← The Dr. Gabrielle Lyon Show
The Dr. Gabrielle Lyon Show
Male Fertility and Sperm Health: What Your Sex Drive and Testosterone Really Mean | Dr. Michael Eisenberg
01:19:08
Loading summary
Transcript260 lines
- [00:00]
A
Are there any sex habits or behaviors that can reduce fertility? Is low libido a sign of poor sperm quality? What about the use of GLP1s? How does that look from a male perspective? Does, say, looking at, increase or decrease sperm quality or volume? How do we define male infertility?
- [00:20]
B
It's a good question. I mean, ultimately fertility is a team sport and so it's sort of defined at a couple level. So trying for a year and not getting pregnant. When we look at male, you know, sometimes when couples are trying to conceive and are not, you know, we worry, is it a male problem? Is it a female problem? Is it both? So usually when we talk about male fertility, we define it in terms of semen quality.
- [00:41]
A
I know that you're really at the forefront is male infertility. And it's a real problem and it's very impactful for people. And all joking, aside from positions and all of that, that it can really affect people's lives. Doctor Eisenberg, welcome to the show.
- [01:01]
B
Thank you so much for having me.
- [01:03]
A
Now, there is a lot of conversation about infertility, sex, testosterone. I mean, I think that you are at the forefront of changing the trajectory of our health because again, sexual health is. It's a dual role. One of the things that has been really on my mind is this idea of performance enhancing medications. And what do I mean by that? Metformin, which you published a really high impact study in a high impact journal which changed how we think about Metformin. A lot of people were using Metformin for longevity, but perhaps it does have an impact on sperm quality, fertility.
- [01:47]
B
Yeah, so that was a study that we did a few years ago, you know, kind of the, I'll give you the backstory, but just, you know, for all your listeners and your viewers, essentially what we showed is that men that took Metformin, their kids had a slightly higher risk of genital birth defects. And, you know, if you think about, you know, how impactful that is, you know, when medications get approved, you know, they look at sort of common endpoints, they look at, you know, any kind of risks, side effects, things like that. But, you know, there's been such a change in demographics patterns. Parents are getting older, fathers are getting older, and a lot of these medications are very much grandfathered in. And so we don't know really the reproductive effects of a lot of these medications. So for Metformin specifically, you know, when we're looking at it, you know, you kind of think about, you know, why you take it and then you know what it does. And you know, generally what we say is that anything that's good for your heart is gonna be good for fertility. That's why we talk about diet, exercise, you know, all those sorts of things. And so Metformin, you know, generally if it's helping with blood sugar control, helping with diabetes, we think it should be beneficial, but there may be some effects. And so when we did this study, and this was like a large cohort study, it basically looked at all births in Denmark over a period of time. We're able to identify the men that took Metformin, men that didn't. We also looked at men that took other diabetic medications. And we found this association between Metformin and birth defects in their, in their sons mostly. And, you know, obviously it's a very impactful finding. You know, a lot of people take Metformin, you know, more and more now. You know, as fathers are getting older, there's more comorbidities for the father. So there's going to be diabetic fathers. And so, you know, it's kind of frightening. We don't want to be alarmist, so we really want to do a lot of kind of other tests to make sure that this was a true association. So we compared other diabetic medications, insulin, others. We didn't see that pattern. We also looked when they were specifically taking Metformin. So spermatogenesis making the sperm takes about two to three months. So that window of exposures, you know, kind of just before conception. So we looked at men that were taking it earlier. We look at men that took it, you know, during the pregnancy, after, you know, the conception was done after delivery, all those times. And really the only time we saw this spike in risk was if they took it just before, you know, they and their, their partner conceived. So it did, you know, kind of strengthen that this was a true finding.
- [04:12]
A
Yeah, I mean, I, I have a few questions. Now, obviously those that were taking Metformin, I'm assuming were diabetic.
- [04:19]
B
Yeah, yeah.
- [04:20]
A
There's been a lot of use of Metformin for longevity purposes. That's where this could really inform our decisions.
- [04:30]
B
Yeah, yeah. I mean, I think that, you know, this is sort of a large, you know, population based cohort. So we don't have specific information about, you know, all the different indications for metformin, but we assume that 99.9% of these men are taking it because they need it for diabetic control. So I think that is part of it. You know, our health really does impact Our fertility as well. And we know that diabetic man, we can see impacts on sperm quality, on fertility as well. So it could be, you know, sort of. It's cause, effect, effect, cause. Exactly what's particularly driving this? I think that's very important. And so, you know, when patients reached out about this, when other providers reached out about this, you know, how should we counsel our patients? I said, this is, you know, a single study. We don't want to, you know, change care in America. But I think it's important for us to consider that, you know, we should, you know, evaluate some of these medications in probably more detail now that more and more of our, you know, fathers and mothers are on these and to see the effects that they're going to have potentially on offspring. Because this is, you know, it's generational, right? You want to do everything you can to set your child up for success. And it would be a shame if a medication that maybe there's alternatives or maybe, you know, you could be without it for a period of time, again, depending on the indication if it could impact your children.
- [05:43]
A
There's a lot more information that we're getting, things that we used to feel are irrelevant to, not just, I don't want to say our health. So obviously metformin is relevant for our health, but I don't believe that the conversation regarding later life, fertility for our children has often even come to the question. It's more of the immediate things, right? If I take this medication, will this impact autism? If I take this medication, will this create an obvious birth defect with the metformin? Do they know the mechanism of action? Because it seemed. You said that it specifically targeted male genitalia.
- [06:21]
B
Yeah, no, it's a good question. So we really don't. I think that again, um, before we change practice, I, you know, I wanted. I was kind of very, you know, careful. We said that in the paper as well. You know, you know, medications may do a lot of different things and it can change sort of, you know, down to gene expression and affect sort of how we, you know, transmit things and, you know, the patterns of, you know, our DNA expression. So that I think that could play a role. But, you know, we don't know exactly what's happening. And I should also say that, you know, other groups have studied this as well. Again, given the impact of this. And, you know, the. I think the results have been mixed, and some say that maybe it's more tied to diabetes than metformin. But, you know, again, we looked at it very extensively in this population, and it really seemed like it was really linked to Metformin. So I think just. I guess the message is just be mindful, but also just appreciate that, you know, the male's important, the father's important, and what we do today will impact not just ourselves, but, you know, again, depending on our reproductive goals, it could have impacts on getting pregnant, staying pregnant, having a healthy child, which is, you know, ultimately the goal.
- [07:28]
A
If someone were to use Metformin, and this might be somewhat of an extrapolation, but if we were to think ahead, if someone were to use Metformin when they're younger, say I. There's two main cases now, obviously you talk about in diabetes, if they are using it when they're diabetic and younger, because we know obesity is shifting earlier. But there's also cohorts that are using Metformin for longevity purposes, which I think now has been replaced with these. The use of GLP1s. If they come off of it, once that spermogenesis window, once that creation, if the sperm. What do you say? That they don't utilize it, where does it go? Dissolves. What happens to sperm if you don't use it?
- [08:09]
B
Well, some of us, you know, we take care of it in some ways, but, yeah, I mean, in general, like after vasectomy, for example, the sperm will die and get reabsorbed in the body.
- [08:16]
A
So it gets reabsorbed. Once an individual goes off of Metformin, do you anticipate that that then would not affect the later. I don't even know. It's interesting. Is it the sperm cohort?
- [08:28]
B
Yeah, yeah. No, it's a great question, but I think so, at least based on this data, you know, if men took it like a year before they conceived, we didn't see the effect. It was really just the window right before. So, you know, in some ways, you can kind of wash off this exposure. Just like, you know, I've seen men that come into clinic after getting the flu and they get these very high fevers. We know sperm production is very sensitive to temperature. So I've seen some men, you know, go from normal counts all the way to zero. You know, when they have these febrile diseases, these febrile illnesses, and, you know, obviously everybody's very concerned about that. But if you let the body recover, you know, go through another spermatogenesis cycle or two, their counts can recover right after that. So I think it'd probably be similar. You can kind of watch the effect of this medication, you know, for chemotherapy as well. We certainly worry about counts, but also just the quality of sperm given what, you know, how a lot of these agents work. And so we counsel men, you know, to wait a year or two years again to try and wash that exposure out before trying to conceive.
- [09:24]
A
What about the use of GLP1s? There's some data to suggest that the use of GLP1s can help female fertility, whether it's from a metabolic perspective or decreasing inflammation. How does that look from a male perspective?
- [09:39]
B
Yeah, so that's like a very big question right now. And I think that know the goal is that there are going to be some upcoming trials that'll look at that specifically. Currently, the best data we have is a randomized trial from one of the makers of the GLP1 where they had men that lost weight through calorie restriction. And, you know, again, when you do that, not everybody will, will be able to do it well, but those that did lose weight, they did see improvements in semen quality. And then these men are randomized to either continue calorie restriction, you know, do sort of aggressive training, or be on a GLP1. And as long as you maintain weight loss, whether it was through calorie restriction or GLP1, the benefit and semen quality maintained. So I kind of take that to mean that it looks like it is safer fertility. I think that we do need data to show that, you know, if a man is overweight, he goes on GLP1, we'll see that benefit in semen quality. I certainly would expect it. But beyond that, I think similar to our discussion of metformin, I think it would make sense to look further, right. To make sure that all these children or conceived or healthy. Because, you know, again, I think that prior GLP1s were just used for diabetes. Now we're again expanding the indication and we just want to make sure that, you know, we're very mindful of looking generationally.
- [10:52]
A
It makes a lot of sense. And again, there's the pathology component, but then there is the performance component, the landscape. With the use of GLP1s, we're seeing a decrease in muscle mass, not because of any magic that the GLP1s magically decrease muscle mass, but again allows for calorie restriction. Testosterone also seems to be getting a bit of a liberation and, and a comeback.
- [11:17]
B
Yeah.
- [11:18]
A
Where do you feel that there is this balance between performance, testosterone use and performance and infertility?
- [11:25]
B
So, you know, testosterone itself has been tested by the World Health Organization as a contraceptive. So for men that are trying to conceive, you know, I would definitely talk to your doctor, but it's probably not gonna be right in isolation to help because, you know, the way that kind of our feedback works is that when you take exogenous testosterone or when you're taking gels, injections or whatever method, oral, oral agents, it basically tells your body there's enough testosterone and you kind of stop that production. So you stop the production of testosterone in the testicles, but also sperm as well.
- [11:55]
A
Does it matter the dose?
- [11:57]
B
It is somewhat dose dependent. Some people think that if it's, you know, if you're taking these doses many times a day, more than once a day, maybe there'll be less fluctuation and maybe you'll see less.
- [12:07]
A
But in like a subcutaneous small dose.
- [12:11]
B
Yeah. Or there have been different. Yeah, there are different formulations that can be given, you know, more, more than once a day. But in general, I think that if men are trying to conceive, it's always a better move to stop testosterone because you will suppress it. Now, again, it's not a perfect contraceptive, you know, works again, depending on what studies you look at, maybe 60 to 90% of the time. So that's not good enough to counsel a man that you're on testosterone enough to worry about, you know, getting your partner pregnant. But you know, if you're trying to conceive, you want to certainly think about being safe. So I think that, you know, there's certainly men that have low testosterone who it's going to be beneficial for. But if they're in that reproductive age, it's certainly a discussion they should have with, you know, their physician about if they want to start that. You know, there's some other off label medications that could be started either with testosterone or instead of testosterone to boost the levels. Or even I talk to patients about potentially cryopreserving sperm just so that they put that aside.
- [13:06]
A
When you say other medications, do you mean Clomid hcg?
- [13:12]
B
Yeah, exactly. Yeah, Clomid hcg and aromatase inhibitors like anastrozole, letrozole. Those are also options that can increase your testosterone and are thought to be
- [13:22]
A
safer for somatogenesis when the kid, you know, the velocity at which information spreads is so much faster now. Do you remember? I'm, I'm hoping that you do. When at least I did. I had to go to the library and pull out the medical journal.
- [13:39]
B
Yes, yeah, I remember. Yeah. In medical school I would spend a lot of time in the journal in the library to look up all these.
- [13:45]
A
And it took forever.
- [13:46]
B
It was very slow. Yes.
- [13:48]
A
So slow. And now you go online and the information velocity is so fast, dangerous, because if it's incorrect or overblown or misstated, it seems to also spread really like wildfire. In addition, if it is correct, there's an opportunity to really be able to help people. Also, the YouTube and the online stratosphere has changed. There's a lot of younger men, so we have all ages that listen to this podcast and actually a lot of physicians as well that are seeing on YouTube these training videos and they're thinking, okay, well, how can I be jacked and tan by the time I'm 25? Or whatever it is. And then they make decisions like choosing, say, performance enhancing drugs, anabolics, which have really gotten a bad rap that from my perspective, I don't think should, um, especially. And when I say anabolics, there was the Houston Buyers Club. And there are ways in which anabolic agents can be used safely and are FDA approved. If someone is on YouTube and is watching early and decides to use, say, anabolic agents or even peptides, Is there a road back? You know that feeling after a really hard training session where the last thing you want to do is sit down and eat a full meal? Yeah, I get it. And I'm not about forcing down a stake when my body just isn't ready for it. But here's the thing. Intense exercise and really all exercise is catabolic, meaning it increases muscle breakdown. So to protect my muscle and build new muscle and recover, I consume essential amino acids around my workout. This helps with the recovery. Body health. Perfect amino helps me hit the protein threshold. I need to stimulate muscle with minimal calories and not a huge digestive burden like a large sink. The workout was the hard part, but the recovery doesn't have to be. Head to bodyhealth.com and use the code Lion20 to get 20% off your first order. That's bodyhealth.com and use the Code Lion20.
- [16:06]
B
Yeah, I mean, I think in general there is, you know, if we just look at these World Health Organization studies, these men were on it for, I mean, it was a relatively short period of time, you know, a year or two. And those men, again, more than 90% chance of recovery. I think, you know, patients that are on it for a decade or two decades, we have seen some effects that you may not get back to where you were before. Most men can get back. But I think whether you're starting or whether you're stopping, I think it's good to have physician guidance because there are protocols to either do it safely for sperm production or also just to boost the likelihood of recovery.
- [16:42]
A
And you've called sperm another vitals. Did you call it a biomarker or vital sign or both?
- [16:46]
B
I've done both. But yeah, vital sign is the one I use most commonly.
- [16:49]
A
Talk to me about what that looks like.
- [16:52]
B
Yeah, so that's, yeah, something that I'm very passionate about because I think reproductive health is very, you know, kind of reciprocal with overall health. So how healthy I am, you know, basically tells, I think, everybody how reproductively healthy I am. And then also semen quality or fertility is really kind of a window into future health as well. So looking at current health, if you look at, you know, men with more comorbidities on more medications, their semen quality actually is much lower. And if you just took a group of men, basically divided them into semen quality, you'd also basically be dividing them into health. You can look at all different measures of obesity, diabetes, hypertension, all those sorts of things. And men with worse semen quality tend to categorize, you know, in kind of the lower, the lower quartiles or deciles of semen quality. And that's probably kind of known. I think, to some extent, men sort of, kind of realize that, but I think it's important to think about. So, you know, when you kind of look at that, it's important to think that, you know, healthy I am can actually impact, you know, fertility. Because if you're trying to conceive, you know, obviously it's a team sport. A lot of our care, I think, is directed towards more the woman when you're trying to pursue goals. But there's a lot that the man can do. So, for example, if you treat one of these comorbidities, you see significant improvement. There is this beautiful study that was done in Japan probably about five to 10 years ago, where they had a group of men that came in to try and help conceive. And they just asked a simple question, who's getting better? Who do we actually help? And one of the categories, one of the only categories was men that had a comorbidity that was treated. So if a man, for example, had hypertension, he got that treated, his sperm count went up 25%. So about a hundred million more sperm if he just had that, that treated. So it's really a, a great opportunity and sort of a carrot for these men to take a little bit more ownership of their health because sometimes they've Never seen the doctor before. They come to see us.
- [18:48]
A
And how do we define sperm quality?
- [18:51]
B
So, you know, we basically look at a semen analysis. So it's, you know, very broad. We look at the volume of a jacket that comes out, how many sperm there are, usually quantified in million of millions of sperm per milliliter. We look at the motility, how many are moving, morphology or shape. And then more recently, we also started to look at DNA fragmentation a little bit more. And as its name implies, it's, you know, sort of the integrity of the DNA within the sperm.
- [19:14]
A
We were chatting before we started recording. We were talking about how there's a landscape of increasing exposures, pfas, environmental toxins, microplastics. You talk about sperm quality, volume, motility. Do you anticipate finding components of environmental toxins in sperm ejaculate?
- [19:40]
B
Yeah, I mean, I think this is something that we talk about a lot, and I think we really are in our infancy because I think that some of the analyses to find these are, you know, some of the techniques, I think are just getting better and better and it's becoming easier and easier to do. Some of these studies, they used to really be done in, you know, very specific labs, maybe only one or two places on Earth. And now I think warn men and women are very concerned about this. So I think as it becomes more commercialized as testing, I think we're going to be able to learn a lot more. But we know that we've seen microplastics in the testicles.
- [20:11]
A
You have seen that? You do see that?
- [20:13]
B
That's been reported? Yeah, we do see that. Usually just about every testicle, it's very rare. You'd find a man who doesn't have that because it's just such a ubiquitous exposure. We see it in semen as well. And I think really the question is, you know, how impactful that is. There have been some studies, mostly out of China at this point, that do correlate the amount of microplastics in semen with the quality of the semen. Again, some of these same parameters. We see, you know, lower motility, lower numbers when there's more microplastics.
- [20:41]
A
That's. I mean, it's really concerning. And I've heard you talk before that you don't let your kids drink out of plastic bottles. It is difficult. I mean, think about even toothpaste. Yeah, toothpaste comes, comes in plastic when individuals are exposed. And I don't know if you've thought about this, but is there a way to remove it. I know that there's the typical excretion, which is probably urine and feces. And, you know, again, I'm not an expert in microplastics, but is there a way to quote, and I hate to use the word detox, but removal of these environmental toxins, you think?
- [21:13]
B
I'm hopeful. I think that mostly it's going to come through education because I think it is such a ubiquitous exposure. You know, I've talked to experts, some that we're collaborating with on some of these projects, and they'd say that it's in the food supply. Not to scare everybody, but it's just very difficult. Right. We need to eat. So unless you're going to grow, you know, your food yourself, maybe you can limit it. But if you're going to eat most meat, I mean, you know, everything, it's in feed, it's. It's just everywhere. So I think that standpoint, it is difficult. I think that you can make some, you know, changes like try not to drink out of plastic bottles, don't microwave plastics. I think there are some sort of easy ways that you can try and, you know, avoid it, but hopefully, as we kind of learn a little bit more about it, where it's coming from, you know, if we do find very clearly that's causing a problem, we can try and, you know, eliminate some of that as well. But, I mean, it's in our clothes. It's really everywhere. I think it's such a ubiquitous exposure. And plastic is so great. Right. I think I would say just from a societal, evolutionary standpoint, industrial standpoint, without plastic. Right. Wouldn't have phones, wouldn't have so much. So it's beneficial in some ways. I think we just need to understand how it's getting inside of us and what it's doing when it's there.
- [22:22]
A
And if sperm quality is a reflection of overall health, which, again, what I think is so interesting in the work that you do is you think about generational health.
- [22:31]
B
Yeah.
- [22:31]
A
And sperm quality likely changes over time and the development. Is there a defining moment in which sperm has now been. Become mature or maybe has hit its stride from an age perspective or.
- [22:48]
B
Yeah, that's a good question. I mean, the oldest father ever is 96. So the biologic potential probably.
- [22:52]
A
Hugh Hefner. No, I'm just kidding.
- [22:53]
B
No, but so the, you know, I think the potential does last forever, but the quality does decline. We know that sperm counts go down, the amount of sperm goes down. We see higher rates of DNA fragmentation in older men as well. So, you know, from an evolutionary standpoint, you know, probably peak fertility is probably late teens to early 20s. But I think that, you know, we continue to make good quality sperm. You know, I. We define older fathers by the American Urologic Association, American Society of Reproductive medicine, as over 40. And it's not that there's sort of a clear transition at that point, but, you know, again, there's sort of risks and benefits to everything. And we think that maybe there's a few more adverse outcomes that are likely to happen. It's more likely to be harder to get pregnant. Rare birth disorders, things like that also go up. But, you know, again, it doesn't change at that point. I think just sort of to think about men, what I always tell men is you don't have an unlimited Runway, right? You should be sort of cognizant that it's going to get harder to get pregnant, you know, and there may be some, some issues. So you should just be aware and try and do everything. You can begin to maintain health too. Because I think to your point, not just does it change your fertility, you know, now, like whether you're going to be able to get pregnant looking at your sperm count, but we've also shown that men that have health problems, you know, have higher risk of, you know, siring like a preterm baby. So it also affects sort of pregnancy trajectory. Men that have more comorbidities have higher risk of miscarriage. And so in their partners, they're really, you know, at again, a sperm level leading to that. And then even if you look at sort of early childhood outcomes, we've also seen effects on that too. So we. I don't want to say that men are as important as women. I think gestation, everything women do is, you know, going to drive 90% of that pregnancy. But to think the man has nothing to do with it, I think is. Is shortsighted. We consider half the. Half the DNA and I think there's lots of other aspects as well. So men should really try and, you know, think about pregnancy kind of early. Just like women start prenatal vitamins, men should really try to take ownership of their health because it will affect getting pregnant and staying pregnant.
- [24:59]
A
As you're talking, I'm just relating it back to what I think is the organ of longevity. Again, urologists usually think it's penis, and I would say that it's muscle. But there are certain nutrients that are essential for muscle, the essential amino acids. We require that there's very specific stimulus and input for skeletal muscle. To allow for the process of muscle protein synthesis per se. Sperm, I'm guessing probably also has very specific nutrients that are required for its overall health and wellness. And then I had one more side thought and my producers hate when I piggyback on multiple thoughts. But you know, metformin decreases B12.
- [25:42]
B
Oh, interesting.
- [25:43]
A
And you know, as I was just kind of thinking about the nutrients for muscle and probably there's specific nutrients for sperm. There is a depletion of B12 and some of the B vitamins with metformin and back to sperm quality. Are there specific nutrients for sperm?
- [26:03]
B
Yeah. So I think again, when we're talking about things that men can do to sort of optimize fertility, I think, you know, try and give them as much agency as they can. So I think you, you know, sort of been like of a world thought leader and you know, good diet, exercise, maintaining good body weights. But there have been some, you know, great studies done looking at specific nutrients. You know, they've done randomized trials and showed improved sperm quality and improved fertility. So I actually work with a, you know, a company called Swim Club that does have a, you know, it's a full stack male fertility supplement. And the idea is that we, you know, we started at first Principles, we actually went back to the data, looked at which, you know, med which nutrients are most beneficial, you know, which studies were a little bit more questionable to come up with it. And you know, it sort of looks at all things. So we look at like mitochondrial health, right? Like coenzyme Q omega 3s. We looked at, you know, antioxidants, penacetyl cysteine, you know, selenium, lycopene and then also you know, cellular DNA integrity as well, like zinc, spermidine. So I, you know, it's very kind of, I was really impressed, you know, this company kind of looking at that. And then the other thing that I've learned about in this journey, which I'm sure you know a lot more about than I do, is that not all supplements the same. Right. And so there's I think differences in quality and so also making sure that when you source it, it's, it's gonna be the best. Because, you know, there have been some studies that show kind of mixed results when it comes to some of these supplements. And you know, my concern with some of those is just, you know, the quality of the ingredients.
- [27:36]
A
Of course it is. And while we can pull some of the data looking at say individual nutrients like zinc, which seem to be really important and some that are in the product that you're mentioning called Swim Club. What about muscle mass? Okay, so hang with me. You know, I was senior author on a paper that was linking muscle mass, muscle quality and strength with erectile function.
- [28:05]
B
Wow. Okay.
- [28:05]
A
And Mo was on there, Shane was on there, Lipschildz was on there. Because I think that muscle is the center point. Because you talk about erectile function and vascular health.
- [28:16]
B
Yeah.
- [28:17]
A
If we think we typically relate that to cardiovascular health, but really it's the muscles that are under the voluntary control that would then help with blood flow. So do you think that sarcopenia would contribute to low sperm quality, low erectile function?
- [28:39]
B
Yeah, I mean, I think your body knows sort of what's important and it's trying to prioritize survival. So anytime, you know, there's a deficit, I think, you know, resources get shipped internally to survival from reproduction. You know, reproduction is certainly one of the, you know, central tenets. Right. We eat, survive, reproduce. That's what every species does and shop.
- [28:59]
A
Okay, fine. No, you don't sometimes.
- [29:02]
B
But. But, you know, we eat to survive, we survive to reproduce, to spread our DNA. And, you know, if you're really worried about survival, I think you're going to deprioritize reproduction just to maintain that. So I think that's the. I mean, as you told that, I thought you were going to say that there's a study linking it to sperm count too. I would not be surprised. And that would be a really exciting study to do.
- [29:22]
A
Maybe that. That would be the next one.
- [29:24]
B
Yeah.
- [29:24]
A
Um, but this is kind of a proof of concept looking at muscle mass strength and quality and erectile function. And we, you know, there always has to be a mechanism of action. And the mechanism of action was better metabolic control, which is what you talk about for sperm health and reducing comorbidities, but then also increasing blood flow. When it comes to fertility, are there things that men are doing, aside from, say, the obvious, which is train. We know they have to train. Does, say, looking at, increase or decrease sperm quality or volume?
- [30:00]
B
So. Yep, I think that has not been studied extensively. I think, you know, you know, I guess in terms of sexual function, it can definitely impact things. And I think that, you know, as men, you know, watch porn or get used to one particular, like masturbation technique, for example, sometimes that can affect partner relationship. You know, again, as we said, fertility is a team sport. So if it limits sort of sexual function in that partnered relationship, that can impact things. But another, you know, and coming up with less interesting study ideas, it'd be very Interesting to see how that affects it.
- [30:36]
A
Is low libido a sign of poor sperm quality?
- [30:41]
B
Well, it could be related to testosterone. And you know, again, the testicle makes sperm makes testosterone. And so we do know that infertile men have lower testosterone. Testosterone levels than their fertile counterparts. So it, it sort of stands to reason that they would have a lot of symptoms. So we have seen, you know, hypogonadism more common in fertile men. So I think if we kind of pulled that string, I think we'd also see low libido.
- [31:03]
A
There are a lot of wives tales out there. And I'm sorry, I know that this is going to be way more embarrassing for me than it is for you. Okay. As I was thinking about bridging this gap between sex and fertility, um, one of the things as I was looking to get pregnant the first time was again, way more embarrassing for me. But they're, they say, okay, there are different sex positions that will help with increasing fertility based on supporting sperm motility. Is there any truth to those types of things?
- [31:34]
B
It's all supposed to help with sex selection as well.
- [31:36]
A
Really?
- [31:37]
B
Yeah.
- [31:37]
A
Okay, well, but again, see, now I don't. I like, I'm like, am I going to turn red while I'm asking this question?
- [31:42]
B
But, but no, like, I think in the, in the 70s, there was some thought that Y chromosome bearing sperm are faster than X because they have. The Y chromosome is smaller than the X chromosome, so it's lighter, maybe it goes faster. I think all that has been disproven. So in general, as long as you get the sperm inside, it should be able to do it.
- [32:02]
A
So it doesn't matter. There's no. So, hey, ladies out there, if you're hearing this on the Internet or there's these chats that, oh, you know, go stand on your head, don't do that. There is no evidence for that. Are there any sex habits or behaviors that can reduce fertility?
- [32:22]
B
Well, you know, I'd say generally when we counsel patients about sort of the time frequency, and I think that could play a role. So, you know, women ovulate and then the egg, you know, goes from the ovary down the fallopian tube and eventually out. And so we want sperm kind of waiting for the egg during that time. So usually we say that sperm can live inside the female genital tract for about two days. So if a woman is going to ovulate, like on day 15, I tell couples have sex 10, 12, 14, 16, and 18. So we do every other day. It's easier for some couples than others. But it's difficult to have sex every day. And you know, again, we want to sort of maximize payload delivery. So if men are, you know, for example, if they're trying to conceive and they're, you know, masturbating several times a day, that's just going to reduce the efficiency of sperm actually making it inside your partner's uterus. Cause there's sort of less there.
- [33:12]
A
So it. Does it decrease volume?
- [33:14]
B
Yeah. The more frequently you ejaculate, like the shorter the abstinence period, there's less volume, less sperm numbers. It's thought to be fresher sperm. Sometimes the motility can improve, sometimes the shape or morphology can improve. Everybody has different sensitivities to that. There are some men that are very sensitive, some that are less so. But in general it's better to, you know, I would say every, every sperm you produce, you want inside your partner when you're trying to conceive.
- [33:39]
A
So space it. It's, you know, just from a very tactical perspective for people because again, which I know that you're really at the forefront is male infertility. And it's a real problem and it's, it's very impactful for people and all joking, aside from positions and all of that, that it can really affect people's lives. So if they are trying to maximize their chances of conceiving and let's say they don't have DNA fragmentation and they've got good sperm volume, then every two days or so seems to be beneficial.
- [34:15]
B
Seems to be beneficial. I would also try and time it with your partner's cycle too. So there's, you know, over the counter kits you can get. You know, if you're regular, I think that's good. But everyone's a little bit different. So I think it's nice to have data. You don't have to do it every month, but you can do it as you're starting just so that you could predict when that ovulation event's gonna occur. So you can try and have sex around them.
- [34:33]
A
And if someone goes for longer periods of time without ejaculating, for example, a week or two weeks, does that decrease sperm quality?
- [34:42]
B
It can. So I think the volume can increase. There could be more sperm. But we do worry some of those sperm are older, so we do see in some cases lower motility, lower morphology. So, yeah, I guess kind of leading up to the event, it's reasonable if you haven't ejaculated in two weeks or a month, you know, to sort of clean the pipe, so to speak, before you, you start to try.
- [35:03]
A
Do you think that there are things that can help? So again, there's all these peptides that people are talking about. Is there space for that?
- [35:11]
B
I think, you know, there's no FDA approved medicine for male fertility. So I think, you know, as your podcast, other kind of sources of information start to bring more attention to male reproductive health, hopefully there'll be some interest. I think there are, you know, lots of different peptides that we don't understand or know about. So hopefully there will be some, you know, ones that do show some promise and some real benefit. I think it's certainly, as you're pointing out, it's an area that's really starved for innovation and, you know, treatments.
- [35:38]
A
And you were responsible for part of the guidelines, the newer guidelines for male infertility?
- [35:45]
B
Yes, yes. It was a joint effort by the American Urologic association, the American Society of Reproductive Medicine. Got to assemble the panel of experts and just reviewed the data to say, you know, what's evidence based and how should we be treating infertile men around the world?
- [35:59]
A
I'm thrilled to announce one of the new sponsors of the show and that is the Carol Bike. Now if you've listened to the show, you know that I believe muscle is the organ of longevity. And of course you need resistance training, but you also need high intensity interval training. And I would say nothing improves cardiovascular fitness like a targeted program and tool. And that is why I'm so excited about the Carol bike. It is an AI powered style stationary bike that delivers, get this, a scientifically validated reduced exertion high intensity interval protocol in just 20 seconds, two 20 second all out sprints. All of this in under five minutes. And this isn't random hit, it's resistance that adapts in real time to your output. So you get precise and personalized stimulus to improve your VO2 max, which is one of the biggest predictors of mortality. And listen, we've all cheated ourselves, ourselves, our efforts on the treadmill and maybe we didn't push as hard as we could on the rower. But with the Carol bike, there is no cheating. For those of you prioritizing muscle, this allows you to focus on cardiovascular training that complements strength work instead of competing with it. It is efficient, it is evidence based and it respects your time. So it allows you to get after it. Visit carolbike.com and use code lion for $100 off your Carol bike. That's C-A R O L B I K E.com and use the code lion for $100 off your bike. How do we define male infertility?
- [37:43]
B
So it's a good question. I mean, ultimately, fertility is a team sport. And so it's sort of defined at a couple levels. So trying for a year and not getting pregnant. When we look at male, you know, sometimes when couples are trying to conceive and are not, you know, we worry, is it a male problem? Is it a female problem? Is it both? So usually when we talk about male fertility, we define it in terms of semen quality. And for all those different numbers that we talked about, the World Health Organization has given us sort of standards, sort of below which you're less likely to conceive. And so that's generally how it's defined.
- [38:15]
A
And do certain areas of the US have better fertility than others?
- [38:21]
B
Sperm count really varies around the country. It is wild. You know, why that is is not known. It's also different, you know, around the world, too. And whether it's unique to, like, sort of genetic makeup, whether it's sort of cultural, I think it's not known. But there was a study that was published around 2000, the study for future families, where they looked at men that had conceived. So, like, when women came in for their first prenatal visit, you know, with their husband or their partner, they asked him to give a semen sample. Not everybody did, but a lot did. And so this was four centers around the US it was New York, California, and then there are a couple in the Midwest as well. And what was really interesting is the highest sperm counts were actually on the coast. The highest was actually New York. So everything.
- [39:08]
A
Very counterintuitive.
- [39:09]
B
Yeah, right. You think that it's very industrial, very concrete, but actually they were highest there. They were lowest in the Midwest. So these authors hypothesized that maybe it was kind of the more rural environment, maybe pesticide exposure that leads to this, but we don't know because, again, the composition of these men varied a little bit. But it is really interesting to think about. So as we think about what's normal or what's average, I think it's very important to look kind of within your own sort of geography, because it'll vary.
- [39:36]
A
I don't think that I've ever thought about that before. If someone was thinking, okay, we've been trying to get pregnant, but you live in New York, it means it reasonable to say that perhaps. Or is that just a skewed perspective? Or is it reasonable to say you live in New York? Typically, your fertility, it should only take you six months to get pregnant.
- [39:57]
B
Oh, it's interesting. Yeah. I don't know. I think that. Yeah, it's a good question also. Just a bit. Everything we'd think that would be bad, right. New York is, you know, you don't get a lot of green exposure, which we think is important. You know, it's congested, there's more maybe pollution. But yeah, it really puts kind of all of our maybe assumptions kind of on their head. But. Yeah, again, why it is is not known. Yeah.
- [40:21]
A
There are multiple tools likely that I'm hoping that you'll talk about that can help improve fertility. And you're doing also some very interesting things like platelet rich plasma, which I've heard for ovaries, I have not heard for sperm.
- [40:37]
B
Yeah. So, you know, I think the first thing we see a man is we'll do a complete, you know, physical exam, we'll do a history to make sure there's things that are not, you know, impacting them. Like we talked about testosterone earlier. You know, there's some other medications, like for example, that we give for urinary symptoms that can affect ejaculation efficiency.
- [40:55]
A
Like what?
- [40:56]
B
Like Flomax or Tamsulosin, these alpha blockers. There's actually some data on like Propecia, you know, medications that are given for hair loss, finasteride. Finasteride. So we say that, you know, when it was FDA approved, they did a randomized controlled trial that showed it was safe. It lowered sperm counts a tiny bit, usually not a clinically significant amount. So it was approved. But what we found now in kind of, you know, you know, when we kind of gone back and looked, you know, after it was approved, post approval analyses, that there are some men that are probably more susceptible than others. And so it is something that we can remove. And again, sort of the same thing that we talked about with other medications. After three months, six months, you know, a few cycles of somatogenesis, most men will, will improve a little bit. So about a, I usually tell men maybe about a 60% improvement in their semen quality. So it is something, you know, actionable. And interestingly, I've seen patients before that don't want to stop it, you know, kind of propecia, propecia, you know, sort of the vanity is, is real. But, you know, most will, most are certainly, you know, are willing to do that.
- [42:01]
A
Would you say that people are no longer prescribing finasteride at this point?
- [42:05]
B
It's gone way down. Yeah. I think when I first started in practice 15 years ago, I would say that every week I saw several patients with concerns of post finasteride syndrome. And I think that's really reduced. And I think there is just a lot more education about potential side effects, you know, and I give it. I obviously, I always talk about it. And I think more men are reluctant to do it just given how important sexual function is. And this concern about the effects or potentially permanent effects really scares a lot of men off.
- [42:31]
A
Yeah. To recap, the main medications that can affect fertility, finasteride. What are the other? Obviously testosterone. Are there a handful of other common medications that perhaps someone's not thinking of?
- [42:45]
B
There have been some studies that say that some antidepressants can affect it, like Paxil, for example. There have been some studies showing it can increase DNA fragmentation in sperm. So I think we probably need a little bit more data. And you know, all these medications I prescribe, you know, tamsulosin and finasteride. So I feel very comfortable telling them to or to not take it. You know, when we talk about antidepressants, that's not a common medication I use, although some off label use for premature ejaculation. But if they're, you know, giving it by their, you know, psychiatrist or primary care doctor, I want to make sure they have that discussion with them. But just to be aware that there's medications we know that affect fertility. And again, I would say also the majority of medications we have no idea, you know, when they're first studied, they give them to, you know, animals in high doses. And if there's not a reproductive effect, they kind of put it on the back burner. But they could have effects, we don't know. So hopefully, you know, over the next decade or two, we'll get some more information.
- [43:37]
A
Do you think that there's one, obviously this is just your personal opinion. Do you think that there's one that maybe perhaps people are missing, that you are seeing patients come in and you're maybe perhaps seeing a trend?
- [43:49]
B
Um, you know, I think I would not be surprised if there's some blood pressure medications that are affecting things to some extent. Yeah. You know, we did a study where we looked at, you know, again, sort of the strong interest I have in overall health and reproductive health. We looked at men that had semen data and also were on different blood pressure medications. And we did found patterns that were, it mattered what you were on. If you were on a beta blocker was different than a calcium channel blocker, you know, then like, like an arb, an Angiotensin receptor blocker. So I think it does make a difference. Yeah, I guess, you know, time will tell if this is sort of validated in other. In other groups as well.
- [44:28]
A
I'm. I would agree with you. And I have seen, again, I don't typically treat fertility. I send them to you guys. But beta blockers, over time, especially with the veteran population, I certainly suspect that that plays a role.
- [44:45]
B
Interesting. Yeah, interesting too. Yeah.
- [44:48]
A
In terms of what we're talking about is, would you say that sperm is, I don't want to say metabolic, but, you know, when we evaluate the health of muscle, like a triglycerides and insulin and glucose, and that probably rides along, there's probably a correlation between sperm health. Yeah, right. I'm sure there's this bidirectional relationship. Would you consider sperm, again as like a metabolic marker perhaps, that those with diabetes have. Seem to have this percentage of sperm? Like, do you think that there is some kind of correlate?
- [45:25]
B
Yeah, I mean, definitely. If you look at sort of metabolic health, kind of all the parameters that you're. You're discussing, there have been groups that have shown associates with semen quality. But interestingly, if you look at semen quality, it'll predict later risk of getting metabolic disorders. So it's interesting. Yeah. So there is a study where we looked at fertility and found that men that were diagnosed with male factor infertility, so had abnormal semen quality, had a significantly higher risk of developing diabetes. So these are men without diabetes. If you just follow them in five years, 5% of these men developed diabetes. So 1 in 20 of these patients that we're seeing somehow years later developed diabetes. And I think that, like you said, it could be an early marker of metabolic health. But again, it also presents potentially an opportunity. Right. If we can understand why this is, maybe we could change that trajectory because we know diabetes is so, so impactful for health.
- [46:15]
A
Is there a certain way to look at the vasculature of maybe the blood supply to sperm? Or again, through ultrasound? As I just think about overall medicine in general, people will do it and echo to limit the heart. Is there imaging that one could do to their genitalia for maybe seeing things before there's a problem? And again, people are thinking, like, why the heck would you do that just to an echo? But if everything that I'm hearing what you're saying is that these are early indicators that probably sperm, genitalia, sexual health probably outpaces diabetes, cardiovascular disease, and everything else.
- [46:57]
B
Yeah. Well, I think doing a semen Analysis will give you kind of a window into that, I think in terms of imaging, you know, we've tried to look at MRIs in the past. We. I did a study about 10 or 15 years ago. It didn't show that much promise. The Baylor College of Medicine group is doing some really cool stuff, looking at ultrasound and showing some very interesting results. I think time will tell, but, you know, in terms of semen quality as a predictor, I think it's fascinating. There is a study, you know, we've done a studies showing that semen quality, like lower semen quality and is associated with a higher risk of cancers, you know, later in life. Talked about metabolic disorders, heart disease, even mortality. There's a really interesting study that came out of Denmark just last year where they had. They have these, you know, very large population registry. So they had about 80,000 men. They followed them for nearly half a century. And they showed that a man, if you did checked his semen analysis, you know, when he's in his 30s, that can tell you when he's going to die decades later. So if you had lower semen quality, lower concentration, lower volume, your average date of death was like three to four years earlier than if you had kind of average or normal semen quality. So it's amazing, right, 40 years later that you would get that information that
- [48:10]
A
would make me think that life insurance, individuals, life insurance evaluations would. Could probably be able to contribute to funding to be able to look at that.
- [48:19]
B
Yeah, it had to write actual actuarial tables. I mean, it's. It gives us a lot of information and it's sort of exciting, I think, that we're getting this new data.
- [48:27]
A
What do you think has the biggest impact on sperm quality? Fertility? Because there's obviously, there's a genetic component, but there's obviously lifestyle and probably for various people, certain things move the needle more.
- [48:41]
B
Yeah, I think it all contributes to some extent. So, you know, about 10% of the male genome is devoted to reproduction. So certainly that's going to be a big driver. I think development is also very important. You know, we know gestation impacts the rest of our lives, so you're not to blame mothers for things. But, you know, whether there's microplastics, I'd
- [49:00]
A
like my mom for everything. So go right ahead.
- [49:02]
B
Microplastic exposures, you know, kind of what you eat, you know, during gestation, that potentially could play roles. I do think health is hugely important. Right. We do have agency, you know, how we're going to, you know, turnout.
- [49:12]
A
So I liked hearing you say that?
- [49:14]
B
Yeah,
- [49:16]
A
it's important. And you speak a lot about personal responsibility and you don't hear that a lot.
- [49:22]
B
Yeah, we don't want to be alarmist. And you don't want people to think that there's nothing they can do, because I think they can play a huge role. So, you know, I've had lots of patients that come in, we have these conversations, and they say, you know what, Dr. Eisenberg, you know, give me three months, give me six months, I'm going to change things, I'm going to get more sleep, I'm going to eat better, and let's see how we do. So I think that is very important as well. I also think to some of this stuff, there is sort of a social aspect to it as well. So it turns out actually, when you look at health, that having children is actually cardio protective. You know, if you have kids, at times it feels like they're trying to kill you. There actually, there's lower risks of heart disease, lower risk of death, and same with having a partner as well. You know, these factors that you go hand in hand with reproduction, they are very important for health and longevity.
- [50:06]
A
Male marijuana use seems to really be increasing. Younger males using marijuana.
- [50:13]
B
Yeah. So there have been some studies looking at reproductive health with that as well. There are some that show maybe some signal. The largest study was done out of Denmark and they showed that men that used it a lot, you know, I would say daily to seem to have lower semen quality. And there certainly may be. I mean, I think everything in moderation is probably better. If you look sort of deeper at that. The men that use it that frequently were also doing other drugs, like kind of harder drugs. They were smoking a lot as well. So it's hard to tease out marijuana. There have been some studies that have done that and it doesn't show a strong association. So people use that for a lot of different things that they use it for. Stress, anxiety, sleep. You know, I never want to discourage them if there's. They can see sort of meaningful benefits. I share the information with them. So I think moderation is better, but I think the data on it is somewhat mixed.
- [51:01]
A
Do you have a perspective? So there's the data and then do
- [51:04]
B
you have a clinical perspective on marijuana? I think it's not good. I think it's not going to be beneficial. So I think that again, if you're using a lot, it depends on why, if you really need it to get by, which, you know, again, some of my patients do see if they can maybe cut it down a little bit. But if it's just purely like recreational and you use it, you know, just with your buddies and you can do without it, then I think that's certainly going to be better.
- [51:29]
A
What about some of the other lifestyle stuff like sleep?
- [51:32]
B
So sleep is sort of funny. It's kind of like a U shaped relationship. So it's, you know, you certainly can get too little sleep. Right, that makes sense. And I think that cutoff seems to be around seven hours. So we do see men that get less than seven hours seem to have higher, you know, rates of lower semen quality. But interestingly, on the other end, men that get too much sleep, 9, 10, 11, 12 hours, we also see that same drop off. I don't know why that is. Maybe these are, I don't know. You know, some men do it for sort of performance reasons. I remember during a Hard Knocks, J.J. watt talked about sleeping 12 hours a day and how boring that was. But, you know, I'm sure he saw real benefits. But in general, if you look at a population of not JJ Watts, it is possible to get too much. But again, there may be some other factors that are play. So I tell men 7 to 9 hours. Ideally.
- [52:16]
A
Do you guys in your clinical practice evaluate for sleep apnea and are there certain metrics that you always look at?
- [52:23]
B
So I do think like sort of sleep hygiene is important. Like again, when you look at men that report not even have gone to like a sleep study and are diagnosed that men that report they snore, men that report they feel sort of tired throughout the day, they don't feel like they sleep well, we do see these same, you know, patterns for men that, you know, don't sleep seven hours. So I think it is really important and we do talk about that. And I, you know, again, recommend to go to a sleep clinic or get evaluated for that.
- [52:46]
A
With the increase in both performance, there's a lot of centers like the male performance center and male infertility. I mean, there are infertility clinics everywhere. I know because we look for our patients. If they can't come to someone like you or at Baylor, Dr. Mahakara or Dr. Lipschultz. How can someone listening to this go, okay, how do I make a good decision based on my area to see a provider? What are the handful of items that they should look for?
- [53:17]
B
Yeah. When evaluating clinicians? Well, I think that, you know, when I first started training, there are very few of our specialty and now there's a lot more. You know, there used to be you know, this sort of super training. So, like, you go through residency to sort of learn a field. So learning urology and then to specialize in fertility, you go through a fellowship. So specialized training.
- [53:35]
A
You did your fellowship at Baylor?
- [53:36]
B
I do my fellowship at Baylor, yeah. Which was great. At a great, A great institution. So there used to just be like a handful, you know, four to five. Now there's about 20. And so I think there's a lot more providers that are going to be available. So I think that looking for that specialty training, I think it'd be important when you're evaluating, you know, urologist. Do you, you know, have you done a fellowship in male reproduction? Are you an expert in the area? I think that's, that's important.
- [53:59]
A
You also make a really good point. It's still really small. If someone were to think about it, if there are 20 different fellowships and maybe there's two. Maybe there's two fellows a year.
- [54:10]
B
Yeah.
- [54:10]
A
You know, you're talking about 40 fellows.
- [54:13]
B
Yeah.
- [54:14]
A
A year.
- [54:14]
B
Yeah.
- [54:15]
A
And that's probably extra.
- [54:17]
B
Yeah, yeah. The number of male reproductive urologists. Yeah, it's in the low hundreds right now.
- [54:22]
A
It's. It's really, really small. What about the use of anabolic agents? And I, I think that there's a lot of misconception in terms of anabolic agents. And when I say anabolic agents, you know, I'm talking about things like nandrolone, which again, is a medication that's FDA approved. How do medications like that affect fertility?
- [54:45]
B
I mean, I think it would be the same pathways as just, you know, testosterone, supionate or others. You know, we're going to see that suppression of the hypothalamic pituitary gonadalaxis. So, you know, again, I think if your goal is reproduction, then you really want to have a, you know, thoughtful discussion with your provider about that. Again, freezing sperm beforehand, just in case, kind of depending on how long you're going to be on these.
- [55:05]
A
How long does the frozen sperm last?
- [55:07]
B
So the longest time, interestingly, between freezing and use ever poured is about 25 years, in theory, just.
- [55:13]
A
And what happened, they actually utilized. Yeah, okay.
- [55:16]
B
But in theory, based on sort of ionizing radiation from the sun, you could freeze sperm for 200 years. So it should be as long enough that you would. You could ever need it. So that's certainly a great option. But whether, you know, with these agents, you're going to take other medications you talked about, like clomiphene or HCG or even fsh to sort of maintain testicular Size and health or whether you know when you eventually stop it and you need to restart things. So I think kind of being thoughtful about it, but I always like an insurance policy. So I think freezing sperm is a backup plan, is a good one.
- [55:46]
A
I also agree we recommend our patients do that. You talked about that the age of a male, the paternal age can really have a big impact on sperm quality. And obviously it's a two person sport. If say a sperm age was younger but the egg was older, are there checks and balances?
- [56:07]
B
So I think the egg is probably more important. So I think that, you know, when you look at risks of older fathers, like in IVF cycles, for example, and you look, you can see that the risks of, you know, poor IVF outcomes, for example, go up as a couple gets older and older and you can track it with the male. But when you go to donor eggs, right. Where that were kind of freezing the eggs, like it in their 20s, then there's no risk. So I think the egg to say can sort of make up for any deficiencies that are in the sperm up to a point. After age 50, we do see some changes in terms of semen quality. You know, I think older eggs, younger sperm, I think we are going to start to have some problems because we do know that as you know, women age, fertility goes down and so we may see some, some issues.
- [56:50]
A
Will there ever be a way to choose the. So let me ask this a different way. Do you think that there is something subconscious is not biological, primal to being able to choose a partner or a mate?
- [57:07]
B
Yeah, it's interesting. I think, you know, we've thought about that a lot like in a reproductive. Because it seems like oftentimes like low sperm counts find low egg quality somehow. You know, we've seen a lot of that matching together and. Right. You wouldn't you. When you're choosing a mate, you have no idea. Right.
- [57:22]
A
I think that there has to be something else.
- [57:24]
B
Yeah.
- [57:25]
A
Beyond what we perceive as connection, whether it's pheromones or maybe it's something that we don't even, we can't even identify yet.
- [57:32]
B
Yeah, maybe. But yeah, it's. I mean it's passing. I know. I think just like when people ask me how I choose urology. Right. I think there's some randomness.
- [57:40]
A
How did you choose urology?
- [57:41]
B
There's some randomness to it.
- [57:42]
A
Right.
- [57:42]
B
It's who you're exposed to. I mean, for me, you know, I met some urologists who are very impactful. They seem to really enjoy their job. So that kind of set me on a path I was, you know, very early exposed to.
- [57:51]
A
Larry Lipschultz, thank you to our sponsor, One Skin, for sponsoring this episode. If you've ever felt burnt out from skincare, Too many products, too many promises, and not much to show for it. You're not alone. What finally made sense to me about One Skin is that they're not focused on surface level fixes. They're focused on changing how your skin functions over time, which is incredibly valuable.
- [58:15]
B
People.
- [58:15]
A
Their products are powered by a peptide called OS01, designed to target senescent cells, the aging cells that drive inflammation, thinning skin, and loss of resilience. I've noticed improvements in skin texture, hydration, and I've talked about this before, especially under my eyes, which has always been a problem area for me. And right now I'm using their eye cream, broad spectrum face sunscreen, and topical body supplement. Supplement. This is skin care for people who care about longevity, not just quick cosmetic wins. You can get 15 off one skin by going to OneSkin Co and using the code DoctorLion. That's 15 off OneSkin Co and use the code DrLion. Did you. Are you from Texas?
- [59:02]
B
I'm from Houston, yeah.
- [59:03]
A
You are?
- [59:03]
B
Okay, yeah, born and raised. But I did a sub internship, you know, at Baylor College of Medicine. Spent time with him, and that really told me that this is the field that was going to make me happy. But similar to mates. Right. I think that, you know, if you go to one school or another, you're exposed to sort of a different pool and you find people that make you happy and make you whole and you
- [59:22]
A
love what you're doing.
- [59:23]
B
I love what I'm doing.
- [59:24]
A
If you. And again, you do quite a few podcasts I've seen you on. My friend Andrew Huberman and Chris Williamson. You've done an amazing job. Is there something that you really want to be able to get out to the public?
- [59:37]
B
Well, I think just sort of more awareness of men's reproductive health. I think that people really don't think about it as much. You know, in the United States, when you look at data, you know, when couples are trying to conceive, the woman goes in, you know, and that's where the journey begins. And probably a quarter to a third of the time, the man's never evaluated, he never gets a semen analysis, never sees you.
- [59:55]
A
Quarter to a third. Never evaluated, Never evaluated. Even now, Even still.
- [59:59]
B
Even still, yeah. Sometimes, you know, these couples go to high vf, but still the man is not evaluated. And I think that there's a lot we can do. I think that, you know, if a man has a low sperm count, we could make it better. I think having some of these discussions about how important his health is going to be for his child, going to be for the pregnancy, I think those are very important discussions. And just having that touch point with the medical community I think is important. You know, if you've never seen a primary care doctor, you should go see, you should get screened for, you know, hypertension, hyperlipidemia, blood sugar. I think all those things are so key because health is so important. Right. And I think we have, you know, a lot of control over that.
- [60:35]
A
And what you've spoken a lot about is it seems that the metabolic health also reflects the sperm health. So if someone has a comorbidity of, like you said, hypertension, diabetes, high cholesterol, then potentially they'll have a lower sperm count.
- [60:49]
B
Right? Yeah. And so then again, that's going to be an opportunity that a primary care doctor or, you know, urologist potentially could put you on a path to improving to be more likely to get pregnant, maybe, if not for this pregnancy, for child number two. But I think there are gonna be
- [61:02]
A
some opportunities and it's a two to three month window where sperm changes over. If someone were to implement that, would you anticipate the sperm quality going up within that next window?
- [61:13]
B
Yeah, I will. But what's, you know, the other sort of part of this is that when we see these men, it's sometimes a little bit delayed so that, you know, again, the woman goes in after they've been trying for six months, a year, then they'll try some other things before they do the first semen analysis. And then we get that and it turns out to be low. And then they'll come to see us and we, you know, again, start on a path to try and improve things. You know, there have been some studies of male fertility that actually, you know, these really important trials that never got done just because it's so difficult to recruit men into these because, you know, couples have been through so much up to the point where the man first is evaluated. Like there was a study of looking at varicocele, so dilated veins in the scrotum, which are very common for infertility. About 40% of infertile men have these. And again, the testicles are outside the body because they need to be cooler. These larger veins can warm things up. And so it's been shown, I think pretty well now that if you fix them, you can see improvements in semen quality, but there is still some question. So I think doing more trials is certainly good. So about 10 to 15 years ago, they tried to do a study looking specifically at varicocele. And after I think about 18 months, they only enrolled three couples.
- [62:21]
A
Oh, my gosh.
- [62:22]
B
And this is like eight centers around the U.S. and when they talked to these couples, they said, how come you're not doing this? And it was sort of a post mortem. And their issue was that these couples had been trying for a year and then the man was finally seen. And to do like, like you talk about, if you're going to do anything, a surgery to fix a varicocele or something, it takes three to six months before you see a benefit. And they didn't want to wait that period of time or they didn't want to potentially not get any treatment. So I think that that is sort of where male fertility was. I think it's now getting more and more pushed to the front forefront, or at least equal to female fertility. That's going to be an upfront evaluation that's done.
- [62:57]
A
And if someone was evaluated very early on for say, avericocele, which is there, does that it happens a little bit later? And is it true that it happens a little bit later?
- [63:06]
B
It usually starts around puberty. I mean, there are certainly adolescent ones that we see, but typically around puberty is where we see it. You know, if you look at older men, like it's more common in secondary infertility where you had, you know, a first child and they're trying to have a second, and it's difficult. So as we get older, you know, we're standing up and then there's just more sort of pressure on the veins. So over time it can. Those veins can grow in size and then they can kind of cross over to that pathology.
- [63:29]
A
Would that also be one reason why individuals have lower testosterone?
- [63:33]
B
Yeah. So varicocyls have been associated with testosterone levels. And there have been some investigators that have shown if you fix a varicocele, you can improve testosterone. It's not one of the primary indications that we offer it for, although there are probably some providers that do that. But, yeah, you can increase Testosterone by about 100 points with a varicocele repair.
- [63:52]
A
And would you consider that clinically significant or would it depend?
- [63:56]
B
I guess it depends where you're starting. But generally 100 points is a lot. I think men would be happy with that.
- [64:01]
A
I would agree with you. Um, talk to me about some of the other more alternative Approaches. So platelet rich plasma or ways to improve sperm pla. Because that's not, I would say, not the standard. It's very innovative.
- [64:14]
B
Yeah. So we started that protocol, you know, a couple years ago. And the idea is that, you know, we take blood and then concentrate it down to this platelet rich sort of concentrate, which is thought to be enriched with growth factors. And then we can inject it into the testicle and through these growth factors. But maybe potentially through stem cell recruitment. I think the mechanisms are still being worked out all across the body because we've seen benefit in orthopedics and dermatology. So I think it does have some legs to it. But we wanted to be very thoughtful about this. So we didn't give it to everybody. We give it to a very specific population. So these are men with azospermia. So no sperm in the ejaculate. And as you.
- [64:55]
A
How common is that in general?
- [64:56]
B
It's probably about 1% of all men. So if you go to like, yeah, if you go to like a football stadium, there's gonna be thousands of men that are afflicted in this. And it could be due to a production issue or a blockage issue. So obviously you never want it. But if you had to choose one, a blockage is better. Cause that's something we could sometimes fix. Or we could get that sperm out that we could use for ivf. But some men have a production issue, and about half the time we can look inside the testicle and get it out, but another half of the time there's just not any sperm being made. And so that's the population we. We looked at for this at first. So they'd gone through sort of conventional standard of care approaches to try and look inside the testicle to find sperm. And it wasn't any there. And those are usually men we say donor sperm adoption, live without children. There's not much else medically that can be done at this point.
- [65:39]
A
Do we know did they at one point produce sperm or is this kind of a genetic.
- [65:43]
B
Some of them did, yeah. So some of them, you know, it's not as common, but sometimes they had kids before sometimes, you know, we know there was a clear exposure like chemotherapy that, you know, probably wiping out. And unfortunately they didn't, you know, cryopreserve sperm beforehand.
- [65:57]
A
What about blast injury?
- [66:00]
B
I think there's, you know, for trauma, I think there's less data around that. I think there's, you know, I've. I've, you know, worked with a lot of great Urologists in military service. And so some of them have done some pretty amazing things, you know, finding sperm in different parts of the genital tract if there was, you know, devastating injury to the genitalia. But yeah, I mean, anything, you know, the testicles are relatively exposed. So I think any injury could impact things.
- [66:24]
A
And the reason I was just thinking about that is because for women, they're born with a certain amount of eggs and then. Yeah, and then they're not. But it seems like for men it's, It's a bit different.
- [66:34]
B
Yeah. So we're born with sort of sperm precursors and after puberty they start to, you know, self renew and then produce sperm, you know, over and over again, you know, until again. Until we die again. The self renewal process is mostly perfect, but there are some mutations that are introduced, so probably about two a year. So that's why, you know, we think that older men have, you know, higher rates of these kind of rare disorders compared to younger fathers.
- [66:58]
A
And does the platelet rich plasma help that make more robust, more youthful.
- [67:03]
B
So we're so right now we've only used it for this population that has failed testicular sperm extraction. We inject into these men, wait, a cycle of spermatogenesis 3 months. And it doesn't always help with sperm production. At about 20% of the time, you know, one in five of these men that didn't have sperm all of a sudden have sperm. And actually just yesterday.
- [67:21]
A
How many? Five.
- [67:23]
B
One in five.
- [67:24]
A
That's amazing. That's the difference between having a child and not.
- [67:27]
B
Yeah. Actually just yesterday I got an email from a patient that just delivered. So that was amazing. I sent it to the whole team. Everyone was really delighted.
- [67:35]
A
You mean that? That's extraordinary. It changes legacies for people.
- [67:40]
B
Yeah. So it's very impactful. So that's how we're using it now. But I think as we see benefit, there have been some groups that are describing it for all patients just with low sperm counts. And I've seen some improvements, I think, to your point. Maybe could be rejuvenative for older fathers, maybe an opportunity. I think we're very much in the infancy, but potentially it's something that could be offered.
- [68:01]
A
Have you thought a lot about exercise and training in sperm quality?
- [68:05]
B
Yeah. So we've also started to look at that as well. You know, I think again, sort of the mantra is anything that's good for your heart is good fertility.
- [68:11]
A
What about muscle?
- [68:13]
B
Yeah, muscle too. I know, but you'll convert me.
- [68:16]
A
I will. Because what happens when you lift? Don't you increase androgen receptor density?
- [68:20]
B
Yeah, that's only going to be good.
- [68:22]
A
I mean, I think that's only a positive, but I don't think when you do cardiovascular activity, I don't. Again, I don't know. But I don't think you increase androgen receptor density to muscle. I don't know.
- [68:35]
B
Yeah, I'm not sure.
- [68:35]
A
Yeah, I'll have to get back to you.
- [68:36]
B
You're the expert. But. But it. So I think exercise is good, but it is possible to over train, certainly under train. You know, that certainly can be done. But, you know, for men that have very vigorous exercise too many times a week, you know, we do see, again, this sort of reverse U shape where benefit, benefit, benefit, and then it starts to decline a little bit. So, you know, I think that cut 0.5 varies for. For men in. Some obviously are gonna have a lot more capacity than others, like Navy SEALs
- [69:02]
A
or things like that, but they can't find their socks.
- [69:04]
B
Yeah. But others may be an issue. So I do think sort of be mindful about, you know, over training. And we have seen that, like in marathon runners, professional athletes, really, people that exercise or push themselves to exhaustion constantly, we do see slightly lower semen quality.
- [69:18]
A
Is that similar to the female triad?
- [69:21]
B
Yeah, yeah, I think that's. Yeah.
- [69:23]
A
A great analogy of amenorrhea, you know, somewhat. Infertility.
- [69:29]
B
Yeah. If you. Yeah. If you're going too hard, if there's no fat, I mean, if there's, you know, that sort of pattern, it can affect reproduction. Right. I think it's sort of the same thing if. If your body senses that you're kind of at the very peak of, you know, you're trying to prioritize survival, that reproduction gets deprioritized to some extent.
- [69:46]
A
Is there a percent body fat you think is most optimal for male fertility?
- [69:50]
B
That's a great question. I'm sure there is. I don't know exactly where that would be, but again, it is possible to overtrain.
- [69:58]
A
Yeah, yeah, it would make sense. Does the overtraining affect the libido or does it actually affect sperm quality and quantity?
- [70:08]
B
Yeah, we've seen it in. Yeah. And like kind of these parameters of the number of sperm, the number moving, kind of the quality of the semen. So I think that's. And again, these men don't go from great to terrible. They just go from great to maybe a little less great. So they kind of stay above that. But we do see when we look at populations of hundreds of men, we can do these studies where we have these very nice surveys. We can see that pattern.
- [70:33]
A
Your top three to five tips for increasing fertility for men.
- [70:40]
B
Yeah, so these are kind of taking. Going inside a clinic with me. So I think we're going to talk about good diet, exercise, which is, I'm curious, which is so whole grains, fruits, vegetables. I think I always hear about sort of shopping on the periphery of a supermarket rather than going into the processed
- [70:56]
A
foods and of course, proteins.
- [70:58]
B
Proteins, yeah, you definitely want to get all those. And then, you know, trying, if to the extent possible, maybe avoiding like non organic food to try and minimize pesticide exposure. I think that's important as well. You know, again, exercise is going to be important for muscle health, bone health, and then, you know, metabolic health. I think that's also important. We're trying to eliminate some things. So like, heat exposures are not good. You know, how much any. Any can be bad.
- [71:24]
A
So any sauna exposure.
- [71:26]
B
Yeah. So again, like we talked about patients that like, have gotten the flu or kind of have this, you know, febrile illness that can impact it. But again, it takes two to three months to make a sperm. So if you, you go on vacation, spend 30 minutes or 20 minutes in a sauna, that can wipe out sort of a generation of sperm. How long have to wait?
- [71:44]
A
And we know that to be true.
- [71:45]
B
We know that to be true. Yeah.
- [71:47]
A
Sauna would not be good if you're trying to go for fertility.
- [71:50]
B
Yeah, yeah. There was a very interesting attempt at a contraceptive. It was a sort of a trust device that men would wear and it would push their testicles up into the groin. Sounds tremendously uncomfortable, right? That he could find men that would do this. But it basically was sort of like a light switch. Like you could see they track sperm counts like every week, and you could see it just go right down. And then they worked for some period of time and then as soon as they took it off, the sperm counts recovered. So we were very sensitive to temperature. Um, so that's also something that we want to.
- [72:17]
A
But not cold, just heat.
- [72:19]
B
Just heat. Yeah. I think cold is sort of interesting whether we could find ways to, to improve that. But like, yeah, some patients talk about, you know, cold exposure and that doesn't seem to be a negative impact.
- [72:31]
A
Diet, exercise, environmental exposures, even though you can't.
- [72:37]
B
And then I think, yeah, we talked about like supplement use. I think there's good data that that can help as well. And then I think sort of being conscious of health. So if you do have, you know, some comorbidities, you know, if you're or you haven't been checked, you want to make sure you don't have high blood pressure, cholesterol, diabetes, you know, metabolic health, and then seeing, you know, your primary care doctor to get those under control, I think that's also going to be really crucial. And then, you know, seeing one of us, seeing Dr. Lipscholz, Dr. Caro, myself, so we can get screened. You know, we do a comprehensive hormone panel, do a semen analysis. We'll do a physical exam to see if you have a varicocele, see if there's other conditions that we can correct to put you on a good path.
- [73:14]
A
Is there a level of estrogen or estradiol that, when you're looking at the blood, I'm assuming the panel is similar to those at Baylor. It's free. Testosterone, testosterone, fsh, lh, estradiol. Is there a level of estrogen? So, for example, in our clinic, we like to see estrogen between 30 and 50.
- [73:33]
B
Yeah.
- [73:33]
A
If estrogen is, say, 50 and beyond, does that affect fertility?
- [73:37]
B
It can. I mean, I think there's a ratio of testosterone, but I think we see, you know, there's certain kind of a body type where we see higher estrogen levels. So most of our estrogen in men is from peripheral conversion of testosterone. And so that happens a lot in fatty tissue where there's more of that aromatase activity. So for men that have a little extra weight, we see more of that conversion, higher estrogen levels. So I think as that really leeches the testosterone, the testosterone goes down, you can sometimes get in a subnormal range or just the ratio between the two. I think normal is probably about, you know, 20 or so. But, you know, I think we start to really get worried when it gets below 10. So for men, you know, with a. Like, for example, like a testosterone of 200 and then an estrogen of 60 or 70, that's some men that we really want to pay attention to. And those men may benefit from aromatase inhibitors or other therapies to try and reverse that. And we do also see improvements in
- [74:27]
A
semen quality and the evaluation for coming in for infertility. Does it also happen to have imaging with it or. This is where you start. You start with blood and you start with semen.
- [74:39]
B
Yeah, we start with blood and semen. I think physical examination is excellent, and then there are certain indications for imaging. Sometimes if the scrotal exam is difficult and men are very shy, or there can be a very tight scrotum, if it's a cold environment, sometimes an ultrasound can be helpful. Sometimes an ultrasound can be helpful just in all of them to sort of evaluate for varicocele, to give precise quantities about how big the veins are. And then there's some cases we image elsewhere. If we worry about sort of the ejaculatory architecture, the prostate, these structures called the seminal vesicles that produce most of the ejaculate fluid, sometimes they can form incorrectly, so we want to check for those as well.
- [75:15]
A
And are there a handful of things or they're your top three to five things that people should not be doing?
- [75:21]
B
Well, I think hot tub, sauna, I think those are going to be key. I think if you're on testosterone, talk to your doctor about it. I think that is also going to be really important. And then I think those are probably the two biggest ones. I think anytime you start the journey, I think it's reasonable to talk to an expert about this stuff. I think obviously maybe it's sort of a bias of mine, but I think that esteem analysis is very important. Again, I kind of license it or market it as a vital sign. So I think it's always reasonable to have that information. I know that nowadays the only time men find out is if they're having difficulty. Essentially I would say that once or twice a year a man will come to see me just in case either has a suspicion he's infertile or before he kind of starts, he just wants to know where he is. But I think that's very much the exception. But you know, how valuable would it be if a 20 year old started to do a semen analysis? Because we know things do change and. Right. We all have experiences where patients had kids in their 20s and then all of a sudden they come to see us when they're 40 and they don't have any sperm left and we don't know why, but again, there may be that opportunity. So maybe he was low. Then we could have told him, you know, cryopreserve or let's find out why, maybe we can reverse it. So I think having that information is important from a reproductive standpoint and then again from a health standpoint, a metabolic standpoint. It would give us so much information.
- [76:41]
A
Dr. Eisenberg, it's wonderful to meet you. And I know that you have a lab at Stanford, you're currently doing research. What are you guys working on now?
- [76:50]
B
Well, I think it's sort of an extension of this. I think one interesting thing we want to look at now is sort of immune profiles and how that influences things. We know that, you know, for female fertility, there's an immune sort of counterpart like endometriosis. And there's so much we don't know about what causes infertility. When they come to see us, we can diagnose most conditions, but probably about a third of the time. Time we don't have a clear explanation why a man's semen count is a little bit low. And so I think, looking again, as technology improves, we have sort of an omic view of everything. We can do genomics now, we can do meta metabolomics. We can also look at immune profiles in a lot of detail. So I think that may give us another opportunity to understand cause and then novel therapies of trying to improve it.
- [77:33]
A
I actually haven't thought about that at all. And when you say immune profiles, are you talking about T cells? What kind of are you looking at? White blood cells? What are you looking at?
- [77:42]
B
Yeah, this is pretty wild. So on a chip with like, this is almost kind of Theranos level, but just with a very small quantity, you can look at. We're looking at 250 different chemokines, cytokines, you know, proteins that are involved in immune pathways. So we can really kind of tease out what's affecting. We have seen differences with men with low sperm counts, no sperm counts. And I think, again, there's so much data, we're just starting to uncover it. So I think hopefully we'll be able to find some meaningful trends.
- [78:11]
A
Wow. And what I'm hearing you say is that you're looking at the things like Interleukin 6, TANF Alpha. These are all cytokines that are released from various cells. Like macrophages.
- [78:23]
B
Right, Exactly.
- [78:24]
A
They're also released from muscle during exercise.
- [78:25]
B
Oh, is that right? Okay.
- [78:26]
A
Yes. And it creates this somewhat of a counterbalance of the immune system and inflammation.
- [78:32]
B
Yeah.
- [78:32]
A
It would be fascinating to see if one was dysregulated and then one could be reregulated.
- [78:36]
B
Yeah. I mean, I think it's a tremendous opportunity. Again, not for everybody, but I think, again, there's this pocket of men that we don't have any idea. And then there's some men, we see some improvement, but we don't get them all the way to normal. And I think this may be, again, an opportunity to try and. Yeah. Help our patients.
- [78:52]
A
Well, truly, I'm looking forward to when your book comes out, Dr. Eisenberg. I'm working on that. And really, it is such a pleasure. Is there a place that people can find you?
- [79:01]
B
Yeah. So if they go to Stanford. Website. Eisenberg Lab.
- [79:05]
A
Thank you so much.
- [79:07]
B
This is a pleasure. Thank you so much.