Male Sexual Health, Function & Fertility

Andrew Huberman:
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. Michael Eisenberg. Dr. Michael Eisenberg is a medical doctor specializing in urology and an expert in male sexual function and fertility. He is both a clinician who sees patients, as well as a research scientist, having published over 300 peer-reviewed articles on male sexual function, urology, and fertility. And he is considered one of the world's foremost experts in male sexual health. Today, we discuss a broad range of topics important to all men, including erectile dysfunction and function. We also discuss prostate health and urinary health. We discuss fertility and sperm count. We discuss even topics seemingly esoteric, such as why penile lengths are actually increasing over time, while sperm counts seem to be decreasing. Today, you'll also learn some very interesting surprises, such as the fact that a very, very small percentage of erectile dysfunction actually stems from hormone dysfunction. Rather, the vast majority of erectile dysfunction stems from issues that are either vascular, that is related to blood flow, or neural. And today, you'll learn about a large variety of treatments for erectile dysfunction. Dr. Eisenberg also dispels a lot of common myths that you hear out there, both on the internet and in popular culture, that relate to male sexual health and function. By the end of today's episode, I assure you that you will have a thorough understanding of what male sexual health is, how it relates to other aspects of health, and how to think about treating, maintaining, and improving all aspects of male sexual health, fertility, and function. 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. And now for my discussion with Dr. Michael Eisenberg. Dr. Eisenberg, welcome.

Dr. Michael Eisenberg:
Thank you. Good to be here.

Andrew Huberman:
I've been looking forward to talking to you for a long time, because these days we hear a lot about the diminishing quality of sperm, which in some ways seems to be attached to the conversation about diminishing quality of environment, people, intelligence. There's a lot woven into this statement that sperm quality is declining.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
And some of it, I think people assume is related to environmental changes. Some of it, I think people assume it are related to changes in behaviors, so maybe less exercise, less sunlight, who knows?

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Hopefully, you'll tell us what's really going on. But the first question I have is, is sperm quality actually declining? And regardless, what is sperm quality?

Dr. Michael Eisenberg:
Yeah, great question. So I think it's very controversial, I think as your question alludes to. So I think we'll start by just talking about what sperm quality is and why it's important. So for reproduction, as you've covered on the podcast before, a man makes semen, and that has sperm in it. And so when we're talking clinically about a semen analysis, there's a few things we look at. We look at the amount of ejaculate, semen, that comes out. We look at the sperm, how many there are. We look at their motility or movement. We look at their morphology or shape. There's some more advanced testing that's done in rare cases, looking at fragmentation of DNA, for example, or there's some newer tests looking at epigenetic profiles of sperm. But essentially, these are all markers for fertility. So fertility in itself is a team sport, right? So it's hard to label a man as fertile or not fertile without knowing about his partner. But nevertheless, based on these different parameters, we try and quantify how likely a man is to be able to achieve a pregnancy. So the World Health Organization, every decade or so, looks over the existing literature and defines these different cut points of what's normal or what's subfertile for those levels. So that's sort of the backdrop of what semen is and how these tests are done, or what these tests represent. Now, the question of whether they've declined over time has been a question for a number of years. There was a landmark paper in the early '90s by Carlsen and a group in Denmark that showed this temporal decline over the last 50 years from that time point. And so what the investigators had done is looked over the literature for studies that reported semen quality around the world and noted that the quality in the earliest studies, like in the mid-20th century, were here, and then over time, they had sort of declined the more recent studies. Now, that study was very controversial. There was questions about weighting from different studies, because as you can imagine, there's not a lot of early studies, so putting a lot more importance on those rather than some of the later ones. And so since then, there's been many other studies that have come out in time. And even today, it remains very controversial. I think if I were to say that I believe there's a decline, some of my colleagues and friends would be very upset with me. If I say I don't believe it, some of my colleagues and friends would be very upset with me. So I would say that my opinion really varies based on whose paper I've read. And there's some very convincing studies on each side of it. Most recently, just in the last year or so, there was a meta-analysis of tens of thousands of men where they looked at, again, a host of these studies over the last number of decades, all around the globe. So prior studies really just focused on the Western hemisphere or Western countries because there was more data from that. But more recently, we've gotten a lot of data from Africa, from Asian countries as well. And those also support this decline. So one of the counterarguments to why we're seeing that is just an evolution of techniques over time. So that's one of the popular ... questions about whether there's really a true decline. I think as you're alluding to why there would be a decline is also unknown, but you've labeled perfectly the most common hypothesis. So whether it's some environmental exposures, right? A lot of things have changed over the last 50 years, and I think chemical exposure is certainly one of those. And there have been some fairly convincing preclinical studies, mostly done in animals, that show that exposure to different chemicals, phthalates, or BPA, other things, may actually harm reproductive function for men and for women as well. And so it may be that these chemicals that we're being exposed to as kids and adults, or even probably more sinisterly, when we're developing in utero. That may be the most harmful exposure. But there's also been an obesity epidemic as well. And there's a strong link between a man's reproductive function and body weight. And so that's also thought to play a role in some of this, too. So I think there are convincing studies, but the other, I guess, aspect to this is that there's variations in semen quality around the country and around the world. There's geographic variation. And so that's also an unknown explanation. There could be different genetic compositions of men, and so there's different reproductive potential in that source. There could be different environmental exposures, diet, exercise, lifestyle. There's a famous study done a number of years ago where they looked at semen quality among fathers. So these are men that had achieved a pregnancy, and at the first prenatal visit, they had the fathers give a semen sample. And so this was done in four centers around the country. I think one in California, there was one in the Midwest, there was one in New York. So they basically found that semen quality was highest in the urban centers, and New York tended to be the highest numbers, where it was lower in the Midwest. And so the hypothesis was potentially because it was a more rural setting, maybe there was pesticide exposure, and that had led to these lower numbers. But another equally plausible explanation may be that a different population and maybe that could explain these differences. So I think it's very important, and I think one of the lacking things in this is there's not really longitudinal data. One of the greatest things would be if we just started tracking semen quality around the country, just like we do obesity, like NHANES, the CDC's survey of health in the US, if we added semen quality onto that. That way you could really see how it varies around the country and compare like to like to see over time if there's really this progression. One of the only studies to do that in Denmark, they started around 2000 and tracked semen quality among volunteers that came in when they were conscripted for military service in Denmark. They were offered the opportunity to participate in this study. And so some men did, and what they found is actually that semen quality was fairly uniform over about 20 years where they had data. But another very interesting part of that study is that only about a quarter of those men had normal semen quality. So it's very concerning. It was, I guess, reassuring that it wasn't further declining, but very concerning that only a quarter of Danish men had normal semen quality. And they're one of the, I think, thought leaders in this field, just because a reproductive crisis there.

Andrew Huberman:
You mentioned that some of this apparent decline in semen quality might be related to the fact that the tools to measure semen quality are getting better and better. And that would make sense if, for instance, one is just looking at total volume, morphology, which means shape, I should have clarified that, how many forwardly motile sperm there are, and then also adding in a very sensitive measure such as DNA fragmentation. Essentially, as the instruments get finer and finer, you discover more and more details, and if you are rating quality along a number of different dimensions, then it would make sense that those would tier out into different levels. So if one were to simply ask for couples who want to get pregnant, and assuming that egg quality is not the issue, what percentage of failures to achieve successful pregnancy are the consequence of deficient sperm, deficient in any way, and is that number increasing over time?

Dr. Michael Eisenberg:
Yeah. So I think that's really key. I think when couples think about fertility, usually it's thought of as a female problem. And I think there's just historic reasons for that. If you look at data in the US, when couples do seek care for fertility, the man is bypassed probably a third of the time, even though when you look at the reasons for infertility, the man contributes probably half of the time to infertility. So I think there's a-

Andrew Huberman:
Half?

Dr. Michael Eisenberg:
Half. Yeah. So I think there's a huge need just to understand and evaluate the man. And one of the reasons for this, I think, is that one of the main treatments for infertility in the US is IVF, which is very powerful. I think one of the greatest marvels of medicine in probably the last quarter-century is our ability to mix a sperm and egg in a dish and create a life. It's really remarkable. But because it now takes just a single sperm through something called intracytoplasmic sperm injection, where you can inject one sperm into an egg, the bar has gone down dramatically. For couples just trying without any assistance, probably need 20 to 40 million moving sperm. But now with these remarkable techniques, you just need one sperm. And so because of that, I think a lot of our innovation and research on male fertility has probably gone to the wayside just because clinically, we just need a few dozen sperm for most couples.

Andrew Huberman:
What about testosterone levels? Are those also declining? We hear this, and when I look at the literature, I can find evidence for that. But the question is also whether or not the amount of decline in testosterone levels is significant in a way that impacts, let's say, fertility, but also vitality in other ways, energy, mood, sexual health, et cetera. What's the story with testosterone levels? Are they indeed declining on average across the male population in the US and elsewhere?

Dr. Michael Eisenberg:
I think there is pretty convincing evidence that that is happening. And I think the reason for that, again, is probably not certain, but there have been some pretty nicely designed cohort studies where they recruited men in the 2000s, the '90s, the '80s. And you can see that depending on when these men are recruited, just matching age for age, these testosterone levels tend to be lower. And then NHANES, which is, again, this sort of longitudinal study run by the CDC, that has also shown, looking at testosterone levels over decades, that testosterone levels have declined over time. So chemical exposure is one possible explanation, again, either in adult or adolescent life or in utero. But obesity, I think, is also a convincing explanation. As we're more sedentary, we get bigger. That's one of the places that testosterone can decline. I think there's different explanations for that. As testosterone's produced, it's aromatized in peripheral tissue, in fatty tissue. Fat has a lot of this aromatase, so that converts testosterone to estrogen. So it necessarily lowers the testosterone level that's circulating in our body. Also, just insulating the testicles. Our thighs get bigger. Insulating the testes can also sometimes lower the efficiency of production a little bit, too.

Andrew Huberman:
Because of heat effects?

Dr. Michael Eisenberg:
Because of heat effects.

Andrew Huberman:
Mm-hmm. Yeah. I was going to ask about this later, but I'll ask about it now since we're talking about heat effects on sperm and testosterone. The heat, of course, being not good for sperm health and testosterone. Which is, I've read a meta-analysis, I don't know how high quality it is, but that explained that there is some evidence for either heat effects or possibly non-heat related effects of cell phone, smartphone in the pocket-

Dr. Michael Eisenberg:
Mm-hmm

Andrew Huberman:
... impairing sperm health, maybe even testosterone levels. Now you hear this more often in kind of biohacky circles, which I'm not a fan of the word biohacking. It's not clear what it means, but it sounds like it means something about taking a shortcut, using one thing for a purpose it wasn't intended.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
But it also makes sense to me that a smartphone could generate some heat, some radiation that might impair testicular function and therefore impair sperm quality and/or testosterone levels. But is there any real solid data that carrying your cell phone in your pocket, let's assume on, that the cell phone is on-

Dr. Michael Eisenberg:
Right

Andrew Huberman:
... is bad for sperm health or testosterone levels?

Dr. Michael Eisenberg:
Yeah. So I think there's not convincing evidence that it's going to help testosterone levels. I think that-

Andrew Huberman:
It's going to hurt testosterone levels.

Dr. Michael Eisenberg:
It's not going to hurt. Yeah. So I should make clear that I think that in terms of production and heat effects, sperm production is much more sensitive than testosterone production. But there have been some studies looking at cell phone exposure because, again, you're getting this, whether it's heat, whether it's the radio frequency waves coming in, I think you could posit different explanations of why that may be harmful. So there have been some studies that looked early on men that used cell phones more or less, they had lower semen quality if they used it more. But you can also imagine there's huge differences in men that do and do not use cell phones. So it's a hard experiment to design. But there have been some studies doing this in vitro, so in the laboratory. So taking sperm in a cup, basically, and putting a cell phone next to it or not next to it to try and see if that played a role. There have been studies done where they normalized the heat. They put it on a special stage so that it's not heat necessarily, but maybe it's RF exposure. So those studies, I think, don't show a clinically meaningful change. But there have been some studies that say that maybe DNA fragmentation of sperm can go up a little bit if there's close proximity to a cell phone. So I think when patients ask me that, which is a common question I get in the clinic, obviously patients are coming in, they want to do whatever they can to try and improve their chances. So I think generally, I think the data's not convincing. But if it's easy enough, certainly to be aware of it. I think putting a laptop on a desk rather than in your lap, I think for heat exposure is probably the biggest thing that we want to minimize.

Andrew Huberman:
About a year and a half ago, I did an episode about testosterone and estrogen, where it's manufactured in the male and female body, et cetera. And I found a very interesting graph in a textbook on behavioral endocrinology by a guy named Randy Nelson, who I happen to know through the field of behavioral endocrinology as it's typically studied in animals. So most of that book centers on animal studies, but there's a fraction of the studies that center on human data. And there was a very interesting graph that showed testosterone levels as a function of age in males. And as one might expect, testosterone levels were on average much higher in late teens, early 20s, 30s, and there was a progressive decline. But what was remarkable to me about that graph is that even when exploring the scatter plots, because they showed individual points, they didn't just show the averages of testosterone levels in men in their 50s, 60s, 70s, 80s, even 90s. There were these outliers, these guys who had testosterone levels that were on par with ... testosterone levels of men in their 30s, but these guys were in their 50s, 60s, 70s, 80s, even 90s. So do you observe this clinically? Do you observe that men are coming in who are older than 40 and have testosterone levels, and presumably free testosterone levels as well, that are still very high? The reason I ask this is I think we've all been told, and we presume that testosterone levels decline with age, and one would expect some outliers. And of course, we don't know whether or not those guys in their 90s who have the testosterone levels that match the averages of men in their 30s didn't have even greater testosterone levels in their 30s. But given that they were ceilinged out around 900 nanograms per deciliter toward the high-end normal, depending on the scale, already at age 90, it's hard to imagine that earlier they were walking around with 2,000 nanogram per deciliter testosterone. So do you see this? Is there just a lot of natural variation in testosterone levels of men who walk into the clinic at any age? And of course, what is special about these individuals that are maintaining high normal testosterone levels into their later years?

Dr. Michael Eisenberg:
Yeah, that's a great question. I think this is such a common question anytime we talk about testosterone. I think anytime we talk about most clinical tests that we do, what is average, what is normal? So we do see great variation. I think, just like you're saying, I usually let everybody know that usually testosterone peaks early 20s, and it tends to go down probably 1% a year forever. But there are people that have very high levels, just mirroring that graph that you describe. I certainly have patients, we screen for testosterone levels when patients come in with complaints where we're worried about that, low energy level, low libido, some of the symptoms of low testosterone, sexual dysfunction. And to my surprise, sometimes these men, I've seen 80-year-olds that certainly have the highest testosterone level I'll see for six months. Why that is, I think is not certain. Maybe it has to do with-- I would think with everything, there's probably a bell-shaped curve and everybody's a little bit different. But androgen sensitivity, sensitivity of the receptor, they make it more efficiently. But I have not really noticed, again, because at least in clinical practice when patients come in, they come in with a complaint. And so even men with very high levels, they may have some of the same dysfunction as men with low levels. So I think with low levels, you can try and treat that, and that may be the solution. But for men with what we would consider high levels, there may be other issues going on.

Andrew Huberman:
Let me frame the question I was going to ask a little bit differently. When someone comes into your clinic and you measure their testosterone levels, as you mentioned, they're likely coming in because they have some issue, prostate issue, sexual function issue, et cetera. But you do get a read on their crude morphology of their body, right? So you could visibly determine whether or not they're likely to be obese or not, regardless of age. So earlier you mentioned obesity as a risk factor for lowering testosterone and sperm quality. You mentioned that fat aromatizes testosterone into estrogen, so that's at least one mechanism by which that could happen. But if you were to just step back and say, okay, if somebody who walks into my clinic tends to be, let's say, healthier looking, not obese. Let's just put the cutoff at what you would presume is obese. Is there a higher probability that their testosterone levels are going to be within normal range? Conversely, when somebody walks in and they're obese, do you fully expect their testosterone levels to be subnormal? Or are you sometimes seeing obese people walking in with high testosterone? And the reason I'm asking this is not to create confusion, is that I think that everybody out there who's thinking about sperm quality and testosterone levels and this apparent decline, trying to figure out, okay, what can we do in order to maintain the health metrics that are going to, of course, increase fertility, but for those that don't want to have kids or who already have kids, are going to at least maintain or improve vitality. Is obesity really the thing to avoid? So is there a, not one for one, but is there a tight correlation between obesity and testosterone levels?

Dr. Michael Eisenberg:
I would say that you cannot predict. I think that would be the take home. And so I think that more information is always better. When I see patients in clinic, some patients are walking around with everything is totally normal. They're very healthy. All the numbers come in at the normal range. But sometimes when men look totally normal, they talked about taking care of their life. They exercise five, seven days a week. Their testosterone levels can be very low. So even despite having what we would consider should really give them symptoms, they're able to compensate. Maybe they've lived their whole life in that they don't know what normal is. Now we get them to normal levels, a lot of times they feel better, and again, because they had no idea how they should feel. But I think that's just important that everybody should be screened. I think that testosterone, semen quality, they've been shown to even be barometers of health. So, men with lower testosterone levels have higher risk of heart disease, diabetes, mortality. The same studies exist for semen quality as well. And again, they may have a similar relationship and explanation why that may be. But I think it's hard to just predict based on appearance what testosterone will be, what semen quality will be, what testicular function will be, without actually getting some objective data. And actually, if you look at the trend of semen quality decline over time, getting back to some of those earlier points you were making, if you were to overlay that on the known association between obesity, its effects on semen quality, that actually doesn't explain the whole decline because the purported decline in semen quality is about 50%. But if you were to say, well, what would we expect if we look at-- Because we are able to track exactly how much fatter we are now Than we used to be. That actually only explains about a 10% decline. So I think there is, to your point, something more, and it is not something that you can just identify by eye.

Andrew Huberman:
What are the dos and don'ts as it relates to, I don't want to use the word optimizing, it's gotten me into trouble before because the word optimize or optimal suggests that there's a perfect number that one should all attain if possible, but in reality, optimal is a day-to-day thing at least. But what should people avoid in order to get their sperm quality as high as possible, their testosterone level? Again, here I will have to be careful. I don't want to say as high as possible because some people might not want excessive androgen. But at the high end of normal, perhaps would be the ideal for many people. What should people do? What should they avoid? And here I'm setting aside any prescription clinical treatments such as testosterone injections or things like human chorionic gonadotropin, things that we can talk about a little bit later. But what should every male be doing in order to optimize these health parameters?

Dr. Michael Eisenberg:
Yeah. So I think that there are some risk factors that we do like. We'll start with semen quality. So we talked about heat. I think that's a big one. So like hot tubs, saunas, try and avoid those. Some light data on seat warmers. Any time we get this external heat source to the scrotum, the testicles are outside the body because they need to be a little cooler, so anything that warms them up can certainly be a problem.

Andrew Huberman:
Could I just briefly interrupt there to ask, we've done episodes on sauna and some of the health benefits of sauna. Is it sufficient for somebody to bring in a cold pack to the sauna and put that up in their groin? I actually have suggested that. That's actually what I do when I go into the sauna, and I have suggested this on podcasts, not just for people who are trying to conceive because it seems like heat, as you mentioned, is bad for sperm, not quite as bad for testosterone levels. But is it also true that heating the testicle too much is generally bad for endocrine function in males, and therefore if one is going to go into a hot sauna for 20 minutes or more to essentially cool the scrotal area?

Dr. Michael Eisenberg:
Yeah, I think the spermatogenesis or sperm production is certainly a lot more sensitive. Whether you can sort of thwart the effects of external heat with a cooling pack, I think it makes sense. There are studies that have looked at different ways to cool the scrotum and have compared semen quality before and after, and there's some data that may help. It just depends how long you're going to spend in the sauna and how cold that pack is going to remain.

Andrew Huberman:
So ice pack and in the sauna for 20 to 45 minutes.

Dr. Michael Eisenberg:
Yeah. And is the ice pack still cold afterwards?

Andrew Huberman:
Yeah. They actually sell, and by the way, I have no relationship to any of these companies, but they actually sell cold packs that are designed to be worn in your shorts. So if you go to a-- I'll go to a Russian banya every once in a while now. I guess I'm outing myself. Yes, I have a cold pack in my shorts when I go to the Russian banya. But they have a sort of an insulation so that the very cold surface is cold enough, but it's not right up in contact with the scrotal skin because that could get-- I want to make a bad joke and say it could get sticky, that situation. You don't want it being so cold that it actually would stick to the skin, and then it could potentially damage the skin when you try and remove the cold pack. So it has a thin insulating layer. And yeah, that's essentially what it is.

Dr. Michael Eisenberg:
Yeah. Frostbite to the scrotum is not theoretical. It could certainly happen. So you do want to be careful.

Andrew Huberman:
Yeah.

Dr. Michael Eisenberg:
So in theory, that should be adequate to decrease the risk of that particular effect. I keep coming back to health, how important that is to maintain adequate sperm production because I think these two are very linked. There have been studies that show that men with more comorbid conditions, so obesity, hypertension, hyperlipidemia, as these sort of stack up, we see a decline in testicular function, so lower testosterone levels and lower sperm quality. So I think taking ownership of your health, I think is important as well. A lot of times, fertility tends to be one of the first touch points that some men have with healthcare, because generally what brings men to the doctor? It's usually pain or kind of a problem. So, if men are in their 20s and 30s getting ready to start a family, or 40s in some cases, sometimes they haven't seen a primary care doctor. So some of these things and some of this relationship has not been established yet. So I think thinking about ways to start that, I think would be important, too. And then I know you don't want to talk about testosterone, but testosterone is actually a fairly common problem that we see in fertility clinics. I would say that estimates say maybe about one in 20 infertile men are that way because of testosterone. So I think when people get testosterone from different places, and hopefully, whatever provider you're getting it from tells you that one of the side effects of this is lower sperm production. It's actually been tested as a contraceptive, and with some other agents, it can actually be fairly effective. So we just want to make sure that if men are starting testosterone, they're doing it for the right reasons and they're doing it safely. I think-

Andrew Huberman:
You're talking about testosterone replacement therapy. Although, as we were talking about before we started recording, I am really on a push now to rename what people call TRT, testosterone replacement therapy, because indeed, some people have low testosterone and need it replaced-

Dr. Michael Eisenberg:
Right

Andrew Huberman:
... the R in TRT. But I think what you're referring to, if I'm not mistaken, is that there are probably millions-

Dr. Michael Eisenberg:
Yeah

Andrew Huberman:
... of young men and older men taking exogenous testosterone, injections, creams, pills, pellets, any number, nasal sprays now. Any number of different routes of delivery of exogenous testosterone, and that- ... dramatically reduces one's endogenous testosterone production and dramatically reduces one's sperm count, and maybe even quality. We'll maybe talk about this a little bit later. I've been told that it can perhaps introduce a DNA fragmentation within the remaining viable sperm as well. So do I have that correct? You're saying that you see 1 in 20 men have issues with fertility because they are taking testosterone.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
So their testosterone levels presumably are going to be high end normal or more, but they are doing presumably not testosterone replacement therapy, but they're doing what I call testosterone augmentation therapy, meaning they were somewhere in the 300 to 900 nanograms per deciliter range, but decided to start taking testosterone anyway, and then their sperm count essentially diminishes to nil or close to it?

Dr. Michael Eisenberg:
In some cases, yeah. So, I think there's various reasons that you would take testosterone. I think some people have been treated years ago, and so they do need to replace testosterone, but some people do it for augmentation. I just usually say testosterone therapy just so it covers-

Andrew Huberman:
Oh, you kill the R. I like that. That's better than the T-A-T, which doesn't sound very good. Okay. Just testosterone therapy.

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
Okay.

Dr. Michael Eisenberg:
But if you had, for example, if we take 100 of my infertile patients that come in to see me in clinic, at least five of those men will be infertile because they're on testosterone therapy. And some of them do have that suspicion. They say, "I'm going to level with you. This is why my levels are probably low." But a lot of men were not told that when they started therapy. So I think certainly for reproductive-age men, that's a very important conversation to have. Because there can be some other ways that we maintain sperm production. I think sperm cryopreservation is a good option for these men as well. Or there may be other therapies they can think about just because of reproductive toxicity.

Andrew Huberman:
What about hCG, human chorionic gonadotropin? I hear about a lot of people who go on testosterone therapy who take hCG every other day or so.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Typically, the dosages that I hear about, because people write to me about this stuff all the time, really, it's one of the most commonly asked questions. I get many questions about many topics, but I would say a full 10 to 20% of them are about penises or testosterone.

Dr. Michael Eisenberg:
Well, this is perfect, then.

Andrew Huberman:
Right. Exactly. So a number of those guys who are taking testosterone will be prescribed hCG to stimulate sperm production, endogenous sperm production to maintain healthy sperm, presumably because they either want to conceive or are intending to conceive in the future. Is that the best line of treatment for maintaining fertility while people are taking testosterone therapy?

Dr. Michael Eisenberg:
Yeah. That's one of the therapies that we use, and I think it can work well. Just a low dose. Usually, again, for those that know, 500 to 1,000 units every other day is usually adequate.

Andrew Huberman:
So if somebody is not taking testosterone exogenously, they've gotten their body fat level down to a point where they're not considered obese, so they're hopefully doing some cardiovascular exercise each week, maybe doing some sport or some resistance training too, with the intention of maintaining all around good health to stave off cerebrovascular, cardiovascular issues. What are some of the other don'ts? I'm going to assume that smoking cigarettes or vaping cigarettes is bad. Are there any studies that have looked specifically at vaping and sperm quality or testosterone levels? And is there any evidence that smoking cigarettes is good for testosterone levels or sperm production? Because I'm guessing the answer is no. I feel like nowadays we just say, "Don't smoke." But the data are the data. Who knows? Maybe nicotine can help sperm. I have no idea.

Dr. Michael Eisenberg:
Right. It's possible. I don't think we have the data on that yet. But yeah, I think to your point, I think lifestyle factors are certainly a big one, and some of these potentially unhealthy habits. So smoking is certainly something you should not do. There have been lots of studies that do link that to lower quality, again, all the different measures that we look at. Also looking at fertility, these men tend to have a longer time to get pregnant. Alcohol, I think, is another very common question we get asked as well, and I think for that, there's less of a strong association that we've seen. So there have been some studies that show that very high levels of alcohol, and I guess that's sort of subjective what some would consider high or not, but when you get above maybe 20 drinks a week, there have been some effects, but usually-

Andrew Huberman:
That's a lot of drinking.

Dr. Michael Eisenberg:
I would think that's a lot, yeah. But some people don't. But yeah.

Andrew Huberman:
I did an episode on alcohol. I know people are going to balk at this, but I think any more than two drinks per week is where you start to see some negative effects on some health parameters. But, I'm not a teetotaler, so yeah.

Dr. Michael Eisenberg:
Yeah. But when you get to this 20 drink, that's when we started to see some effects on semen quality. But the thing about that is that usually if these men are drinking 20, they're doing other things too, smoking. There can be other drug use as well. So it's hard to tease that out, but in general, I think certainly anything in moderation is probably better, and so that's how I counsel patients. I think, again, it's very rare that I see men that are at that level, but I certainly let them know when I do. There's some new data coming out that we've started to work on looking at if there are different sensitivities to alcohol. So, some East Asians have a mutation that leads to flushing, and so that may put those men at higher risk. When they mix alcohol, we may see some slightly lower sperm parameters.

Andrew Huberman:
You mean skin flushing because they don't make alcohol dehydrogenase? Is that the idea?

Dr. Michael Eisenberg:
Exactly, yeah.

Andrew Huberman:
Yeah. I've heard about that in Asian cultures. In Asian population, excuse me. But is there any evidence that other populations might have slight variants on alcohol dehydrogenase that perhaps maybe they don't lack it altogether, but they have, I don't know, they're hypomorphs for whatever gene makes alcohol dehydrogenase, and therefore, they don't metabolize it as well, and therefore, the toxic form of alcohol is- active in their system longer. Is there any evidence for that?

Dr. Michael Eisenberg:
No, I think, yeah, you're exactly right. I think the one that we think about is East Asian cultures, where it can be, depending on the region, like Chinese, Taiwanese, probably about 40 to 50% of the population has a mutation in the ALDH2 gene. But other populations, in people of African ancestry, there's a rate of mutation, I think, I'm not going to remember the exact percentage, but I think a few percentage points. Some individual with Hispanic ancestry, Ashkenazi Jewish ancestry. So in this particular gene, there's a mutation, not the same one that East Asians have. But again, I think it gets to why a mutation where we see negative effects would persist. And the hypothesis that millennia ago, potentially it gave some sort of benefit for maybe an infectious disease or something, similar to cystic fibrosis, why again, this mutation would persist in our population if there's not some sort of advantage to those carrying it. But we do see in other men as well. So I think it's a simple question. Do you flush? If you flush, then maybe alcohol may have more of a harm than someone else. And then, getting along the lines, I think drug use is also something that we should try and-- We do counsel patients about, because that can also negatively affect semen quality.

Andrew Huberman:
Do you think it's fair to say that, okay, moderation is best, but if somebody had the option to either not drink or drink in moderation, that they should not drink? Would that be even better? Is there any evidence for that? It seems like nowadays we take the stance that not smoking at all is better than smoking a little bit. Actually, when I was a postdoc at Stanford from 2005 to end of 2010, you could still smoke on the Stanford campus. I'm not a smoker, but there was this collection of-- I have to be careful what I say here. There was a particular group on campus of postdocs and graduate students that would colonize this little area outside the hospital and smoke because that's where you could smoke. That was eventually eliminated as a possibility. You can't smoke on Stanford campus as far as I know. But they would smoke right outside the hospital. Actually, a lot of the hospital workers would take a cigarette on their break. This is very common.

Dr. Michael Eisenberg:
The irony. Yeah.

Andrew Huberman:
Right.

Dr. Michael Eisenberg:
Exactly.

Andrew Huberman:
Yeah. And this was common all over the country. This isn't unique to Stanford, but nowadays, you just don't see that because it's not allowed. And we hear, "Don't smoke. It's terrible for X, Y, Z," and every other letter of the alphabet. With alcohol, we tend to hear that if you're going to drink, drink in moderation. It's not clear exactly what number that is. But is it possible that zero alcohol is better for sperm and endocrine health than any alcohol, or is that not a fair assumption?

Dr. Michael Eisenberg:
I think that's a good question. I think your point about tobacco is an excellent one, because I think any smoking is bad. But alcohol, I think we don't have that data for yet. And so I think it's harder for me to make that recommendation to patients, especially because people do it for different reasons. And if it's not necessarily going to help them, it'll harm them in social situations or other things. Yeah, I usually give the moderation one. Unless, again, for the very high drinkers, I definitely talk about that.

Andrew Huberman:
You mentioned other drug use. I'm going to assume that unless prescribed for post-surgical pain or something like that, that benzodiazepines, heroin, opioids of any kind are just bad for sperm and testosterone. I think that we could probably make that a short discussion, right?

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
I can't imagine any of that would be good for reproductive health.

Dr. Michael Eisenberg:
Yeah, that's true. There's, again, you'd imagine, or maybe not, but there's not a lot of data on it. It'd be difficult to enroll or maybe easy to enroll, but a lot of those studies have not been done. But there's limited ones of people in rehab where they have shown these associations with addicts or users and lower quality. So yeah. That's how we talk to patients.

Andrew Huberman:
What about cannabis? I did an episode of this podcast about cannabis, and I did highlight some of the medical applications of cannabis. I also highlighted that very high THC cannabis may predispose, especially young males, to later psychotic episodes. There are more and more data coming out about that all the time. I got a lot of flak for saying that, but that's my take on the data. And I know a lot of people use cannabis recreationally and in a kind of pseudo-therapeutic way. I say pseudo-therapeutic because I think a lot of people use cannabis to manage their anxiety and as an alternative to alcohol for a number of reasons. What is the relationship between cannabis use and testosterone and sperm production? Or I should say sperm quality, excuse me.

Dr. Michael Eisenberg:
Yeah. So this is also a very common question. Again, with this wave of legalization across the country, I think more and more men and women are exposed to it. So again, there's data that the more men are exposed to it, it can lead to some harm in terms of sperm morphology and sperm numbers as well. One of the landmark studies was about 1,200 men, and it found that men that used cannabis daily had significantly lower concentration, motility, morphology compared to those that didn't use it. So I think that's generally how men are counseled, but there's also other data that shows really a null effect, and I think that it goes into probably the composition, how men are taking it, the frequency, because a lot of that data is not well teased out in a lot of these studies. So I think I sometimes struggle with this with patients, because some of them are taking it for some what they consider legitimate reasons, anxiety, sleep, pain. And if there's not very convincing evidence that it's going to help, and they're taking it maybe lower than the threshold where I know that there's good data that'll cause harm, I guess I try and be honest about where we are. But I think with a lot of things related to sperm, I think our level of evidence is not great.

Andrew Huberman:
Are there any common over-the-counter medications that can negatively impact sperm quality and/or testosterone? Things like non-steroid anti-inflammatory drugs, Tylenol, Advil type stuff, ibuprofen, acetaminophen, things of that sort that I and others might not be aware of. I'm not probing for anything in particular here. I know that a lot of over-the-counter drugs have effects that we're just simply not aware of.

Dr. Michael Eisenberg:
Yeah, I think we probably need more data, but I think currently we think all those are safe.

Andrew Huberman:
I'm curious about the pituitary. Pituitary gland, as many listeners of this podcast already know, is a gland that receives signals from the brain. The gland sits near the roof of the mouth I think that's fair, and releases critical hormones into the bloodstream that control the output of testosterone from the testes as well as output of hormones from other glands. I know a number of people end up playing sports like football or rugby or even lacrosse or even soccer. I've read, there are data on this. They're heading the soccer ball quite a lot, or martial arts, or they get a head injury at some point. And I certainly hear a lot from people who played these high-contact sports, and then to their surprise, later they have diminished testosterone levels. I also work with a number of military groups that talk about this. That they leave, and maybe it's from combat-related stress, et cetera, but they wonder whether or not there's any traumatic head injury or maybe pituitary injury-related impairment to the reproductive axis that includes brain, pituitary, and the testes. Do you see that? And if somebody played a contact sport, in particular a contact sport where the head was hit or they were hitting things with their head often, or if they have a TBI or had a TBI, that their reproductive health can be impaired.

Dr. Michael Eisenberg:
That's fascinating. I have not. It's interesting, I guess, what the pituitary does. You've obviously covered this before, but it does go to a lot of our therapies. So, for your listeners, the pituitary produces two hormones, LH, luteinizing hormone, and FSH, follicle-stimulating hormone, which then stimulates the testicle. So the luteinizing hormone stimulates the Leydig cells to make testosterone, and then the follicle-stimulating hormone, or FSH, stimulates sperm production. So both of those are very key in terms of production. And interestingly, when exogenous testosterone is used, it shuts down that axis, as you know, so we get less of these gonadotropins, this LH, FSH, to stimulate the testicle. And the other reason that sperm production is lost with exogenous testosterone use is actually the intratesticular testosterone is much higher than serum levels. So our serum levels are between 300 and 900 nanograms per deciliter on average, but in the testicle are probably tenfold higher at least. So when men are given exogenous testosterone and they're not producing their own, the levels of testosterone in the testicle, which are necessary for sperm production, are much, much lower. But it's interesting because I think I'm not aware of how traumatic injuries would do that.

Andrew Huberman:
Okay. That's good to know. I'm curious about the non-endocrine, non-chemical effects on sperm quality and testosterone levels. So here I'm thinking about a bunch of news stories we heard a few years ago about how bicycle seat pressure on the prostate, or maybe it was other portions of the-- maybe it was the nerves running to the penis itself, or surrounding areas, maybe it was pelvic floor related, and somehow, you'll tell us, I'm sure, was impairing sexual function. Was it impairing sexual function in any way by impairing testosterone levels, cutting off blood flow to the testes? And here, perhaps the most important thing to ask straight off is, is riding a bicycle bad for male reproductive health and sexual health?

Dr. Michael Eisenberg:
Yeah. These are great questions. These, again, living in the Bay Area, working in the Bay Area, cycling is very, very popular, so these are questions that I get a lot. So I think, in general, like we talked about before, anything that's good for your heart, it's going to be good for fertility. So a good diet and exercise, maintaining good body weight. And so I always try and encourage physical fitness. I think that's important. But it's maybe possible that some particular activities may put men at more risk. So I think cycling could be one of them, but it would depend on exactly why we think that may be a problem. So I guess the theory is heat. If you're in the saddle for a long time, for these prolonged rides that men take on weekends, hours, that maybe if there's too much heat exposure, that may be the mechanism where sperm production would decline. So there have been some studies say maybe five hours a week that may be too much. So if you're above that level, the sperm counts have shown to be lower. If you're less than that, that may be okay. So when I talk to patients about it, I try and just encourage them to stand up in the saddle, to try and, again, air things out, to try and dissipate heat if that's the mechanism we're going to think. Regarding sexual dysfunction, that is thought to be pressure, as you're alluding to. So the way that the saddle is configured, ideally, all the pressure is put on our ischial tuberosities or our sit bones. That's what I'm sitting on now. But on the saddle, there's obviously the rigid nose, and if there's too much pressure on that, that actually squeezes between the ischial tuberosities where the main blood flow to the penis goes and- ... the main nerve supply is too. And so if there's compression on this, you get this sort of lack of blood flow or ischemia, and you can get a neuropraxia as well if you crush these nerves. And so that, over time, can lead to problems. So, some patients will say that, "After I cycle, things are numb down there for 30 minutes or a day," or, "I don't get erections for that sort of same amount of time." Or sometimes, men just sort of ride through it, and hopefully things come back in a day or two. So that could be the mechanism. There are some saddles that hopefully will be a little safer. And, I think that this sort of first was noted probably around 2000 or so, and there was a big redesign in terms of saddles to try and make them a little bit more anatomically correct, to try and minimize some of this. And there's cycle fit that can be done, or saddle fit, rather, that can be done at some of the cycling shops to try and look at your body position, look at your size, and try and find a saddle that's safer. This doesn't happen to everybody. I would say maybe if you were to survey cyclists, maybe 20% to 30% of men and women tend to be susceptible to this. So I think if you are having discomfort when you cycle, whether it be pain, numbness, or you notice dysfunction, I think certainly you should think about changing saddles or think about changing riding style. There's other strategies that are sometimes used, but it's absolutely something that everybody should be aware of.

Andrew Huberman:
I meant to ask this earlier, but I seem to recall a study that drew a correlation between amount of walking, and maybe it was sperm quality, but I think it was testosterone levels. Maybe some other metrics of male sexual health. Forgive me, I'm not recalling the details now. Is there any evidence that walking more, standing more, maybe even using a standing desk, is beneficial for pelvic floor health, blood flow, prostate health, who knows, could be any and all of those things, in some way that is beneficial for sperm quality, testosterone level, and/or overall male sexual health?

Dr. Michael Eisenberg:
Yeah. I think one of the ways that we can characterize activity is step count. I think I have a watch that tells me that. It's something that I look at every day and kind of strive for. And it turns out that the more active you are, it's been shown, looking at large national data pools across different age ranges, that it is associated with testosterone levels. So being more active, I think, is very important, and that's another thing that everybody can do to try and improve sort of testicular function broadly, but testosterone specifically.

Andrew Huberman:
And do you know whether or not that can be separated out from the relationship between being more active and less obese? I mean, is this something that's independent of obesity? In other words, can we incentivize people to walk more simply on the promise of improved sexual health?

Dr. Michael Eisenberg:
Well, I don't know. Yeah, sexual health will be a different one. But I think there is association between testosterone levels and step count, across different BMI, straight up. So I think, whether you have the ideal body weight, whether you have a few pounds to lose perhaps, if you walk more, you will see higher levels of testosterone.

Andrew Huberman:
Okay. And another question I meant to ask earlier, and then we can close the hatch on exogenous testosterone therapy, at least for the time being, maybe we'll come back to it, is assuming that somebody can maintain adequate sperm production through the use of hCG or some other therapy, or perhaps they don't care if they're still making sperm because they've already had children, or they don't care to have children, maybe they've banked sperm. In any event, assuming that somebody takes testosterone therapy because they were prescribed that, let's say in your clinic.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Let's just use you-

Dr. Michael Eisenberg:
Okay

Andrew Huberman:
... and your clinic as an example. And they are happy with the psychological and physical consequences of that, and they are comfortable with the trade-offs. Is there any increased risk of, say, prostate cancer or other forms of cancer? And here I'm going to assume that this person is keeping their lipid levels in check, right? Because you hear about some hyperlipidemia with testosterone therapies. Let's assume that they're either taking a statin or they're not taking a statin, they're getting enough cardiovascular exercise, that things are in check in terms of LDL, HDL, ApoB, and all of that.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
And their testosterone levels are now high normal, and they're feeling better, and they don't have to worry about sperm production because they're either maintaining it or it's been banked, or they don't care about that. Is there an increased risk of prostate cancer? My understanding is the answer is no, but what's the real deal? Does taking testosterone therapy, assuming all other things are being held in check, in a healthy check, does it increase the risk of any kind of cancer?

Dr. Michael Eisenberg:
Yeah, this is another great question because I think there's a lot of myths around testosterone, and that's one of them. The origin is that prostate cancer is thought to be or is sort of androgen mediated. One of the Nobel Prizes, again, decades ago, was awarded because it was found that when we lowered men's testosterone, the prostate cancer would regress dramatically. So that put that association between testosterone and prostate cancer. So then the concern began, if we were to either replace testosterone or augment testosterone or give a man testosterone, is that going to alter his risk or increase his risk? So I think we have pretty convincing data that that's not the case. There's lots of longitudinal data spanning decades where if a man is given testosterone, it doesn't change his risk. The reason for that, in a sort of seeming contradiction between prostate cancer therapy where we lower testosterone, where if you give a man testosterone, it doesn't change his prostate cancer risk, is not certain. But there's this popular model called the saturation model, so that once there's enough testosterone in the body, and it tends to be a fairly low level, that all the sort of the prostate Testosterone receptors, you can think of as have been filled. So if you were to give men more testosterone, it doesn't change anything regarding the prostate cancer, prostate growth, any of that. So it is safe when we're looking at prostate cancer as an outcome.

Andrew Huberman:
Getting back to prostate health and neural innervation of the penis and blood flow to the penis, you mentioned the bike seat-related issues. Are there other things that men should do in order to maintain prostate health, stave off prostate diseases, and to maintain healthy blood flow and neural innervation of the penis, for obvious reasons? And we'll get into the specifics of those reasons in our later discussion.

Dr. Michael Eisenberg:
Yeah, I always think of the penis as a use it or lose it organ. So that doesn't mean necessarily that you have to have sex, but normally we get erections every night, so that should be maintained. And if there's any reason to suspect that that may not be going on, usually in my practice, that would be from some pelvic surgical intervention or something like that. Sometimes we can intervene to try and maintain that.

Andrew Huberman:
You're talking about spontaneous erections during sleep.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
And short of assigning one's partner to check frequency and tumescence, what is the way that men would know that that's happening? Are you talking about waking up with an erection? Is that a requisite for knowing that nocturnal erections are occurring?

Dr. Michael Eisenberg:
Well, yeah. I think you've caught me. I think that's a good question. So I think a lot of times you won't know, but I think if you have normal response, when either by yourself, with a partner, I think that generally means that you are going to get normal erections. So I guess when I say use it or lose it, it doesn't mean necessarily that the man has to stimulate himself or make sure that he does have adequate function. Because usually, most of that normal function just occurs with this nocturnal penile tumescence, which we all get. I think sometimes men do notice when they wake up at night. Sometimes in the morning, you wake up with an erection. Men notice that. But the absence of that doesn't mean it's not happening. It likely is, just most people sleep through it, which is normal. Otherwise, men would never get any sleep because it happens many, many times a night. So I think, again, if you're not having normal function, I think that's something you should probably see a physician about. And then same for urinary function. I think if it bothers you, if you're waking up at night, if you have to go to the bathroom often, if your stream is getting weaker, those are all complaints that we hear about.

Andrew Huberman:
What is often? My understanding is that it's normal to wake up perhaps once during the night to urinate. And this is, of course, assuming, and again, forgive me for all the caveats, but I've done this long enough that if I don't get really granular about some of this, then people will say, "Well, what if I drank 32 ounces of fluid right before sleep and I'm urinating three times per night?" Well, we're assuming that people are tapering their liquid intake as they approach bedtime. And that waking up once, maybe twice, but once in the middle of the night to urinate is normal for somebody, let's say age, I don't know, 18 to 40, and maybe from 40 to 100, that number might be in the one to two times per night. Is that about right?

Dr. Michael Eisenberg:
Yeah. I think once a night is normal for most men. And then I think, if things start to bother you, I think you could certainly see somebody, but it's hard to get better than once or twice a night, yeah, for most men.

Andrew Huberman:
My understanding is that there's a pretty good relationship between the nocturnal erection and the amount of REM sleep, rapid eye movement sleep, that one is getting. That this tends to be more frequent toward morning as the proportion of rapid eye movement sleep increases. I don't know if that's true or not, but I found a couple of studies that at least point in that direction. No pun intended. So that raises a bigger issue that we haven't talked about yet, which is getting adequate amounts of quality sleep each night. And, I think for most people, that's seven to nine hours ideally. Which means getting sufficient slow-wave, deep sleep, as well as rapid eye movement sleep. But nowadays, a lot of people, including young people who are not working excessive hours, are getting four, five, six hours of sleep per night. Is there a direct relationship between getting less than sufficient amounts of sleep and sperm quality, testosterone levels, and sexual health?

Dr. Michael Eisenberg:
Yeah, I think certainly there's reasonable data for semen quality. And there tends to be, what we call in science a U-shaped relationship, so that it's not linear. So as you get more sleep, things are better. There's this concept of too much sleep and not enough sleep. So the ideal, I think as you pointed out, is seven to nine hours. And for men that are not getting that, semen quality tends to be lower. And then for men getting too much, we also see a decline. And why that is, is again, not certain. Again, if you're able to get that much sleep, maybe there's other things as well that we should look at. So I think getting in that ideal sleep amount is best for semen quality and probably for broad testicular function as well.

Andrew Huberman:
You keep bringing up semen quality in a way that makes me wonder whether or not-- Is semen quality a proxy for overall vitality and health? Or is testosterone level a proxy for overall vitality and health? It sounds like semen quality is the metric that you keep coming back to in a way that I have to assume reflects your clinical experience and the many papers that you've authored in this area. I think for people that hear semen quality and who are not interested in conceiving children now, which of course could include people who've already had children or who don't want children, semen quality sounds like something that relates to fertility. But is semen quality something that is a good goal for those who are interested in overall male vitality and health? Is it one of the better metrics of overall male vitality and health?

Dr. Michael Eisenberg:
Well, I think it's an excellent marker for overall health. I think there are studies that support it can be a measure of how healthy you are. If you look at men with more health problems, they tend to have lower semen quality. But also if you look at semen quality just by itself, and then you look into the future how these men tend to do. If they have higher semen quality, they tend to live longer, need to go to the doctor less, lower rates of cancer. So I think there's a lot of different ways that semen quality may be a good barometer of health. Why that link exists, I think is not known, but there's lots of theories. So one is that probably about 10% of the male genome is devoted to reproduction. And so it makes sense given that we only have about 24,000 genes in the body, that there's a lot of overlap. So one gene that plays a role in reproduction may play a role in the cardiovascular system or the neurological system. And so if we get the first sign that reproduction is not perfect, there may be some other health consequences down the line. Another hypothesis is that, again, going along this line, that reproduction is one of the first things that we see, is that gestation is very critical to our existence, right? Perturbations to that system have prolonged effects, the so-called developmental origin of adult disease or the Barker hypothesis. And so we know that premature children have higher risk of cardiovascular disease. There have been studies to show that. But we also know that these gestational effects can also play out on reproductive function too. So that also may be a link, early seeding of reproductive function, and then that's maybe the first marker that we're going to have for other health effects later on. There are also just inherent similarities between reproduction and some other social effects. So one confounding factor when we're looking at some of these studies I talked about, looking at mortality, for example, and semen quality, is that there's factors that necessarily involve reproduction. So your children and having a partner. And having a partner prolongs life, having kids prolong life. Even though it feels like kids are killing you, if you look at studies, men with kids tend to live longer. So that's another possible explanation. But I think really this health link between fertility, I think is a powerful one. So I do think it should be a barometer. When I've given lectures on this, I call it the sixth vital sign. I think it's something that we should probably check, because if there is lower levels, that may tell us about something else going on. When men come in for infertility evaluations, a lot of times we do diagnose these new medical problems. Sometimes we diagnose cancer, alluding to some of the questions you've asked, diabetes, and some other very significant genetic conditions as well. And the first way that we would identify it is reproductive failure because their sperm counts are low, and other things. So it is something, I think that it's very important, I think, for people to realize. And it would be great, I think, another advantage to the Centers for Disease Control, for example, to start tracking it.

Andrew Huberman:
Would it be a good idea for males in their 20s and 30s to get a sperm analysis just to have a baseline? I confess, I'm 47 now. One thing I wish I had done in my 20s was to get my blood hormone profiles and lipid profiles done when I was in my teens and 20s because I'd have something to compare to. I started doing that in my mid-30s, and I'm so glad I did because I can now compare to my mid-30s levels. I started including sperm analysis about eight years ago with the intention of freezing sperm and-

Dr. Michael Eisenberg:
Mm-hmm

Andrew Huberman:
... did that because I was also reading at that time about the increased risk of autism in offspring of males older than 40, something that I really would like your take on. But it seems like it's inexpensive enough to do a sperm analysis. I think now people can get it done at home. They have mail kits, although I don't understand how the motility could be maintained if you're mailing your sperm back at room temperature, or it's heading through the post office. Now everyone's imagining all these sperm traveling through the postal service. They're out there, folks. Yeah, what are your thoughts? Should people invest the, I think it was a couple of hundred dollars to get a sperm analysis. More costly to get the DNA fragmentation, then you get up into the low thousands. But if people have the disposable income, is it a good idea for them to do?

Dr. Michael Eisenberg:
I think it's a worthwhile test. I think more information is always good. I think one of the same reasons that you were talking about checking lipid levels or we tell men and women to get blood pressure checked. I think getting that early health indicator, I think can be important. I think, going back to not knowing exactly why semen quality is telling us about health, what the exact link may be, means that if somebody is coming in with a low sperm count or a completely absent sperm count, it's hard to know exactly how to counsel that person other than there may be reproductive difficulties. But I think just as a marker for reproductive potential, I think it's useful. And like you said, I think it's become a lot easier. One of the innovations in the space, and as somebody that is in the reproductive world, I think it's just really great to see this influx in capital and new companies coming in that try to just decrease the barrier to getting a semen test. It used to be you have to go to a lab, schedule an appointment. Sometimes they would send you to a bathroom, which can be uncomfortable, because you know what people do in a bathroom just next door while you're trying to collect semen.

Andrew Huberman:
Or they would send them into a common space bathroom.

Dr. Michael Eisenberg:
A common space bathroom, yeah.

Andrew Huberman:
They wouldn't even give them the quiet room with the red light.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Which is what I hear they do now. Yeah.

Dr. Michael Eisenberg:
Some of them do have videos. So there are some higher level-

Andrew Huberman:
Oh, I didn't even mean videos. Okay, yes, I've done this. I'm trying to normalize things related to all aspects of mental health, physical health. So yeah, I decided to freeze sperm, and basically they Sent me to a room. I went to a university-based clinic.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
It actually wasn't Stanford, but a different university. And yeah, they put the cup through the window. They give you the cup, they close the door, and they tell you that as long as that red light is on over the door, no one's going to walk in.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
And then they leave. And I think the assumption now is that you figure it out one way or another, how to provide the sample, and then you put the sample back through the thing. And then one thing these clinics really need to work out is that anytime you're walking out, you see the people processing your sample as you walk out. So there's all this feigning of anonymity, but really it isn't there.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Because they're like, "See you later." And you're like, "Great." They rarely ask you questions on the way out. But it's a pretty simple process overall. And I must say that the data are informative.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
You get the volume, number motile, forwardly motile. I did opt for the DNA fragmentation data. And I just love data, so I think it's really interesting. But again, and maybe this is a good time to flag this set of findings, I believe that there seems to be a small but statistically significant increase in the number of autistic births due to pregnancies where the male was over 40 at the time of conception. So I figured why not freeze some sperm, and it's relatively inexpensive. Yeah.

Dr. Michael Eisenberg:
Yeah. So I think paternal age is also something that's increasing in this country. So over the last 40 years or so, we've seen that the average paternal age has increased from about 27 and a half to about 31. And I should say that this is all fathers. So birth certificate data or birth data is collected at maternal level. So, when a child is born, somebody comes in to collect data on the birth. So they ask all the characteristics of the mother, and they also ask characteristics of the father. Age, education, obviously region of the country the child was born. So we don't know what number child that was for the father. We know it for the mother, they do ask is this your first, second, third, et cetera, child. So the father, unfortunately, we just have data that's sort of all lumped together. But over the last, again, 40 years, we've seen that increase. Interesting, over the last 40 years, the youngest father was 11 and the oldest was 88.

Andrew Huberman:
11.

Dr. Michael Eisenberg:
Quite a span. Yeah.

Andrew Huberman:
88.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Goodness. Unrelated.

Dr. Michael Eisenberg:
Well, I don't know. I assume.

Andrew Huberman:
Goodness gracious.

Dr. Michael Eisenberg:
It's anonymized data, but I assume.

Andrew Huberman:
11. I have to ask this, sorry to take us on a slight tangent, but what is the average age of puberty in males in the United States now?

Dr. Michael Eisenberg:
Yeah. So you're asking about, I guess, sort of sperarchy, when sperm production begins.

Andrew Huberman:
Mm-hmm.

Dr. Michael Eisenberg:
So-

Andrew Huberman:
Yeah, there are a lot of markers of puberty-

Dr. Michael Eisenberg:
Yeah

Andrew Huberman:
... secondary sexual characteristics, beard growth, deepening of voice, et cetera. They happen at different rates in different people. But yeah, thank you. At what point are males undergoing puberty-

Dr. Michael Eisenberg:
Yeah

Andrew Huberman:
... at the level that we're talking about here?

Dr. Michael Eisenberg:
Yeah. There has been data that we're going through puberty a little bit earlier now than we used to. But it really varies. So, just like testosterone ranges between 300 and 900, that's a wide range for anybody. I think for most individuals, puberty is probably 12 to 15, 16, in general. So I just give sort of a very wide range when we're going to say that's okay. And some of the data I'm basing it on is when sperm production begins in boys. And it's actually not that simple to be able to figure that out because we don't generally talk to young boys about how to masturbate, how to collect, and then check on that. But there's something called first-morning voided urine, where we can actually look at that, and there have been some studies done, and they see if there are nocturnal emissions, whether there's sperm in there. And so generally, it probably starts around, the earliest would be 11, 12, 13, but usually most is probably a little later. So maybe I'll refine that puberty and move it a little bit later. Probably 14 to 16 is when probably about 70, 80% of boys are going to have started producing sperm.

Andrew Huberman:
My understanding is that in females, puberty is also shifting earlier, perhaps at a more dramatic rate than appears to be the case for males.

Dr. Michael Eisenberg:
Well, I think there is some data for males, too. But again, for your listeners, I don't want to have this onslaught of pediatricians seeing kids when boys haven't gone through puberty by a certain age. So I think it's still fairly wide.

Andrew Huberman:
Let's get back to age of the father and issues like autism. What are the data there? And this to me is a practical issue because I think if there's one obvious takeaway from our discussion today, it's that males should probably not wait until they're trying to conceive in order to assess their reproductive health at the level of sperm quality, testosterone levels perhaps, but at least sperm quality. But perhaps men should also be freezing their sperm if, in fact, conceiving children after 40 places their children at far greater risk for autism. My understanding is that the rates of autism are somewhere between 1 in 80. You'll hear as high as 1 in 50 male births, but I think it's probably more like 1 in 60 to 80. Is that about right? And that the age of the father is a risk factor.

Dr. Michael Eisenberg:
Yeah. I think that this gets into sort of the larger issue of how men perceive fertility. So, we know that as women age, fertility declines. But the oldest father ever is 96, so the biologic potential certainly persists.

Andrew Huberman:
Wait, I want to know how long he lived to see his child grow up. He conceived at 96? Amazing.

Dr. Michael Eisenberg:
Supposedly. Yeah.

Andrew Huberman:
Wow. I'm assuming he did not meet his grandchildren, at least not the grandchild of that child. So wow, how long did he live?

Dr. Michael Eisenberg:
Well This is a man in India. It's a sort of a famous story, but supposedly, he had a child. He had that child with him on a-- They're waiting at a bus stop. He fell asleep. The child was kidnapped.

Andrew Huberman:
Oh, Jesus.

Dr. Michael Eisenberg:
That led to divorce. So, yeah.

Andrew Huberman:
Dreadful.

Dr. Michael Eisenberg:
Sort of a horrible end. But the wife was also old. Not that old, but in her 50s.

Andrew Huberman:
My goodness.

Dr. Michael Eisenberg:
So, yeah.

Andrew Huberman:
Wow. Tragic and an incredible story for separate reasons.

Dr. Michael Eisenberg:
Yes.

Andrew Huberman:
Okay. I'll get my head around this 96-year-old conceiving a child. Okay. Please continue.

Dr. Michael Eisenberg:
Yeah. So people, I think, or men think that their fertile road is sort of infinite. But I think that's very much not the case. So as you're alluding to, people have looked into risks for older fathers. So, about 100 years ago, it was first noticed that dwarfism or achondroplasia was more common in last-born children. So eventually, that link was made. And since then, other conditions, too. So there's these neuropsychiatric conditions you're talking about, like autism is certainly one. Bipolar, schizophrenia, people have looked at and also linked that with older age. Less attainment in school, failing grades, all that has been shown to be a little bit more common with older fathers. So, why I think all these exist, there can be different explanations. One explanation for the autism association, I'll talk about some of this more genetic or mutational reasons. But one thing that some people say is that it could be a hereditary trait. And so it may be that men that display some sort of autistic characteristics, maybe they take a little longer to meet a partner, and so it sort of delayed childbearing. So maybe that's one possible explanation. But I think there's been a lot of convincing evidence that there could be real epigenetic changes that occur with age and mutational changes that occur with age. I think I read a statistic, and you would know more, being a neuroscientist, that 84% of the genes in our body expressed somewhere in the central nervous system. Is that maybe-

Andrew Huberman:
Sounds about right. Yeah.

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
I don't want to stamp my name to that. But that sounds about right.

Dr. Michael Eisenberg:
So, it's estimated that every year, we generate about two mutations in our sperm DNA. So you can imagine that a 40-year-old is going to have 20 or, sorry, 40 more mutations than a 20-year-old. So that rate does go up. And if you're just randomly sprinkling mutations in a genome, that they're more likely to manifest in maybe neuropsychiatric conditions. So there are convincing data that shows that that does occur. Now, again, there's billions of base pairs in the body, so these random mutations, likely most of them will not result in anything. But there can be some meaningful ones. So, for example, achondroplasia is due to a mutation in fibroblast growth factor receptor. And what's interesting is that this condition is not that rare. Based on these rare mutations, you'd expect this would occur maybe about one in 100 million. But it turns out these conditions occur in about one in, I think, 30 to 50,000 or so. So there's this discrepancy based on mutational rate that we expect based on age and the rate that we actually see. So the explanation for this is something called selfish spermatogonial selection. So what this suggests is that some of these mutations that occur randomly occur in proliferation pathways, and so it gives the sperm that contain these advantages over their brothers and sisters that don't have them, for example. And so then they outcompete the other sperm, and so they're more likely to lead to a child rather than a random smattering. You can actually see that some of these mutations are more common in older men than younger men, if you screen for some of these mutations in some of these pathways. Again, the longer that we're exposed to life, there's just more likely to be different chemical exposures or other exposures. And so people have looked at epigenetic signatures, these signatures that dictate which genes are going to be expressed and which aren't. And there are different patterns between older and younger fathers. And what triggering those is not known, but there are differences. So those could also potentially explain some of these risks that we see. It used to be that people thought that if you're an older father, maybe there's a lot of advantages for the kids. Because if you're more resourced. I always tell patients that when they come to see me for erection problems or anything, I always say nothing gets better with age. And that's mostly true, although they pointed out that salary often goes up with age and wisdom goes up with age. So you would imagine if you're more resourced, maybe the kids are going to also have an advantage to that. But, again, there's a lot of convincing data that that's probably not the case. There's one study that I saw that showed that if you look at MRIs of brains of children just after birth, they're actually a little smaller for older fathers compared to younger fathers. So, I think there are some talking about neurocognitive development, some of those effects. And there's also been studies looking at cancer risk, too. So higher risk of breast cancer, prostate cancer in adult children, higher risk of leukemia or CNS cancers in children as well. So I think the more we look, the more we find out of these associations with paternal age. So I think it's something to certainly be aware of. I think talking about mitigation strategies, I think education would be important for couples to try earlier or individuals to try earlier to conceive. If we think it's a mutational reason, I think certainly freezing sperm, I think is a good option as well.

Andrew Huberman:
My understanding is that analysis of DNA fragmentation in sperm does not allow for selection of the best sperm on the basis of ... DNA composition translated to English, what I mean is in order to tell whether or not the DNA are mutated in a sperm, you have to kill the sperm, basically. And since in a given pool of sperm, so to speak, there will be forward motile, non-motile, twitchers twitching in place, dead sperm, some percentage of dead sperm or immotile sperm is presumably normal. Some small percentage-

Dr. Michael Eisenberg:
Mm-hmm

Andrew Huberman:
... hopefully. And that some might have some DNA fragmentation, some might not. So, is the way to address this averages? What I'm hearing here is that if you haven't already had kids or if you want more kids, that you might want to know about your sperm quality. I would say you do. And that if you can afford it, you might want to take a look at DNA fragmentation data. But having done this, what one receives is a chart that goes from red, bad, to green, good. And then they put the arrow, hopefully in the green zone. And then you say, "Oh, good. I'm in the green zone. I don't have fragmented DNA in my sperm." But really that's an averaging of all the sperm, right?

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
It could be that as you age, that some percentage of those sperm have fragmented DNA. And if one of those is the one that successfully wins the egg, so to speak, fertilizes the egg, then that fragmented DNA-containing sperm is going to propagate that into your offspring. So are there any technologies that can allow men to select or improve the DNA of their sperm, not just the motility?

Dr. Michael Eisenberg:
Yeah, I wish, right? That's sort of the Holy Grail, because I think you pointed out sort of a variant of the Heisenberg uncertainty principle, is that if we identify which sperm is bad, we're necessarily going to destroy it. So to tell which one is harboring these mutations would be great, but I think we're not there yet. One thing that we do do is wash sperm, so we do sort of select the most motile sperm. We clear out the dead ones. And I think embryologists are pretty good at telling which sperm they think are better, but again, we don't have any real objective data to try and understand which are harboring something or other. But I think if we understood more about this link with age or again, other conditions, hopefully we would be able to stop some of this pass-through.

Andrew Huberman:
Let's get back to the prostate, this incredible gland. Tell us about the prostate. I think we hear about the prostate. We hear about prostate cancer. People might have heard that it's involved in the ejaculatory response. It's involved in erections. It's involved in a number of things. If you could give us a catalog of things that the prostate does. You've spent a lot of time thinking about this gland. What are some of the cooler things that it does that we don't know about? How do we keep it healthy? And what are the consequences of not keeping it healthy?

Dr. Michael Eisenberg:
Yeah. So the prostate is a gland about the size of a walnut. It sits behind the bladder, and it's involved in reproduction. It produces some of the proteins, enzymes that are necessary for sperm to be supported in the ejaculate to kind of keep the sperm healthy in the female reproductive tract. So it functions in reproduction, and then basically after reproduction is done, it doesn't really serve any useful function, so then it just becomes a problem, essentially. So the urethra, which is where we pee through, so it connects the bladder to exits the body, runs right through the prostate. And as we age, the prostate does get bigger. That's sort of a known thing. And as the prostate gets bigger, it creates more resistance in this pipe, and so it makes the bladder have to work harder, and that leads to a lot of the symptoms that we've been talking about already. Waking up at night, weak stream, this need to urinate urgently, sometimes feeling like you're not emptying all the way. So it's sort of a consequence of the prostate being there. In terms of ways that you can keep the prostate healthy, I think that there's really nothing necessarily you can do. I think that one thing I talk to patients about when these sort of symptoms start is to know some of the triggers. So like you mentioned, drinking a lot before you go to bed. So if you don't want to wake up at night, that's not a good practice. You may even want to go into bed sort of a little dehydrated, just so you can try and last the night. There are some particular drinks or foods that tend to be more irritating. So like spicy foods, acidic foods, those can sometimes irritate the lining of the bladder and make you have to pee a little bit more. Caffeine is a diuretic, so it makes us urinate more, and it also can irritate the bladder and give you that sensation. Alcohol will do the same thing. So I think knowing some of those triggers may stave off some of the symptoms a little bit. But again, if you enjoy those vices and you're willing to tolerate it, that's okay, too.

Andrew Huberman:
I'm hearing more and more about a practice of people taking low dose tadalafil, Cialis. Low dose meaning in the neighborhood of 2.5 to five milligrams per day. Not necessarily for erectile dysfunction, but for prostate health, and was somewhat surprised to learn that those drugs were actually developed first for treatment of prostate health, to increase blood flow to the prostate. Is that true? And is there good reason to think about taking 2.5 to five milligrams of tadalafil per day simply for maintaining blood flow to the prostate and thereby maintaining or improving prostate health?

Dr. Michael Eisenberg:
Certainly it can do that. It can definitely help with some of these urinary symptoms that we've been talking about. Looking at placebo-controlled trials, our highest level of evidence does show that low dose of tadalafil is two and a half to five milligram. These daily dosing can help with these urinary symptoms. So I think that not necessarily as a preventative measure, but for men that are bothered. Otherwise, I think most men probably wouldn't want to take a pill every day. But certainly, if you have some of these symptoms, it can definitely help with urinary bother. And then the added benefit as you also alluded to, is it can help with erectile function as well.

Andrew Huberman:
Even at the 2.5 to five milligram dosage?

Dr. Michael Eisenberg:
Even at those. Mm-hmm.

Andrew Huberman:
Interesting. Yeah, my experience is that there are a lot of people who would love to take pills every day. There seems to be a kind of binary distribution where, and here I'm just thinking about the males that I hear from, because I hear from, of course, males and females. But I get a lot of questions about what can I take. But as you point out, there's also a category of men who seem to not want to take anything, not want to measure anything, not want to take anything, but especially not take anything. And then there's the other group, and the other group, somewhat surprisingly, seem to be the younger population who maybe grew up in the YouTube era, or maybe in the era where sexual health was discussed more openly than it was certainly when I was in college. The extent of sexual health discussions at my high school, and I went to a very good high school, were it only takes one sperm, which as you pointed out is true for IVF, but more is better if you're trying to conceive naturally. And there were discussions about communication and consent, obviously super important. And then they just kind of turned us loose to learn from our friends and other sources. And family sometimes had the discussion, sometimes didn't. Different families, different discussions, obviously. So very little information. Nowadays, I think there's a lot more discussion about these things, and so the 20-to-40-year-old male crowd seems to be the crowd that are asking, "Yeah. What can I take?" These are also the people who are getting on testosterone therapy early, perhaps without the need. I just want to flag that because, if I understand correctly, you're seeing a lot of testosterone therapy that perhaps people don't need. Is that right?

Dr. Michael Eisenberg:
Well, I think it's a mix. Some people probably do need it, but I think that before starting it, everybody should be aware of all the risks, and you've kind of highlighted some. But testosterone, any medication, is going to have some risks, and so everybody needs to be aware of what those are. And for testosterone, reproduction is certainly one of them.

Andrew Huberman:
And if they're not already doing all the other things, getting adequate sleep, limiting their alcohol intake, not smoking, getting exercise, et cetera, it seems that testosterone therapy would not be the primary entry point. First work out all the-

Dr. Michael Eisenberg:
Right

Andrew Huberman:
... all the basics. I think that's the big difference. I think nowadays the what should I take question comes up early when people aren't necessarily doing all the other things that they could do to promote their health. Anyway, this is observational on my part. You're the one whose clinic they're showing up to. I have a question about UTIs. We hear about UTIs, urinary tract infections, in women pretty often. Do men get UTIs? If they're getting more than one UTI per year, is that abnormal? Should men be examined for this bladder, urethra, prostate, penile architecture? I know there are ways that people can come in, I was reading about this prior to this episode, that you can ingest a dye and then they can dye image the whole apparatus. Is that right?

Dr. Michael Eisenberg:
That's true, yeah.

Andrew Huberman:
Without having to cut anything. Is that right?

Dr. Michael Eisenberg:
Mm-hmm. Yeah.

Andrew Huberman:
Is that worth people doing, or is that only under conditions where people are experiencing some vexing issue?

Dr. Michael Eisenberg:
Yeah. I think that some of those tests should only be done if there's a problem, but I think a male urinary tract infection is rare enough that it should be evaluated. So women have very short urethras, but men have a very long urethra. It has to go through the entire penile urethra, the prostatic urethra, up into the bladder. And so the way a urinary tract infection would happen, one way would be that a bacteria actually gets all the way back, and that's just a much longer trek. And so if something rare like that does happen, we look for anatomic causes for that. So there can be different scar tissue in the urethra, for example. There can be stones in the bladder. There can be stones in the kidney. Sometimes men aren't emptying their bladders all the way. So those men should be evaluated because there can be some pathology that we could hopefully identify and correct.

Andrew Huberman:
Let's talk about erectile dysfunction. I put out the call for questions in anticipation of this episode, and no surprise, at least 30% of the questions from males were about erectile dysfunction, or questions about what's normal in terms of libido level. Kind of interesting, right? And we'll deal with the first question first, but what are the most common causes of erectile dysfunction? Are they hormonal in nature? I think that's a common belief, that if people are experiencing erectile dysfunction, that it's because their testosterone levels are too low, hence all the interest in testosterone therapy. Or are there other, say, blood flow related, pelvic flow related, neural, brain to body neural connections that are responsible? I'm guessing it's all of these things. How do we parse this? And tell us about erectile dysfunction, what you most commonly see, what you most commonly do in order to treat it.

Dr. Michael Eisenberg:
Yeah. So erectile dysfunction as you know is sort of the inability to consistently achieve and maintain an erection, and it's fairly common. Of all the conditions I see, that's definitely the number one. So if you look at men over the age of 40, over half will have some trouble with erections. Under age of 40, it's probably about 15% to 20%, so this is a very common condition that we see. In terms of the etiology, it can vary a little bit. We used to think that they were primarily psychogenic, but that was decades ago. Now we know that most of them are organic, so it's actually a blood flow issue. So the most common conditions, just sort of nationally, would be the same things that cause blood flow problems anywhere in the body, so high blood pressure, diabetes, atherosclerosis, anything that sort of can impair blood getting to the end organ. And sometimes there has been data that trouble with erections can actually predate other more serious vascular conditions. So the blood vessels in the penis, the penile arteries are about one millimeter and The heart and the brain are much larger. So, it's much easier to occlude a small vessel than a large vessel. So that's why there have been some studies to support that it's sort of an early marker for vascular disease. So I think looking at those risk factors, of sort of lifestyle, obesity again is a common one. Endocrine disorder is actually fairly small. It's probably less than 10%, probably around 5% or so. Pelvic cancer treatment is another very common one. After treatment for prostate cancer, whether it be radiotherapy or surgical therapy, bladder cancer, sometimes rectal, colorectal cancer, that treatment also, anytime we're involving some of the nerves and the vasculature in the pelvis, that can also impact erectile function as well.

Andrew Huberman:
What about hernia?

Dr. Michael Eisenberg:
Hernia, that should be separate. So sometimes if they're-- I always say that in medicine you can never say never. But generally, if that was going to manifest as erectile function, it would probably be due to maybe some pain symptoms, which can rarely happen during just the early postoperative period. But the blood supply, the nervous supply is separate.

Andrew Huberman:
So you said something very important for people to hear, so I'm going to highlight it. You said that less than 10% of erectile dysfunction is due to a hormonal issue. I don't know how much time you're spending on YouTube and the internet, but that is going to be a shocker for a lot of males out there because so much of the discussion around testosterone is around libido and sexual function. So, it's key for people to hear that. It's also key for them to know about this other 90%. When you say blood flow issue, then what is the common first pass for treatment? And again, and forgive me for listing this off over and over, but we are assuming here that people have gotten their body weight down, they're sleeping enough, they're not ingesting excessive alcohol, they're not smoking or vaping, they're not smoking cannabis, or doing the edibles. Although maybe we should talk about edibles and cannabis and endocrine effects. We'll do that later. Doing all the things right, avoiding doing the wrong things too often or at least completely. So we're assuming they're doing all that correctly. Their testosterone levels are somewhere in that 300 to 900 nanogram per deciliter range. That's typical for the so-called reference range, at least in the US. I think it goes up to 1,200 or maybe 1,400 in other countries. But as other countries like to point out, but it starts at two... No, I'm just kidding. But assuming they're doing everything correctly and it's not a testosterone issue, then if it's a blood flow issue, meaning they haven't had treatment for some pelvic cancer, what is the first line of treatment?

Dr. Michael Eisenberg:
Yeah. So assuming that lifestyle and all that has been optimized, medical treatment has been optimized, there's a lot that we can do. I always tell men, "As long as you have a penis, we can always make it hard." So there's a tremendous amount.

Andrew Huberman:
I'm sure that you're the most popular doctor in your field as a consequence.

Dr. Michael Eisenberg:
People like to hear that. Yeah. That usually does kind of ease everybody. So usually we start with oral therapy, so phosphodiesterase inhibitor therapy. So that would be like sildenafil or Viagra, tadalafil, Cialis, avanafil, Stendra, or vardenafil, Levitra.

Andrew Huberman:
Would you be willing to talk about some of the specifics there? Is the typical thing to put people on this 2.5 to 5 milligrams per day low dose, or to give the higher doses that are more commonly used for erectile dysfunction, per se?

Dr. Michael Eisenberg:
I think it depends why we're putting them on it and how much sex they have too. On average, people probably have sex, partnered sex maybe once a week on average, when we're looking at men in their 30s and beyond. Sometimes it can be a few more times a week than that. But if they're having sex every day or very often, then sometimes a daily dose can be useful. But generally, most men are on just on-demand, because they're going to fall into that maybe about a few times a month category. So that's usually where we start. And there is sort of a titration that can be done. You can go slightly higher doses or lower doses. So usually we start in the middle to the higher doses, and we talk about some of the side effects they may have. But those probably help 60 to 70% of men, and they work well. In terms of another common question is how do we decide which one we're going to start? Sometimes insurance will tell us which one we're going to do. That's a common one. All these medications tend to be somewhat similar. One difference tends to be the time of onset, how quickly they reach peak levels in the body, and then also how quickly they're cleared from the body. So tadalafil is somewhat different in that it lasts longer. The half-life is about 20 hours or so, so it's sort of marketed as a weekend pill. So some people like the idea of that, taking a pill on Friday, still having some left on Saturday. But for others, we start with one of the other ones.

Andrew Huberman:
The fact that these drugs like tadalafil, also called Cialis, right?

Dr. Michael Eisenberg:
Cialis, yeah.

Andrew Huberman:
Is Cialis the brand name?

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Okay. And Viagra, is that a brand name?

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Stands for, what is the generic name?

Dr. Michael Eisenberg:
Oh, sildenafil.

Andrew Huberman:
Sildenafil. Okay. So because they are effective in such a large percentage of cases, what does that say about the vascular system of all these males that are having erectile dysfunction, but then it's getting resolved by these drug treatments? In other words, somebody comes into your clinic, they're having this issue, you prescribe one of these drugs. They come back and say everything's working great, or maybe they don't come back, they just send an email, say everything's great. But do you need to have a discussion with that person about their overall vascular health? Because a few minutes ago, you told us that the fact that they weren't getting erections due to what now appears to be a vascular issue, can be resolved for the penile tissue. But is it going to solve their other vascular issues, or should those people be on the lookout for cerebrovascular, cardiovascular disease that can potentially cause things at least as bad as erectile dysfunction or maybe worse?

Dr. Michael Eisenberg:
Yeah, no, absolutely. Well, I think they should be screened. So- Sometimes I'm diagnosing and the first doctor that they're seeing in a long, long time. But otherwise, I do encourage them to see a primary care doctor to be screened for blood pressure, lipid levels, fasting blood glucose, all those things, again, sort of for early markers of some of these. Sometimes they're identified, sometimes not. But I think we talked about the ideal patient that's perfect body weight, nothing else is going on. But that's, as you know, a very rare entity. So usually there's something that can be done to be optimized. And I try not to be alarmist about this, but I do want to encourage men to take ownership of their health, because that sometimes can improve some of these conditions. But again, we have terrific medications for men in whom we cannot.

Andrew Huberman:
What are the common side effects of these drugs?

Dr. Michael Eisenberg:
So they're vasodilators. They open up blood vessels, so we get some off-target effects. So headache, facial flushing, backaches, leg cramps, indigestion, nasal congestion, those would be the most common.

Andrew Huberman:
Before the last Super Bowl, there was some press about the fact that a lot of the players were taking these drugs at low dosages before the game, presumably to increase blood flow to their muscles and brain. Is that what the rationale was?

Dr. Michael Eisenberg:
I think so, yeah. In other words, we talked about how cycling may lead to erectile problems or sexual problems. There has been some data looking at taking like Viagra or one of these medications, Cialis, Tadalafil, before a ride, again, to try and increase circulation to decrease the chance of any of the negative effects of prolonged saddle pressure.

Andrew Huberman:
So it sounds like just increasing blood flow and lowering blood pressure slightly is just a good thing all around.

Dr. Michael Eisenberg:
Yeah, I think there's certainly a benefit. Yeah, because these medications were originally, I think as you're alluding to, were developed as a blood pressure treatment, and this was sort of an amazing off-target effect that has turned into a billion-dollar industry.

Andrew Huberman:
So you mentioned about 10% or less of erectile dysfunction is due to endocrine issues.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Was it 60% to 70% can be resolved with these blood flow enhancers?

Dr. Michael Eisenberg:
Right. Mm-hmm.

Andrew Huberman:
I know it's a terribly non-clinical, non-scientific way to describe the Viagra, Cialis, Tadalafil, et cetera. What about the remaining percentage, and are there other treatments that you prescribed or given? In which cases do you need to resort to, I guess, more invasive approaches?

Dr. Michael Eisenberg:
Yeah. So another therapy we have is urethral suppositories. So you can actually put a medication in the tip of the penis. It's then absorbed by the rest of the penis. Also-

Andrew Huberman:
It's suppository, not an injection.

Dr. Michael Eisenberg:
A suppository or a gel, or a jelly, yeah. So it's also a vasodilator. The concept is very similar. Sometimes that is okay for men, and they tolerate it. It's safe for partners as well. It can tingle a little bit, so we definitely let men know because one of the main medications does cause a little bit of a burn as well.

Andrew Huberman:
Why would somebody do this as opposed to taking the pill form of the drugs we were just talking about?

Dr. Michael Eisenberg:
Mostly efficacy would be a big one.

Andrew Huberman:
Mm-hmm.

Dr. Michael Eisenberg:
And so this can sometimes help where others cannot. So that's one. Penile injections are another common therapy. So the efficacy of penile injections are probably 80% to 90%. Again, we're injecting vasodilators into the penis. So the idea is it just opens up blood vessels, easier to get and to keep erections. You can imagine there's a huge psychological barrier to putting a needle in your penis. But-

Andrew Huberman:
Is this something that the patients are doing for themselves at home, or that you're doing? Is it long-lasting? Is that something you do at the clinic, and then they come back every few weeks or so?

Dr. Michael Eisenberg:
No. Yeah, this is an on-demand treatment. So we teach them how to do it the first time they do it with us in clinic. Ideally, we try and get an erection that lasts probably 20 or 30 minutes. So we usually start at a low dose, and then they just increase at home until they get an erection that lasts for that amount of time.

Andrew Huberman:
Is it injected subcutaneous or actually into the goodness, the meatier tissue of the penis?

Dr. Michael Eisenberg:
That's right, yeah. Into the erectile bodies directly. Yeah, and you only have to inject one side. They do communicate with each other. Most men say it's fine. It's a very small gauge needle, about as big as a few strands of hair.

Andrew Huberman:
Like I have an appointment over in ophthalmology, and I've seen injections into the human eyeball, and it is incredible how fast and how painless that procedure is when it's done by the right person. Nobody should try that at home on their own.

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
But when it's done by a skilled ophthalmologist, it's just striking. You think about needle in the eye, what's worse? It's like the childhood rhyme, right? Stick a needle in my eye.

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
It's like you can't think of anything worse, but maybe an injection in the penis sounds almost as bad. But you're telling me that if patients are prescribed this, that they can do this with limited, if any, discomfort.

Dr. Michael Eisenberg:
Well, it does have a high dropout rate.

Andrew Huberman:
Surprise, surprise.

Dr. Michael Eisenberg:
Yeah. I think no one's excited about it. I guess the mood can sometimes be affected. But a lot of couples are very comfortable with it. Again, it's very efficacious. The man can do it. His partner can do it. So it does work well.

Andrew Huberman:
Mm-hmm. And I guess here we're sort of ascending the list of invasiveness.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
What is at the top tier of invasiveness for erectile dysfunction?

Dr. Michael Eisenberg:
So then we go into penile implants. So there's actually a surgical procedure we can do to put a device inside the penis that can help men be hard when they want to. And that comes in two main forms. There's either non-inflatable or inflatable. So the non-inflatable is sort of a bendable. It has a metal core, and so when men don't want to have sex, they bend it down. When they're ready for sex, they can bend it up. So-

Andrew Huberman:
It's really just there on demand.

Dr. Michael Eisenberg:
Yes.

Andrew Huberman:
Hmm.

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
Interesting.

Dr. Michael Eisenberg:
Yeah. So it's very simple to use. The more, I guess, natural form would be the inflatable. So when you're not using it, it's deflated, and then when you're ready to use it, it's inflated. And you inflate it with basically a pump that's in the scrotum. So all this is surgically implanted inside a man, all under the skin. Unless you know what you're looking for, it'd be very difficult to tell if a man has it or doesn't have it. But when he's ready, he pumps it up, and it moves fluid from a reservoir, which usually is also surgically implanted into the penis to get a rigid erection.

Andrew Huberman:
What is the relationship between psychological arousal and erection as it relates to these technologies? The way you're describing it sounds purely mechanical.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Right? We're talking about nocturnal erections, which I suppose people could be having erotic dreams, but I don't think that's a prerequisite for nocturnal erections at all.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Right? So, is the idea that if adequate blood flow is achieved, then any signal from the brain can initiate a cascade of blood flow that creates the erection? Or is it the case with some of these treatments that it sounds like blood flow is almost autonomous?

Dr. Michael Eisenberg:
Right. Well, I think a lot of these, yeah, the blood flow is not adequate, and that's why we're having to sort of go beyond. But generally, as you point out, there's different stimulation, whether it be visual, tactile, or olfactory, that sort of starts that cascade that releases neurotransmitters in the penis that leads to this vasodilation naturally, and men get erections.

Andrew Huberman:
A few years ago, I was reading about vasopressin inhalants. There was a bunch of stuff hitting the market. By the way, I don't suggest that people get experimental with this stuff. As a neuroscientist who also knows a thing about neuropeptides and neurohormones that can impact the hypothalamus, I just cover my eyes and kind of cringe when I think about people inhaling vasopressin thinking, "Oh, yeah, there's a study that vasopressin increases sexual desire," or something like that. But nowadays, I'm reading a lot more about a really interesting peptide treatment, which I think is a FDA-approved prescription drug, which relates to a melanocyte-stimulating hormone that comes out of the medial pituitary that is used to increase sexual desire. It's prescribed for women, but men are starting to take it. And it seems to have, at least from what you read on the internet, a pretty profound impact on libido and on erectile frequency and persistence. Is this something that you're using in your clinic? What about these peptides that people are inhaling and injecting? And some of them are taken in oral form, but most often I think it's nasal inhalant or it's a subcutaneous injection.

Dr. Michael Eisenberg:
Yeah. So, those are not ones that we use in clinic. But I think, looking at sort of just sexual dysfunction broadly, there are a lot of things that we do try and help. And one of the things that kind of relates to that, it's been a proposed treatment for it, is this concept of delayed orgasm or delayed ejaculation. So I think everybody's familiar with premature ejaculation, where men ejaculate too quickly. But on the other end of the spectrum, there's men that it takes a long time to ejaculate. And what that is is sort of defined differently, but generally most people would say two standard deviations above average. So on average, probably around five minutes or so. Two standard deviations would be 20 to 25 minutes. So for men that take that long to ejaculate, that would be considered delayed, or sometimes they don't ejaculate every time that they have relations. So for those, I think there is a need for treatment because there's no FDA-approved therapy for that. And so that's why I think providers are trying some of these other, more experimental things. There's some that we use, just not that one in particular. There's also some devices that have been trialed as well, but it's a challenge because I certainly really feel for these men. It's one of the pleasures in life, and some of them are never able to have sex or only-- or sorry, never able to orgasm, and some are only able to do it very rarely. So we do want to offer them benefit.

Andrew Huberman:
What about pelvic floor health more generally? The topic of pelvic floor health is something that comes up more often around female reproductive health and urology. You hear about Kegels. Kegels. Kegels. I don't know. I guess we'll have to ask him, because it turns out Kegel was a person who named the exercise a- after himself. Whether or not he did them or not, I do not know. But my understanding is that Kegels are a pelvic floor strengthening exercise, and my understanding is that some people experience urinary or sexual dysfunction because of an overly relaxed, AKA weak pelvic floor, but that some people have the exact same problems because of a hypercontracted, AKA overly tense, tight, strong pelvic floor. Meaning, don't run out and start doing Kegels just because you heard about them. They're not good for everybody. They might be bad for certain people. But what about pelvic floor health? Should men be paying attention to pelvic floor health? Should men be doing pelvic floor exercises?

Dr. Michael Eisenberg:
I think it's really key that you say that, because not everything you hear about is good, and I think it's not good for the right person. So there are certainly men that I see that have just a lot of tension, a lot of anxiety. Sometimes these men urinate every hour. There's other things, and you can just tell they're just sort of very wound up. And I think for that man, one of the issues you kind of allude to is he probably needs to relax more. So pelvic floor physical therapy can still benefit you because there are some just different feedback exercises that can be done to help with relaxation. So in any urologist office, there's usually a list of a lot of different providers around the region that can help with some of these. Kegel exercises, though, can be useful. For example, for prostate cancer rehabilitation, some of these men where we're trying to kind of rebuild some of the strength or maintain or improve continence in these men. We do want to strengthen some of these muscles just so that they can sort of recreate or replace what was lost when the prostate was removed. So I think for the right man, they can be useful. But yeah, it could be a dangerous tool in the wrong hands.

Andrew Huberman:
And you mentioned that if people want to learn more about pelvic floor therapy, they can contact their local urologist and find a good pelvic floor Good male pelvic floor specialists, do they tend to specialize male, female?

Dr. Michael Eisenberg:
They're usually pretty much gender or sex agnostic, so they usually are able to help all.

Andrew Huberman:
And forgive me for asking for an abridged anatomy lesson here, but could you describe the pelvic floor muscles and how they relate to the bladder, prostate, urethra, penis anatomy that you talked about before? Because I have the picture of the bladder, urethra, prostate, penis in my brain. I know my life experience where the testes and scrotum are relative to all of that, but now I'm trying to figure out. So the pelvic floor, a bunch of muscles that are attached to the pelvis, but how do they interact with those organs?

Dr. Michael Eisenberg:
Yeah. It's a good question. So they sit beneath, sort of in the perineum, so the area between the scrotum and the anus, and back beyond too. So they basically support all the structures there. They support the base of the penis, the prostate, the bladder, the rectum. And they keep adequate tension to keep all those structures up. They relax when different functions are necessary. They're very important for ejaculation. Some people think that they kind of trigger some of the orgasmic response as well. Sometimes men will have pain in that area, and the perineal area can transmit to other parts of the body like the scrotum. One cause of scrotal pain, and there can be many, can sometimes be pelvic floor dysfunction. So I think, again, pelvic floor therapy can be useful for a constellation of symptoms, again, some urinary symptoms as well. So I think for some patients it can be helpful, but again, if you get things too tense, that can sometimes be harmful.

Andrew Huberman:
So presumably these pelvic floor therapists also help people achieve a more relaxed pelvic floor if that's what they need.

Dr. Michael Eisenberg:
Exactly.

Andrew Huberman:
Got it. Going to some of the questions that came back to me when I solicited for questions in anticipation of this episode. Several, not a few . Let's say a couple dozen people asked about split urine stream. Is that a signature of prostate overgrowth? Is that a urethral issue? Is it perfectly normal? I'm assuming here they mean a split stream of urine that doesn't unify at any point. They're talking about a consistently split urine stream. And for those of you that don't know what I'm talking about, we're talking about a urine stream that's actually two urine streams, and we're assuming one urethral opening, because I hit the literature on this.

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
And there is a case of a failure to fully fuse the urethral duct during development, where some, I'm assuming small fraction of males, have a urethral opening on the base of the penis and at the tip of the penis. Let's rule that out as a-

Dr. Michael Eisenberg:
Okay

Andrew Huberman:
... possibility for now. But now that it's on the table, what percentage of males have that two urethral openings?

Dr. Michael Eisenberg:
Well, hypospadias, which you're describing, where the actual meatus is not at the tip, but it's along the proximal urethra or even further down sometimes in the scrotum, probably about 1% of births. And usually it's recognized at birth, and oftentimes it's surgically corrected because it's better to repair it early rather than later.

Andrew Huberman:
Okay. So ruling that out, what is the cause of split urine stream, and is it a signature of a larger issue?

Dr. Michael Eisenberg:
One of the reasons that we urinate from an evolutionary standpoint, is to basically deposit in a convenient time, our waste, and we don't want to get it everywhere because we don't want to label ourselves with the smell of urine, because that'll be easier for predators to be able to identify. So just similar to today, we'd like everything to get in the toilet without creating a mess. So anytime there's turbulent flow, it certainly could signal an issue. So it could be urethral issues, or as you're pointing out, a prostatic issue, inadequate speed of getting the urine out the meatus. So you definitely should see a physician to get evaluated because there's likely some issue that could be improved.

Andrew Huberman:
The most popular question I received from males, however, was about, perhaps no surprise, penis length. You're an expert in this, actually.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Not just because you're a urologist male reproductive health expert, but you published a study recently on the changing trends in penile length. Tell us about that study. I have so many questions about the methodology because I have to assume this didn't involve self-report, right?

Dr. Michael Eisenberg:
Those were excluded, yeah.

Andrew Huberman:
Yeah, so lying was excluded. I'm being facetious here. But yeah, how was this study done? Pretty incredible study, and the results are, I don't know if they're surprising or not. At first I thought, "Oh, this is surprising," but the results were only surprising in light of what you were talking about earlier about sperm and testosterone levels.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
I think I'll let you describe the study now rather than giving people the punchline here.

Dr. Michael Eisenberg:
Yeah. So the origin was that we wanted to know average lengths for another project that we were doing, and going down the rabbit hole, this has been reported for decades. There's different reasons that people have reported penile length. Sometimes they do it just on volunteers, again, to get the average lengths of different populations. Sometimes it's done pre and post-surgically to try and understand what changes would occur. So we just culled the literature, found data on 55,000 men all over the world, and wanted to see if there was a time pattern with that. And similar to your hypothesis, we assumed, based on all the other data, that we would likely see a decline, whether it be chemical environmental exposure. But if nothing else, if we're getting bigger, the functional penile length should decline because the suprapubic fat pad will get a little bit bigger, and so we'll lose penile length with that. And so much to our surprise-

Andrew Huberman:
The suprapubic fat pad, excuse me, being the pad of fat directly over the penis.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Okay.

Dr. Michael Eisenberg:
And so if that gets bigger, that'll necessarily compromise penile length. But as you alluded to, what we found is actually the opposite, that penises were getting longer with time. So how it's measured, it measured differently. So one of our inclusion criteria was that all the studies have measured in an office, in a clinical setting. So whether it be a clinician or whether it be a researcher that actually did it. So there's different ways you can measure a penis. You could just do a stretch length So you kind of stretch it up as much as you can, and then use sort of a ruler to measure how long it is. Again, from as deep as you can get, the pubic bone ideally up to the tip of the glans or the-

Andrew Huberman:
Okay, guys. So here's what he's describing. He's talking about measuring from the top, not from the bottom. Believe it or not, people ask questions about this. Measuring from the top, not from the bottom. No cheating. You're talking about stretching the penis while it's flaccid, presumably.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
And then measuring from essentially a location that's contact with the pubic bone to the tip.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Okay. So that length was recorded in 50,000 men?

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Wow.

Dr. Michael Eisenberg:
Yeah. So that was one, and then we also looked at erect length. And so there's different ways that an erection can be achieved sort of in a clinical setting. So one is you could ask the man to stimulate himself and then measure. So that was some of the studies, and then the other method, as we have alluded to earlier, is you could inject the man with a medicine to give him an erection, and then measure it.

Andrew Huberman:
And did 50,000 men participate in that aspect of the study?

Dr. Michael Eisenberg:
It was less. No, I think that was about probably 10 to 15,000 men.

Andrew Huberman:
I have to wonder whether or not it's easy or difficult for people to recruit subjects for these studies. I don't know. I could see it going both ways.

Dr. Michael Eisenberg:
Yeah, some of the studies actually had a tremendous number, had about 15,000 men. Some individual studies contributed to that. And actually, interestingly, after we published it, there were some men that volunteered for the next study to be measured.

Andrew Huberman:
I'm sure you'll hear from some of them after this episode. What was the major finding?

Dr. Michael Eisenberg:
So the major finding we wanted to do is just give normative data. We found that it varied around the world. So based on different regions, the average lengths varied a little bit. But generally, on average, an erect penis is probably between about five to six inches, somewhere in that neighborhood. So that was kind of the take home we wanted.

Andrew Huberman:
That was the average?

Dr. Michael Eisenberg:
The average for erect length.

Andrew Huberman:
Did you publish the full distributions?

Dr. Michael Eisenberg:
We didn't. Our plan was actually to make a follow-on study, so we could show everybody, I guess probably they were interested where they kind of fell on the graph.

Andrew Huberman:
Mm-hmm.

Dr. Michael Eisenberg:
But it was fairly normally distributed.

Andrew Huberman:
Yeah. I would think that despite the wide availability of pornography, that the distributions, like the scatter plots of all the data would be interesting to men. For the same reason that the testosterone by function of age data published as a scatter plot in that textbook I referred to earlier-

Dr. Michael Eisenberg:
Right

Andrew Huberman:
... were interesting because the scatter plot distributions, I feel like point to other takeaways. That one can be in their 70s and have testosterone levels equivalent to a healthy male in his 30s. That one can be in their 30s and have testosterone levels that are twice as much or half as much as age-matched cohort, this kind of thing. I think there's value in that. So what other takeaways arrived with the data from the penis length study that perhaps we didn't hear about? What did you find most interesting about the data?

Dr. Michael Eisenberg:
Well, that there was any change over time. This was a fairly short study. It was probably about 30 years or so. But we did find that penile length has been increasing over time. So that was just sort of fascinating that we would see in such a short interval of time that there would be a change, number one, but that we'd see a lengthening, number two. So again, similar to the concerns that arose for these relatively short period of time where you would see changes in semen quality. It suggests something sinister, right? It's unlikely to be a genetic change because that would take centuries probably. Certainly several generations. So the fact that this happened so quickly was just surprising.

Andrew Huberman:
This brings to mind some of work that I was involved in years ago. When I was a master's student, I studied early organizing effects of hormones on the brain and body, and I'm sure this has been updated since then, but my recollection is that during embryonic development, males are exposed to a certain amount of dihydrotestosterone. Not testosterone, but dihydrotestosterone, which organizes the brain male, as they used to say.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Now the verbiage around that would probably be a little bit different. But the idea is that males are born with penile tissue, of course, but then it's during puberty that the same hormone, dihydrotestosterone, then exerts an activating effects on the genitals, and the genitals grow during puberty. Penis length increases.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
So assuming that the study that you did was on males post-puberty-

Dr. Michael Eisenberg:
Right

Andrew Huberman:
... I'm assuming it was.

Dr. Michael Eisenberg:
Yes.

Andrew Huberman:
Then it would imply that something's changing about the levels or the signaling related to dihydrotestosterone. How could that happen? Do we have any ideas about what might be happening? This is the opposite of environmental endocrine disruptors preventing sperm from being as high quality and numerous as they could be, or for-

Dr. Michael Eisenberg:
Mm-hmm

Andrew Huberman:
... environmental factors, either in utero or post utero, suppressing testosterone levels. Here we're talking about the opposite effect. We're talking about dihydrotestosterone levels presumably being higher in males over the last 30 years, and thereby longer penises.

Dr. Michael Eisenberg:
Right. So I think there's different conjectures that you could make about why this could happen. It could be maybe endocrine-disrupting chemicals in utero, some early exposure that some of the mothers had to androgenic effects during the male programming window that may have led to some longer lengths. Another hypothesis we had is that if males are going through puberty earlier, the earlier one goes through puberty, the longer length tends to be. So maybe that provides sort of this link.

Andrew Huberman:
Sure. So earlier puberty tends to be longer, potentially means longer duration exposure to dihydrotestosterone-

Dr. Michael Eisenberg:
Right

Andrew Huberman:
... longer penises.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Yeah. You may be surprised to know you might not be surprised to know that there is a subculture online, I know because they contacted me in anticipation of this episode of post-pubertal males who take a combination of dihydrotestosterone and low levels of growth hormone in efforts to try and increase their penile length. And the ones taking dihydrotestosterone, they're not taking pure DHT, they're taking things like oxandrolone, which very closely mimics the structure of DHT. They report some success. Fortunately, they did not send me pictures. Otherwise, I would've just forwarded them to you for your next study. But this stuff is happening in post-pubertal males, so it all rests on this dihydrotestosterone hypothesis. I don't know, just a point of interest.

Dr. Michael Eisenberg:
Yeah. I don't know. Just physiologically, it doesn't make sense why that would work, as you're pointing out, post-pubertally, unless they're doing other things. Some sort of stretching exercises or a thing called jelqing, but yeah, I would not recommend that.

Andrew Huberman:
Mm-hmm. Thank you. That was the response I was looking for. So, that community will be listening with open ears. Don't do it. As long as we're talking about DHT, dihydrotestosterone, it's only fair to discuss the drugs that many people take to suppress dihydrotestosterone in hopes to keep or grow their hair. Things like finasteride, dutasteride. Some, maybe many, not all people who take these drugs, particularly in oral form, experience sexual dysfunction issues, and other issues related to suppressing DHT. That said, my understanding is that these drugs are also quite useful, maybe even life-saving in some cases, for staving off certain forms of prostate cancer. What are your thoughts about finasteride, dutasteride? Do you see people coming into your clinic who are having sexual dysfunction or other types of issues because of their hair, or attempt to maintain or grow their hair issues? And equally important is that we talk about so-called post-finasteride syndrome. I got a lot of questions about post-finasteride syndrome, because I'll describe it in a couple of minutes. It sounds pretty devastating for these people's lives. And I'll explain why it's so devastating for them in a moment. But yeah, what about finasteride, dutasteride, and these drugs that are effectively DHT blockers? DHT levels, if they get too high, indeed can miniaturize the hair follicle, cause people to lose their hair, typically up front or in the back, so-called crown or whatever, widow's peak, or everywhere in some cases.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
It also induces hair growth on the back, beard growth, as we understand. But then people go and take these drugs to try and maintain or grow their hair, and oftentimes they have erectile dysfunction or other issues. Is that surprising to you?

Dr. Michael Eisenberg:
I think the men that we see these side effects tend to be younger men in their 20s, 30s, and 40s. And they take it, as you're pointing out, for hair loss. So before it was FDA approved for that indication, or at least finasteride was, they did randomized controlled trials to look. And one of the other things that we'll talk about, too, is just reproductive effects. So they did lots of studies to see if there were changes in semen quality for men on finasteride versus the placebo. And there were some very subtle changes, but in post-marketing, now we see these patients in clinic. Everybody to enroll in these studies had normal function, so I think that's important to understand. And obviously that's not life, right? That people come in with different baselines and different amounts of reserve. And so we now know that there's probably people that are a lot more sensitive to these medications than others. And so there are some men that drop their sperm counts dramatically. And usually, if we stop these medications, their sperm counts can recover. And usually a spermatogenic cycle is probably about two to three months, so usually in maybe three to six months, we usually see recovery for most men. But similarly for sexual function. I certainly have a number of patients that do complain of low libido, erectile function, this post-finasteride syndrome. And the mechanisms, I think, are less certain because measuring testosterone levels, which we do, sometimes if androgens are low, or even if androgens seem to be in the maybe normal range or low normal range, we'll try and increase testosterone through a variety of means. Testosterone, clomiphene sometimes we'll give. It helps some men, but not all. So I think the exact mechanism of what is going on here, what is changing, I think we need more understanding about the exact sort of pathophysiology neurochemically.

Andrew Huberman:
It seems like a pretty serious trade-off to either maintain or grow hair or lose sexual function. I talked about DHT and some of these side effects of finasteride, dutasteride on previous episodes. And I'm not a clinician, but my encouragement is always for people to approach these drugs with a real level of seriousness, if not caution. The post-finasteride syndrome was described in these online questions as seemingly permanent, even though people had ceased to take finasteride or dutasteride. So in other words, they were taking this stuff, I don't know how they felt while they were on it, but they stopped taking it, and the sexual dysfunction issues don't seem to be resolving. Does that mean they should go see you or another male urologist, reproductive health specialist?

Dr. Michael Eisenberg:
Yeah, oftentimes they do for these complaints. They start to notice it when they're on the medication, then when they, usually through online research, learn about this potential entity. Sometimes they discontinue. Now, some men do have resolution when they stop, but there is this permanence in some handful of men. They've done MRI imaging to try and understand more anatomically or functionally what exactly is going on. I think there's still a lot of Unknowns about it, but it can be permanent for some. So they come in and they see me in clinic, erectile dysfunction, low libido, and then we go down all the host of treatments that we talked about and the evaluations that we talked about. Again, we have resolution in some, but there are some that seem treatment refractory.

Andrew Huberman:
Yikes. That's my only response. Permanent effects on sexual health as a consequence of an attempt to maintain one's hair. This is where, in all seriousness, it just sounds like something that people need to think very seriously about because as I understand, there's nothing that can predict whether or not someone will have post-finasteride syndrome. Right?

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
And I did a bit of reading on this within the scientific journals as well. There isn't a lot of information, as you point out, because it's a fairly recent phenomenon. That highlights a different issue. This may be the first time in history where young males are taking finasteride and dutasteride, and that might be the cause of the post-finasteride syndrome. I think you alluded to this earlier.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
These drugs have proven to be very beneficial for older men treating prostate issues.

Dr. Michael Eisenberg:
Exactly, yeah.

Andrew Huberman:
Right. So post-finasteride syndrome, I think falls under the category of medical conditions that a few years ago, we would hear the same about chronic fatigue syndrome, even fibromyalgia not long ago was considered one of these, "Oh, is it all a psychosomatic issue?" Now we now clearly know that's not the case for fibromyalgia, by the way. But I can recall a time not that long ago when people in the medical profession were like, "Well, yeah, I don't know if this is a real thing," but post-finasteride syndrome sounds certainly real for the people that are suffering from it.

Dr. Michael Eisenberg:
Exactly, yeah.

Andrew Huberman:
Okay. Well, the reason I'm spending so much time on this is that I get a lot of questions about it, and there are clearly a lot of young males who take finasteride or dutasteride or are thinking of doing that for cosmetic reasons, and I think they should be aware of the potentially serious consequences.

Dr. Michael Eisenberg:
Yeah, agreed.

Andrew Huberman:
Yeah. But you did say earlier that if someone has a penis, you can get it hard.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
So all is not lost even for these post-finasteride syndrome-

Dr. Michael Eisenberg:
That's true

Andrew Huberman:
... individuals. Good. Okay. We'll hold you to that. You mentioned clomiphene. Could you explain what clomiphene is and what it's used for? Because again, we want this discussion to be centered around the real science, the real medicine, but there is a growing sub community of people out there who are saying, "Okay, testosterone therapy can cause us these sperm suppressive issues and perhaps some other issues," but doing nothing might not be an option for somebody who wants to increase their libido, other aspects of androgen function. And so there are a growing number of people out there who are taking clomiphene only in order to presumably increase testosterone, but my understanding is that it would impact the estrogen pathway as well.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
Yeah. What's clomiphene? What are your thoughts about people using clomiphene sort of off-label simply to increase androgens?

Dr. Michael Eisenberg:
Yeah.

Andrew Huberman:
Seems sketchy to me for reasons related to changes in neural circuits, but you'll tell us how it works.

Dr. Michael Eisenberg:
Yeah. Well, thank you for including the off-label disclosure. Anytime I talk about this, I always have to say that. So clomiphene is a selective estrogen receptor modulator. So basically, it blocks estrogen. And so from our earlier discussions of how the pituitary works, there's sort of an elaborate feedback loop between the pituitary and the gonads in the man, the testes. And so what happens is FSH, LH, these gonadotropins stimulate the testicle to make sperm and testosterone. Testosterone's peripherally converted to estrogen, and that feeds back on the hypothalamus to stop that. So again, you don't get an overproduction. So by blocking the estrogen receptor at the level of the pituitary or the hypothalamus, you'll stop that. And so the idea behind blocking that is that you'll get more production of FSH, LH, more of these drivers, so you get more testosterone. You get higher stimulation of the testicle. The hope is that for fertility, that sometimes it can improve sperm production too, and there's some limited data that can help. But I think as you're alluding to, it's sort of a way to just augment your body's own production of testosterone. So it certainly does that. I think there's no question that testosterone levels do rise. I think that the reason that doesn't always help is because not every problem is solved by testosterone. We kind of talked about some in this discussion, but also that you do need some estrogenic signaling as well. And so by blocking that, even partially, because there's also some partial agonist effects of clomiphene as well, it may limit it. And it turns out that estrogen signaling is important for a lot of things. It's important for bone health, but sexual health too. It's important for libido. So that may be partially blunting some of the hoped-for benefits of testosterone. I found that men tend to be happier on testosterone than some of these other forms, and that could be a possible explanation. But one of the advantage of clomiphene, if we are thinking about this as a treatment for low testosterone hypogonadism, is that it doesn't have the same toxic effects on sperm production. So by maintaining the body's own production of testosterone, by maintaining production of FSH, LH, we'll continue to get sperm production. So for this reproductive-aged man that has low testosterone and symptomatic low testosterone, low energy levels, sex drive, mood, sleep problems, it can be a worthwhile treatment. And it does help a lot of men, but not everybody.

Andrew Huberman:
I've always been curious why if the goal is to increase sperm production, that the most common treatment is hCG, human chorionic gonadotropin. Because as you mentioned earlier, luteinizing hormone and FSH, follicle-stimulating hormone, are deployed from the pituitary and travel to the testes where they stimulate testosterone production and sperm production. But it's the FSH specifically that encourages- ... sperm production. So why wouldn't a man who's taking maybe testosterone therapy, or who perhaps just wants increased sperm count and quality, take FSH instead of human chorionic gonadotropin, which is more or less a proxy for luteinizing hormone?

Dr. Michael Eisenberg:
That's a really good question. And so what FSH does, like you said, is it stimulates sperm production, so it seems like it'd be a much more logical treatment. And actually, in randomized placebo-controlled trials, it does do that. So one of the reasons-

Andrew Huberman:
It does not?

Dr. Michael Eisenberg:
It does do that.

Andrew Huberman:
Oh, okay.

Dr. Michael Eisenberg:
It does help.

Andrew Huberman:
Okay.

Dr. Michael Eisenberg:
So it's beneficial, and we should give it more. But one of the reasons that we don't is cost. So it's rarely covered by insurance. And hCG, a month of that is in the hundreds of dollars, so let's say like $300 to $500. But a month of sort of therapeutic FSH is probably $2,000 to $3,000. So that cost is really limiting. It takes two to three months to make a sperm, so men often would have to be on it for several months. But there is reasonable data that would help, and it does make a lot more sense that that should be given as adjuvant therapy with testosterone rather than hCG. But hCG does work. Everyone's surprised it does actually help. But yeah, I agree, there is sort of a contradiction there. So if the price came down, this is another off-label medication for that indication. It could be worthwhile.

Andrew Huberman:
One hormone that we haven't discussed is prolactin. I'm familiar with prolactin from a variety of perspectives, but I always think of dopamine and prolactin as kind of a seesaw relationship.

Dr. Michael Eisenberg:
Mm-hmm.

Andrew Huberman:
Dopamine's up, prolactin is down. Dopamine is elevated with sexual desire, sexual activity. Post-ejaculation, prolactin goes up, sets perhaps the refractory period on erection, ejaculation for some period of time, and then dopamine comes back up. But this kind of thing. And I realize that's far too simplistic, that prolactin is doing many things in the brain and body besides that. But how often do you see hyperprolactinemias? I don't know if plural, prolactinemias, is clinically correct. But elevated levels of prolactin that are causing problems for men. What are some of the telltale signs of that? And this I'd like to use as a segue to talking about some of the sexual dysfunction that is commonly discussed around the use of SSRIs and other drugs to treat depression and mental health issues that sometimes create endocrine and/or sexual health issues.

Dr. Michael Eisenberg:
Yeah. So prolactin, hyperprolactinemia, it's a diagnosis. Not that many times. I would say less than 1% of the patients that we see will end up having that. But usually it's a handful of times a year because we see a lot of patients. Typically, the telltale sort of symptoms would be ones of low testosterone. That's a common one. But in my practice, I see it a lot with men with very low sperm production. So I've diagnosed several prolactin-secreting tumors, and the manifestation of that was they weren't getting pregnant. We checked the sperm count, it was very low. That mandates a check of testosterone, which is also very low, and then that leads to a prolactin, which is very high, and then that was diagnosed. So it's something, I think, to be aware of, but there's not usually a lot of symptoms, and sort of going to a clinician when you're having sexual dysfunction symptoms, low testosterone, or fertility problems will usually be able to diagnose it if it's present.

Andrew Huberman:
Are there any other hormones in the galaxy of sexual health-related hormones that fall into common clinical practice for you?

Dr. Michael Eisenberg:
I check estrogen as well. So I think that's another one.

Andrew Huberman:
Okay.

Dr. Michael Eisenberg:
Again, because of the relationship with obesity, I think that can be important. Sometimes there's too much aromatization, and so sometimes that can be a problem. I think just like we talked about normal estrogen signaling is important, I think too much can be bad. So there are some men where we do see manifestations that it can manifest as gynecomastia in some cases.

Andrew Huberman:
Male breast tissue.

Dr. Michael Eisenberg:
Male breast tissue, yeah.

Andrew Huberman:
Mm-hmm. As I was told, what was it? That the male breast tissue is sort of like the appendix. It's there, but it's not very interesting.

Dr. Michael Eisenberg:
Right. Yeah. Everybody has some, and we just don't want the growth to get out of control.

Andrew Huberman:
Could you tell us about one of the world's most difficult to pronounce words, which is varicocele?

Dr. Michael Eisenberg:
Yes. So varicocele, it's a very common condition. Probably about 15% of all men have it, and it's a very common cause of infertility. If you look at all the etiologies, it can be 30% to 40%. So basically what it is, is dilated veins in the scrotum. So obviously we need veins to get blood out of the testicles. But sometimes they can be a little larger than average, and there's sort of a normal thermal regulation. So if the veins get too big, it's thought to warm up the testicle. The other thought is that it doesn't adequately clear some of the metabolites. So exactly the pathophysiology is somewhat debated, but I think those probably contribute. And it's something that everybody should be evaluated for if you're concerned about fertility. So again, we see it very commonly. Given the fact that a lot of men have it, about one in seven men have it, it doesn't always cause a problem, but maybe about 20% to 25% of the time it does. So men will manifest with low sperm counts. We see sometimes discomfort, ache, worse at the end of the day than at the beginning, worse with activity. Anytime blood can pool, sometimes it stretches and some men feel that. And then in kids, sometimes it can lead to either stunted testicular growth or shrinkage of the testicle. It's also thought to be a progressive lesion, so the longer a man has it, the more damage it can do. It usually manifests around puberty in general. So it's not a concern for everybody, but I think certainly if couples are having difficulty conceiving, you're having discomfort in the area, and you have one, it's a discussion you should have.

Andrew Huberman:
What about Peyronie's disease?

Dr. Michael Eisenberg:
Yeah, so Peyronie's is a scarring of the penis, which leads to curvature or deformity. So the way erections work is everything swells. And you can imagine if there's a scar tissue, it doesn't swell symmetrically, so you'll get like a curvature deviation. Sometimes you can get an hourglass or sort of a banding. If you look it up on the internet, you can see a host of different deformities that men get. Probably present in about 5 to 10% of men. So it's very common. Sometimes it could be from injury, from a penile fracture or other less severe form of injury to the penis. Sometimes men have described hitting it on different things. Potentially that could lead to it. Sometimes it can manifest after prostate cancer surgery or other kinds of surgeries, which can stun the penis or injure some of the nerves of the penis. So that's another condition we see commonly. Obviously, it can lead to bother, when erections are not straight. That can just cause psychologic bother to men. It can also physically make it difficult for a man to have sex. Sometimes it can limit certain positions. So that's another common complaint we see. I think it's something that men should be aware of. There's now awareness campaigns now that there's an FDA-approved medicine for it, Collagenase or Xiaflex, which is a medicine that dissolves scar tissue. So that's one of the treatments we have for it. There's also different devices, sort of stretching devices, where we try and just mechanically remodel the penis to allow it to be a little bit straighter. And then there's also surgical options, too. So there's a lot we can do. I always tell men, again, as long as they have a penis, we can make it hard, but we can also make it straight.

Andrew Huberman:
I'm wondering why in the study about penis length, testicular size and volume wasn't also measured. And that's something that we haven't discussed. What is the relationship between testicular size and volume, and some of the other parameters we've been talking about? And maybe this is also a good time to highlight any kind of morphological signals that would warrant people coming to the clinic. So asymmetry in testicle size, for instance, changes in testicular size. Obviously, a pea-sized lump, they taught us in high school is a warning sign of potential testicular tumor or cancer. We didn't really talk about testicles.

Dr. Michael Eisenberg:
Yeah. So I think that, yeah, being aware. The average size of a testicle for a man is about a walnut. So it's about 16 to 20 ccs. Usually, if you were going to measure it, it'd be about four to four and a half centimeters in longest axis to give your listeners or viewers some idea. If it changes, certainly let people know. If you feel anything, let people know. Although, our national guidelines on screening practices recommends against regular testicular self-exams, interestingly, because I think the concern is that it leads to more anxiety than cancers that it would diagnose. But I always tell men, "No one knows your scrotum better than you, so if you identify a problem, you should bring it to attention." So the classic appearance or the way that a testis cancer would manifest is a firm, painless mass that you kind of feel coming from the testicle.

Andrew Huberman:
I find it interesting that, at least as I understand, women are encouraged to do regular self-exams of their breasts for lumps. But you're telling me that men are actually discouraged from doing regular exams of their testicles for lumps that could be cancer? That feels like an unfair asymmetry. It does. Both seem very important.

Dr. Michael Eisenberg:
Oh, yeah. Well, I think there's no question. Obviously, I'm very biased.

Andrew Huberman:
Yeah.

Dr. Michael Eisenberg:
Men's-

Andrew Huberman:
I was trying to say it so you didn't have to, right?

Dr. Michael Eisenberg:
Oh, yeah.

Andrew Huberman:
Yeah.

Dr. Michael Eisenberg:
I don't want to get in trouble with the US Preventative Services Task Force.

Andrew Huberman:
I don't want anyone to get cancer. I don't even want a dog to get cancer. So I'm surprised that they discourage self-exam. But is it because men are getting it wrong? They're coming into the clinic thinking they have testicular cancer, and then most of the time they don't?

Dr. Michael Eisenberg:
I think that's the concern, that the number of cancers that are diagnosed versus the false lumps that they identify just lead to more anxiety and end up causing more harm than good, I think is the concern. But, yeah, it was a surprising recommendation when it came down. Usually, if patients ask about it, I certainly don't discourage them from doing these exams. And we've certainly identified cancers through that means before.

Andrew Huberman:
Well, I saw the episode of "ER" where the guy was having trouble breathing when he was an elite runner, and it turned out he had testicular cancer, and he had overlooked the lump on his testicle. So I'm going to continue to self-screen.

Dr. Michael Eisenberg:
Okay. Fair enough.

Andrew Huberman:
Numerous times today, we've talked about the potential benefit of getting a blood test for hormone profiles, lipid profiles, and other things, as well as a sperm analysis. My understanding is that one can only do that if they have the disposable income to elect to do that through some commercial online service. But is there any way that patients who have insurance can approach their physician in a way that this would be covered by insurance? I don't want to get you into any trouble here, but it's always such a shame. It is such a shame when we're talking about something that is really pervasively related to health, as is sexual health, reproductive health, and people are not aware of a potential problem in the present or in the future that could've been mitigated simply because they didn't get a blood test or do something as simple as a sperm analysis. So we can't be presumptuous in saying, "$200 or $1,000, no big deal." For a lot of people, that's a huge deal.

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
It's prohibitive for many people. So how can people get this stuff assessed? Should they talk to their primary care physician? Should they call a urologist? What's the best approach?

Dr. Michael Eisenberg:
Yeah, I think both are good strategies. I think insurance is becoming a lot more open to covering some infertility, at least testing, sometimes treatment as well. So I think a lot of insurance does cover that now. Sometimes we check semen analyses for other ejaculatory issues. But I think that, again, as more of this data gets out, I think as more recognition of how important the male is, I think we'll get more buy-in and coverage. Obviously, women have the automatic feedback of ovulatory cycles, so they kind of know if there's a problem, they can bring that to the attention. But men don't have that feedback without some of these testing.

Andrew Huberman:
Yeah, and we probably should have mentioned this earlier, so forgive me. This was on me to mention that when we talk about sperm quality, and we sort of shifted back and forth to semen quality, it's possible to have normal semen volume and have very low sperm count, right?

Dr. Michael Eisenberg:
Right.

Andrew Huberman:
We're not talking about the total amount of ejaculate per se. We're talking about the density of forwardly motile, healthy, non-DNA fragmented sperm in that semen. Right? So, in other words, it's not sufficient to just assume because you can ejaculate that your sperm are healthy.

Dr. Michael Eisenberg:
That's exactly right. Yeah, I think about 15% of men have low semen quality, whether it be concentration, movement, shape. About 1% of men have no sperm in the ejaculate, and that's something sometimes they have no idea about. So the only way to know would be to actually do a formal test.

Andrew Huberman:
Well, I'm encouraging people to get these parameters assessed, and I'm making that statement because it's very clear, based on everything that you've told us today, that sperm quality and hormone levels are just oh so important, not just for sexual health, but for urinary health and for reflecting prostate health and other aspects of whole body health. And sexual health relates directly to mental health. We didn't talk so much about the psychogenic issues, but the two go hand in hand.

Dr. Michael Eisenberg:
Exactly.

Andrew Huberman:
I want to thank you so much for coming here today and sharing so much knowledge with us. These really are the issues that males think about and wonder about and have questions about. And they do so to varying degrees, depending on where they're at in life. But I think especially for younger men who are hearing this, who are not at the point where they want to conceive, it's really important to start thinking about these issues for all the reasons you mentioned. I think these issues are really important for women to know about as well, just as it's important for men to understand female reproductive health and not just to improve communication, but this, after all, is at the heart of the presence and proliferation of our species. So thanks for taking care of the male half and thanks for doing the work you do. It's incredible. The large-scale studies, the more detailed the studies on smaller populations. You ask the questions that it seems many people are just afraid to ask, and you get right in there and come out with the really rigorous data and answers. So thank you so much for what you do.

Dr. Michael Eisenberg:
My pleasure. Thank you. Thank you for highlighting men's reproductive health.

Andrew Huberman:
Thank you for joining me for today's discussion with Dr. Michael Eisenberg. To learn more about his research and his clinical practice, please check out the links in the show note captions. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please subscribe to the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests that you'd like me to consider hosting on the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. Not during today's episode, but on many previous episodes of the Huberman Lab podcast, we discuss supplements. While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like enhancing sleep, hormone support, and improving focus. If you'd like to learn more about the supplements discussed on the Huberman Lab podcast, you can go to Live Momentous, spelled O-U-S, so livemomentous.com/huberman. If you're not already following me on social media, it's Huberman Lab on all social media platforms. So that's Instagram, Twitter, now called X, Threads, Facebook, LinkedIn. And on all those places, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the content on the Huberman Lab podcast. So again, it's Huberman Lab on all social media platforms. If you haven't already subscribed to our monthly Neural Network Newsletter, the Neural Network Newsletter is a completely zero-cost newsletter that gives you podcast summaries as well as toolkits in the form of brief PDFs. We've had toolkits related to optimizing sleep, to regulating dopamine, deliberate cold exposure, fitness, mental health, learning and neuroplasticity, and much more. Again, it's completely zero cost to sign up. You simply go to hubermanlab.com, go over to the Menu tab, scroll down to Newsletter, and supply your email. I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Michael Eisenberg. And last but certainly not least, thank you for your interest in science.