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

In this episode, my guest is Dr. Michael Eisenberg, MD, a urologist and professor specializing in male sexual function and fertility at Stanford University. Based on his clinical work and research, he is considered a top world expert on male sexual and reproductive health. We discuss testosterone levels and what really impacts them, testosterone therapy, sperm quality and counts, penile and testicular health and function, pelvic floor and prostate and urinary tract health, erectile function and dysfunction and the various causes and treatments for common male sexual, hormonal and reproductive challenges. We also address post-finasteride syndrome and trends in penile length. This episode is rich in actionable information about men’s sexual and reproductive health, including key tests and at-home evaluations, and the behavioral, nutritional, exercise and prescription-based tools that can support male sexual and reproductive health. For show notes, including referenced articles and additional resources, please visit hubermanlab.com. Use Ask Huberman Lab, our new AI-powered platform, for a summary, clips, and insights from this episode. Thank you to our sponsors AG1: https://drinkag1.com/huberman LMNT: https://drinklmnt.com/hubermanlab Waking Up: https://wakingup.com/huberman Momentous: https://livemomentous.com/huberman Timestamps (00:00:00) Dr. Michael Eisenberg (00:02:05) Sponsors: LMNT & Waking Up (00:04:20) Sperm Quality, Geographic & Environmental Factors (00:12:00) Fertility & Sperm Quality; Testosterone, Cell Phones & Heat (00:19:26) Testosterone, Age, Obesity (00:26:49) Tool: Optimize Sperm Quality, Exogenous Testosterone, hCG (00:35:56) Sponsor: AG1 (00:36:57) Tool: Lifestyle Factors & Sperm Quality, Alcohol (00:43:27) Sperm Quality, Recreational & Over-the-Counter Drugs, Cannabis (00:46:56) High-Impact Sports, Traumatic Brain Injury (TBI), Pituitary & Testosterone (00:49:55) Bicycling, Numbness & Sexual Dysfunction; Walking & Testosterone (00:55:39) Exogenous Testosterone Therapy & Cancer (00:59:57) Sexual & Urinary Health, Nighttime Urination (01:03:12) Sleep & Semen Quality; Overall Health (01:09:19) Tool: Sperm Analysis & Overall Health; Sperm Banking (01:13:21) Paternal Age & Puberty Trends; Older Fathers & Child Health Risk (01:26:42) Tool: Prostate Health, Urination; Tadalafil (Cialis) (01:33:02) Urinary Tract Infections (UTIs); Erectile Dysfunction Causes (01:38:21) Blood Flow & Erectile Dysfunction, Medication; Cardiovascular Health (01:44:30) Mechanical Erectile Dysfunction Treatments; Peptides; Delayed Ejaculation (01:52:36) Pelvic Floor Health, Urology & Physical Therapy; Split-Stream Urination (01:59:03) Penile Length & Trends; Dihydrotestosterone (DHT), Puberty (02:09:01) Hair Loss, Dutasteride, Finasteride & Sexual Health; Post-Finasteride Syndrome (02:16:11) Clomiphene, Testosterone & Estrogen Signaling (02:19:31) Follicle-Stimulating Hormone (FSH) Therapy; Prolactin, Estrogen (02:24:15) Varicocele; Peyronie’s Disease (02:27:26) Testis & Cancer Risk; Insurance, Blood Profiles & Semen Analysis (02:35:03) Zero-Cost Support, Spotify & Apple Reviews, Sponsors, YouTube Feedback, Momentous, Social Media, Neural Network Newsletter Disclaimer Learn more about your ad choices. Visit megaphone.fm/adchoices

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

• 0:00Andrew D. Huberman?

  Welcome to the Huberman Lab Podcast where we discuss science and science-based tools for everyday life.

• 0:09Andrew D. Huberman?

  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.

• 0:52Andrew D. Huberman?

  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.

• 1:33Andrew D. Huberman?

  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.

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• 3:05Andrew D. Huberman?

  And now for my discussion with Dr. Michael Eisenberg. Dr. Eisenberg, welcome.

• 3:11Speaker 05

  Thank you. Good to be here.

• 3:12Andrew D. 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 way seems to be taxed to the conversation about diminishing quality of environment, people, intelligence, you know, there's a lot woven into this statement that sperm quality is declining. And some of it, I think people assume is related to environmental changes. Some of it, I think people assume are related to changers in behaviors. So maybe less exercise, less sunlight, who knows? Hopefully you'll tell us what's really going on.

• 3:54Andrew D. Huberman?

  But the first question I have is, is sperm quality actually declining? And regardless, what is sperm quality?

• 4:03Speaker 05

  Yeah, great question. So I think it's very controversial, I think is 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 of fertility. So fertility in itself is a team sport, right? So it's hard to, you know,

• 4:49Speaker 05

  Label a man as fertile or not fertile without knowing about his partner. But nevertheless, based on different, 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, you know, these, these tests are done, or, you know, what these tests represent. Now, the question of whether they've declined over time has been, you know, a question for a number of years. There was a landmark paper in the early 90s by Carlson and a group in Denmark that showed this temporal decline, you know, over the last 50 years from that time point.

• 5:34Speaker 05

  And so what the investigators had done is looked over the literature for studies that reported semen quality around the world and noted that, you know, the quality in the earliest studies, like in kind of the mid 20th century, were here, and then over time it sort of declined, the more recent studies. Now, that study was very controversial. There was questions about weighting from different studies, putting, because 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, that have come out in time. And even today, it remains very controversial.

• 6:14Speaker 05

  I think, you know, 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, you know, my opinion really varies based on whose paper I've read. And I, there's some very convincing, you know, studies on each side of it. You know, they're, most recently, just in the last year or so, there was a meta-analysis of, you know, 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, 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.

• 6:56Speaker 05

  And those also support this decline. So, you know, one of the counterarguments to why we're seeing that is just sort of an evolution of techniques over time. So that's one of the, the, sort of the popular.

• 7:11Speaker 05

  Questions about whether there's really a true decline. You know, I think as you're alluding to, why there would be a decline is also, you know, unknown and but you've sort of labeled, you know, perfectly that kind of most common hypothesis. So whether there's some environmental exposures, right? A lot of things have changed over the last 50 years and I think, you know, chemical exposure is certainly one of those. And there have been some fairly convincing, you know, preclinical studies, so, you know, mostly done in animals that show that like exposure to different chemicals, phthalates, BPA, other things may actually harm, you know, reproductive function for men and for women as well. And so it may be that, you know, these chemicals, you know, that are, that we're being exposed

• 7:55Speaker 05

  to as kids and adults, or even probably more sinisterly, like when we're, you know, kind of developing in utero, that may be kind of the most harmful exposure. But there's also been, you know, 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 sort of an unknown explanation. You know, there could be different sort of genetic, you know, compositions of men.

• 8:40Speaker 05

  And so there's different reproductive potential in that source. There could be different environmental exposures, diet, exercise, lifestyle. And 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, you know, prenatal visit, they had the fathers give a semen sample. And so this was done in four centers around the country. I think it, one in California, there was one in the Midwest, there was one in New York. So they basically found that semen quality was sort of highest in the urban centers. And New York tended to be the highest numbers where it was, you know, lower in the Midwest. And so the hypothesis was potentially because it was a more rural setting, maybe there

• 9:23Speaker 05

  was pesticide exposure and that had led to these lower numbers. But, you know, another equally plausible explanation may be that, you know, different, sort of a different population and maybe, you know, That that could explain these differences. So I think it's it's, you know, very important. And I think, you know, one of the sort of 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, you know, Anne Haines, CDC's survey of health in in the US. If we added semen quality onto that, that way you could really see, you know, how it varies around the country and, you know, sort of compare like to like to see over time if there's really this progression. You know,

• 10:04Speaker 05

  one of the only studies to do that in Denmark, they started around, you know, around 2000 and tracked semen quality among, you know, 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 sort of another very interesting part of that study is that only about a quarter of those men had normal semen quality. So it's sort of very concerning, you know, it was, I guess, reassuring that it wasn't further declining, but very concerning that only a quarter of Danish men had, you know, normal semen quality. And they're one of the, I think, thought leaders in this field, just because sort of a reproductive crisis there.

• 10:49Andrew D. 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, you know, a very sensitive measure such as DNA fragmentation. You know, 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

• 11:32Andrew D. Huberman?

  to simply ask four 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?

• 11:54Speaker 05

  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. You know, if you look at data in the US, when couples do seek care for fertility, the man has bypassed probably a third of the time, even though when you look at the reasons for infertility, man contributes probably half of the time to infertility. So I think there's a

• 12:17Andrew D. Huberman?

  Half?

• 12:18Speaker 05

  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, you know, one of the main treatments for infertility in the US is IVF, which is very powerful. I think one of the, you know, greatest marvels of medicine in probably the last, you know, 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, you know, through something called intracellular plasmic sperm injection, where you can inject one egg or one sperm into an egg, you know, the bar has gone down dramatically. You know, for couples just trying without, you know, any assistance, probably need 20 to 40 million moving sperm. But now with, you know, these remarkable techniques, you just need one sperm.

• 13:02Speaker 05

  And so because of that, you know, I think a lot of our innovation and research on male fertility has probably gone to the wayside just because clinically, you know, we just need, you know, a few dozen sperm for most couples.

• 13:14Andrew D. 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?

• 13:46Andrew D. Huberman?

  Across the male population in the US and elsewhere.

• 13:49Speaker 05

  I think there is pretty convincing evidence that that is happening. And I think the reason for that, again, is probably not certain. But you know, there have been, you know, some pretty nicely designed cohort studies where they recruited, you know, men in the 2000s, the 90s, the 80s. And you can see that depending on when these men are recruited, just, you know, 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, you know, decades, the testosterone levels have declined over time. So there, you know, chemical exposure is one possible explanation, again, either in adult or adolescent life or in utero. But obesity, I think, is also sort of a convincing explanation as we're more sedentary.

• 14:35Speaker 05

  You know, we get bigger. That's one of the places that testosterone can decline. I think there's different sort of explanations for that. You know, as testosterone is produced, it's aromatized in peripheral tissue. You know, in fatty tissue, fat has a lot of this aromatase. So that converts testosterone to estrogen. So it necessarily, you know, 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.

• 15:04Andrew D. Huberman?

  Because of heat effects?

• 15:06Speaker 05

  Because of heat effects.

• 15:07Andrew D. Huberman?

  Yeah, I was going to ask about this later, but I'll ask about it now since we're talking about heat effects and 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 cellphone, you know, smartphone in the pocket impairing sperm health, maybe even testosterone levels. Now, you hear this more often in kind of biohacky, I don't know, circles, which, you know.

• 15:54Andrew D. Huberman?

  I'm not a fan of the word biohacking. It's not clear what it means, but it it it sounds like it means something about taking a shortcut, using one thing for a purpose it wasn't intended. But, you know, 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 cellphone in your pocket, let's assume on, that the cellphone is on, is bad for sperm health or testosterone levels?

• 16:30Speaker 05

  Yeah, so I think there's not convincing evidence that it's going to help testosterone levels. I think that, you know-

• 16:38Andrew D. Huberman?

  It's gonna hurt testosterone.

• 16:39Speaker 05

  It's not gonna hurt, yeah. So I should, you know, make clear that I think that in terms of production and heat effects, you know, sperm production is much more sensitive than testosterone production. But there have been some studies looking at cellphone exposure because, again, you're getting this, whether it's heat, whether it's sort of the, you know, radio frequency, you know, waves coming in, I think you could posit sort of different explanations of why that may be harmful. So there have been some studies that, you know, looked early on, you know, men that use cellphones 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 cellphones. So, you know, it's it's it's a hard experiment to design, but there have been some studies doing this in vitro, so in the laboratories, so taking, you know, sperm in a cup, basically,

• 17:23Speaker 05

  and putting a cellphone next to it or not next to it to try and see if that played a role. There have been studies done where they sort of normalized the the heat, you know, they kind of put on sort of a special stage so that it's not heat necessarily, but maybe it's RF exposure. So those studies, I think, don't show sort of 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 cellphone. So I think, you know, when patients ask me that, which is a common question I get in clinic, obviously, patients are coming in, they want to do, you know, whatever they can to try and improve their chances. So I think generally, I think the data's not convincing, but, you know, if it's easy

• 18:06Speaker 05

  enough, certainly to be aware of it, you know, 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.

• 18:14Andrew D. 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 twenties, thirties, and there was a progressive decline.

• 18:58Andrew D. Huberman?

  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, you know, who are older than 40 and have testosterone levels, and presumably free testosterone levels as well, that are still very high? You know, the reason I ask this is that I think we've all been told, and we presume

• 19:43Andrew D. Huberman?

  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 of, 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, you know, toward the high-end normal, depending on the scale, already at age 90, it's kind of hard to imagine that earlier they were walking around with, you know, 2,000 nanogram per deciliter testosterone. So, do you see this? Are there some, 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, you know, maintaining high-normal testosterone levels into their later years?

• 20:30Speaker 05

  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 sort of clinical tests that we do, you know, what is average, what is normal. So we do see great variation. I mean, I think, just like you're saying, I usually let everybody know that, you know, usually testosterone peaks, you know, kind of early twenties and it tends to go down probably 1% a year forever. But there are people that have very, you know, very, very high levels. I, you know, just mirroring, you know, that graph that you described, I certainly have patients, you know, we screen for testosterone levels, you know, when patients come in with complaints where we're worried about that, low energy level, you know, low libido, some of the symptoms of low testosterone, sexual dysfunction. And, you know, to my surprise, sometimes these men, you know, I've seen 80

• 21:15Speaker 05

  year olds that certainly have the highest testosterone level I'll see, you know, for six months. You know, why that is, I think, is not certain. Maybe it has to do with, you know, I would think with everything, there's probably sort of a bell shaped curve and everybody's a little bit different. But androgen sensitivity, you know, sensitivity of the receptor, you know, they make it more efficiently. But I have not really noticed, again, because at least in clinical practice, you know, when patients come in, they come in with a complaint. And so even men, you know, with very high levels, they may have some of the same dysfunction 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, you know, these, what we would consider high levels, you know, there may be other issues going on.

• 21:57Andrew D. 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.

• 22:11Andrew D. Huberman?

  But you do get a read on their, you know, sort of 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, you know, 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

• 22:55Andrew D. Huberman?

  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, you know, 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, you know, 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?

• 23:36Andrew D. Huberman?

  So is there a, not one for one, but is there a tight correlation between obesity and testosterone levels?

• 23:42Speaker 05

  I would say that you cannot predict. I think that sort of would be the take home. And so I think that, you know, more information is always better. You know, when I see patients in clinic, you know, some patients are walking around, you know, with, yeah, everything is totally normal, they're very healthy, all the numbers come in at the normal range. But sometimes when men, you know, look totally normal, they talked about taking care of their life, they exercise, you know, five, seven days a week, their testosterone levels can be very low. So even despite, you know, having what we would consider should really give them, you know, symptoms, they're able to compensate. You know, maybe they've lived their whole life and that they don't know what normal is. Now, we get them, you know, to sort of normal levels, a lot of times they feel better, again, because they had no idea how they should feel. But I think that that's just sort of important, that

• 24:27Speaker 05

  everybody, you know, should be screened. I think that, you know, testosterone, semen quality, there have been shown to even be barometers of health. So, you know, men with lower testosterone levels have higher risk of, you know, heart disease, diabetes, mortality. The same studies exist for semen quality as well. And, you know, again, they may have sort of a similar relationship and explanation why that may be. But I think it's hard to just predict. You know, based on appearance, what, you know, 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, kind of getting back to some of those earlier points you're making, if you were to overlay that on the

• 25:08Speaker 05

  known association between obesity, its effects on semen quality, that actually doesn't explain the whole decline because the, you know, the purported decline in semen quality is about 50%, but if you just, if you were to say, well, what would we expect if, you know, we look at, you know, because we were 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, you know, to your point, something more, and it is not something that you can just identify by eye.

• 25:38Andrew D. Huberman?

  What are the do's 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.

• 26:20Andrew D. Huberman?

  What should people do? What should they avoid? And here I'm setting aside any prescription clinical treatments that, such as testosterone injections or things like a chorionic gonadotrop, human chorionic gonadotrop and things that we can talk about a little bit later, but what should every male be doing in order to optimize these health parameters?

• 26:39Speaker 05

  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 tub saunas, try and avoid those, some, you know, light data on seat warmers. Anytime, you know, we kind of get this external heat source to the scrotum, you know, 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.

• 26:59Andrew D. 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,

• 27:41Andrew D. Huberman?

  to essentially cool the scrotal area?

• 27:45Speaker 05

  Yeah, I mean, I think the spermatogenesis or sperm production is certainly a lot more sensitive. You know, 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, you know, 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, you know, that pack is going to remain.

• 28:07Andrew D. Huberman?

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

• 28:12Speaker 05

  And is the ice pack still cold afterwards?

• 28:14Andrew D. Huberman?

  Yeah, 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, you know, I'll go to a Russian banya every once in a while now. I guess I'm outing myself. Yes, I have, yes, I have a cold pack in my shorts when I go to the Russian banya. But, but they have a sort of an insulation so that you're the cold, the very cold surface is cold enough, but it's not right up in contact with the scrotal skin, because that could get, I don't want to make a bad joke and say it could get sticky, that situation. You don't want it getting so cold that it actually would stick to the skin and then it could potentially damage the skin when you're trying to remove the cold pack. So it has a thin insulating layer.

• 28:57Andrew D. Huberman?

  And yeah, that's essentially what it is.

• 29:00Speaker 05

  Yeah, I mean, frostbite to the scrotum is not theoretical. It could certainly happen. So you do want to be careful. So I mean, in theory, that should be, that should be adequate to sort of, you know, to decrease the risk of that particular effect. You know, I keep coming back to health, how important that is to maintain, you know, adequate sperm production because I think these two are very linked. You know, there have been studies that show that men with more comorbid conditions, so obesity, hypertension, hyperlipidemia, these sort of stack up. We see a decline in testicular function, so lower testosterone levels and lower sperm quality. So I think, you know, taking ownership of your, your health, I think is important as well. You know, a lot of times fertility tends to be one of the first touch points that some men have with healthcare.

• 29:43Speaker 05

  You know, because generally what brings men to the doctor, it's usually pain or, you know, kind of a problem. So, you know, if men are in their twenties and thirties, getting ready to start a family or forties in some cases, sometimes they haven't, you know, seen a primary care doctor. So some of these things, some of this relationship has not been established yet. So I think, you know, 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, you know, estimates say maybe about one in 20 infertile men are that way because of testosterone. So I think when, you know, people get testosterone in different places and hopefully, you know, whatever provider you're getting it from tells you that one of the side effects of this is lower sperm production.

• 30:26Speaker 05

  It's actually been tested as a contraceptive and, you know, with some other agents, it can actually be fairly effective. So we just want to make sure that, you know, if men are starting testosterone, they're doing it for the right reasons and they're doing it safely.

• 30:37Andrew D. Huberman?

  You're talking about testosterone replacement therapy, although as we were talking about before we started recording, I, 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, the R in TRT. But I think what you're referring to, if I'm not mistaken, is that there are probably millions

• 31:01Speaker 05

  Yeah.

• 31:02Andrew D. Huberman?

  of young men and older men taking exogenous testosterone, injections, creams, pills, pellets, you know, any number of nasal sprays now, you know, any number of different routes of delivery of exogenous testosterone. And that

• 31:19Andrew D. Huberman?

  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, but maybe even can there's, 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 one in 20 men have issues with fertility because they are taking testosterone.

• 31:45Speaker 05

  Right.

• 31:45Andrew D. Huberman?

  So their testosterone levels presumably are going to be high and 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, their sperm count essentially diminishes to nil or close to it.

• 32:11Speaker 05

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

• 32:26Andrew D. Huberman?

  You kill the R. I like that. That's better than the T A T, which doesn't help very good. Okay. Just testosterone therapy.

• 32:32Speaker 05

  Yeah.

• 32:33Andrew D. Huberman?

  Okay.

• 32:33Speaker 05

  But if you had, you know, for example, 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, you know, have that suspicion. They say, you know, I'm going to level with you. This is why my levels are probably low. But a lot of men were not told that, you know, when they started therapy. So I think certainly for reproductive age men, that's in a very important conversation to have because there can be some other, you know, ways that we kind of 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.

• 33:09Andrew D. 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. 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.

• 33:37Speaker 05

  Well, this is perfect then.

• 33:39Andrew D. Huberman?

  Right, exactly. So.

• 33:43Andrew D. Huberman?

  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?

• 34:04Speaker 05

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

• 34:14Speaker 01

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• 34:45Andrew D. 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, 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 look 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's

• 35:27Andrew D. Huberman?

  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.

• 35:35Speaker 05

  Right. It's possible. I don't think we have the data on that yet. But yeah, I mean, I think, like, to your point, I think lifestyle factors are certainly a big one. And, you know, some of these, you know, potentially... You know, kind of unhealthy habits. So smoking is certainly something you should not do. There have been, you know, lots of studies that do link that to, you know, 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, you know, I think less of a strong association that we've seen. So there, you know, 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 higher or not.

• 36:17Speaker 05

  But, you know, when you get above maybe 20 drinks a week, there have been some effects. But usually-

• 36:22Andrew D. Huberman?

  That's a lot of drinking.

• 36:23Speaker 05

  I would think that's a lot. Yeah. But some people don't. But yeah.

• 36:26Andrew D. Huberman?

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

• 36:40Speaker 05

  Yeah. But when you get to this 20 drink, that's when we started to see some effects on semen quality. But the other, you know, 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, that's, you know, I think certainly anything in moderation is probably, you know, 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 of, that we've started to work on, looking at if there are different sensitivities to alcohol. So, you know, 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, you know,

• 37:25Speaker 05

  slightly lower sperm parameters.

• 37:27Andrew D. Huberman?

  You mean skin flushing because they don't make alcohol dehydrogenase?

• 37:30Speaker 05

  Exactly, yeah.

• 37:32Andrew D. Huberman?

  And is it, I've, I've heard about that in Asian cultures. Is there, in Asian populations, excuse me. But is there any evidence that other populations might have slight variance 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?

• 38:01Speaker 05

  No, I think you're exactly right. I mean, I think the one that we think about is East Asian cultures where it can be, you know, depending on, you know, the region like Chinese, Taiwanese, probably about forty to fifty percent of the population has, you know, mutation in the ALDH2 gene. But other populations and people with 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, you know, again, I think it gets to why a mutation, you know, where we see sort of negative effects would persist. And the hypothesis that, you know, millennia ago,

• 38:46Speaker 05

  potentially, you know, gave some sort of benefit for maybe an infectious disease or something, similar to cystic fibrosis, why, you know, again, this mutation would persist in our population if there's not, you know, some sort of advantage to those carrying it. But we do see in other, you know, other men as well. So I think if, you know, it's a simple question, do you flush? If you flush, then maybe alcohol may have, you know, more of a harm than than someone else. And then, you know, I get sort of getting along the lines, I think drug use is also something that we should try and, you know, we do counsel patients about because that can also negatively affect semen quality.

• 39:19Andrew D. 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? I mean, 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 two thousand five, yes, two thousand five to end of two thousand ten, 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 post docs and graduate students that would, you know, that would colonize this little area outside the hospital and smoke, because that's where you could smoke. That was eventually eliminated

• 40:04Andrew D. Huberman?

  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, you know, take a cigarette on their break. This is very common.

• 40:13Speaker 05

  The irony, yeah, exactly.

• 40:14Andrew D. Huberman?

  Yeah, and this was common all over the country, right? 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 XYZ and everything, 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, not a fair assumption?

• 40:46Speaker 05

  I mean, I think that's a good question. I think, you know, the, 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, it's harder for me to make that recommendation to patients, especially because, you know, people do it for different reasons. And if it's not necessarily going to help them, you know, or harm them in social situations or other things, yeah, I usually just, I usually give the moderation one. Unless, again, for the, the very high drinkers, I definitely talk about that.

• 41:14Andrew D. Huberman?

  You mentioned other drug use. I'm going to assume that unless prescribed for sort of 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?

• 41:35Speaker 05

  Yeah.

• 41:35Andrew D. Huberman?

  You know, I can't imagine any of that would be good for reproductive health.

• 41:40Speaker 05

  Yeah, that's true. I mean, there's, again, you'd imagine, or maybe, 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, you know, people in rehab where they have shown, you know, these associations with, you know, addicts or users and lower quality, so.

• 42:01Speaker 05

  Yeah, that's how we talk to patients.

• 42:02Andrew D. 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 flack 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

• 42:43Andrew D. Huberman?

  of reasons. What is the relationship between cannabis use and testosterone and sperm production, or I should say sperm quality, excuse me?

• 42:52Speaker 05

  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. You know, one of the sort of landmark studies was about 1,200 men, and it found that men that use 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, you know, other data that shows really a null effect. And I think that it's, it goes into probably the composition,

• 43:34Speaker 05

  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, you know, I think I sometimes struggle with this with patients because some of them are taking it for, you know, you know, some what they consider legitimate reasons, anxiety, sleep, pain. And if there's not sort of 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 it'll cause harm, you know, I guess I'm trying to be sort of 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.

• 44:10Andrew D. 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, you know, ibuprofen, acetaminophen, things of that sort that...

• 44:29Andrew D. Huberman?

  I and others might not be aware of. I'm not, I'm not probing for anything in particular here. I just, I know that, um, you know, a lot of over the counter drugs have effects that we're just simply not aware of.

• 44:40Speaker 05

  Yeah, I mean, I think we probably need more data, but I think currently we think all those are safe.

• 44:44Andrew D. 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. Um, the gland sits near the roof of the mouth. Um, I think that's fair. Um, 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. Um, I know a number of people end up playing sports like football or rugby or even lacrosse or even soccer. I've read or data on this, you know, they're heading the soccer ball quite a lot or martial arts or they get a head injury at some point.

• 45:27Andrew D. Huberman?

  And, um, 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, you know, that they leave and maybe it's from combat related stress, et cetera, but, um, they wonder whether or not there's any traumatic head injury or maybe pituitary injury related, um, impairment to the reproductive axis that includes brain, pituitary and the testes. Do you see that? Um, and if somebody played a contact sport, in particular a contact sport where the head was hit or they were

• 46:07Andrew D. Huberman?

  hitting things with their head often, um, or if they have a TBI or had a TBI, that um, their reproductive health can be impaired?

• 46:16Speaker 05

  That's fascinating. Um, I have, I have not. I mean, I think, you know, it's interesting, I guess, you know, what the pituitary does. You've obviously covered this before, but it does go to a lot of our therapies. I mean, so, you know, For your listeners, you know that 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, you know, in terms of production. And interestingly, when exogenous testosterone is used, you know, it shuts down that axis, as you know. So we get less of these gonadotropins, this

• 46:56Speaker 05

  LH/FSH, to stimulate the testicle. And the other sort of reason that sperm production is lost with exogenous testosterone use is actually the intratesticular testosterone is much higher than serum levels. So, you know, our serum levels are, you know, 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 am not aware of sort of how traumatic injuries would do that.

• 47:39Andrew D. 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 you 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

• 48:20Andrew D. Huberman?

  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?

• 48:34Speaker 05

  Yeah. These are great questions. 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, you know, I, in general, like we talked about before, anything that's good for your heart, it's gonna be good for fertility. So good diet and exercise, maintaining good body weight. And so I always try and encourage physical fitness. I think that's important. But, you know, it may be possible that some particular activities may put men at more risk. So I think cycling could be one of them if, but it would sort of 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, you know, for these prolonged, you know, rides that men take, you know, on weekends, you

• 49:17Speaker 05

  know, hours, that may be 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 would be, you know, that may be too much. So if you're above that level, the sperm counts are 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, you know, stand up in the saddle to try and again, sort of air things out, to try and dissipate heat, if that's the mechanism we're gonna think. Regarding sexual dysfunction, that is thought to be pressure, as you're alluding to. So, you know, 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, you know, there's obviously kind of the rigid

• 50:01Speaker 05

  nose. And if there's too much pressure on that, that actually squeezes between the ischial tuberosities where, you know, 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 nerve fracture as well if you crush these nerves. And so that over time can lead to problems. So, you know, some patients will say that, you know, after I cycle, you know, 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, you know, men just sort of, you know, Ride through it and you know, hopefully things come back in a day or two. So that's that could be the mechanism. There are some saddles that you know, hopefully it'll be

• 50:45Speaker 05

  a little safer. And you know, I think that this sort of first was noted probably around the 2000 or so. And there is 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 you know, cycle fit that can be done or saddle fit rather that can be done at some of the cycling shops to try and you know, look at your body position, look at your size and try and find a saddle that's safer. You know, not this doesn't happen to everybody. I would say maybe if you were to survey cyclists, maybe 20 or 30% of men and women tend to be susceptible to this. So I think if you are having discomfort and when you cycle, whether it be pain, numbness, or you notice dysfunction, I think certainly you should

• 51:29Speaker 05

  you know, think about changing saddles or think about changing riding style. There's other strategies are sometimes used, but you know, absolutely something that that everybody should be aware of.

• 51:39Andrew D. 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 you know, 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?

• 52:21Speaker 05

  Yeah, I think you know, one of the ways that we can characterize activity is step count, right? 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 sort of looking at you know, 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 you know, Everybody can do to try and improve sort of testicular function broadly, but testosterone specifically.

• 52:50Andrew D. 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 on the promise of improved sexual health?

• 53:09Speaker 05

  Well, I don't know. Yeah, sexual health will be a different one, but we can, I think, there is association between testosterone levels and step count across different BMI straight up. So I think, you know, whether you're 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.

• 53:26Andrew D. Huberman?

  Okay. And another question I meant to ask earlier, and then we can close the hatch on 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, let's just use you and your clinic as an example, and they are happy with the psychological and physical consequences of that, and they are

• 54:07Andrew D. Huberman?

  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 their lipid levels in check, like this, 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, 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?

• 54:49Andrew D. Huberman?

  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 a in check, in a healthy check, does it increase the risk of any kind of cancer?

• 55:02Speaker 05

  Yeah, I mean, this is another great question because I think there's a lot of myths around testosterone, and that's one of them. You know, the origin is that prostate cancer is thought to be, or is, sort of androgen mediated. You know, one of the Nobel Prizes, you know, again, decades ago, was awarded because it was found that when we lowered a man'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, you know, either replace testosterone or augment testosterone, 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. You know, there's lots of longitudinal data spanning decades where if man is given testosterone, it doesn't change his risk.

• 55:47Speaker 05

  The reason for that, in a sort of seeming contradiction, you know, this contradiction between, you know, prostate cancer, a 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 know, you can kind of think of as, have been filled. So if you were to give man more testosterone, it doesn't change anything regarding the prostate cancer, prostate growth, any of that. So it is, it is safe when we're looking at prostate cancer as, as an outcome.

• 56:27Andrew D. Huberman?

  Getting back to prostate health and neural innervation of the penis and, 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, in our later discussion.

• 56:56Speaker 05

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

• 57:19Andrew D. Huberman?

  You're talking about spontaneous erections during sleep?

• 57:22Speaker 05

  Right.

• 57:22Andrew D. Huberman?

  So, and short of assigning one's partner to 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 requisite for knowing that nocturnal erections are occurring?

• 57:40Speaker 05

  Well, I, yeah, I think you've, yeah, you've kind of 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 sort of normal response, you know, when either by yourself, with a partner, I think that generally means that you are going to get normal erection. So I think, I guess when I say use it or lose it, it doesn't mean necessarily that the man has to stimulate himself or kind of make sure that he does have, you know, adequate function. Because usually, most of that normal function just occurs, you know, with this nocturnal penile tumescence, which we all get. You know, I think sometimes men do notice when they wake up at night. Sometimes in the morning, you wake up with an erection, and men notice that. But the absence of that doesn't mean it's not happening. It likely is, just, you know, most people sleep through it, which is normal. Otherwise, men would never get

• 58:24Speaker 05

  any sleep, because it happens many, many times at night. So I think, you know, again, if you're not having normal function, I think that's something you should probably see, you know, a physician about. And then same for like urinary function. I think if it bothers you, if there's, you know, 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 sort of complaints that we hear about.

• 58:46Andrew D. Huberman?

  What is often? My understanding is that it's a 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, you know, if I don't get really granular about some of this, then people say, well, what if I drank, you know, 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?

• 59:31Speaker 05

  Yeah, I mean, I think once a night, yeah, is normal for most men. And then I think, you know, 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.

• 59:42Andrew D. 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

• 1:00:22Andrew D. Huberman?

  young people who are not working excessive hours, are getting, you know, 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?

• 1:00:39Speaker 05

  Yeah, I mean, I think certainly there's reasonable data for semen quality. And there tends to be, you know, we call like, in science, sort of a U-shaped relationship, so that it's not sort of linear, so as you get more sleep, things are better. There's sort of, 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, you know, why that is, is not certain. Again, if you're able to get that much sleep, maybe there's other things as well that we should look at. But so I think kind of getting in that ideal sleep amount is best for semen quality and probably for broad testosterone function as well.

• 1:01:23Andrew D. 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, you know, 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, or who are, which of course could include people who've already had children or who

• 1:02:02Andrew D. Huberman?

  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, is it one of the better metrics of overall male vitality and health?

• 1:02:22Speaker 05

  Well, I think, you know, it's, 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. You know, if you look at men with more health problems, they can 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. You know, it's, you know, why that link exists, I think, is not, is not known, but there's lots of theories. So one is that, you know, probably about 10% of the male genome is devoted to reproduction.

• 1:03:06Speaker 05

  And so it makes sense, given that we only have about, you know, 24,000 genes in the body, that there's a lot of, you know, overlap. So one gene that plays a role in reproduction may play a role in, you know, the cardiovascular system or the neurological system. And so if we get the first, you know, sort of sign that reproduction is not perfect, there may be some other health consequences down the line. Another sort of hypothesis is that, again, sort of going along this line that reproduction is one of the first things that we see, is that, you know, gestation is sort of very critical to our, you know, existence, right? And perturbations to that system have prolonged, you know, effects, sort of the so-called sort of developmental origin of adult disease,

• 1:03:49Speaker 05

  or the Barker hypothesis. And so, we know that, you know, premature children have higher risk of cardiovascular disease, or have been studies to show that. But we also know that, you know, these gestational effects can also play out on reproductive function, too. So that also may be kind of a link, you know, sort of 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 sort of inherent, sort of similarities between reproduction and some other sort of social effects. So, you know, kind of one sort of confounding factor, when we're looking at some of these studies, I talked about looking at mortality, for example, and semen quality, is that, you know, there's sort of factors that necessarily

• 1:04:34Speaker 05

  involve reproduction. So, 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, you know, that's another possible explanation. But I think, you know, really sort of this health, you know, link between fertility, I think is sort of a powerful one. So, I do think it should be a barometer. I think that, you know, it should be a, sort of, 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, you know, sort of lower levels, that may tell us about something else going on. You know, when, when men come in for fertility evaluations, a lot of times, we

• 1:05:16Speaker 05

  do diagnose, you know, these new medical problems. Sometimes we diagnose cancer, you know, sort of alluding to some of the questions you've asked, diabetes, and some other, you know, very significant genetic conditions as well. And, you know, 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, you know, another, I think, advantage to like the Centers for Disease Control, for example, to start tracking it.

• 1:05:48Andrew D. Huberman?

  Would it be a good idea for males in their twenties and thirties to get a sperm analysis, just to have a baseline? I confess, I'm forty-seven now. One thing I wish I had done in my twenties was to get my blood hormone profiles and lipid profiles done when I was in my teens and twenties because I'd have something to compare to. I started doing that in my mid-thirties, and I'm so glad I did because I can now compare to my mid-thirties levels. I started including sperm analysis about eight years ago with the intention of freezing sperm. Did that because I was also reading at that time about the increased risk of autism in offspring of males older than forty, something that I really would like your take on.

• 1:06:32Andrew D. Huberman?

  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, you know, it's heading through the post office. Now everyone's imagining all these sperm traveling through the postal service. It's out, they're out there, folks. Yeah, what are your thoughts? Should people invest the, I think it was a couple hundred dollars to get a sperm analysis, more costly to get the DNA fragmentation than you get up into the low thousands? But if people have the disposable income, is it a good idea for them to do?

• 1:07:13Speaker 05

  I mean, I think it's a worthwhile test. I think more information is always good. You know, I think sort of one of the same reasons that, you know, you're talking about checking like lipid levels or we tell, you know, men and women to get blood pressure checked. I think, you know, getting that sort of early health indicator, I think, can be important. I think, you know, going back to not knowing exactly why semen quality is telling us about health, what the exact link may be. You know, means that if somebody is coming in with a low sperm count or completely absent sperm count, it's hard to know exactly how to counsel that that person, other than there may be reproductive difficulties. But I think just as sort of a marker for reproductive potential, I think it's useful. And like you said, I think it's become a lot easier.

• 1:07:55Speaker 05

  One of the innovations in the space, and you know, somebody that, you know, is in the reproductive world, I think it's just really great to see sort of this influx in capital and new companies coming in to try to just decrease the barrier to, you know, 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, you know, because people are doing, you know, you know what people do in a bathroom, just next to you or you're trying to collect.

• 1:08:20Andrew D. Huberman?

  Oh, they would send them into a, in a common space bathroom. They wouldn't even give them the quiet room with the, with the red light, which is, uh, what I hear they do now. Yeah.

• 1:08:28Speaker 05

  Some of them do have videos. So there are some higher level.

• 1:08:31Andrew D. Huberman?

  Oh, I didn't even mean videos. I just, I, I think that, um, okay, yes, I've done this. I'll just say, I mean, I, I've been trying to normalize things related to all aspects of mental health, physical health. So, um, yeah, I, I decided to freeze sperm and basically they sent me to a room. I went to a university, basically. It actually wasn't Stanford, but a different university. And, um, uh, yeah, they put the cup through the window, they give you the cup, they, um, 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. And then they leave. And I think the, the assumption now is that you figure it out one way or another, um, how to provide the sample, and then you put the sample back through the, the thing. And then one thing these clinics really need to work out is that anytime you're walking

• 1:09:15Andrew D. Huberman?

  out, you, you see the people processing your sample as you walk out. So there's all this, um, this feigning of, of, uh, you know, anonymity, but really it isn't there, you know, because they're like, see you later. And you're like, great, you know, did you, you know, they, they rarely ask you questions on the way out, but it's a pretty simple process overall. And, um, and I must say that, that the data are informative. You get the, you know, you get the volume, number, motile, forward and the motile. I did opt for the DNA fragmentation.

• 1:09:45Andrew D. Huberman?

  Data and I just love data. So I think it's really interesting. But again, maybe this is a good time to flag this what 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 of conception. So I figured, you know, why not freeze some sperm and it's relatively inexpensive?

• 1:10:12Speaker 05

  Yeah. Yeah. So I think paternal age is also, you know, 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, you know, when a child is born, somebody comes in to collect data on the birth. So they ask, you know, all the characteristics of the mother and they also ask characteristics of the father, you know, age, education, obviously, region of the country the child was born. So we don't know, you know, what number child that was for the father. We know for the mother, they do ask, you know, is this your first, second, third, et cetera,

• 1:10:54Speaker 05

  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.

• 1:11:07Andrew D. Huberman?

  11?

• 1:11:08Speaker 05

  Quite a span, yeah.

• 1:11:09Andrew D. Huberman?

  88?

• 1:11:10Speaker 05

  Mm hmm.

• 1:11:11Andrew D. Huberman?

  Goodness, unrelated.

• 1:11:12Speaker 05

  I don't know. I assume. I assume.

• 1:11:14Andrew D. Huberman?

  Goodness.

• 1:11:15Speaker 05

  It's anonymized data.

• 1:11:16Andrew D. Huberman?

  But 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?

• 1:11:28Speaker 05

  Yeah. So you're asking, I guess, sort of super murky when like sperm production begins. So.

• 1:11:34Andrew D. Huberman?

  Yeah, there are a lot of markers of puberty, secondary sexual characteristics, beard growth, deepening of voice. It's there. They happen at different rates and different people. But yeah, thank you. At what point are, yeah, males undergoing puberty?

• 1:11:46Speaker 05

  Yeah.

• 1:11:47Andrew D. Huberman?

  At the at the level of of that we're talking about here?

• 1:11:50Speaker 05

  Yeah, so it's, 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 you don't, I think it's not, you know, just like testosterone ranges between like 300 and 900, that's a wide range for anybody. I think for most individuals, you know, puberty is, you know, probably 12 to kind of 15, 16 in general. So I just give sort of a very wide range when we're going to say that's okay. And, you know, some of the data I'm basing it on is when sperm production begins in boys. And it's actually, you know, not that simple to be able to figure that out because, you know, we don't generally talk to, you know, 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

• 1:12:35Speaker 05

  done, and they see if there were sort of, you know, nocturnal emissions, whether there's sperm in there. And so generally, it probably starts around, the earliest would be kind of 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 produced, started producing sperm.

• 1:12:59Andrew D. 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.

• 1:13:08Speaker 05

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

• 1:13:23Andrew D. 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, 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. I mean, my understanding is that the rates of autism are somewhere

• 1:14:06Andrew D. Huberman?

  between 1 and 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 right? And that the age of the father is a risk factor.

• 1:14:19Speaker 05

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

• 1:14:32Andrew D. Huberman?

  Wait, I want to know how long he lived to see how long his child grew up. He conceived at 96?

• 1:14:39Speaker 05

  Supposedly, supposedly, yeah.

• 1:14:41Andrew D. Huberman?

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

• 1:14:47Speaker 05

  Um, you know, I, well, so this is a man in India. It's sort of a famous story, but supposedly, um, he had a child. He had that child with him on, uh, like they're waiting at a bus stop. He fell asleep, the child was kidnapped, it led to divorce, so, yeah.

• 1:15:04Andrew D. Huberman?

  Dreadful.

• 1:15:04Speaker 05

  Sort of a horrible end, but the wife was also old, not that old, but in her 50s. So, yeah.

• 1:15:13Andrew D. Huberman?

  Wow, tragic and incredible story for separate reasons.

• 1:15:17Speaker 05

  Yes.

• 1:15:18Andrew D. Huberman?

  Okay, I'll get my head around this 96-year-old conceiving a child. Okay, please continue, yeah.

• 1:15:25Speaker 05

  Uh, so people, I think, or men, think that the, sort of the, um, you know, their, you know, 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, you know, about 100 years ago was first noticed that dwarfism or achondroplasia was more common in lastborn children. So eventually that link was made. And since then, other conditions too. So there's like 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, you know, less attainment in school, you know, failing grades, all that has been shown to be a little bit more common with older fathers.

• 1:16:09Speaker 05

  So, you know, why I think all these exist, there can be sort of different explanations. You know, one explanation for the autism association, I'll talk about. You know, some of this more genetic or kind of mutational reasons. But one thing that some people say is that, you know, it could be sort of a hereditary trait. And so it may be that, you know, men that display some sort of autistic characteristics, you know, maybe they take a little longer to meet a partner. And so it's sort of delayed childbearing. So maybe that's, that's one possible explanation. But I think, you know, there's been a lot of convincing evidence that there could be, you know, real epigenetic changes that occur with age and mutational changes that occur with age.

• 1:16:52Speaker 05

  I think I read a statistic and you would know more, being a neuroscientist, that 84% of the genes in our body express somewhere in the central nervous system. Is that?

• 1:17:02Andrew D. Huberman?

  Sounds about right. Yeah. I don't want to stamp my name to that, but that sounds about right.

• 1:17:09Speaker 05

  So it's estimated that every year we generate about two mutations in our, you know, sperm DNA. So you can imagine that, you know, a 40-year-old is going to have, you know, 20 or 40 more mutations than a 20-year-old. So that rate does go up. And if you're just randomly sprinkling mutations, you know, in, you know, a genome, that they're more likely to sort of manifest in, you know, maybe neuropsychiatric conditions. So there are, you know, data, 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.

• 1:17:51Speaker 05

  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, right? Based on sort of these rare mutations, you'd expect this would, you know, occur maybe about 1 in 100 million. But it turns out these, these conditions occur in about 1 in, I think, 30,000 to 50,000 or so. So there's sort of this discrepancy based on sort of 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 sort of advantages

• 1:18:34Speaker 05

  over their, you know, 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 sort of a random smattering. You can actually see that some of these mutations are more common in older men than younger men. If you look, you screen for some of these mutations in, you know, some of these pathways. Again, the longer that we're exposed to life, there's just more likely to be, you know, different chemical exposures, other exposures. And so people have looked at epigenetic signatures, sort of these signatures that, you know, that dictate which genes are going to be expressed and which aren't. And there are different patterns between older and younger fathers. And, you know, why, what triggering those is not known, but there are differences. So those could also potentially explain, you know, some of these risks that we see. You know, it used to be that people

• 1:19:18Speaker 05

  thought that, you know, if you're an older father, maybe there's a lot of advantages, you know, for the kids, right? Because if you're, you're more resourced. But I always tell patients that, you know, when they come to see me for like erection problems or anything, I always say, nothing gets better with age, right? And that's mostly true, although they pointed out that salary often goes up with age and wisdom goes up with age. So you'd imagine if you're more resourced, maybe the kids are going to also have an advantage to that. But, you know, again, there's a lot of convincing data that that's, that's probably not the case. There's, even 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, you know, sort

• 1:20:01Speaker 05

  of talking about kind of 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, you know, 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 we certainly be aware of. I think talking about mitigation strategies, I think sort of education would be important for, you know, couples to try earlier, you know, individuals to try earlier to conceive. You know, if we think it's a mutational reason, I think, you know, certainly freezing sperm, I think, is a, is a good option as well.

• 1:20:41Andrew D. Huberman?

  My understanding is that analysis of DNA fragmentation in sperm doesn't, 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. So, and since in a given pool of sperm, so to speak, there will be forward motile, non-motile, twitches, twitching in place, dead sperm, some percentage of dead sperm or immotile sperm is presumably normal, some small percentage, hopefully. And that some might have some DNA fragmentation, some might not.

• 1:21:24Andrew D. Huberman?

  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, you know, 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? It could be that as you age, that some percentage of those sperm have fragmented DNA.

• 1:22:07Andrew D. Huberman?

  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 for or improve the DNA of their sperm, not just the motility?

• 1:22:33Speaker 05

  Yeah, I wish, right? That's sort of the holy grail. Because I think you pointed out sort of a variant of, right, the Heisenberg uncertainty principle is that we can't, if we identify which sperm is bad, we're necessarily going to destroy it. So to tell, you know, which one is harboring these mutations would be great. But I think we're not there yet. I mean, one thing that we do do is wash sperm. So we do sort of select the most modal 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, you know, 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.

• 1:23:11Andrew D. 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, you know, a catalog of things that the prostate does. I mean, 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? You know, how do we keep it healthy? And what are the consequences of not keeping it healthy?

• 1:23:47Speaker 05

  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, you know, sperm to be supported and ejaculate to kind of keep the sperm healthy in the female reproductive tract. So, you know, 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, you know, 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 sort of more resistance in this pipe.

• 1:24:29Speaker 05

  And so it makes the bladder have to work harder and that leads to a lot of the symptoms, you know, that we've been talking about already, you know, waking up at night, weak stream, this need to urinate urgently, sometimes feeling like you're not emptying all the way. 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 that, you know, necessarily you can do. I think that, you know, one thing I talk to patients about when these sort of symptoms start is to know some of the triggers. So, you know, 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, you know, particular drinks or foods that tend to be more irritating.

• 1:25:13Speaker 05

  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. You know, caffeine is a diuretic, so it makes us urinate more. And it also can also irritate the bladder and give you that sensation. Alcohol will do the same thing. So I think, you know, kind of knowing some of those triggers may kind of stave off some of the symptoms a little bit. But, you know, again, if you enjoy those vices and you're willing to tolerate it, that's okay, too.

• 1:25:39Andrew D. 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 5 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 5 milligrams of Tadalafil per day, simply for maintaining blood flow to the prostate and thereby maintaining or improving prostate health?

• 1:26:22Speaker 05

  I mean, certainly it can do that. It can definitely help with some of these urinary symptoms that we've been talking about. You know, looking at placebo-controlled trials, sort of our highest level of evidence, does show that, you know, low dose of Tadalafil is 2.5 to 5 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. You know, 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.

• 1:26:54Andrew D. Huberman?

  Even at the 2.5 to 5 milligram dosage? Interesting. Yeah, my experience is that there are a lot of people who would love to take pills every day.

• 1:27:04Andrew D. Huberman?

  There seems to be a kind of binary distribution where.

• 1:27:08Andrew D. Huberman?

  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? What can I take? 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, seemed to be the younger, excuse me, 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. I mean, 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

• 1:27:52Andrew D. Huberman?

  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, 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,

• 1:28:32Andrew D. Huberman?

  perhaps without the need. I just want to flag that because I think, if I understand correctly, you're seeing a lot of testosterone therapy that perhaps people don't need? Is that right?

• 1:28:45Speaker 05

  Well, I think it's a mix. Some people probably do need it, but I think that, you know, before starting it, everybody should be aware of all the risks. And you've kind of highlighted some. Testosterone, any medication, right, 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.

• 1:29:01Andrew D. 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, seems that testosterone therapy would not be the primary entry point, like first workout, 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?

• 1:29:42Andrew D. Huberman?

  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 can ingest a dye and then they can dye image the whole apparatus. Is that right?

• 1:30:05Speaker 05

  That's true.

• 1:30:05Andrew D. Huberman?

  Without having to cut anything?

• 1:30:07Speaker 05

  Yeah.

• 1:30:08Andrew D. Huberman?

  Is that worth people doing? Or is that only under conditions where people are experiencing some vexing issue?

• 1:30:15Speaker 05

  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, right? 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, you know, one way would be that a bacteria actually gets all the way, you know, 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 are 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.

• 1:31:00Andrew D. 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.

• 1:31:43Andrew D. Huberman?

  Or are there other, say, blood flow related, pelvic floor related, neural, brain to?

• 1:31:52Andrew D. Huberman?

  To body neural connections that are responsible. I'm guessing it's all of these things. How do we parse this?

• 1:32:00Andrew D. Huberman?

  And yeah, what? Tell us about erectile dysfunction, what you most commonly see, what you most commonly do in order to treat it.

• 1:32:07Speaker 05

  Yeah. So erectile dysfunction is, you know, is sort of the inability to consistently achieve and maintain an erection. And it's fairly common. You know, of all the conditions I see, that's definitely the number one. So, you know, if you look at men over the age of 40, over half will have some trouble with erections. Under age of 40 is 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. You know, we used to think that they were primarily psychogenic. But that was, you know, years, 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.

• 1:32:48Speaker 05

  So high blood pressure, diabetes, you know, atherosclerosis, anything that sort of can impair blood getting, you know, to the end organ. And sometimes, you know, there has been data that, you know, trouble with erections can actually predate other more, you know, serious, you know, vascular conditions. So the blood vessels in the penis, the penile arteries are about one millimeter, you know, and the heart and the brain, they're much larger. So, you know, 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, you know, sort of lifestyle, obesity, again, is another, is a common one. Endocrine disorder is actually fairly small. It's probably less than 10%, probably around 5% or so.

• 1:33:34Speaker 05

  Pelvic cancer treatment is another very common one. After, you know, treatment for prostate cancer, whether it be radiotherapy or surgical therapy, bladder cancer, sometimes erectile colorectal cancer, that treatment also. Anytime we're, you know, involving some of the nerves and the vasculature and the pelvis, that can also impact erectile function as well.

• 1:33:55Andrew D. Huberman?

  What about hernia?

• 1:33:57Speaker 05

  Hernia, that should be separate. So sometimes if there, you know, I always say that in medicine, you can never say never. But, you know, generally if that was going to manifest as erectile function, it would probably be due to maybe some pain syndromes can rarely happen during just the early post-operative period. But the blood supply, the nervous supply is separate.

• 1:34:15Andrew D. 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.

• 1:34:29Andrew D. Huberman?

  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

• 1:35:11Andrew D. Huberman?

  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 1200 or maybe 1400 in other countries, but as other countries like to point out. But it starts at 2. No, I'm just kidding. But assuming they're doing everything correctly, and it's not a testosterone issue, then if

• 1:35:50Andrew D. Huberman?

  it's a blood flow issue, meaning they haven't had treatment for some pelvic cancer, what is the first line of treatment?

• 1:36:00Speaker 05

  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.

• 1:36:10Andrew D. Huberman?

  I'm sure you're the most popular doctor in your field.

• 1:36:13Speaker 05

  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 solithopil or Viagra, tadalafil, Cialis, avonafil, stendra, or vardenafil, levitra.

• 1:36:28Andrew D. Huberman?

  Would you be willing to talk about some of the specifics there? Are you, is the typical thing to put people on this 2.5 to 5mg per day low dose? Or to give the higher doses that are more commonly used for erectile dysfunction per se?

• 1:36:42Speaker 05

  I think it depends, you know, why we're putting them on it and how much sex they have too. You know, on average, people probably have sex, you know, partnered sex maybe once a week on average. You know, when we're looking at men in their kind of 30s and beyond, you know, sometimes it can be a few more times a week than that. But, you know, 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, you know, maybe about, you know, a few times a month category. So that's usually where we start. And, you know, there is sort of a titration that can be done. You can go slightly, you know, higher doses or lower doses. So usually we start in the middle to the higher doses.

• 1:37:21Speaker 05

  And, you know, we talk about some of the side effects they may have, but those probably help 60 to 70% of men and they work well. You know, 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. You know, all these medications tend to be somewhat similar. One difference tends to be the time of onset, you know, 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 and then 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, you know, taking a pill on Friday, so having some left on Saturday. But for others, you know, we start with one of the other ones.

• 1:38:04Andrew D. Huberman?

  The fact that these drugs like Tidelphil, also called Cialis, right?

• 1:38:09Speaker 05

  Cialis, yeah.

• 1:38:09Andrew D. Huberman?

  Is Cialis the brand name?

• 1:38:10Speaker 05

  Right.

• 1:38:11Andrew D. Huberman?

  Okay. And Viagra, is that a brand name?

• 1:38:14Speaker 05

  Right.

• 1:38:14Andrew D. Huberman?

  Stands for, what is the generic name?

• 1:38:17Speaker 05

  Oh, sildenafil.

• 1:38:18Andrew D. 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? Is that, 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, you know, 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.

• 1:39:01Andrew D. Huberman?

  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 and maybe worse?

• 1:39:13Speaker 05

  Yeah, absolutely. Well, I think they should be screened. So, you know, sometimes I'm diagnosing in 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, you know, blood pressure, lipid levels, you know, 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 it's, you know, I think we kind of talked about sort of 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 don't, I try not to be alarmist about this, but I do want to, you know, encourage men to sort of take ownership of the health because that sometimes can improve, you know, some of these conditions. But again, we have terrific medications for, for men in whom we cannot.

• 1:39:57Andrew D. Huberman?

  What are the common side effects of these drugs?

• 1:40:00Speaker 05

  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.

• 1:40:12Andrew D. 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, is that what the rationale was?

• 1:40:23Speaker 05

  I think so, yeah. You know, another is, we talked about sort of 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, Tadalphil, before a ride, again, to try and increase circulation to decrease the chance of any of the negative effects of prolonged saddle pressure.

• 1:40:42Andrew D. Huberman?

  So it sounds like just increasing blood flow and lowering blood pressure slightly is just a good thing all around?

• 1:40:48Speaker 05

  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.

• 1:41:00Andrew D. Huberman?

  So you mentioned about 10% or less of erectile dysfunction is due to endocrine issues. Was it 60 to 70% can be resolved with, with these blood flow enhancers? I know it's a terribly non, uh, non-clinical, non-scientific way to describe the Viagra, Cialis, Tadalphil, et cetera. What about the remaining percentage? And are there other treatments that you, you prescribed or, or given? In which cases do you need to resort to, I guess, more invasive approaches?

• 1:41:36Speaker 05

  Yeah. So another therapy we have is urethral suppository. So you can actually put a medication in the tip of the penis and send it absorbed by the rest of the penis.

• 1:41:44Andrew D. Huberman?

  Is it inject, it's suppository?

• 1:41:45Speaker 05

  A suppository or a gel, or a jelly, yeah. So it's also a vasodilator. Sort of the concept is very similar. Sometimes that, you know, is, is okay for men and tolerated. 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 like a little bit of a burn as well.

• 1:42:07Andrew D. Huberman?

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

• 1:42:12Speaker 05

  Mostly efficacy would be a big one. And so this, this, 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 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.

• 1:42:38Andrew D. 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?

• 1:42:46Speaker 05

  No, yeah, this is an on-demand treatment. So we, 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, you know, an erection that lasts for that amount of time.

• 1:43:01Andrew D. Huberman?

  Is it injected subcutaneous or actually into the, goodness, the mediocre tissue of the penis?

• 1:43:09Speaker 05

  That's right, into the erectile bodies directly. Yeah. And they, you only have to inject one side, they do communicate with each other. Most men say it's fine. It's a small, it's a very small gauge needle, about as big as, you know, a few strands of hair.

• 1:43:20Andrew D. 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, but when it's done by a skilled ophthalmologist, it's just striking. You know, you hear, you think about needle in the eye, you know, what's worse? It's like the childhood rhyme, right? Stick a needle in my eyes. I can't think of anything worse, but maybe, you know, 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, with limited, if any, discomfort?

• 1:43:52Speaker 05

  Well, it does have a high dropout rate.

• 1:43:55Andrew D. Huberman?

  Surprise, surprise.

• 1:43:56Speaker 05

  Yeah, I think no one's excited about it. You know, it's, I guess the mood can sometimes be affected, but a lot of couples are very comfortable with it. Again, it's very efficacious. The part, the man can do it, his partner can do it. So it does work well.

• 1:44:10Andrew D. Huberman?

  And I guess here we're sort of ascending the, the list of invasiveness.

• 1:44:15Speaker 05

  Right.

• 1:44:16Andrew D. Huberman?

  What, what is at the, the sort of top tier of invasiveness for erectile dysfunction?

• 1:44:22Speaker 05

  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 sort of two main forms. There's either non-inflatable or inflatable. So the non-inflatable is sort of a bendable. It's, you know, has sort of 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 kind of bend it up.

• 1:44:45Andrew D. Huberman?

  It's really just there on demand?

• 1:44:46Speaker 05

  Yes.

• 1:44:48Andrew D. Huberman?

  Yeah. Interesting.

• 1:44:49Speaker 05

  Yeah. So it's very simple to use. Sort of the more, I guess, kind of. Sort of 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 sort of surgically implanted inside a man all under the skin. You know, 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.

• 1:45:22Andrew D. Huberman?

  What is the relationship between psychological arousal and erection as it relates to these technologies? I mean, the way you're describing it sounds purely mechanical, 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, 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?

• 1:46:00Speaker 05

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

• 1:46:21Andrew D. Huberman?

  A few years ago, I was reading about vasopressin inhalants. You know, there was a bunch of stuff hitting the market. By the way, I don't suggest that people get experimental with this stuff, you know, as a neuroscientist who also knows the thing about neuropeptides and neurohormones that can impact the hypothalamus. You know, I just, I just cover my eyes and kind of cringe when I think about people inhaling vasopressin, thinking, oh, yeah, you know, 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 is relates to a melanocyte stimulating

• 1:47:04Andrew D. Huberman?

  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? Yeah, 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.

• 1:47:45Speaker 05

  Yeah, so those are not ones that we use in clinic. But I think, you know, looking at sort of just sexual dysfunction broadly, there are a lot of things that, you know, we do try and help. And one of the things sort of that I kind of relates to that, that is 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, right? Where men ejaculate too quickly. But on the other end of the spectrum, there's men that takes, you know, a long time to ejaculate. And you know what that is, is it sort of defined differently, but generally, most people would say like sort of two standard deviations about the average. So on average, probably around five minutes or so, two standard deviations would be kind of 20 to 25 minutes. So for men that take that long to ejaculate, that would be considered delayed.

• 1:48:30Speaker 05

  Or sometimes they don't ejaculate every time that they, you know, 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, you know, providers are trying some of these other, you know, 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 it's a challenge because, you know, 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.

• 1:49:06Andrew D. 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.

• 1:49:18Andrew D. Huberman?

  You hear about kegels, kegels, kegels, I don't know. I guess we'll have to ask him because it turns out kegel, kegel was a person who named the exercise 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 a 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.

• 1:50:01Andrew D. Huberman?

  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? I mean, should men be paying attention to pelvic floor health? Should men be doing pelvic floor exercises?

• 1:50:13Speaker 05

  I mean, I think it's really key that you say that because, you know, 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 very, you know, just a lot of tension, a lot of anxiety. Sometimes these men, you know, urinate every hour. I mean, there's other things and you could just tell they're just sort of very wound up. And I think for that man, you know, one of the issues you kind of allude to is he probably needs to relax more. So, you know, pelvic floor, physical therapy can still benefit you because there are some just different feedback exercises that could be done to help with relaxation. So, you know, in the urologist's office, there's usually a list, a lot of different providers around the region that can help with some of these. Kegel exercises though can be useful, you know, for example, for like prostate cancer rehabilitation, some of these men, where we're trying to kind of rebuild some of the strength

• 1:50:57Speaker 05

  or maintain or improve continence in these men. We do want to strengthen some of these muscles 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.

• 1:51:13Andrew D. 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 specialist. Do they tend to specialize male, female?

• 1:51:27Speaker 05

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

• 1:51:33Andrew D. 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 by life experience where the testes and scrotum are relatives to all of that, but now I'm trying to figure out how like so the pelvic floor, a bunch of muscles that that are attached to the pelvis, but how do they interact with those with those organs?

• 1:52:10Speaker 05

  Yeah, it's a good question. So they sit beneath, you know, the 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, you know, the base of the penis, the prostates, the bladder, the rectum. And, you know, they're, they kind of keep main, you know, adequate tension to keep all those structures up. They relax when, you know, different functions are necessary. They're very important for ejaculation. You know, some people think that they kind of trigger some of the orgasmic response as well. You know, sometimes men will have, you know, pain in that area, in the perineal area can transmit to other parts of the body like the scrotum. You know, one of the one cause of scrotal pain, and there can be many, can sometimes

• 1:52:52Speaker 05

  be pelvic floor dysfunction. So I think, you know, again, pelvic floor therapy can be useful for sort of a constellation of symptoms, again, some urinary symptoms as well. So I think for some patients it can be helpful, but, you know, again, there if you get things too tense, that can sometimes be harmful.

• 1:53:10Andrew D. Huberman?

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

• 1:53:15Speaker 05

  Exactly.

• 1:53:16Andrew D. Huberman?

  Got it. Going to some of the questions that. Came back to me when I solicited for questions in anticipation of this episode.

• 1:53:26Andrew D. Huberman?

  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?

• 1:53:41Andrew D. Huberman?

  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. And there is a case of a failure to fully fuse the urethral duct during development where people, 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 possibility for now.

• 1:54:16Andrew D. Huberman?

  But now that it's on the table, what percentage of males have that two urethral openings?

• 1:54:21Speaker 05

  So well, hypospadias, which you're describing where the, the actual meatus is not at the tip, but it's kind of along the proximal urethra or, you know, 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.

• 1:54:41Andrew D. Huberman?

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

• 1:54:49Speaker 05

  You know, one of the reasons that we, you know, urinate sort of from an evolutionary standpoint, right, is to, you know, basically deposit in sort of a convenient time our waste and we don't want to get it everywhere because we don't want to sort of label ourselves with smell of urine because that'll be easier for predators to, 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 like a urethral issue, as you're pointing out, a prosthetic issue, inadequate speed, you know, of getting urine out of meatus. So you definitely should see, you know, a physician to get evaluated because there's likely some issue that can be improved.

• 1:55:33Andrew D. Huberman?

  The most popular question I received from males, however, was about, perhaps no surprise, penis length.

• 1:55:43Andrew D. Huberman?

  You're an expert in this, actually. 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?

• 1:56:08Speaker 05

  Those were excluded, yeah.

• 1:56:09Andrew D. Huberman?

  Yeah, so lying was excluded. Being facetious here, but yeah, how was this study done? I mean, pretty incredible study. And the results are, I don't know if they're surprising or not. 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. I think I'll let you describe the study now rather than giving people the punchline here.

• 1:56:37Speaker 05

  Yeah. So, I mean, the origin was that we were looking at, we wanted to know average lengths for another project that we were doing. And, you know, going down the rabbit hole, this has been reported for decades. You know, there's different reasons that people have reported penile length. You know, sometimes they do it just on volunteers, again, to sort of 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 sort of called the literature, found data on 55,000 men all over the world and wanted to see if there was a, you know, sort of 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, you know, whether it be, you know, chemical environmental exposure.

• 1:57:18Speaker 05

  But if nothing else, if we're getting bigger, you know, the functional penile length should decline because, you know, the suprapubic fat pad will get a little bit bigger and so we'll kind of lose penile length with that. And so, much to our surprise.

• 1:57:30Andrew D. Huberman?

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

• 1:57:35Speaker 05

  Right, right. And so, you know, if that gets bigger, that'll necessarily compromise penile length. But, you know, as you alluded to, what we found is actually the opposite, that the penises were getting, getting longer with time. So, how it's measured, measured differently. So, one of our inclusion criteria was that all the studies had, have measured. Sort of in an office, sort of in a clinical setting. So whether it be a, you know, 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, you know, the pubic bone ideally up to the tip of the, uh, the glands or the.

• 1:58:14Andrew D. 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. And then measuring from essentially contact with a location that's contact with the pubic bone to the, the tip.

• 1:58:35Speaker 05

  Right.

• 1:58:35Andrew D. Huberman?

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

• 1:58:40Speaker 05

  Mm hmm.

• 1:58:41Andrew D. Huberman?

  Wow.

• 1:58:42Speaker 05

  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 a man to stimulate himself and then measure. So that was some of the studies. And then the other method, as we alluded to earlier, is you could inject the man with the medicine to give him an erection and then measure it.

• 1:58:59Andrew D. Huberman?

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

• 1:59:03Speaker 05

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

• 1:59:08Andrew D. 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.

• 1:59:15Speaker 05

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

• 1:59:28Andrew D. Huberman?

  I'm sure you'll hear from some of them after this episode. Um, what was the major finding?

• 1:59:34Speaker 05

  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, um, the averages lengths, you know, varied a little bit, but generally on average, um, erect penis is probably between about five to six inches, somewhere in that neighborhood. So that was kind of the take home we wanted.

• 1:59:51Andrew D. Huberman?

  That was the average.

• 1:59:51Speaker 05

  The average for rect length.

• 1:59:53Andrew D. Huberman?

  Did you publish the full distributions?

• 1:59:56Speaker 05

  Uh, we didn't. I think we were, we're, we're, our plan was actually to make a follow on study. So we could show everybody, you know, I guess probably they were interested where they kind of fell on the graph. But it was fairly, you know, it was normally distributed.

• 2:00:08Andrew D. Huberman?

  Yeah, we think that, um, despite the, um, you know, the wide availability of pornography that, um, 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.

• 2:00:32Speaker 05

  Right.

• 2:00:32Andrew D. Huberman?

  Were interesting because the scatter plot distributions, I feel like, point to other takeaways, that one can be in their seventies and have testosterone levels equivalent to a male and healthy male in his thirties, that one can be in their thirties and have testosterone levels that are twice as much or half as much as age match 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? Like, what did you find most interesting about the data?

• 2:01:08Speaker 05

  Well, that there was any change over time. You know, this was a fairly short study. It was probably about, you know, thirty years or so. But we did find that penis length has been increasing over time. So, you know, that was just sort of fascinating that we would see sort of 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, you know, again, similar to the concerns that arose for these, you know, relatively short period of time where you would see changes in semen quality, you know, it suggests something sinister, right? It's unlikely to be a genetic change because that would take, you know, centuries probably, certainly several generations. So the fact that this happened so quickly was just surprising.

• 2:01:49Andrew D. 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. Now, the verbiage around that would probably be a little bit different, but the idea is that

• 2:02:29Andrew D. Huberman?

  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. So assuming that the study that you did was on males post puberty.

• 2:02:49Speaker 05

  Right.

• 2:02:49Andrew D. Huberman?

  I'm assuming it was. 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? I mean, this is the opposite of environmental endocrine disruptors preventing sperm from being as, you know, high quality and numerous as they could be, or for, you know, or 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.

• 2:03:29Speaker 05

  Right. So, I mean, I think there's different conjectures that you can make about why this could happen. I mean, it could be, you know, maybe endocrine disrupting chemicals, you know, in utero, some early exposure, you know, that some of the mothers had to kind of 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.

• 2:03:57Andrew D. Huberman?

  So earlier puberty tends to be longer, potentially means longer duration exposure to dihydrotestosterone, longer penises.

• 2:04:06Speaker 05

  Right.

• 2:04:06Andrew D. 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 postpubertal 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.

• 2:04:49Andrew D. Huberman?

  Otherwise, I would have just forwarded them to you for your next study. But this stuff is happening in postpubertal males. So it all rests on this dihydrotestosterone hypothesis. Just a point of interest.

• 2:05:04Speaker 05

  Yeah, I don't know. It just physiologically, it doesn't make sense why that would work as you're pointing out postpubertally. And then unless they're doing other things, you know, some sort of stretching exercises or I think called jelking, but yeah, I would not recommend that.

• 2:05:17Andrew D. Huberman?

  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.

• 2:05:59Andrew D. Huberman?

  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 postfinasteride syndrome. I got a lot of questions about postfinasteride 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.

• 2:06:43Andrew D. Huberman?

  But yeah, what about finasteride, dutasteride, and these drugs that are effectively DHT blockers?

• 2:06:49Andrew D. Huberman?

  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, you know, widow's peak, or everywhere in some cases. It also induces hair growth on the back, beard growth as we understand. But then people go in 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?

• 2:07:15Speaker 05

  You know, I think the men that we see these, these side effects are, tend to be, you know, younger men in their twenties, thirties, and forties. And they take it, as you're pointing out, for hair loss. So before it was FDA approved for that indication, at least finasteride was, you know, 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, you know, lots of studies to see if there were changes in semen quality, you know, for men on finasteride versus the placebo. And there were some very subtle changes. But, you know, sort of in post-marketing, now we see these patients in clinic, you know, everybody to enroll in these studies had normal function. So I think that's sort of important to understand. And obviously, that's not life, right? That people come in with sort of different baselines and different

• 2:07:59Speaker 05

  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're, 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, you know, sexual function, I certainly, you know, have a number of patients, you know, that do complain of low libido, erectile function, this post finasteride syndrome. You know, and the mechanisms, I think, are less certain because, you know, measuring testosterone levels, which we do, you know, 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

• 2:08:40Speaker 05

  increase testosterone through a variety of means. Testosterone, clomiphene, sometimes we'll give, you know, it helps some men, but not all. So I think the exact mechanism of what is going on here, what is changing, I think, you know, we need more, you know, more understanding about the exact sort of path of physiology, you know, neurochemically.

• 2:09:01Andrew D. Huberman?

  It seems like a pretty serious trade-off to either maintain, grow hair, or lose sexual function. I mean, I talked about DHT in some of these.

• 2:09:12Andrew D. Huberman?

  Side effects of finasteride, dutasteride on previous episodes and you know, I'm not a clinician, but my encouragement is always for people to approach these drugs with a 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, they, 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?

• 2:09:54Speaker 05

  Yeah, I mean, oftentimes they do for, you know, these complaints. You know, they start to notice it when they're on the medication, then when they usually through online research kind of 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. You know, they've done, you know, MRI imaging to try and understand sort of more anatomically or functionally what exactly is going on. I think there's still a lot of unknowns about it, but it can be, you know, permanent for some. So they come in, you know, and they see me in clinic, erect all this function, low libido, and then we go down all the host of treatments that we talked about and evaluations that we talked about. Again, we have resolution in some, but there are some that seem treatment refractory.

• 2:10:34Andrew D. Huberman?

  Yikes. That's my only response. I mean, permanent effects on sexual health in it as a consequence of an attempt to maintain one's hair. I mean, this is where, you know, 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.

• 2:11:01Speaker 05

  Right.

• 2:11:02Andrew D. Huberman?

  And I did.

• 2:11:05Andrew D. Huberman?

  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, and 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, right? I think you alluded to this earlier, right? These drugs have proven to be very beneficial for older men treating prostate issues. Exactly, yeah. Right, so this is a post finasteride syndrome, I think, falls under the category of medical conditions that, you know, 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?

• 2:11:50Andrew D. Huberman?

  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, kind of like, oh, yeah, this, 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. Exactly, yeah. 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. Yeah, agree. Yeah. But you did say earlier that if someone has a penis, you can get it hard. So, so all is not lost even for these post finasteride syndromes. That's true. Good, okay, we'll hold use that.

• 2:12:37Andrew D. Huberman?

  You mentioned clomiphene.

• 2:12:40Andrew D. Huberman?

  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 kind of sub community of people out there who are saying, okay, testosterone therapy can cause us these sperm suppressive issues and perhaps some other issues.

• 2:13:03Andrew D. Huberman?

  But doing nothing might not be an option for somebody who wants to increase their whatever 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.

• 2:13:25Speaker 05

  Right.

• 2:13:26Andrew D. Huberman?

  Yeah. What's Clomiphene? What are your thoughts about people using Clomiphene sort of off-label, simply to increase androgens? It seems sketchy to me for reasons related to changes in neural circuits. But you'll tell us how it works.

• 2:13:41Speaker 05

  Yeah. Well, thank you for including the off-label disclosure. Anytime I talk about this, I always have to say, say that. But so Clomiphene is a selective estrogen receptor modulator. So basically it blocks estrogen. And so from our earlier discussions of how the pituitary works, you know, there's sort of an elaborate feedback loop between the pituitary and the gonads and the man that testes. And so what happens is, you know, FSHLHCs can add a troponin 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, the level of the pituitary or the hypothalamus, it'll stop that. And so the idea behind blocking that is that you'll get more production of FSHLHCs,

• 2:14:25Speaker 05

  more of these drivers. So you get more testosterone. You get a higher stimulation of the testicle. You know, 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 someone in this, this discussion. But also that, you know, you do need some estrogenic signaling as well. And so by blocking that, you know, even partially, because there's also some partial agonist effects of Clomiphene as well. It may limit it. And, you know, it turns out that estrogen signaling is important for a lot of things.

• 2:15:10Speaker 05

  It's important for, you know, bone health, but sexual health too. It's important for libido. So that may be partially blunting some of the hopeful 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 hypergonadism, 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 age man that has low testosterone and symptomatic low testosterone, you know, low, you know, low energy level, sex drive, mood, sleep problems,

• 2:15:50Speaker 05

  it can be a worthwhile treatment, and it does help a lot of men, but not everybody.

• 2:15:58Andrew D. 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?

• 2:16:43Speaker 05

  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

• 2:16:54Andrew D. Huberman?

  It does not?

• 2:16:55Speaker 05

  It does do that. It does help.

• 2:16:56Andrew D. Huberman?

  Okay.

• 2:16:56Speaker 05

  So it's beneficial, and we should, 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 three to $500. But a month of sort of therapeutic FSH is probably two to $3,000. So that cost is really limiting. It takes two to three months to make a sperm. So, you know, men often have to be, would have to be on it for several months. But there is reasonable data that would help. And it does make You know, a lot more sense that that should be given is adjuvant therapy with testosterone rather than HCG. But HCG does work, you know, sort of everyone's surprised it does actually help. But yeah, I agree, there is sort of a contradiction there. So if the price came down, it doesn't, you know, this is another off-label medication for that indication.

• 2:17:41Speaker 05

  It would be, it could be worthwhile.

• 2:17:44Andrew D. 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. Dopamine's up, prolactin is down, you know, dopamine is elevated with sexual desire, sexual activity, post-ejaculation, prolactin goes up, sets perhaps the refractory period on erection and ejaculation for some period of time, and then dopamine comes back up. But you know, 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 hyperprolactinemia's, I don't know, plural prolactinemia is clinically correct, but

• 2:18:26Andrew D. Huberman?

  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, other drugs to treat depression and, and mental health issues that sometimes create endocrine and/or sexual health issues?

• 2:18:53Speaker 05

  Yeah, so prolactin is sometimes, it's a diagnosis, hyperprolactinemia, it's a diagnosis, not that many times. I would say, you know, 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, you know, we see a lot of patients. Typically, the telltale sort of symptoms would be, you know, ones of low testosterone, that's a common one. But, you know, 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, you know, they weren't getting pregnant, we checked the sperm count, it was very low, you know, 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, that was diagnosed. So it's something I think to be aware of,

• 2:19:38Speaker 05

  but I don't know that there's not usually a lot of symptoms. And sort of going to a clinician when you're having sexual dysfunction, symptoms of low testosterone, or fertility problems will usually, you know, be able to diagnose it if it's present.

• 2:19:51Andrew D. Huberman?

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

• 2:20:05Speaker 05

  I check estrogen as well. So I think that's another one. 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 is certainly is important. I think too much can be bad. So there are some men where you see manifestations. That can manifest as gynecomastia in some cases.

• 2:20:24Andrew D. Huberman?

  Male breast tissue.

• 2:20:25Speaker 05

  Male breast tissue, yeah.

• 2:20:27Andrew D. Huberman?

  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?

• 2:20:36Speaker 05

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

• 2:20:40Andrew D. Huberman?

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

• 2:20:47Speaker 05

  Yes. So varicose, 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 sort of 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, you know, 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. You know, given the fact that a lot of men have it, about 1 in 7 men have it, it doesn't

• 2:21:31Speaker 05

  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, you know, 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.

• 2:22:09Andrew D. Huberman?

  What about Peyronie's disease?

• 2:22:11Speaker 05

  Yes, 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.

• 2:22:27Speaker 05

  If you look it up on the internet, you can see, you know, a host of different deformities that men get. It probably present in about five, 10% of men, so it's very common. Sometimes it could be from injury, you know, from, you know, like a penile fracture or other, you know, sort of 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 kind of surgeries, which can, you know, sort of stun the penis or injure some of the nerves of the penis. So that's another condition we see commonly.

• 2:23:04Speaker 05

  You know, obviously it can lead to bother, you know, and erections are not straight. That can just, you know, cause, you know, psychological bother to men. It can also physically make it difficult for a man to have sex. You know, 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 Ziaflex, which is a medicine that solves scar tissue.

• 2:23:31Speaker 05

  So that's one of the treatments we have for it. There's also, you know, 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 you have a penis, we can make it, we can make it hard, but we can also make it straight.

• 2:23:52Andrew D. 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.

• 2:24:15Andrew D. Huberman?

  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. You know, we didn't really talk about testicles.

• 2:24:38Speaker 05

  Yeah, so I think that, yeah, kind of being aware, you know, the average size of a testicle for a man is about, you know, it's sort of about a walnut, so it's about 16 to 20 cc's. Usually if you're going to measure it, it'd be about four to four and a half centimeters in longest axis to give, you know, your listeners or viewers some idea. If it changes, certainly let people know. If you feel anything, let people know, although our, you know, 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 think, you know, I always tell men, no one knows your scrotum better than you. So if you identify, you know, a problem, you should bring it to attention.

• 2:25:22Speaker 05

  So, you know, the classic appearance or the way that a testis cancer manifests is a firm, painless mass that you kind of feel coming from the testicle.

• 2:25:32Andrew D. Huberman?

  I find it interesting that, at least as I understand, women are encouraged to do regular self-exams of their breasts for, for lumps. So, 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 a unfair asymmetry.

• 2:25:52Andrew D. Huberman?

  It does, I mean, cancer, I mean, both, both seem very important.

• 2:25:56Speaker 05

  Oh, yeah. Well, I think there's no question, obviously, I'm very biased.

• 2:25:58Andrew D. Huberman?

  Yeah, yeah. I was trying to say it so you didn't have to, right?

• 2:26:01Speaker 05

  Oh, yeah. I don't want to get in trouble with the US.

• 2:26:03Andrew D. Huberman?

  I mean, I don't want anyone to get cancer. I mean, I so 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?

• 2:26:19Speaker 05

  I think that's the concern that, you know, the number of cancers that are diagnosed versus the false, you know, the false, you know, lumps that they identify just lead to more anxiety and end up not actually, you know, 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 I have, we've certainly identified cancers through that means before.

• 2:26:45Andrew D. 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.

• 2:26:56Speaker 05

  Okay, fair enough.

• 2:26:58Andrew D. 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 you know, it's, it's always such a shame. It is such a shame when we're talking about something that is really pervasively related

• 2:27:40Andrew D. Huberman?

  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 have 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, oh, well, you know, $200 or $1,000, no big deal. I mean, for a lot of people, that's a huge deal. 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?

• 2:28:17Speaker 05

  Yeah, I think both are good strategies. I think, you know, 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. You know, sometimes we check semen analyses for other ejaculatory issues.

• 2:28:33Speaker 05

  But I think that, you know, again, as more of this data gets out, I think as more recognition how important the male is, I think we'll get sort of more buy-in and coverage. Obviously, women have, you know, the automatic feedback of obituary 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.

• 2:28:52Andrew D. 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? 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.

• 2:29:25Speaker 05

  That's exactly right. Yeah, I mean, I think, you know, 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.

• 2:29:39Andrew D. 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, right? We didn't talk so much about the psychogenic issues, but the two go hand in hand.

• 2:30:13Speaker 05

  Exactly.

• 2:30:14Andrew D. Huberman?

  I want to thank you so much for coming here today and sharing so much knowledge with us. I mean, 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 to, not just to improve communication, but this, after all, is at the heart of the...

• 2:30:59Andrew D. Huberman?

  Presence and proliferation of our species. So thanks for taking care of the male half. And, um, uh, and thanks for doing the work you do. It's incredible. The large scale studies, the, the more detailed, the studies, the, uh, on smaller populations, the, you asked the questions that it seems, um, uh, many people are just, uh, afraid to ask. And, and you get right in there and, and come out with the, the really rigorous data and answer. So thank you so much for what you do.

• 2:31:25Speaker 05

  My pleasure. Thank you. Thank you for highlighting men's reproductive health.

• 2:31:29Andrew D. 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 comment 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.

• 2:32:14Andrew D. Huberman?

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• 2:32:57Andrew D. Huberman?

  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.