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

Transcription for the video titled "Dr. Michael Eisenberg: Improving Male Sexual Health, Function & Fertility".

1970-01-02T04:31:11.000Z

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Introduction: Guest Speaker

Dr. Michael Eisenberg (00:00)

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


Discussion On Sperm Quality And Influencing Factors

Sponsors: ROKA & Eight Sleep (01:49)

It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Roka. Roka makes eyeglasses and sunglasses that are the absolute highest quality. The company was founded by two all-American swimmers from Stanford, and everything about Roka eyeglasses and sunglasses were designed with performance in mind. I've spent a lifetime working on the biology of the visual system, and I can tell you that your visual system has to contend with an enormous number of challenges in order for you to be able to see clearly. Roka understands this and has designed eyeglasses both for sport and for wearing in casual settings or to work or to dinner that always allow you to see with crystal clarity. Their eyeglasses are extremely lightweight, and they won't slip off your face even if you get sweaty. I wear Roka sunglasses when I'm driving into direct sunlight or when it's particularly bright during the middle of the day. If you'd like to try Roka eyeglasses or sunglasses, go to Roka. That's R-O-K-A dot com and enter the code "HUBERMAN" to save 20% off your first order. Again, that's Roka, R-O-K-A dot com and enter the code "HUBERMAN" at checkout. Today's episode is also brought to us by 8Sleep. 8Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. I've spoken many times before on this podcast about the fact that getting a great night's sleep really is the foundation of mental health, physical health, and performance. One of the key things to getting a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. With 8Sleep, you can program the temperature of your sleeping environment in the beginning, middle, and end of your night. It has a number of other features like tracking the amount of rapid eye movement and slow wave sleep that you get, things that are essential to really dialing in the perfect night's sleep for you. I've been sleeping on an 8Sleep mattress cover for well over two years now, and it has greatly improved my sleep. I fall asleep far more quickly. I wake up far less often in the middle of the night, and I wake up feeling far more refreshed than I ever did prior to using an 8Sleep mattress cover. If you'd like to try 8Sleep, you can go to 8sleep.com/huberman to save $150 off your POD 3 cover. 8Sleep currently ships to the USA, Canada, UK, select countries in the EU, and Australia. Again, that's 8sleep.com/huberman. And now for my discussion with Dr. Michael Eisenberg.


Sperm Quality, Geographic & Environmental Factors (04:20)

Dr. Eisenberg, welcome. Thank you. Good to be here. I've been looking forward to talking to you for a long time because these days we hear a lot about the diminishing quality of sperm, which in some ways seems to be tacked to the conversation about diminishing quality of environment, people, intelligence. 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 changes in behaviors. So maybe less exercise, less sunlight, who knows? Maybe you'll tell us what's really going on. But the first question I have is, is sperm quality actually declining? And regardless, what is sperm quality? 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 label a man as fertile or not fertile without knowing about his partner. But nevertheless, based on these different parameters, we try and quantify how likely a man is to be able to achieve a pregnancy. So the World Health Organization every decade or so looks over the existing literature and defines these different cut points of what's normal or what's subfertile for those levels. So that's sort of the backdrop of what semen is and how these tests are done or what these tests represent. Now, the question of whether they've declined over time has been a question for a number of years. There was a landmark paper in the early '90s by Carlson and a group in Denmark that showed this temporal decline over the last 50 years from that time point. And so what the investigators had done is looked over the literature for studies that reported semen quality around the world and noted that the quality in the earliest studies, like in kind of the mid 20th century, were here. And then over time, they had sort of declined the more recent studies. Now that study was very controversial. There was questions about waiting from different studies, 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 come out in time. And even today, it remains very controversial. I think if I were to say that I believe there's a decline, some of my colleagues and friends would be very upset with me. If I say I don't believe it, some of my colleagues and friends would be very upset with me. So I would say that my opinion really varies based on whose paper I've read. There's some very convincing studies on each side of it. Most recently, just in the last year or so, there was a meta-analysis of tens of thousands of men where they looked at, again, a host of these studies over the last number of decades all around the globe. So prior studies really just focused on the Western Hemisphere, Western countries, because there was more data from that. But more recently, we've gotten a lot of data from Africa, from Asian countries as well. And those also support this decline. So one of the counterarguments to why we're seeing that is just sort of an evolution of techniques over time. So that's one of the popular questions about whether there's really a true decline. I think as you're alluding to why there would be a decline is also unknown. But you've sort of labeled perfectly that kind of most common hypothesis. So whether there's some environmental exposures. A lot of things have changed over the last 50 years. And I think chemical exposure is certainly one of those. And there have been some fairly convincing preclinical studies. So mostly done in animals that show that exposure to different chemicals, phthalates, BPA, other things may actually harm reproductive function for men and for women as well. And so it may be that these chemicals that we're being exposed to as kids and adults or even probably more sinisterly when we're kind of developing in utero. And they'd be kind of the most harmful exposure. But there's also been an obesity epidemic as well. And there's a strong link between a man's reproductive function and body weight. And so that's also thought to play a role in some of this too. So I think there are convincing studies. But the other, I guess, aspect to this is that there's variations in semen quality around the country and around the world. There's geographic variation. And so that's also sort of an unknown explanation. There could be different sort of genetic compositions of men. And so there's different reproductive potential in that source. There could be different environmental exposures, diet, exercise, lifestyle. There's a famous study done a number of years ago where they looked at semen quality among fathers. So these are men that had achieved a pregnancy. And at the first prenatal visit, they had the fathers give a semen sample. And so this has done four centers around the country. I think one in California, there was one in the Midwest, there was one in New York. So they basically found that semen quality was sort of highest in the urban centers. And New York tended to be the highest numbers where it was lower in the Midwest. And so the hypothesis was potentially because it was a more rural setting, maybe there was pesticide exposure and that has led to these lower numbers. But another equally plausible explanation may be that sort of a different population and maybe that could explain these differences. So I think it's very important. And I think 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 NHANES, CDC's survey of health in the United States, if we added semen quality onto that. That way you could really see how it varies around the country and sort of compare like to like to see over time if there's really this progression. One of the only studies to do that in Denmark that have started around 2000 and tracked semen quality among volunteers that came in when they were conscripted for military service in Denmark, they were offered the opportunity to participate in this study. And so some men did. And what they found is actually that semen quality was fairly uniform over about 20 years where they had data. But sort of another very interesting part of that study is that only about a quarter of those men had normal semen quality. So sort of very concerning, you know, I guess reassuring that it wasn't further declining, but very concerning that only a quarter of Danish men had normal semen quality. And they're one of the, I think, thought leaders in this field just because sort of a reproductive crisis there. 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.


Fertility & Sperm Quality; Testosterone, Cell Phones & Heat (12:00)

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 tear out into different levels. So if one were to simply ask for couples who want to get pregnant and assuming that egg quality is not the issue, what percentage of failures to achieve successful pregnancy are the consequence of deficient sperm, deficient in any way? And is that number increasing over time? 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 U.S., when couples do seek care for fertility, the man is bypassed probably a third of the time, even though when you look at the reasons for infertility, man contributes probably half of the time to infertility. So I think there's a half. 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 U.S. 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 intracidic plasma 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. 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. 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, etc. What's the story with testosterone levels? Are they indeed declining on average across the male population in the US and elsewhere? 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, that 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, 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, 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. So just insulating the testicles or thighs get bigger, insulating the testes can also sometimes lower the efficiency of production a little bit too. Because of heat effects? Because of heat effects. 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 cell phone, you know, smartphone in the pocket in pairing sperm health, maybe even testosterone levels. Now you hear this more often in kind of bio-hacky, I don't know, circles, which, you know, I'm not a fan of the word bio-hacking. It's not clear what it means, but it sounds like it means something about taking a shortcut using one thing for a purpose it wasn't intended. 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 cell phone in your pocket, let's assume on that the cell phone is on, is bad for sperm health or testosterone levels? Yeah, so I think there's not convincing evidence that it's going to help testosterone levels. I think that, you know, it's going to hurt testosterone. It's not going to hurt, yeah. So I should 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 cell phone 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 used cell phones more or less, they had lower semen quality if they used it more. But you can also imagine there's huge differences in men that do and do not use cell phones. So you know, it's a hard experiment to design, but there have been some studies doing this in vitro. So in the laboratory, so taking, you know, sperm in a cup basically and putting a cell phone next to it or not next to it to try and see if that played a role. There have been studies done where they sort of normalized 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 cell phone. So I think, you know, when patients ask me that, which is a common question I get in the 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 is not convincing. But you know, if it's easy enough, certainly to be aware of it, you know, I think putting a laptop on a desk or other than in your lap, I think for heat exposure is probably the biggest thing that we want to minimize. 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, etc.


Testosterone, Age, Obesity (19:26)

And I found a very interesting graph in a textbook on behavioral endocrinology by a guy named Randy Nelson, who I happen to know through the field of behavioral endocrinology as it's typically studied in animals. So most of that book centers on animal studies, but there's a fraction of the studies that center on human data. And there was a very interesting graph that showed testosterone levels as a function of age in males. And as one might expect, testosterone levels were on average much higher in late teens, early 20s, 30s, and there was a progressive decline. But what was remarkable to me about that graph is that even when exploring the scatter plots, because they showed individual points, they didn't just show the averages of testosterone levels in men in their 50s, 60s, 70s, 80s, even 90s, there were these outliers, these guys who had testosterone levels that were on par with testosterone levels of men in their 30s, but these guys were in their 50s, 60s, 70s, 80s, even 90s. So do you observe this clinically? Do you observe that men are coming in, 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 asked is that I think we've all been told and we presume that testosterone levels decline with age, and one would expect some outliers. And of course, we don't know whether or not those guys in their 90s who have the testosterone levels 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 sealing out around 900 nanograms per deciliter, you know, toward the high end normal, depending on the scale, in already at age 90, it's kind of hard to imagine that earlier they're walking around with, you know, 2000 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? Yeah, that's a great question. I think this is such a common question. Anytime we talk about testosterone, I think, right, 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 20s and it tends to go down probably 1% a year forever. But there are people that have very, you know, very, very high levels, you know, just mirroring, you know, that graph that you describe. I certainly have patients, you know, we screen for testosterone levels, you know, when patients come in with complaints or 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 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, everything -- 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. Let me frame the question I was going to ask a little bit differently. When someone comes in to 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, etc. 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 cut off at what you would presume is obese, is there a higher probability that their testosterone levels are going to be within normal range? Conversely, when somebody walks in and they're obese, do you fully expect their testosterone levels to be subnormal? Or are you sometimes seeing obese people walking in with, 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 are 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 already have kids are going to at least maintain or improve vitality, is obesity really the thing to avoid? So is there a, not one for one, but is there a tight correlation between obesity and testosterone levels? 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've 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 everybody, you know, should be screened. I think that, you know, testosterone, semen quality, they've 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 test 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 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 percent. 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 fat are we are now than we used to be, that actually only explains about a 10 percent decline. So I think there is, you know, to your point, something more. And it is not something that you can just identify by high.


Tool: Optimize Sperm Quality, Exogenous Testosterone, hCG (26:49)

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 have to be careful. I don't want to say as high as possible because some people might not want excessive androgen. But at the high end of normal, perhaps would be the ideal for many people. What should people do? What should they avoid? And here I'm setting aside any prescription clinical treatments that such as testosterone injections or things like a chorionic kinatotropin, human chorionic kinatotropin, things that we can talk about a little bit later. But what should every male be doing in order to optimize these health parameters? Yeah, so I think that there are some risk factors that we do, like we'll start with semen quality. We talked about heat. I think that's a big one. So like hot tub saunas, try and avoid those, some light data on sea warmers. Anytime we kind of get this external heat source to the scrotum, the testicles are outside the body because they need to be a little cooler. So anything that warms them up can certainly be a problem. 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've actually 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? Or if one is going to go into a hot sauna for 20 minutes or more to essentially cool the scrotal area? Yeah, I mean, I think the spermatogenesis or sperm production is certainly a lot more sensitive. Whether you can sort of thwart the effects of external heat with a cooling pack, I think it makes sense. There are studies that have looked at different ways to cool the scrotum and have compared semen quality before and after. And there's some data that may help. It just depends how long you're going to spend in the sauna and how cold that pack is going to remain. So ice pack and in the sauna for 20 to 45 minutes. And is the ice pack still cold afterwards? Yeah. They actually sell, and by the way, I have no relationship to any of these companies, but they actually sell cold packs that are designed to be worn in your shorts. So if you go to a, I'll go to a Russian bonya every once in a while now, I guess I'm outing myself. Yes, I have a cold pack in my shorts when I go to the Russian bonya. But they have a sort of an insulation so that 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 want to make a bad joke and say it could get sticky. That situation, you don't want it being so cold that it actually would stick to the skin and then it could potentially damage the skin when you try and remove the cold pack. So it has a thin insulating layer. And yeah, that's essentially what it is. Yeah. So the scrotum is not theoretical. It could certainly happen. So you do want to be careful. So I mean, in theory, that should be adequate to decrease the risk of that particular effect. I keep coming back to health, how important that is to maintain adequate sperm production, because I think these two are very linked. There have been studies that show that men with more co-morbid conditions, so obesity, hypertension, hyperlipidemia, as these sort of stack up, we see a decline in testicular function, so lower testosterone levels and lower sperm quality. So I think taking ownership of your health, I think, is important as well. A lot of times, fertility tends to be one of the first touch points that some men have with health care, because generally what brings men to the doctor, it's usually pain or kind of a problem. So if men are in their 20s and 30s getting ready to start a family or 40s in some cases, sometimes they haven't seen a primary care doctor. So some of these things, some of this relationship has not been established yet. So I think thinking about ways to start that, I think, would be important too. And then I know you don't want to talk about testosterone, but testosterone is actually a fairly common problem that we see in fertility clinics. I would say that estimates say maybe about one in 20 in fertile men are that way because of testosterone. So I think when people get testosterone in different places, and hopefully whatever provider you're getting it from tells you that one of the side effects of this is lower sperm production. So if you test it as a contraceptive and with some other agents, it can actually be fairly effective. So we just want to make sure that if men are starting testosterone, they're doing it for the right reasons and they're doing it safely. I think about testosterone replacement therapy. Although as we were talking about before we started recording, I am really on a push now to rename what people call TRT, testosterone replacement therapy, because indeed some people have low testosterone and need it replaced, the R in TRT. But I think what you're referring to, if I'm not mistaken, is that there are probably millions of young men and older men taking exogenous testosterone, injections, creams, pills, pellets, any number of nasal sprays now, any number of different routes of delivery of exogenous testosterone. And that dramatically reduces one's endogenous testosterone production and dramatically reduces one's sperm count and maybe even quality. We'll maybe talk about this a little bit later, but maybe even can there, I've been told that it can perhaps introduce a DNA fragmentation within the remaining viable sperm as well. So do I have that, Craig? You're saying that you see one in 20 men have issues with fertility because they are taking testosterone. So their testosterone levels presumably are going to be high end normal or more, but they are doing presumably not testosterone replacement therapy, but they're doing what I call testosterone augmentation therapy, meaning they were somewhere in the 300 to 900 nanograms per deciliter range, but decided to start taking testosterone anyway. And then their sperm count essentially diminishes to nil or close to it. In some cases, yeah. So I mean, I think there's various reasons that you would take testosterone. I think some people have been treated years ago and so they do need to replace testosterone, but some people do it for augmentation. I just usually say testosterone therapy, just so encouraging. You kill the R. I like that. That's better than the TAT, which doesn't have very good. Okay. Just testosterone therapy. Yeah. Okay. But if you had, you know, for example, we take a hundred of my infertile patients that come in to see me in clinic, at least five of those men will be infertile because they're on testosterone therapy. And some of them do have that suspicion. They say, 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 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. 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. Maybe 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 percent of them are about penises or testosterone. This is perfect, though. Right, exactly. So a number of those guys who are taking testosterone will be prescribed HCG to stimulate sperm production, endogenous sperm production to maintain healthy sperm presumably because they either want to conceive or intending to conceive in the future. Is that the best line of treatment for maintaining fertility while people are taking testosterone therapy? Yeah, that's one of the therapies that we use and I think it can work well. You know, just a low dose usually for those that know 500 to 1,000 units every other day is usually adequate. As we all know, quality nutrition influences, of course, our physical health, but also our mental health and our cognitive functioning, our memory, our ability to learn new things and to focus.


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Tool: Lifestyle Factors & Sperm Quality, Alcohol (36:57)

So if somebody is not taking testosterone exogenously, they 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 is no. I feel like nowadays we just say don't smoke, but the data or the data, who knows? Maybe nicotine can help sperm. I have no idea. 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 some of these potentially kind of unhealthy habits. So smoking is certainly something you should not do. There have been lots of studies that do link that to lower quality. Again, all the different measures that we look at. Also looking at fertility, these men tend to have a longer time to get pregnant. Alcohol I think is another very common question we get asked as well. And I think for that, there's I think less of a strong association that we've seen. So there have been some studies that show that very high levels of alcohol, and I guess that's sort of subjective what some would consider higher or not. But when you get above maybe 20 drinks a week, there have been some effects. But usually a lot of drinking. I would think that's a lot. Yeah. I did an episode on alcohol. I think anything more than two, I know people are going to, 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 not a teetotaler. So yeah. Yeah. But when you get to this 20 drink, that's when we started to see some effects on semen quality. But 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, slightly lower sperm parameters. You mean skin flushing because they don't make alcohol dehydrogenase? Exactly. Yeah. Yeah. And is it, I've heard about that in Asian cultures. Is there an Asian population, 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? 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 40 to 50 percent of the population has, you know, mutation in the ALDH2 gene, but other populations and people of African ancestry, there's a rate of mutation, I think, I'm not going to remember the exact percentage, but I think a few percentage points is some individual of 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 mutation, you know, where we see sort of negative effects would persist and the hypothesis that, you know, millennia ago, pretend 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 another, 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 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. 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 2005, yes, 2005 to end of 2010, you could still smoke on the Stanford campus. I'm not a smoker, but there was this collection of, I have to be careful what I say here, there was a particular group on campus of postdocs and graduate students that would, you know, that would colonize this little area outside the hospital and smoke because that's where you could smoke. That was eventually eliminated as a possibility. You can't smoke on Stanford campus as far as I know, but they would smoke right outside the hospital. The hospital workers would take a cigarette on their break. This is very common. Yeah, exactly. 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 here don't smoke. It's terrible for X, Y, Z 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 a fair assumption? 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 you yet. And so I think it's harder to, 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, it'll harm them in social situations or other things. Yeah, I usually just, I usually give them the moderation one, unless again, for the very high drinkers, I definitely talk about that. You mentioned other drug use.


Sperm Quality, Recreational & Over-the-Counter Drugs, Cannabis (43:27)

I'm going to assume that unless prescribed for post surgical pain or something like that, that benzodiazepines, heroin, opioids of any kind are just bad for sperm and testosterone. I think we could probably make that a short discussion, right? Yeah. I can't imagine any of that would be good for reproductive health. Yeah, that's true. I mean, there's again, you'd imagine, or maybe not, that 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 yeah, that's how we talk to patients. 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 of reasons. What is the relationship between cannabis use and testosterone and sperm production, or I should say sperm quality? Excuse me. Yeah. So this is also a very common question. Again, with wave of legalization across the country, I think more and more men and women are exposed to it. So again, there's data that even more men are exposed to it, it can lead to some harm in terms of sperm morphology and sperm numbers as well. One of the sort of landmark studies was about 1200 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 other data that shows really a null effect. And I think that it goes into probably the composition, how men are taking it, the frequency, because a lot of that data is not well teased out in a lot of these studies. So I think I sometimes struggle with this with patients because some of them are taking it for some what they consider legitimate reasons, anxiety, sleep, pain. And if there's not 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'll cause harm. 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. Are there any common over the counter medications that can negatively impact sperm quality and/or testosterone? Things like non-steroid anti-inflammatory, drugs, Tylenol, Advil type stuff, ibuprofen, acetaminophen, things of that sort that I and others might not be aware of. I'm not probing for anything in particular here. I know that a lot of over the counter drugs have effects that we're just simply not aware of. Yeah. I mean, I think we probably need more data, but I think currently we think all those are safe.


High-Impact Sports, Traumatic Brain Injury (TBI), Pituitary & Testosterone (46:56)

I'm curious about the pituitary. Pituitary gland, as many listeners of this podcast already know, is a gland that receives signals from the brain. The gland sits near the roof of the mouth. I think that's fair and releases critical hormones into the bloodstream that control the output of testosterone from the testes as well as output of hormones from other glands. I know a number of people end up playing sports like football or rugby or even lacrosse or even soccer I've read or data on this. They're heading the soccer ball quite a lot or martial arts or they get a head injury at some point. I certainly hear a lot from people who played these high contact sports and then to their surprise later they have diminished testosterone levels. I also work with a number of military groups that talk about this, that they leave and maybe it's from combat related stress, et cetera, but they wonder whether or not there's any traumatic head injury or maybe pituitary injury related impairment to the reproductive axis that includes brain, pituitary, and the testes. Do you see that? If somebody played a contact sport, in particular a contact sport where the head was hit or they were hitting things with their head often or if they have a TBI or had a TBI that the reproductive health can be impaired. That's fascinating. I have not. I think it's interesting I guess what the pituitary does, you've obviously covered this before, but it does go to a lot of our therapies. For your listeners, pituitary produces two hormones, LH luteinizing hormone and FSH, follicle stimulating hormone, which then stimulates the testicle. The luteinizing hormone stimulates the late excelles to make testosterone and then the follicle stimulating hormone or FSH stimulates sperm production. Both of those are very key in terms of production. Interestingly, when exogenous testosterone is used, it shuts down that axis as you know, so we get less of these gonadotropins, this LH FSH to stimulate the testicle. The other reason that sperm production is lost with exogenous testosterone is actually the intratesticular testosterone is much higher than serum levels. Our serum levels are between 300 and 900 nanorepsil deciliter on average, but in the testicle are probably 10 fold higher at least. 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. It's interesting because I think I'm not aware of how traumatic injuries would do that. It's good to know.


Bicycling, Numbness & Sexual Dysfunction; Walking & Testosterone (49:55)

I'm curious about the non-endocrine, non-chemical effects on sperm quality and testosterone levels. Here I'm thinking about a bunch of news stories we heard a few years ago about how bicycle seat pressure on the prostate or maybe it was other portions of the, it was the nerves running to the penis itself or surrounding areas, maybe it was pelvic floor related and somehow you'll tell us I'm sure, was impairing sexual function. Was it impairing sexual function in any way by impairing testosterone levels, cutting off blood flow to the testes? Here perhaps the most important thing to ask straight off is, is riding a bicycle bad for male reproductive health and sexual health? Yeah, these are great questions. Again, living in the Bay Area, working in the Bay Area, cycling is very, very popular. These are questions that I get a lot. In general, like we talked about before, anything that's good for your heart, it's going to be good for fertility. It's a good diet and exercise, maintaining good body weight. I always try and encourage physical fitness. I think that's important. It may be possible that some particular activities may put men at more risk. I think cycling could be one of them, but it would depend on exactly why we think that may be a problem. I guess the theory is heat. If you're in the saddle for a long time, for these prolonged rides that men take on weekends, hours, that maybe if there's too much heat exposure, that may be the mechanism where sperm production would decline. There have been some studies that say maybe five hours a week would be, that may be too much. At that level, the sperm counts are shown to be lower. You're less than that, that may be okay. When I talk to patients about it, I try and just encourage them to stand up in the saddle, to try and again air things out, to try and dissipate heat, if that's the mechanism we're going to think. Regarding sexual dysfunction, that is thought to be pressure, as you're alluding to. The way that the saddle is configured, ideally all the pressure is put on our ischial tuberosity, or our sit bones. That's what I'm sitting on now. On the saddle, there's obviously the rigid nose. If there's too much pressure on that, that actually squeezes between the ischial tuberosities, where the main blood flow to the penis goes and the main nerve supply is too. If there's compression on this, you get this lack of blood flow or ischemia, and you can get a nerve practice as well if you crush these nerves. That over time can lead to problems. Some patients will say that after I cycle, things are numb down there for 30 minutes. Or a day, or I don't get erections for that sort of same amount of time. Or sometimes men just sort of ride through it. Hopefully things come back in a day or two. That could be the mechanism. There are some saddles that hopefully will be a little safer. I think that this sort of first was noted probably around 2000 or so. 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. Cycle fit that can be done, or saddle fit rather than can be done at some of the cycling shops to try and look at your body position, look at your size, and try and find a saddle that's safer. This doesn't happen to everybody. I would say maybe if you were to serve a cyclist, maybe 20% or 30% of men and women tend to be susceptible to this. I think if you are having discomfort when you cycle, whether it be pain, numbness, or you notice dysfunction, I think certainly you should think about changing saddles or think about changing riding style. There's other strategies that are sometimes used, but it's absolutely something that everybody should be aware of. I meant to ask this earlier, but I seem to recall a study that drew a correlation between amount of walking and maybe it was sperm quality, but I think it was testosterone levels, maybe some other metrics of male sexual health. Forgive me, I'm not recalling the details now. Is there any evidence that walking more, standing more, maybe even using a standing desk is beneficial for pelvic floor health, blood flow, prostate health, who knows? Could be any and all of those things in some way that is beneficial for sperm quality, testosterone level, and/or overall male sexual health. One of the ways that we can characterize activity is step count. I have a watch that tells me that it's something that I look at every day and strive for. It turns out that the more active you are, it's been shown looking at large national data pools across different age ranges that it is associated with testosterone levels. Being more active, I think, is very important. That's another thing that everybody can do to try and improve testicular function broadly but testosterone specifically. Do you know whether or not that can be separated out from the relationship between being more active and less obese? Is this something that's independent of obesity? In other words, can we incentivize people to walk more simply on the promise of improved sexual health? Well, I don't know. Sexual health will be a different one, but I think there is association between testosterone levels and step count across different BMI straight up. I think whether you have the ideal body weight, whether you have a few pounds to lose perhaps, if you walk more, you will see higher levels of testosterone. Another question I meant to ask earlier and then we can close the hatch on exogenous testosterone therapy, at least for the time being.


Exogenous Testosterone Therapy & Cancer (55:39)

Maybe we'll come back to it. 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 comfortable with the trade-offs. Is there any increased risk of say prostate cancer or other forms of cancer? Here I'm going to assume that this person is keeping their lipid levels in check, because you hear about some hyperlipidemia with testosterone therapies. Let's assume that they're either taking a statin or they're not taking a statin, they're getting enough cardiovascular exercise that things are in check in terms of LDL, HDL, APOB and all of that. Their testosterone levels are now high normal and they're feeling better and they don't have to worry about sperm production because they're either maintaining it or it's been banked or they don't care about that. Is there an increased risk of prostate cancer? My understanding is the answer is no, but what's the real deal? Does taking testosterone therapy, assuming all other things are being held in check, in a healthy check, does it increase the risk of any kind of cancer? 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. The origin is that prostate cancer is thought to be or is sort of androgen mediated. One of the Nobel Prizes, again, decades ago was awarded because it was found that when we lowered men's testosterone, the prostate cancer would regress dramatically. So that put that association between testosterone and prostate cancer. So then the concern began if we were to either replace testosterone or augment testosterone, give a man testosterone, is that going to alter his risk or increase his risk? So I think we have pretty convincing data that that's not the case. There's lots of longitudinal data spanning decades where if man is given testosterone, it doesn't change his risk. The reason for that in sort of seeming, this contradiction between prostate cancer therapy where we lower testosterone, where if you give a man testosterone, it doesn't change his prostate cancer risk, is not certain, but there's this popular model called the saturation model so that once there's enough testosterone in the body and it tends to be a fairly low level that all the sort of the prostate testosterone receptors, you know, you 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 safe when we're looking at prostate cancers as an outcome.


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Discussion On Sexual & Urinary Health

Sexual & Urinary Health, Nighttime Urination (59:57)

Getting back to prostate health and neural innervation of the penis and blood flow to the penis. You mentioned the bike seat related issues. Are there other things that men should do in order to maintain prostate health, stave off prostate diseases and to maintain healthy blood flow and neural innervation of the penis for obvious reasons? And we'll get into the specifics of those reasons in our later discussion. Yeah, I mean I think that I always kind of think of the penis as a user or a loser organ. So that doesn't mean necessarily that you have to have sex. But normally we get erections every night. So that should be maintained. And if there's any reason to sort of suspect that that may not be going on, usually in my practice that would be from some pelvic surgical intervention or something like that. Sometimes we can intervene to try and maintain that. You're talking about spontaneous erections during sleep. And short of assigning one's partner to check frequency and tumescence, what is the way that men would know that that's happening? Are you talking about waking up with an erection? Is that a requisite for knowing that nocturnal erections are occurring? Well yeah, I think you 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 erections. 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 with this nocturnal, you know, 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, 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 any sleep because it happens many, many times a 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, you have to go to the bathroom often, if your stream is getting weaker, those are all sort of complaints that we hear about. What is often, my understanding is that it's normal to wake up perhaps once during the night to urinate. And this is, of course, assuming, and again, forgive me for all the caveats, but I've done this long enough that, you know, if I don't get really granular about some of this, then she was, oh, 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? 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 for most men. 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.


Sleep & Semen Quality; Overall Health (01:03:12)

I don't know if that's true or not, but I found a couple of studies that at least point in that direction, no pun intended. So that raises a bigger issue that we haven't talked about yet, which is getting adequate amounts of quality sleep each night. And I think for most people, that's seven to nine hours, ideally, which means getting sufficient slow wave, deep sleep, as well as rapid eye movement sleep. But nowadays, a lot of people, including young people who are not working excessive hours, are getting, 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? 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, is 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 testicular function as well. 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 don't want children, semen quality sounds like something that relates to fertility. But is semen quality something that is a good goal for those who are interested in overall male vitality and health? Is it one of the better metrics of overall male vitality and health? 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, why that link exists I think 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. 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 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. So the so-called sort of developmental origin of adult disease or the Barker hypothesis. And so we know that, you know, premature children have higher risk of cardiovascular disease or 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 involve reproduction. So your children and having a partner. And having a partner prolongs life, having kids prolong life, even though it feels like kids are killing you. If you look at studies, men with kids tend to live longer. So 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 six-pital 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 men come in for fertility evaluations, a lot of times we 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 sort of, 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. Would it be a good idea for males in their 20s and 30s to get a sperm analysis, just to have a baseline?


Tool: Sperm Analysis & Overall Health; Sperm Banking (01:09:19)

I confess I'm 47 now. One thing I wish I had done in my 20s was to get my blood hormone profiles and lipid profiles done when I was in my teens and 20s because I'd have something to compare to. I started doing that in my mid 30s. And I'm so glad I did because I can now compare to my mid 30s levels. I started including sperm analysis about eight years ago, with the intention of freezing sperm. But did that because I was also reading at that time about the increased risk of autism in offspring of males older than 40, something that I really would like your take on. But it seems like it's inexpensive enough to do a sperm analysis. I think now people can get it done at home. They have male 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. 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? 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 were talking about checking like lipid levels, or we talk, 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 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. One of the sort of innovations in the space, and you know, as 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 that 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 because people are doing, you know, you know, people do in a bathroom just next to you or you're trying to collect. So they would send them into a common space, common space, but they would even give them the quiet room with the with the red light, which is right. What I hear they do now. Yeah, some of them do have video. So there are some higher level. Oh, I didn't even mean video. I just I think that, okay, yes, I've done this. I'll just say, I mean, I've been trying to normalize things related to all aspects of mental health, physical health. So yeah, I decided to free sperm. And basically, they sent me to a room. I went to a university basically, it actually wasn't Stanford, but different university. And yeah, they put the cup through the window. They give you the cup, they 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 assumption now is that you figure it out one way or another, how to provide the sample, and then you put the sample back through the thing. And then one thing these clinics really need to work out is that anytime you're walking out, you see the people processing your sample as you walk out. So there's all this, this feigning of, 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 and I must say 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 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 conception.


So I figured, you know, why not free some sperm and it's relatively inexpensive. Yeah. Yeah. So I think the eternal 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 eternal 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, etc, child. So the father, unfortunately, we just have data that 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. 11. Quite a span. Yeah. 88. Goodness. Unrelated. I don't know. I assume. Goodness. It's anonymized data. But I said. 11. I have to ask this. Sorry to take us on a slight tangent. What is the average age of puberty in males in the United States now? Yeah. So I guess sort of sperm arky when sperm production begins. So there are a lot of markers of puberty, secondary sexual characters, a beard growth, deepening of voice, etc. They happen at different rates and different people. But yeah, thank you. At what point are males undergoing puberty at the level of that we're talking about here? Yeah. So, yeah, there has been data that we're going through puberty a little bit earlier now that we used to. But it really varies. So I think it's not just like testosterone ranges between like 300 and 900. It's a wide range for anybody. I think for most individuals, puberty is probably 12 to 15, 16 in general. So I just give sort of a very wide range when we're going to say that's okay. And some of the data I'm basing it on is when sperm production begins and boys. And it's actually not that simple to be able to figure that out because we don't generally talk to young boys about how to masturbate, how to collect, and then check on that. But there's something called first morning voided urine where we can actually look at that. And there have been some studies done and they see if there are sort of 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 started producing sperm. 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. Well, I think there is some data for males too. But again, for your listeners, I don't want to have this onslaught of pediatricians seeing kids that haven't, you know, when boys haven't gone through puberty by a certain age. So I think it's still fairly wide. Let's get back to age of the father and issues like autism. What are the data there? And this to me is a practical issue, because I think if there's one obvious takeaway from our discussion today, it's that males should probably not wait until they're trying to conceive in order to assess their reproductive health at the level of sperm quality, testosterone levels perhaps, but at least sperm quality. But perhaps men should also be freezing their sperm if in fact, conceiving children after 40 places their children at far greater risk for autism. My understanding is that the rates of autism are somewhere between one and 80. You'll hear as high as one in 50 male births, but I think it's probably more like one in 60 to 80, is that right? And that the age of the father is a risk factor. Yeah, I think that this gets into sort of the larger issue of, you know, how men sort of perceive fertility. So we know that as women age, fertility declines, but the oldest father ever is 96. So the biologic potential certainly persists. Wait, I want to know how long he lived to see how long his child grow up. He conceived at 96? Supposedly, supposedly. Well, I'm assuming he did not meet his grandchildren, at least not the grandchild of that child. So wow, how long did he live? You know, well, so this is a man in India. It's sort of a famous story, but supposedly he had a child. He had that child with him on like they're waiting at a bus stop. He fell asleep. The child was kidnapped, led to divorce. So yeah, dreadful, sort of a horrible end. But the wife was also not that old, but in her fifties. So yeah. Wow. Tragic and incredible story for separate reasons. Yes. Okay, I'll get my head around this 96 year old conceiving a child. Okay, please continue. Yeah. So people I think are men think that the sort of the, you know, their fertile road is sort of infinite. But I think that's very much not the case. So as you're alluding to, people have looked into risks for older fathers. So you know, about a hundred years ago, I was first noticed that dwarfism or achondroplasia was more common in last born children. So eventually that link was made. And since then other conditions too. So there's 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. 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 about 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 sort of delayed childbearing. So maybe 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. I think I read a statistic and you would know more being a neuroscientist that 84% of the genes in our body expressed somewhere in the central nervous system. That sounds about right. Yeah. Yeah. I don't want to stamp my name to that. But that sounds about right. 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. So for example, chondroplasia is due to a mutation in fibroblasts 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 one in a hundred million, but it turns out these conditions occur in about one in, I think, 30 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 self-re-spermatic glenial 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 over their, you know, brothers and sisters that don't have them, for example. And so then they out-compete 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 or 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 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 more resourced -- right, 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 would 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 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 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 certainly to 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 good option as well. My understanding is that analysis of DNA fragmentation in sperm does not allow for selection of the best sperm on the basis of DNA composition translated to English. What I mean is in order to tell whether or not the DNA are mutated in a sperm, you have to kill the sperm basically. So and since in a given pool of sperm, so to speak, there will be forward motile, non-motile, witchers twitching in place, dead sperm, some percentage of dead sperm or motile sperm is presumably normal, some small percentage, hopefully, and that some might have some DNA fragmentation, some might not. So is the way to address this averages? What I'm hearing here is that if you haven't already had kids or if you want more kids, that you might want to know about your sperm quality, I would say you do, and that if you can afford it, you might want to take a look at DNA fragmentation data. But having done this, what one receives is a chart that goes from red, bad to green, good, and then they put the arrow hopefully in the green zone. And then you say, oh, good, 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. 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? I mean, yeah, I wish, right? That's sort of the holy grail, because I think he pointed out sort of a variant of 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 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 motile sperm, we clear out the dead ones. And I think embryologists are pretty good at telling which sperm they think are better. But again, we don't have any real objective data to try and understand which are harboring something or other. 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. Let's get back to the prostate.


Tool: Prostate Health, Urination; Tadalafil (Cialis) (01:26:42)

This incredible gland. Tell us about the prostate. I think we hear about the prostate, we hear about prostate cancer. People might have heard that it's involved in the ejaculatory response, it's involved in erections, it's involved in a number of things. If you could give us a catalog of things that the prostate does. I mean, you spent a lot of time thinking about this gland. What are some of the cooler things that it does that we don't know about? How do we keep it healthy? And what are the consequences of not keeping it healthy? Yeah, so the prostate is a gland about the size of a walnut. It sits behind the bladder and it's involved in reproduction. It produces some of the proteins, enzymes that are necessary for sperm to be supported in the ejaculate to kind of keep the sperm healthy in the female reproductive tract. So it functions in reproduction and then basically after reproduction is done, it doesn't really serve any useful function. So then it just becomes a problem essentially. So the urethra, which is where we pee through, so it connects the bladder to exits the body, runs right through the prostate. And as we age, the prostate does get bigger. That's sort of a known thing. And as the prostate gets bigger, it creates sort of more resistance in this pipe. And so it makes the bladder have to work harder. And that leads to a lot of the symptoms that we've been talking about already, waking up at night, weak stream, this need to urinate urgently, sometimes feeling like you're not emptying all the way. So it's sort of a consequence of the prostate sort of being there. In terms of ways that you can keep the prostate healthy, I think that there's really nothing that necessarily you can do. I think that one thing I talk to patients about when these sort of symptoms start is to know some of the triggers. So like you mentioned, drinking a lot before you go to bed. So if you don't want to wake up at night, that's not a good practice. You may even want to go into bed sort of a little dehydrated just so you can try and last the night. There are some particular drinks or foods that tend to be more irritating. So like spicy foods, acidic foods, those can sometimes irritate the lining of the bladder and make you have to pee a little bit more. And it 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. I'm hearing more and more about a practice of people taking low dose to Dalifil 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 a good reason to think about taking 2.5 to 5 milligrams of to Dalifil per day simply for maintaining blood flow to the prostate and thereby maintaining or improving prostate health? 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 to Dalifil, these 2.5 to 5 milligrams, these daily dosing can help with these urinary symptoms. So I think that not necessarily it's 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 is you also alluded to is it can help with erectile function as well. Even at the 2.5 to 5 milligram dose. Interesting. Yeah, my experience is that there are a lot of people who would love to take pills every day. There seems to be a kind of binary distribution where, and here I'm just thinking about the males that I hear from because I hear from of course males and females. But I get a lot of questions about what can I take? What can I take? What can I take? And, 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, where it only takes one sperm, which as you pointed out is true for IVF, but more is better if you're trying to conceive naturally. And there were discussions about communication and consent, obviously super important. And then they just kind of turned us loose to learn from our friends and other sources. I mean, that, 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? So the people who are getting on testosterone therapy early, perhaps without the need. I just want to flag that because I think I understand correctly, you're seeing a lot of testosterone therapy that perhaps people don't need. Is that right? Well, I think it's a mix. Some people probably do need it, but I think that before starting it, everybody should be aware of all the risks and you've kind of highlighted some. Testosterone, any medication, right, is going to have some rest. And so everybody needs to be aware of what those are. And for testosterone, reproduction is certainly one of them. 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.


Urinary Tract Infections (UTIs); Erectile Dysfunction Causes (01:33:02)

We hear about UTIs, urinary tract infections, in women pretty often. Do men get UTIs? If they're getting more than one UTI per year, is that abnormal? Could 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? That's true. Without having to cut anything? Is that right? Yeah. Is that worse people doing or is that only under conditions where people are experiencing some vexing issue? Yeah, I think that some of those tests should only be done if there's a problem. I think a male urinary tract infection is rare enough that it should be evaluated. Women have very short urethras, but men have a very long urethra. It has to go through the entire penile urethra or the prostatic urethra up into the bladder. The way a urinary tract infection would happen, one way would be that a bacteria actually gets all the way back. That's just a much longer trek. If something rare like that does happen, we look for anatomic causes for that. 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. Those men should be evaluated because there can be some pathology that we could hopefully identify and correct. Let's talk about erectile dysfunction. I put out the call for questions and anticipation of this episode. 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? We'll deal with the first question first. 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. That's all the interest in testosterone therapy. Or are there other say blood flow related, pelvic flow related, neural brain to body neural connections that are responsible? I'm guessing it's all of these things. How do we parse this? Tell us about erectile dysfunction, what you most commonly see, what you most commonly do in order to treat it. Yeah. Erectile dysfunction is the inability to consistently achieve and maintain an erection. It's fairly common. Of all the conditions I see, that's definitely the number one. If you look at men over the age of 40, over half will have some trouble with erections. Under age of 40, it's probably about 15 to 20%. This is a very common condition that we see. In terms of the etiology, it can vary a little bit. We used to think that they were primarily psychogenic, but that was years, that was decades ago. Now we know that most of them are organic, so it's actually a blood flow issue. The most common conditions, just nationally, would be the same things that cause blood flow problems anywhere in the body. High blood pressure, diabetes, atherosclerosis, anything that can impair blood getting to the end organ. Sometimes there has been data that trouble with erections can actually predate other more serious vascular conditions. The blood vessels in the penis, the penile arteries are about one millimeter. The heart and the brain are much larger. It's much easier to occlude a small vessel than a large vessel. That's why there have been some studies to support that it's an early marker for vascular disease. I think looking at those risk factors, lifestyle, obesity again is a common one. Endocrine disorder is actually fairly small. It's probably less than 10%, probably around 5% or so. Pelvic cancer treatment is another very common one after treatment for prostate cancer, whether it be radiotherapy or surgical therapy, bladder cancer, sometimes rectal, colorectal cancer, that treatment also. Anytime we're involving some of the nerves and the vasculature and the pelvis that can also impact erectile function as well. What about hernia? Hernia, that should be separate. Because I always say that in medicine, you can never say never. But generally, if that was going to manifest as an erectile function, it would probably be due to maybe some pain syndromes which can rarely happen during just the early post-operative period. But the blood supply, the nervous supply is separate. You said something very important for people to hear, so I'm going to highlight it. You said that less than 10% of erectile dysfunction is due to a hormonal issue. I don't know how much time you're spending on YouTube and the internet, but that is going to be a shocker for a lot of males out there because so much of the discussion around testosterone is around libido and sexual function. 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?


Discussion On Erectile Dysfunction & Pelvic Health

Blood Flow & Erectile Dysfunction, Medication; Cardiovascular Health (01:38:21)

Again, forgive me for listing this off over and over, but we are assuming here that people have gotten their body weight down, they're sleeping enough, they're not ingesting excessive alcohol, they're not smoking or vaping, they're not smoking cannabis or doing the edibles. Although maybe we should talk about edibles and cannabis and endocrine effects, we'll do that later. Doing all the things right, avoiding doing the wrong things too often or at least completely. So we're assuming they're doing all that correctly. Your 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 two. No, I'm just kidding. But assuming they're doing everything correctly and it's not a testosterone issue, then if it's a blood flow issue, meaning they haven't had treatment for some pelvic cancer, what is the first line of treatment? 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. There's a tremendous amount. I'm sure that you're the most popular doctor in your field. People like to do that. Yeah, that usually does kind of ease everybody. So usually we start with oral therapy, so phosphodiesterase inhibitor therapy. So that would be like sildenafil or Viagra, Tidalafil, Cialis, Avanafil, Stendre, or Vardenafil or Libetro. Would you be willing to talk about some of the specifics there? Is the typical thing to put people on this 2.5 to 5 milligrams per day low dose or to give the higher doses that are more commonly used for erectile dysfunction per se? I think it depends. You know, why we're putting them on it and how much sex they have too. On average, people probably have sex, partnered sex maybe once a week on average. When we're looking at men in their kind of 30s and beyond, sometimes it can be a few more times a week than that. But if they're having sex every day or very often, then sometimes a daily dose can be useful but generally, most men are on just on demand because they're going to fall into that maybe about a few times a month category. So that's usually where we start. And there's sort of a titration that can be done. You can go slightly higher doses or lower doses. So usually we start in the middle to the higher doses. And we talk about some of the side effects they may have. But those probably help 60 to 70% of men and they work well. In terms of another common question is how do we decide which one we're going to start? Sometimes insurance will tell us which one we're going to do. That's a common one. All these medications tend to be somewhat similar. One difference tends to be the time of onset. You know how quickly they reach peak levels in the body and then also how quickly they're cleared from the body. So Tidalafil 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, taking a pill on Friday, still having some left on Saturday. But for others, we start with one of the other ones. The fact that these drugs like Tidalafil also called Cialis, right? Cialis. Cialis the brand name? Okay. And Viagra is that a brand name? Stands for what is the generic name? Oh, Cialis. Cialis. Okay. So because they are effective in such a large percentage of cases, what does that say about the vascular system of all these males that are having erectile dysfunction but then it's getting resolved by these drug treatments? In other words, somebody comes into your clinic, they're having this issue, you prescribe one of these drugs, they come back and say, "Everything's working great," or maybe they don't come back, they just send an email, say, "Everything's great." But do you need to have a discussion with that person about their overall vascular health? Because a few minutes ago, you told us that the fact that they weren't getting erections due to what now appears to be a vascular issue can be resolved for the penile tissue, but is it going to solve their other vascular issues or should those people be on the lookout for cerebrovascular cardiovascular disease that can potentially cause things at least as bad as erectile dysfunction or maybe worse? Yeah, absolutely. Well, I think they should be screened. So 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 blood pressure, lipid levels, fasting, blood glucose, all those things, again, sort of for early markers of some of these. Sometimes they're identified, sometimes not. But I think we 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'd try not to be alarmist about this, but I do want to encourage men to sort of take ownership of the health because that sometimes can improve some of these conditions. But again, we have terrific medications for men in whom we cannot. What are the common side effects of these drugs? So they're vasodilators, they open up blood vessels, so we get some off-target effects. So headache, facial flushing, back aches, leg cramps, indigestion, nasal condition, those would be the most common. Before the last Super Bowl, there was some press about the fact that a lot of the players were taking these drugs at low dosages before the game, presumably to increase blood flow to their muscles and brain. Is that what the rationale was? 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 Biagra or one of these medications, Cialis Tidalifil, before a ride, again, to try and increase circulation to decrease the chance of any of the negative effects of prolonged saddle pressure. So it sounds like just increasing blood flow and lowering blood pressure slightly is just a good thing all around. 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. So you mentioned about 10% or less of erectile dysfunction is due to endocrine issues.


Mechanical Erectile Dysfunction Treatments; Peptides; Delayed Ejaculation (01:44:30)

Is it 60 to 70% can be resolved with these blood flow enhancers? I know that's a terribly non-clinical, non-scientific way to describe the Biagra, Cialis, Tidalifil, et cetera. What about the remaining percentage and are there other treatments that you prescribed or given? In which cases do you need to resort to, I guess, more invasive approaches? Yeah. So another therapy we have is erythral suppositories. So you can actually put a medication in the tip of the penis and then absorbed by the rest of the penis. Also inject, it's suppository. A suppository or a gel, or a jelly, yeah. So it's also a vasodilator. Sort of the concept is very similar. Sometimes that is okay for men and they tolerate it. It's safe for partners as well. It can tingle a little bit. So we definitely let men know because one of the main medications does cause like a little bit of a burn as well. Why would somebody do this as opposed to taking the pill form of the drugs we were just talking about? Mostly efficacy would be a big one. And so this can sometimes help where others cannot. So that's one. Penile injections are another common therapy. So the efficacy of penile injections are probably 80 to 90%. Again we're injecting vasodilators into the penis. So the idea 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. Was 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? No, yeah, this is an on demand treatment. So we teach them how to do it the first time they do it with us in clinic. Ideally we try and get an erection that lasts probably 20 or 30 minutes. So we usually start at a low dose and then they just increase at home until they get an erection that lasts for that amount of time. Is it injected subcutaneous or actually into the, goodness, the meatier tissue of the penis? That's right, into the erectile bodies directly. And you only have to inject one side, they do communicate with each other. Most men say it's fine. It's a very small gauge needle, about as big as a few strands of hair. 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 think about needle in the eye, what's worse? It's like the childhood rhyme, right? Stick a needle in my eye. It's like, can't think of anything worse, but maybe an injection in the penis sounds almost as bad, but you're telling me that if patients are prescribed this, that they can do this with limited, if any, discomfort. Well, it does have a high dropout rate. Surprise, surprise. Yeah, I think no one's excited about it. I guess the mood can sometimes be affected, but a lot of couples are very comfortable with it. Again, it's very efficacious. The man can do it, his partner can do it. So it does work well. And I guess here we're sort of ascending the list of invasiveness. What is at the sort of top tier of invasiveness for erectile dysfunction? So then we go into peanut 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 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. It's really just there on demand. Yes. Yeah. Interesting. Yeah. So it's very simple to use. Sort of the more, I guess, kind 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. 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. 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. 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 sounds like blood flow is almost autonomous? Right. Well, I think a lot of these, yeah, the blood flow is not adequate. And that's why we're having to go beyond. But generally, as you point out, there's different stimulation, whether it be visual, tactile, or factory that starts that cascade that releases neurotransmitters in the penis that leads to this vasodilation naturally and then get erections. A few years ago, I was reading about vasopressin inhalants. There was a bunch of stuff hitting the market. By the way, I don't suggest that people get experimental with this stuff. But as a neuroscientist who also knows the thing about neuropeptides and neurohormones that can impact the hypothalamus, I just cover my eyes and kind of cringe when I think about people inhaling vasopressin thinking, "Oh, yeah, there's a study that vasopressin increases sexual desire," or something like that. But nowadays, I'm reading a lot more about a really interesting peptide treatment, which I think is a FDA-approved prescription drug, which relates to a melanocyte-stimulating hormone that comes out of the medial pituitary that is used to increase sexual desire. It's prescribed for women, but men are starting to take it. And it seems to have, at least from what you read on the internet, a pretty profound impact on libido and on erectile frequency and persistence. Is this something that you're using in your clinic? What about these peptides that people are inhaling and injecting? Some of them are taken in oral form, but most often, I think it's nasal inhalant or it's a subcutaneous injection. Yeah, so those are not ones that we use in clinic. But I think looking at sort of just sexual dysfunction broadly, there are a lot of things that we do try and help. And one of the things that relates to that, it's been a proposed treatment for it, is this concept of delayed orgasm or delayed ejaculation. So I think everybody's familiar with premature ejaculation, where men ejaculate too quickly. But on the other end of the spectrum, there's men that takes a long time to ejaculate. And what that is is sort of defined differently. But generally, most people would say two standard deviations above average. 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. Or sometimes they don't ejaculate every time that they have relations. So for those, I think there is a need for treatment because there's no FDA-approved therapy for that. And so that's why I think providers are trying some of these other more experimental things. There's some that we use, just not that one in particular. There's also some devices that have been trialed as well, but it's a challenge because, 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 are sorry, never able to orgasm, and some are only able to do it very rarely. So we do want to offer them benefit.


Pelvic Floor Health, Urology & Physical Therapy; Split-Stream Urination (01:52:36)

What about pelvic floor health more generally? The topic of pelvic floor health is something that comes up more often around female reproductive health and urology. You hear about Kegels, Kegels, Kegels, I don't know. I guess we'll have to ask him because it turns out Kegel was a person who named the exercise 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. 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? I mean, I think that'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 that 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 office, there's usually a list of a lot of different providers around the region that can help with some of these. Kegel exercise, though, can be useful, you know, for example, for prostate cancer rehabilitation, some of these men where we're trying to kind of rebuild some of the strength or maintain or improve continents 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. 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? They're usually pretty much gender or sex agnostic. So they usually are able to help all. And forgive me for asking for an abridged anatomy lesson here. Could you describe the pelvic floor muscles and how they relate to the bladder, prostate, urethra, penis anatomy that you talked about before? Because I have the picture of the bladder, urethra, prostate, penis in my brain. I know my life experience where the testes and scrotum are relative to all of that. But now I'm trying to figure out the pelvic floor, a bunch of muscles that are attached to the pelvis. But how do they interact with those organs? Yeah, that's a good question. So they sit beneath 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 the base of the penis, the prostates, the bladder, the rectum. And they kind of keep main adequate tension to keep all those structures up. They relax when different functions are necessary. They're very important for ejaculation. Some people think that they kind of trigger some of the orgasmic response as well. Sometimes men will have pain in that area, in the perineal area, can transmit to other parts of the body like the scrotum. One cause of scrotal pain, and there can be many, can sometimes be pelvic floor dysfunction. So I think, again, pelvic floor therapy can be useful for sort of a constellation of symptoms, again, some urinary symptoms as well. So I think for some patients it can be helpful, but again, if you get things too tense, that can sometimes be harmful. So presumably these pelvic floor therapists also help people achieve a more relaxed pelvic floor if that's what they need. Exactly. Got it. Going to some of the questions that came back to me when I solicited for questions and anticipation of this episode. Several, not a few. Let's say a couple dozen people asked about split urine stream. Is that a signature of prostate overgrowth? Is that a urethral issue? Is it perfectly normal? I'm assuming here they mean a split stream of urine that doesn't unify at any point. They're talking about a consistently split urine stream. And for those of you that don't know what I'm talking about, we're talking about a urine stream that's actually two urine streams. And we're assuming one urethral opening, because I hit the literature on this. There is a case of failure to fully fuse the urethral duct during development where some, I'm assuming small fraction of males have a urethral opening on the base of the penis and at the tip of the penis. Let's rule that out as a possibility for now. And now that it's on the table, what percentage of males have that two urethral openings? So well, hypospatia is what you're describing where the actual meatus is not at the tip, but it's kind of along the proximal urethra or even further down sometimes in the scrotum, probably about 1% of births. And usually it's recognized at birth and oftentimes it's surgically corrected because it's better to prepare it early rather than later. Okay. So to bring that out, what is the cause of split urine stream and is it a signature of a larger issue? One of the reasons that we urinate from an evolutionary standpoint is to basically deposit in a convenient time our waste. And we don't want to get it everywhere because we don't want to label ourselves with the smell of urine because that'll be easier for predators to be able to identify. So just similar to today, we'd like everything to get in the toilet without creating a mess so anytime there's turbulent flow, it certainly could signal an issue. So it could be like urethral issues or pointing out a prostatic issue, inadequate speed of getting urine out to meatus. So you definitely should see a physician to get evaluated because there's likely some issue that can be improved. The most popular question I received from males, however, was about, perhaps no surprise, penis length.


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? Those were excluded. Yeah. So lying was excluded. I'm 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 punch line here. Yeah. And the origin was that we were looking at, we wanted to know average lengths for another project that we were doing. And going down the rabbit hole, this has been reported for decades. There's different reasons that people have reported penile length. Sometimes they do it just on volunteers, again, to get the average lengths of different populations. Sometimes it's done pre and pro surgically to try and understand what changes would occur. So we just called the literature, found data on 55,000 men all over the world, and wanted to see if there was a sort of a time pattern with that. And similar to your hypothesis, we assume based on all the other data that we would likely see a decline, whether it be chemical environmental exposure. But if nothing else, if we're getting bigger, the functional penile length should decline because the super pubic 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, the super pubic fat pad, excuse me, being the pad of fat directly over the penis. Right. And so if that gets bigger, that'll necessarily compromise penile length. But as you alluded to, what we found is actually the opposite, that the penises were getting longer with time. So how it's measured, it measured differently. So one of our inclusion criteria was that all the studies have measured sort of in an office, sort of in a clinical setting. So whether it be a clinician or whether it be a researcher that actually did it. So there's different ways you can measure a penis. You could just do a stretch length. So you kind of stretch it up as much as you can and then use sort of a ruler to measure how long it is, again, from as deep as you can get, you know, the pubic bone ideally up to the tip of the glands or the. Okay, 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. My daughter made that joke, actually. Oh, yeah. Yeah. Yeah. 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 tip. Right. Okay. So that that length was recorded in 50,000 men. Wow. Yeah. So that was one. And then we also looked at a rect length. And so there's different ways that an erection can be achieved sort of in a clinical setting. So one is you can ask a man to stimulate himself and then measure. So that was some of the studies. And then the other method, so we alluded to earlier, is you can inject the man with the medicine to give an erection and then measure it. And did 50,000 men participate in that aspect of the study? It was less. No, that was, I think that was about probably 10 to 15,000 men. 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. Yeah. Some of the studies actually had a tremendous number, had about like 15,000 men. Some individual studies contributed to that. And actually interesting, after we published it, there were some men that volunteered for the next study to be measured. I'm sure you'll hear from some of them after this episode. What was the major finding? So the major finding we wanted to do is just give normative data. We found that it varied around the world. So based on different regions, the average length varied a little bit. But generally on average, erect penis is probably between about five to six inches somewhere in that neighborhood. So that was kind of the take home we wanted. That was the average. That was the average for erect length. Did you publish the full distributions? Our plan was actually to make a follow on study so we could show everybody, I guess probably they were interested, where they kind of fell on the graph. But it was fairly, it was normally distributed. Yeah. I would think that despite the wide availability of pornography, that the distributions, like the scatter plots of all the data would be interesting to men. For the same reason that the testosterone by function of age data published as a scatter plot in that textbook I referred to earlier, very interesting because the scatter plot distributions, I feel like point to other takeaways that one can be in their 70s and have testosterone levels equivalent to a male and healthy male in his 30s. One can be in their 30s 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? What did you find most interesting about the data? Well, that there was any change over time. This was a fairly short study. It was probably about 30 years or so. But we did find that penile length has been increasing over time. So that was just fascinating that we would see in such a short interval of time that there would be a change, number one, but that we would see a lengthening, number two. So again, similar to the concerns that arose for these relatively short period of time where you would see changes in semen quality, it suggests something sinister. It's unlikely to be a genetic change because that would take centuries probably, certainly several generations. So the fact that this happened so quickly was just surprising. 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. So the idea is that males are born with penile tissue, of course, but then it's during puberty that the same hormone, dihydrotestosterone, then exerts an activating effects on the genitals and the genitals grow during puberty, penis length increases. So assuming that the study that you did was on males post puberty, 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 high quality and numerous as they could be, 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. Right. So, I mean, I think there's different conjectures that you could 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 length. So earlier puberty tends to be longer, potentially means longer duration exposure to dihydrotestosterone, longer penises. Right. Yeah. You may be surprised to know you might not be surprised to know that there is a subculture online I know because they contacted me in anticipation of this episode of post-pubertal males who take a combination of dihydrotestosterone and low levels of growth hormone in efforts to try and increase their penile length. And the ones taking dihydrotestosterone, they're not taking pure DHT, they're taking things like oxandrelone, which very closely mimics the structure of DHT. They report some success. Fortunately, they did not send me pictures. Otherwise, I would have just forwarded them to you for your next study. But this stuff is happening in post-pubertal males. So it all rests on this dihydrotestosterone hypothesis. Just a point of interest. Yeah. I don't know. Physiologically, it doesn't make sense why that would work as you're pointing out post-pubertally. And then unless they're doing other things, some sort of stretching exercises or I think called jelking, but yeah, I would not recommend that. Thank you. That was the response I was looking for. So that community will be listening with open ears. Don't do it.


Hair Loss, Dutasteride, Finasteride & Sexual Health; Post-Finasteride Syndrome (02:09:01)

As long as we're talking about DHT, dihydrotestosterone, it's only fair to discuss the drugs, the drugs that many people take to suppress dihydrotestosterone in hopes to keep or grow their hair. Things like finasteride, dutasteride. Some, maybe many, not all people who take these drugs, particularly in oral form, experience sexual dysfunction issues and other issues related to suppressing DHT. That said, my understanding is that these drugs are also quite useful, maybe even life-saving in some cases, for staving off certain forms of prostate cancer. What are your thoughts about finasteride, dutasteride? Do you see people coming into your clinic who are having sexual dysfunction or other types of issues because of their hair or attempt to maintain or grow their hair issues? And equally important is that we talk about so-called post-finasteride syndrome. I got a lot of questions about post-finasteride syndrome because I'll describe it in a couple of minutes. It sounds pretty devastating for these people's lives. I'll explain why it's so devastating for them in a moment. What about finasteride, dutasteride, and these drugs that are effectively DHT blockers? DHT levels, if they get too high, indeed can miniaturize the hair follicle because people lose their hair typically up front or in the back, so-called crown or whatever, 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, 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? I think the men that we see these side effects are tend to be younger men in their 20s, 30s, and 40s, and they take it as you're pointing out for hair loss. So before it was FDA approved for that indication, at least finasteride was, they did range randomized controlled trials to look. And one of the other things that we'll talk about too is just reproductive effects. So they did lots of studies to see if there were changes in semen quality for men on finasteride versus the placebo. And there were some very subtle changes, but in post-marketing now we see these patients in clinic, everybody to enroll in these studies had normal functions. So I think that's important to understand. And obviously that's not life, right? The people come in with sort of different baselines and different amounts of reserve. And so we now know that there's probably people that are a lot more sensitive to these medications than others. And so there are some men that drop their sperm counts dramatically. And usually if we stop these medications, their sperm counts can recover. And usually a spermatogenic cycle is probably about two to three months. So usually in maybe three to six months, we usually see recovery for most men. But similarly for sexual function, I certainly have a number of patients that do complain of low libido erectile function, this post-penasteride syndrome. And the mechanisms I think are less certain because measuring testosterone levels, which we do, sometimes if androgens are low or even if androgens seem to be in the maybe normal range or low normal range, we'll try and increase testosterone through a variety of means, testosterone, chlamyphine sometimes we'll give. It helps some men, but not all. So I think the exact mechanism of what is going on here, what is changing, I think we need more understanding about the exact sort of pathophysiology or neurochemically. It seems like a pretty serious trade off to either maintain a grow hair or lose sexual function. I mean, I talked about DHT and some of these side effects of finasteride, detasteride on previous episodes. And I'm not a clinician, but my encouragement is always for people to approach these drugs with a real level of seriousness, if not caution. The post-penasteride syndrome was described in these online questions as seemingly permanent, even though people had ceased to take finasteride or detasteride. So in other words, they were taking this stuff, I don't know how they felt while they were on it, but they stopped taking it and the sexual dysfunction issues don't seem to be resolving. But does that mean they should go see you or another male urologist reproductive health specialist? Yeah, I mean, oftentimes they do for these complaints. They start to notice that 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. They've done MRI imaging to try and understand sort of more anatomically or functionally what exactly is going on. And I think there's still a lot of unknowns about it, but it can be permanent for some. So they come in and they see me in clinic erect all this function, low libido, and then we go down all the host of treatments that we talked about and the evaluations that we talked about. Again, we have resolution in some, but there are some that seem treatment refractory. Yikes. That's my only response. I mean, permanent effects on sexual health as a consequence of an attempt to maintain one's hair. I mean, this is where in all seriousness, it just sounds like something that people need to think very seriously about because as I understand, there's nothing that can predict whether or not someone will have post-phonasteride syndrome. And I did a bit of reading on this within the scientific journals as well. There isn't a lot of information, as you pointed out, because it's a fairly recent phenomenon that highlights a different issue. This may be the first time in history where young males are taking finasteride and dutasteride, and that might be the cause of the post-phonasteride syndrome. I think you alluded to this earlier. These drugs have proven to be very beneficial for older men treating prostate issues. Exactly. Yeah. Right. So this is a post-phonasteride syndrome, I think falls under the category of medical conditions that a few years ago, we would hear the same about chronic fatigue syndrome. Even fibromyalgia not long ago was considered one of these, "Oh, is it all a psychosomatic issue?" Now, we now clearly know that's not the case for fibromyalgia, by the way. But I can recall a time not that long ago when people in the medical profession kind of like, "Oh, yeah, I don't know if this is a real thing." But post-phonasteride 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 do task-rider or are thinking of doing that for cosmetic reasons. And I think they should be aware of the potentially serious consequences. Yeah. Agreed. Yeah. But you did say earlier that if someone has a penis, you can get it hard. So all is not lost even for these post-phonasteride syndrome. That's true. Good. Okay. We'll hold you to that.


Clomiphene, Testosterone & Estrogen Signaling (02:16:11)

You mentioned clomaphene. Could you explain what clomaphene 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." 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 clomaphene only in order to presumably increase testosterone. But my understanding is that it would impact the estrogen pathway as well. Right. Yeah. What's clomaphene? What are your thoughts about people using clomaphene sort of off-label simply to increase androgens? Yeah. That's a question from me for reasons related to changes in neural circuits, but you'll tell us how it works. Yeah. Well, thank you for including the off-label disclosure. Anytime I talk about this, I always have to say that. So clomaphene is a selective estrogen receptor modulator. So basically it blocks estrogen. And so from our earlier discussions of how the pituitary works, there's sort of an elaborate feedback loop between the pituitary and the gonads and the man-to-testes. And so what happens is, you know, FSHLHC is gonadotropin-stimulated testicle to make sperm and testosterone. Testosterone is 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, you'll stop that. And so the idea behind blocking that is that you'll get more production of FSHLHCs, more of these drivers. So you get more testosterone. You get higher stimulation of the testicle. The hope is that for fertility that sometimes it can improve sperm production too, and there's some limited data that can help. But I think as you're alluding to, it's sort of a way to just augment your body's own production of testosterone. So it certainly does that. I think there's no question that testosterone levels do rise. I think that the reason that doesn't always help is because not every problem is solved by testosterone. We kind of talked about someone in this discussion. But also that you do need some estrogenic signaling as well. And so by blocking that, even partially, because there are also some partial haginess effects of chlomaphene as well, it may limit it. And it turns out that estrogen certainly is important for a lot of things. It's important for bone health, but sexual health too. It's important for libido. So that may be partially blunting some of the hope for benefits of testosterone. I found that men tend to be happier on testosterone than some of these other forms, and that could be a possible explanation. But one of the advantages of chlomaphene, if we are thinking about this as a treatment for low testosterone hypergonalism, 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 FSHLH, we'll continue to get sperm production. So for this reproductive age man that has low testosterone and symptomatic low testosterone, low energy level sex drive mood sleep problems, it can be a worthwhile treatment. And it does help a lot of men, but not everybody.


Discussion On Hormone Therapy & Urological Conditions

Follicle-Stimulating Hormone (FSH) Therapy; Prolactin, Estrogen (02:19:31)

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 counting quality, take FSH instead of human chorionic gonadotropin, which is more or less a proxy for luteinizing hormone? That's a really good question. And so what FSH does, like you said, is it simulates sperm production. So it seems like it'd be a much more logical treatment. And actually, in randomized placebo controlled trials, it does do that. So one of the reasons-- It does not. It does do that. It does help. Okay. So it's beneficial. And we should give it more. But one of the reasons that we don't is cost. So it's rarely covered by insurance. And HCG, a month of that is in the hundreds of dollars. So let's say like three to five hundred dollars. But a month of sort of therapeutic FSH is probably two to three thousand dollars. So that cost is really limiting. It takes two to three months to make a sperm. So men often would have to be on it for several months. But there is reasonable data that would help. And it does make a lot more sense that that should be given as adjuvant therapy with testosterone rather than HCG. But HCG does work. Everyone's surprised. It does actually help. But yeah, I agree. There is sort of a contradiction there. So if the price came down, it doesn't-- this is another off-label medication for that indication. It could be worthwhile. 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 is up, prolactin is down. 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 this kind of thing. And I realize that's far too simplistic. But prolactin is doing many things in the brain and body besides that. But how often do you see hyperprolactinemia? I don't know if plural, prolimia is clinically correct. But elevated levels of prolactin that are causing problems for men. What are some of the telltale signs of that? And this I'd like to use as a segue to talking about some of the sexual dysfunction that is commonly discussed around the use of SSRIs and other drugs to treat depression and mental health issues that sometimes create endocrine and/or sexual health issues. Yeah. So prolactin is sometimes, it's a diagnosis, hyperprolactinemia, it's a diagnosis, not that many times. I would say less than 1% of the patients that we see will end up having that. But usually it's a handful of times a year because we see a lot of patients. Usually the telltale sort of symptoms would be ones of low testosterone, that's a common one. But in my practice, I see it a lot with very low sperm production. So I've diagnosed several prolactins creating tumors. And the manifestation of that was they weren't getting pregnant. We checked the sperm count, it was very low. That mandates a check of testosterone, which is also very low. And then that leads to a prolactin, which is very high. And then that was diagnosed. So it's something I think to be aware of. But 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 be able to diagnose if it's present. Are there any other hormones in the galaxy of sexual health related hormones that fall into common clinical practice for you? I check estrogen as well. So I think that's another one. And because of the relationship with obesity, I think that can be important. Sometimes there's too much aromatization. And so sometimes that can be a problem. I think just like we talked about normal, estrogen signaling is important. I think too much can be bad. So there are some men where we do see manifestations that it can manifest as gynecomastia in some cases. Male breast tissue. Male breast tissue, yeah. 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. Right. So everybody has some and we just don't want the growth to get out of control.


Varicocele; Peyronie’s Disease (02:24:15)

Could you tell us about one of the world's most difficult to pronounce words, which is varicoseal? Yes. So varicoseal, 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 it 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 somewhat debated, but I think those probably contribute. And it's something that everybody should be evaluated for if you're concerned about fertility. So again, we see it very commonly. Given the fact that a lot of men have it, about one in seven men have it, it doesn't always cause a problem, but maybe about 20 to 25% of the time it does. So mental manifests with low sperm counts. We see sometimes discomfort, ache, worse at the end of the day than at the beginning, worse at the 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 or having discomfort in the area and you have one, it's a discussion you should have. What about Peroni's disease? Yes, the Peroni's is a scarring of the penis, which leads to curvature or deformity. So the way erections work is everything swells. And you can imagine if there's a scar tissue, it doesn't swell symmetrically. So you'll get like a curvature deviation. Sometimes you can get an hourglass or sort of a banding. If you look it up on the internet, you can see a host of different deformities that men get. It's probably present in about 10% of men, so it's very common. Sometimes it could be from injury, from like a penile fracture or other 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 surgery, which can sort of stun the penis or injure some of the nerves of the penis. So that's another condition we see commonly. Obviously, it can lead to bother. Interrections are not straight. That can just cause psychological bother to men. It can also physically make it difficult for a man to have sex. Sometimes it can limit certain positions. That's another common complaint we see. I think it's something that men should be aware of. There's now awareness campaigns. Now there's an FDA approved medicine for it, collagenase or xioflex, which is a medicine that dissolves scar tissue. That's one of the treatments we have for it. There's also different devices, sort of stretching devices where we try and just mechanically remodel the penis to allow it to be a little bit straighter. And then there's also surgical options too. There's a lot we can do. I always tell men, again, as long as we have a penis, we can make it hard, but we can also make it straight. I'm wondering why in the study about penis length, testicular size and volume wasn't also measured.


Testis & Cancer Risk; Insurance, Blood Profiles & Semen Analysis (02:27:26)

And that's something that we haven't discussed. What is the relationship between testicular size and volume and some of the other parameters we've been talking about? And maybe this is also a good time to highlight any kind of morphological signals that would warrant people coming to the clinic. So asymmetry and testicle size, for instance, changes in testicular size. Obviously a pea-sized lump they taught us in high school is a warning sign of potential testicular tumor or cancer. We didn't really talk about testicles. Yeah. So I think that kind of being aware, the average size of a testicle for a man is about a walnut. It's about 16 to 20 cc. If you were going to measure it, it would be about 4.5 cm and longest axis to give your listeners or viewers some idea. If it changes, certainly let people know. If you feel anything, let people know. Our national guidelines on screening practices recommends against regular testicular self-exams, interestingly, because I think the concern is that it leads to more anxiety than cancers that it would diagnose. But I always tell men, no one knows your scrotum better than you. So if you identify a problem, you should bring it to attention. So the classic appearance or the way that a testis cancer manifests is a firm painless mass that you kind of feel coming from the testicle. I find it interesting that, at least as I understand, women are encouraged to do regular self-exams of their breasts for lumps. But you're telling me that men are actually discouraged from doing regular exams of their testicles for lumps that could be cancer? That feels like an unfair asymmetry. It does. I mean, cancer, I mean, both seem very important. Oh, yeah. Well, I think there's no question. Obviously, I'm very biased. Yeah. I was trying to say it so you didn't have to. Oh, yeah. I don't want to get in trouble with the US Mental Services Task Force. I don't want anyone to get cancer. 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? I think that's the concern, that the number of cancers that are diagnosed versus the false lumps that they identify just lead to more anxiety and end up not actually causing more harm than good, I think is the concern. But yeah, it was a surprising recommendation when it came down. Usually, if patients ask about it, I certainly don't discourage them from doing these exams. And we've certainly identified cancers through that means before. 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 a lump on his testicle. So I'm going to continue to self-screen. Okay, fair enough. Numerous times today, we've talked about the potential benefit of getting a blood test for hormone profiles, lipid profiles, and other things as well as a sperm analysis. My understanding is that one can only do that if they have the disposable income to elect to do that through some commercial online service. But is there any way that patients who have insurance can approach their physician in a way that this would be covered by insurance? I don't want to get you into any trouble here, but it's always such a shame. It is such a shame when we're talking about something that is really pervasively related to health as is sexual health, reproductive health. And people are not aware of a potential problem in the present or in the future that could 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, $200 or $1,000 is no big deal." 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? I think both are good strategies. I think insurance is becoming a lot more open to covering some infertility, at least testing, sometimes treatment as well. So I think a lot of insurance does cover that now. Sometimes we check semen analyses for other jacketory issues. But I think that, again, as more of this data gets out, I think as more recognition how important the male is, I think we'll get more buy-in and coverage. Obviously, women have the automatic feedback of urologist cycles, so they 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. 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. That's exactly right. Yeah. I mean, I think about 15% of men have low semen quality, whether it be concentration, movement, shape. About 1% of men have no sperm in the ejaculate, and that's something sometimes they have no idea about. So the only way to know would be to actually do a formal test. Well, I'm encouraging people to get these parameters assessed, and I'm making that statement because it's very clear based on everything that you've told us today that sperm quality and hormone levels are just oh so important, not just for sexual health, but for urinary health and for reflecting prostate health and other aspects of whole body health. And sexual health relates directly to mental health. We didn't talk so much about the psychogenic issues, but the two go hand in hand. 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 not just to improve communication, but this after all is at the heart of the presence and proliferation of our species. So thanks for taking care of the male half and thanks for doing the work you do. It's incredible. The large scale studies, the more detailed studies on smaller populations, you asked the questions that it seems many people are just afraid to ask and you get right in there and come out with the really rigorous data and answers. So thank you so much for what you do. My pleasure. Thank you. Thank you for highlighting men's reproductive health.


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Zero-Cost Support, Spotify & Apple Reviews, Sponsors, YouTube Feedback, Momentous, Social Media, Neural Network Newsletter (02:35:03)

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. It'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 while supplements aren't necessary for everybody. Many people derive tremendous benefit from them for things like enhancing sleep, hormone support and improving focus. If you'd like to learn more about the supplements discussed on the Huberman lab podcast, you can go to live momentous spelled O U S so live momentous.com/huberman. If you're not already following me on social media, it's Huberman lab on all social media platforms. Instagram, Twitter, now called X threads, Facebook, LinkedIn. And on all those places, I discuss science and science related tools. Some of which overlaps with the content of the Huberman lab podcast, but much of which is distinct from the content on the Huberman lab podcast. So again, it's Huberman lab on all social media platforms. If you haven't already subscribed to our monthly neural network newsletter, the neural network newsletter is a completely zero cost newsletter that gives you podcast summaries as well as toolkits in the form of brief PDFs. We've had toolkits related to optimizing sleep, to regulating dopamine, deliberate cold exposure, fitness, mental health, learning and neuroplasticity and much more. Again, it's completely zero cost to sign up. You simply go to Huberman lab.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.


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