SPEAKERS
Dr Gabrielle Lyon , Dr. Michael Eisenberg

Dr Gabrielle Lyon 00:00
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 GLP ones? 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?

Dr. Michael Eisenberg 00:19
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 we talk about male fertility, we define it in terms of semen quality.

Dr Gabrielle Lyon 00:40
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.

Dr Gabrielle Lyon 00:59
Dr Eisenberg, welcome to the show. Thank you so much for having me. 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.

Dr. Michael Eisenberg 01:46
Yeah, so that was a study that we did a few years ago. You know, kind of the I’ll give you the back story, 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 general 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. 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, anything that’s good for your heart is going to be good for fertility. That’s what we talk about. 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, were 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 it was 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 a sperm, takes about two to three months, so that window of exposure is, you know, kind of just before conception. So we looked at men that were taking it earlier. We looked 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. Yeah.

Dr Gabrielle Lyon 04:12
I mean, I have a few questions now, obviously, those that were taking Metformin, I’m assuming, were diabetic, yeah, yeah, there’s been a lot of use of metformin for longevity purposes. That’s where this could really inform our decisions.

Dr. Michael Eisenberg 04:29
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 its 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 and that, you know, we should, you know, evaluate some of these medications in probably more detail now that more and more of our fathers and mothers are on these and just see the effects that they’re going to have potentially on offspring. Because this is, you know, 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, there’s a lot

Dr Gabrielle Lyon 05:43
more information that we’re getting. Things that we use 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.

Dr. Michael Eisenberg 06:21
Yeah. No, it’s a good question. So we really don’t, I think that again, before we change practice, I, you know, wanted, I was kind of very 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 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 again, we looked at it very extensively in this population, it really seemed like it was really linked to Metformin. So I think just, I guess, the message, just be mindful, but also just appreciate that the male is important. The Father is important, and what we do today will impact not just ourselves, but 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

Dr Gabrielle Lyon 07:27
goal 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, there’s two main cases now obviously 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 GLP ones if they come off of it, once that spermagenesis window, once that creation if the sperm, what do you say they don’t utilize it? Where does it go? Dissolves? What happens to the sperm if you don’t use it?

Dr. Michael Eisenberg 08:09
Well, some of it’s, 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.

Dr Gabrielle Lyon 08:16
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?

Dr. Michael Eisenberg 08:27
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 wash 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.

Dr Gabrielle Lyon 09:24
What about the use of GLP ones? And there’s some data to suggest that the use of GLP ones can help female fertility, whether it’s from a metabolic perspective or decreasing inflammation. How does that look from a male perspective?

Dr. Michael Eisenberg 09:38
Yeah, so that’s like a very big question right now. And I think that, you know, the goal is that there are going to be some upcoming trials that will look at that specifically. Currently, the best data we have is a randomized trial from one of the makers of the GLP one, 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. 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 your calorie restriction, do sort of aggressive training, or be on a GLP one. And as long as you maintain weight loss, whether it was through calorie restriction or GLP one, the benefit and semen quality maintain. So I kind of take that to mean that it looks like it is safe for fertility. I think that we do need data to show that. You know, if a man is overweight, he goes on GLP one, 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 are conceived or healthy. Because again, I think that prior GLP ones 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.

Dr Gabrielle Lyon 10:52
It makes a lot of sense. And again, there’s the pathology component, but then there is the performance component. The the landscape, with the use of GLP ones, we’re seeing a decrease in muscle mass, not because of any magic that the GLP ones magically decrease muscle mass, but again, that allows for calorie restriction. Testosterone also seems to be getting a bit of a liberation. And to come back, where do you feel that there is this balance between performance testosterone using performance and infertility.

Dr. Michael Eisenberg 11:24
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 going to be right in isolation to help. Because, you know, the way that kind of our feedback works is that when you take exogenous testosterone, 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. Does it matter the dose? 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

Dr Gabrielle Lyon 12:07
but in like, a subcutaneous small dose, yeah, or there

Dr. Michael Eisenberg 12:11
have been different, yeah, there are different formulations that can be given, you know, 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 so that they put that aside.

Dr Gabrielle Lyon 13:06
When you say other medications, do you mean common hCG?

Dr. Michael Eisenberg 13:11
Yeah, exactly, yeah, Clomid, HCG and aromatase inhibitors, like anastrozole, letrozole, those are also options that can increase your testosterone and it thought to be safer for metagenesis

Dr Gabrielle Lyon 13:23
when the kid, you know, the velocity at which information spreads is so much faster. Now, do you remember? I’m hoping that you do when, at least I did. I had to go to the library and pull out the medical journal.

Dr. Michael Eisenberg 13:38
Yes, yeah. I remember, yeah, in medical school, I would spend a lot of time in the journal and the library to look up all these forever. It was very slow.

Dr Gabrielle Lyon 13:46
Yes, so slow. And now you go online and the 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 tanned 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 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 steak 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 body health.com and use the code lion 20 to get 20% off your first order, that’s a body health.com and use the code lion 20. Yeah.

Dr. Michael Eisenberg 16:06
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 get 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.

Dr Gabrielle Lyon 16:41
And you’ve called sperm Another vital sign. Did you call it a biomarker or vital sign, or both?

Dr. Michael Eisenberg 16:46
I’ve done both, but yeah, vital sign is the one I use most commonly. Talk to me about what that looks like, 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 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 divided 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 was 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 100 million more sperm if he just had that treated. So it’s really 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.

Dr Gabrielle Lyon 18:47
And how do we define sperm quality? So, you

Dr. Michael Eisenberg 18:50
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 millions 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 sort of the integrity of the DNA within the sperm.

Dr Gabrielle Lyon 19:14
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, in sperm, ejaculate? Yeah.

Dr. Michael Eisenberg 19:40
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 analyzes to find these are 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 very specific labs, maybe only one or two places on earth. And now I think. I worn. 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. You have seen that. You do see that it’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 this quality of the semen. Again, some of these same parameters, we see, lower motility, lower numbers when there’s more microplastics.

Dr Gabrielle Lyon 20:40
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

Dr. Michael Eisenberg 21:12
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, and 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 ubiquitous exposure. And plastic is so great, right? I think we 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.

Dr Gabrielle Lyon 22:21
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, yeah, and sperm quality likely changes over time in 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.

Dr. Michael Eisenberg 22:46
Or that’s a good question. I mean, the oldest spot there ever is 96 so the biologic potential

Dr Gabrielle Lyon 22:52
probably Hugh Hefner, no, no, I’m just

Dr. Michael Eisenberg 22:54
kidding, 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, we define older fathers by the American urologic Association, American Society of Reproductive Medicine is over. Medicine, is over 40, and it’s not that there’s sort of a clear transition at that point. But 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 they 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 partner. So really, you know, it 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 short sighted. We continue to have 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

Dr Gabrielle Lyon 24:57
staying pregnant as you’re talking I. 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 B 12. Oh, interesting. 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 B 12 and some of the B vitamins with metformin. And back to sperm quality, are there specific nutrients for sperm? Yeah.

Dr. Michael Eisenberg 26:03
So I think again, 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 know, sort of been like kind 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 should improve sperm quality and improve fertility. So actually, work with a, you know, a company called swim club that does have a, it’s sort of a full stack mill 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, sort of looks at all things. So we look at, like, mitochondrial health, right? Like cleans on Q, omega threes. We looked at, you know, antioxidants, pen, acetyl cysteine, you know, selenium, lycopene. And then also, you know, cellular DNA integrity as well, like zinc spermidine. So, 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 that it’s it’s going to be the best, because 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,

Dr Gabrielle Lyon 27:35
of course it is. And what 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. Wow. Okay. And Mo was on there, Shane was on there, lip Schultz was on there, because I think that muscle is the center point, because you talk about erectile function and vascular health, yeah, 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?

Dr. Michael Eisenberg 28:37
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 then shop,

Dr Gabrielle Lyon 28:57
shop. Okay, fine. Yeah, no, you don’t sometimes.

Dr. Michael Eisenberg 29:02
But, um, 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 deep, 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,

Dr Gabrielle Lyon 29:21
maybe that that would be the next one, yeah, 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? So.

Dr. Michael Eisenberg 30:00
Um, 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 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.

Dr Gabrielle Lyon 30:35
It is low libido, a sign of poor sperm quality.

Dr. Michael Eisenberg 30:41
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 levels than their fertile counterparts. So 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 little libido.

Dr Gabrielle Lyon 31:02
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, 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?

Dr. Michael Eisenberg 31:33
It’s all supposed to help with sex selection as well. Really? Yeah, okay, well, but

Dr Gabrielle Lyon 31:37
again, see now I don’t I like, I’m like, am I gonna turn red while I’m asking this question?

Dr. Michael Eisenberg 31:42
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.

Dr Gabrielle Lyon 32:02
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.

Dr. Michael Eisenberg 32:22
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 on the fallopian tube and eventually out. And so we want sperm kind of waiting for the egg during that time. So usually we’d say that sperm can live inside the female genital tract for about two days. So if one is going to ovulate, like on day 15, I tell couples have sex 1012, 1416, and 18. So we do every other day, because 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

Dr Gabrielle Lyon 33:09
partner’s uterus, because you’re sort of less there. So it does a decrease volume.

Dr. Michael Eisenberg 33:13
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’s some 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

Dr Gabrielle Lyon 33:38
conceive so space it, it’s Yeah, or 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. Seems to be beneficial.

Dr. Michael Eisenberg 34:15
I would also try and time out with your partner cycle too. So there’s 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 is going to occur. So you can try and have sex around them.

Dr Gabrielle Lyon 34:33
And if someone goes for longer periods of time without ejaculating, for example, a week or two weeks, does that decrease sperm quality?

Dr. Michael Eisenberg 34:41
It can so I think the volume can increase. There could be more sperm. But we do worry some of the 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. Yeah, you start to try.

Dr Gabrielle Lyon 35:02
Do you think that there are things that can help so that, again, there’s all these peptides that people are talking about. Is there space for that?

Dr. Michael Eisenberg 35:10
I think, you know, there’s no FDA approved medicine for male fertility. So I think you know, 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,

Dr Gabrielle Lyon 35:38
and you were responsible for part of the guidelines, the newer guidelines for male infertility.

Dr. Michael Eisenberg 35:44
Yes, yeah. So 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 what’s evidence based and how should we be treating infertile men around the world?

Dr Gabrielle Lyon 35:58
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Dr. Michael Eisenberg 37:42
So 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 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, 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.

Dr Gabrielle Lyon 38:15
Do certain areas of the US have better fertility than others?

Dr. Michael Eisenberg 38:21
Sperm count really varies around the country. It is wild. You know why this 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 them 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 would be were in actually on the coast. The highest was actually New York. So everything very counterintuitive. Yeah, right. You’d 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.

Dr Gabrielle Lyon 39:35
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 cute 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.

Dr. Michael Eisenberg 39:56
Oh, it’s interesting. Yeah, I don’t know. I think that. Yeah, it’s a good question. And 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.

Dr Gabrielle Lyon 40:19
Yeah, 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.

Dr. Michael Eisenberg 40:37
Yeah. So, you know, I think the first thing when 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, like what, 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 on kind of, you know, you know, when we kind of gone back and looked, you know, after it was approved, post approval analysis 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 other medications after three months, six months, you know, a few cycles of spermatogenesis, most men will will improve a little bit. So about us, 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, you know, it’s sort of the vanity is, is real. But you know, most will, most are certainly, you know, are willing to do that.

Dr Gabrielle Lyon 42:00
Would you say that people are no longer prescribing finasteride at this point,

Dr. Michael Eisenberg 42:05
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.

Dr Gabrielle Lyon 42:30
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? There have

Dr. Michael Eisenberg 42:45
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 and 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 men 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 given it by their 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.

Dr Gabrielle Lyon 43:36
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,

Dr. Michael Eisenberg 43:49
you know, I think I would not be surprised if there are 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 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,

Dr Gabrielle Lyon 44:28
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.

Dr. Michael Eisenberg 44:45
Interesting, yeah, yeah.

Dr Gabrielle Lyon 44:47
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 you when we evaluate the health of muscle, I 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 bi directional 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? Yeah.

Dr. Michael Eisenberg 45:24
I mean, definitely, if you look at sort of metabolic health, kind of all the parameters that you’re discussing, there have been groups that have shown that associates with semen quality. But interestingly, if you look at semen quality, it’ll predict later risk of getting metabolic disorder. 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 one 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.

Dr Gabrielle Lyon 46:15
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 an echo to limit the heart. Is there imaging that one could do to the 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,

Dr. Michael Eisenberg 46:56
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 did a study about 10 or 15 years ago. 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 studies showing that semen quality, like lower semen quality, 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, I can tell you when he’s going to die decades later. So if you had a lower semen quality, lower concentration, lower volume, your 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.

Dr Gabrielle Lyon 48:09
That 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,

Dr. Michael Eisenberg 48:18
yeah, it had to write actual actuarial tables. I mean, it’s it gives us a lot of interest. Information, and it’s sort of exciting. I think that we’re getting this new data.

Dr Gabrielle Lyon 48:27
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?

Dr. Michael Eisenberg 48:41
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 not to blame mothers for things. But you know whether there’s microplastics, like my mom for everything, so go right ahead. 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 gonna, you know, turn out.

Dr Gabrielle Lyon 49:12
So like hearing you say that, yeah, it’s important. And you speak a lot about personal responsibility, and you don’t hear that a lot, yeah,

Dr. Michael Eisenberg 49:22
we don’t want to be alarmist. So 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. So 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, though, at times it feels like they’re trying to kill you. They’re actually there’s lower risks of heart disease, lower risks of death. And same with having a partner. As well. You know, these factors that go hand in hand with reproduction. They are very important for health and longevity.

Dr Gabrielle Lyon 50:06
Male marijuana use seems to really be increasing. Younger males using marijuana, yeah.

Dr. Michael Eisenberg 50:12
So there have been some studies looking at reproductive health with that as well. There’s 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’d say daily, to seem to have a 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.

Dr Gabrielle Lyon 51:00
Do you have a perspective? So there’s the data, and then do you have a clinical perspective

Dr. Michael Eisenberg 51:06
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 just with your buddies and you can do without it, then I think that’s certainly going to

Dr Gabrielle Lyon 51:28
be better. What about some of the other lifestyle stuff, like sleep?

Dr. Michael Eisenberg 51:31
So sleep is sort of funny. It’s, it’s kind of like a U shaped relationship. So it’s, you know, you certainly get too little sleep, right? That makes sense. And I think that cut off 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, 910, 1112, hours, we also see that same drop off. I don’t know why that is. Maybe these are no you know, some men do it for sort of performance reasons. I remember during a hard knocks. JJ Watt talked about sleeping 12 hours a day and how boring that was. But 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 played. So I tell men, seven to nine hours ideally. Do you

Dr Gabrielle Lyon 52:16
guys in your clinical practice evaluate for sleep apnea, and are there certain metrics that you always look at.

Dr. Michael Eisenberg 52:22
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 studying or diagnosed, but 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.

Dr Gabrielle Lyon 52:46
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 lip Schultz. 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?

Dr. Michael Eisenberg 53:16
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. You did your fellowship at Baylor. I do my fellowship at Baylor, yeah, which was great, 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 have you done a fellowship in male reproduction? Are you an expert in the area? I think that’s that’s important.

Dr Gabrielle Lyon 53:59
You also make a really good point. It’s so, 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, yeah, you know you’re talking about 40 fellows, yeah, a year, yeah. And that’s probably extra,

Dr. Michael Eisenberg 54:17
yeah, yeah, the number of male reproductive urologists, yeah, it’s in the low hundreds right now.

Dr Gabrielle Lyon 54:22
It’s, it’s really, really small. What about the use of anabolic agents? And 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 nyandrolone, which, again, is a medication that’s FDA approved. How do medications like that affect fertility?

Dr. Michael Eisenberg 54:45
I mean, I think it’d be the same pathways as just, you know, testosterone subunit or others, you know, we’re gonna see that suppression of the hypothalamic pituitary, gonadal axis. 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

Dr Gabrielle Lyon 55:04
you’re going to be on these, how long does the frozen sperm last? So the longest time,

Dr. Michael Eisenberg 55:08
interestingly, between freezing and use ever port is about 25 years. In theory, just and what happened, they actually utilized, yeah, okay. But in theory, based on sort of ionizing radiation from the sun, you could freeze sperm for 200 years. So it should be 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.

Dr Gabrielle Lyon 55:45
I also agree we recommend our patients do that. You talked about that the the age of a male, the paternal age, can really have a big impact on sperm quality, yeah, if, 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?

Dr. Michael Eisenberg 56:06
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 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 we’re 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.

Dr Gabrielle Lyon 56:50
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.

Dr. Michael Eisenberg 57:06
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 qualities 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? I think that there

Dr Gabrielle Lyon 57:22
has to be something else, yeah, beyond what we perceive as connection, whether it’s pheromones or maybe it’s something that we don’t even, we can’t even

Dr. Michael Eisenberg 57:31
identify yet, yeah, maybe. But, yeah, it’s, I mean, it’s fascinating. I think, just like when people ask me, how I choose urology, right, I think there’s some red did you choose Urology? There’s some randomness to it, right? It’s who you’re exposed to. I mean, exposed to. I mean, for me and I met some urologists who were very impactful. They seem to really enjoy their job. So that kind of set me on a path I was very early, exposed to Larry lips.

Dr Gabrielle Lyon 57:52
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Dr. Michael Eisenberg 59:01
I’m from Houston. Yeah, you are 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 envy 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 love what you’re doing. I love what I’m doing.

Dr Gabrielle Lyon 59:24
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? Well, I think just sort

Dr. Michael Eisenberg 59:37
of more awareness of men’s reproductive health. I think that people really don’t think about it as much. You know, 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

Dr Gabrielle Lyon 59:54
your quarter to a third, never evaluated, never even now, even

Dr. Michael Eisenberg 59:58
still, even still. You. Yeah, sometimes, you know, these couples go to IVF, 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.

Dr Gabrielle Lyon 1:00:35
And of what you’ve spoken a lot about is it seems that the metabolic health also reflects the sperm helps. So if someone has a comorbidity of, like you said, hypertension, diabetes, high cholesterol, then potentially they’ll have a lower sperm count, right?

Dr. Michael Eisenberg 1:00:49
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 going to be some opportunities,

Dr Gabrielle Lyon 1:01:02
and it’s a two to three month window where sperm changes over, yeah, if someone were to implement that, would you anticipate the sperm quality going up within that next window?

Dr. Michael Eisenberg 1:01:12
Yeah, I will. But what’s, you know, the other sort of part of this is that when we see these men, is 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 the 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 varicoceles, so dilated veins in the scrotum, which are very common for infertility, about 40% of infertile men have these. And you know, 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 pretty, 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, you know, about 10 to 15 years ago, they tried to do a study looking specifically at berica seal. And after, I think, about 18 months, they only enrolled three couples, and this was like eight centers around the US. 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 have 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 berica seal 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 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

Dr Gabrielle Lyon 1:02:56
done, and if someone was evaluated very early on for, say, avarica seal, which is there, does that it happens a little bit later? And is it true that it happens a little bit later? It usually starts

Dr. Michael Eisenberg 1:03:07
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, 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 vein. So over time it can those veins can grow in size, and then they can kind of cross over to that pathology.

Dr Gabrielle Lyon 1:03:28
Would that also be one reason why individuals have lower testosterone?

Dr. Michael Eisenberg 1:03:33
Yeah, so varicoceles 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 the varicocele repair.

Dr Gabrielle Lyon 1:03:51
And would you consider that clinically significant? Or would it depend? I guess it

Dr. Michael Eisenberg 1:03:56
depends where you’re starting, but generally, 100 points is a lot. I think men would be happy

Dr Gabrielle Lyon 1:04:00
with that. I I would agree with you. Talk to me about some of the other, more alternative approaches, so platelet rich plasma, or ways to improve sperm quality, because that’s not, I would say, not the standards, very innovative. Yeah.

Dr. Michael Eisenberg 1:04:14
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 Ridge, 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, it does have some legs to it, but we, you know, we wanted to be very thoughtful about this, so we don’t want to, 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 know, common is that, in general, probably about 1% of all men. So if you go to like, yeah, if you go to like. A football stadium, there’s going to be 1000s of men that are afflicted on 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, because 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 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’ve gone through sort of conventional standard of care approaches to try and look inside the testicle to find sperm, and there wasn’t any there. And those are usually men. We say, Wow, donor sperm, adoption. Live without children. There’s not much else medically that can be done at this point.

Dr Gabrielle Lyon 1:05:39
Do we know? Did they at one point produce sperm, or is this kind of a genetic

Dr. Michael Eisenberg 1:05:43
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 wiped it out. And unfortunately, they didn’t, you know, cryopreserve sperm beforehand. What about blast injury? I think there’s, you know, for trauma. I think there’s less data around that. I think there’s, you know, I’ve 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.

Dr Gabrielle Lyon 1:06:23
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, yeah.

Dr. Michael Eisenberg 1:06:34
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 to younger fathers.

Dr Gabrielle Lyon 1:06:57
And does the platelet rich plasma help that make more robust, more youthful.

Dr. Michael Eisenberg 1:07:02
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 cycles from out of Genesis three months, and it doesn’t always help with sperm production, but 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

Dr Gabrielle Lyon 1:07:21
yesterday, how many five? One in five? That’s amazing. That’s the difference between having a child and not Yeah.

Dr. Michael Eisenberg 1:07:27
Actually, just yesterday, I got an email from a patient that just delivered. So it was, that was amazing. I sent it to the whole team. Everyone was really delighted.

Dr Gabrielle Lyon 1:07:35
I mean, that’s yeah, that’s extraordinary. Judges, legacies for people, yeah, so

Dr. Michael Eisenberg 1:07:40
it’s very impactful. So that’s how we’re using it now. But I think as we see benefit, there been some groups that are describing it, you know, for all patients, you know, just with low sperm counts, and I’ve seen some improvements. I think, to your point, maybe could be rejuvenative for, you know, older fathers, maybe an opportunity. I think we’re very much in the infancy, but potentially it’s something that could be offered.

Dr Gabrielle Lyon 1:08:00
Have you thought a lot about exercise and training and sperm quality?

Dr. Michael Eisenberg 1:08:04
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. What about muscle? Yeah, muscle too. I know, but you’ll convert me.

Dr Gabrielle Lyon 1:08:15
I will, because what happens when you lift? Don’t you increase androgen receptor density? Yeah, that’s only gonna be good. I mean, I think that’s only a positive, yeah, 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.

Dr. Michael Eisenberg 1:08:33
I don’t know. Yeah, I’m not sure. Yeah. After you back to you, you’re the expert, but, but 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 point five varies for for men in some obviously gonna have a lot more capacity than others, like Navy SEALs or things like that, but they can’t find their socks, yeah? But others may be an issue. So I do think to 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 seams quality.

Dr Gabrielle Lyon 1:09:17
Is that similar to feed the female triad? Yeah, yeah. I think that’s a great analogy of amenorrhea, you know, somewhat infertility,

Dr. Michael Eisenberg 1:09:28
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.

Dr Gabrielle Lyon 1:09:45
Is there a percent body fat you think is most optimal for male fertility? That’s a

Dr. Michael Eisenberg 1:09:50
great question. I’m sure there is. I don’t, yeah. I don’t know exactly where that would be, but again, it is possible to over train,

Dr Gabrielle Lyon 1:09:58
yeah, yeah. It would make sense. Yes, does the overtraining affect the libido, or does it actually affect sperm quality and quantity?

Dr. Michael Eisenberg 1:10:07
Yeah, we’ve seen it in like, kind of these parameters of the number of sperm, the number and moving kind of the quality of of the semen. So I think that’s and again, these men don’t go from great to terrible. They just go from, you know, great to maybe a little less great, so they kind of stay above that. But we do see, you know, when we look at populations of hundreds of men, we can do these studies where we have, you know, these very nice surveys, we can see that pattern

Dr Gabrielle Lyon 1:10:32
your top three to five tips for increasing fertility for men, yeah.

Dr. Michael Eisenberg 1:10:40
So these are, yeah, kind of taking going inside a clinic with me. So I think we’re going to talk about good diet,

Dr Gabrielle Lyon 1:10:47
exercise, which is what I’m curious, which is so

Dr. Michael Eisenberg 1:10:49
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 foods. And, of course, proteins, 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. So any sauna exposure, yeah. So again, like, I mean, 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 go on vacation, spend 30 minutes or 20 minutes in a sauna that can wipe out sort of a generation of sperm to wait.

Dr Gabrielle Lyon 1:11:44
And we know that to be true. We know that to be true. Yeah, sauna would not be good if you were trying to go for a fertility Yeah, yeah.

Dr. Michael Eisenberg 1:11:51
There was a very interesting attempt at a contraceptive. It was a sort of a trust device that men would wear and 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 tracked 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 were covered. So we were very sensitive to temperature. So that’s also something that we want, but not cold, just heat. 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,

Dr Gabrielle Lyon 1:12:30
diet, exercise, environmental exposures.

Dr. Michael Eisenberg 1:12:36
And then I think, you know, yeah, we talked about, like, supplement use. I think there’s good data 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, 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, you know, one of us seeing, Dr lipscholz, Dr Kara myself, so we can get screen. 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.

Dr Gabrielle Lyon 1:13:14
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 and 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, yeah, if estrogen is, say, 50 and beyond, does that affect fertility?

Dr. Michael Eisenberg 1:13:36
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 the sub normal 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. 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

Dr Gabrielle Lyon 1:14:28
in 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.

Dr. Michael Eisenberg 1:14:38
Yeah, we start with blood and semen. I think physical examination is 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, 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. Yeah. And then there’s some cases we image elsewhere, if we worry about sort of the ejaculatory architecture, the prostate, the structure 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.

Dr Gabrielle Lyon 1:15:14
And are there a handful of things? Are there your top three to five things that people should not be doing well.

Dr. Michael Eisenberg 1:15:21
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 those are, 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 a steam analysis is very important. Again, I kind of license it or mark 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 there, 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 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

Dr Gabrielle Lyon 1:16:41
us so much information. 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?

Dr. Michael Eisenberg 1:16:49
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 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 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, you know, novel therapies to try and improve it.

Dr Gabrielle Lyon 1:17:32
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?

Dr. Michael Eisenberg 1:17:41
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 hemokines, cytokines, you know, proteins that are involved in immune pathways. So we can really kind of tease out what’s effect. And we have seen differences with now, 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. Wow.

Dr Gabrielle Lyon 1:18:11
And what I’m hearing you say is that you’re looking at the things like interleukin six, TANF, alpha, these are all cytokines that are released from various cells, like macrophages, right? Exactly. They’re also released from muscle during exercise. Oh, is that right? Okay, yes. And it creates this somewhat of a counterbalance of the immune system and inflammation. Yeah. It would be fascinating to see if one was dysregulated, and then one could be re regulated, yeah.

Dr. Michael Eisenberg 1:18:36
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.

Dr Gabrielle Lyon 1:18:52
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,

Dr. Michael Eisenberg 1:19:01
yeah, so if they go to Stanford website, Eisenberg lab,

Dr Gabrielle Lyon 1:19:05
thank you so much. This

Dr. Michael Eisenberg 1:19:07
is a pleasure. Thank you so much.