Male Fertility and Sperm Health: What Your Sex Drive and Testosterone Really Mean | Dr. Michael Eisenberg

13:47Dr. Gabrielle Lyon: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, OK, 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.

14:41Dr. Gabrielle Lyon: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.

15:24Dr. Gabrielle Lyon: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 steak. 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. Yeah.

16:06Dr. Michael Eisenberg: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.

16:41Dr. Gabrielle Lyon:And you've called sperm another vital, did you call it a biomarker or a vital sign or both?

16:46Dr. Michael Eisenberg:I've done both. But yeah, vital sign is the one I use most commonly.

16:49Dr. Gabrielle Lyon:Talk to me about what that looks like.

16:51Dr. Michael Eisenberg:Yeah. So that's 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 divide them into health.

17:29Dr. Michael Eisenberg: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 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, how 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.

18:04Dr. Michael Eisenberg: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, you know, 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.

18:38Dr. Michael Eisenberg: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.

18:47Dr. Gabrielle Lyon:And how do we define sperm quality?

18:50Dr. Michael Eisenberg:So, you know, we basically look at a semen analysis. So it's, you know, very broad. We look at the volume of a jaculate that comes out, how many sperm there are, usually quantified in 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.

19:14Dr. Gabrielle Lyon: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?

19:40Dr. Michael Eisenberg: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. It used to really be done in very specific labs, maybe only one or two places on Earth. And now I think more 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.

20:10Dr. Gabrielle Lyon:You have seen that.

20:11Dr. Michael Eisenberg:You do see that. 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.

20:40Dr. Gabrielle Lyon:I mean, that'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 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 uh you know again i 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

21:12Dr. Michael Eisenberg: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 your food yourself, maybe you can limit it. But if you're going to eat most meat, I mean, everything, it's in feed, it's just everywhere. So I think that standpoint, it is difficult. I think that you can make some changes, like try not to drink out of plastic bottles, don't microwave plastics.

21:45Dr. Michael Eisenberg: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, you know, 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.

22:16Dr. Michael Eisenberg:I think we just need to understand how it's getting inside of us and what it's doing when it's there.

22:21Dr. Gabrielle Lyon: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.

22:30Dr. Michael Eisenberg:Yeah.

22:31Dr. Gabrielle Lyon:And sperm quality likely changes over time in the development. Is there a defining moment in which sperm has now become mature or maybe has hit its stride from an age perspective?

22:47Dr. Michael Eisenberg:Yeah, that's a good question. I mean, the oldest spot there ever is 96. So the biologic potential.

22:52Dr. Gabrielle Lyon:Probably Hugh Hefner. No, I'm just kidding. No.

22:54Dr. Michael Eisenberg:But so, 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. from, you know, we define older fathers by the American Neurologic Association, American Society of Reproductive Medicine is over 40. And it's not that there's sort of a clear transition at that point.

23:27Dr. Michael Eisenberg: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, you know, 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 issues. So you should just be aware and try and do everything you can, again, 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.

24:14Dr. Michael Eisenberg: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, to get 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, going to drive 90 % of that pregnancy. But to think the man has nothing to do with it, I think, is short-sighted. We continue to have the DNA, and I think there's lots of other aspects as well. So men should really try and think about pregnancy kind of early, just like women start prenatal vitamins.

24:53Dr. Michael Eisenberg:Men should really try to take ownership of their health because it will affect getting pregnant and staying pregnant.

24:58Dr. Gabrielle Lyon: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 the 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 metformin decreases B12.

25:41Dr. Michael Eisenberg:Oh, interesting.

25:42Dr. Gabrielle Lyon:And 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?

26:03Dr. Michael Eisenberg:Yeah. 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've, 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 showed improves sperm quality and improve fertility. So I actually work with a, you know, a company called Swim Club that does have a, it's over a full stack male fertility supplement.

26:35Dr. Michael Eisenberg: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, 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, penicetylcysteine, 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.

27:13Dr. Michael Eisenberg: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 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.

27:35Dr. Gabrielle Lyon:Of course. It is. And 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 seeing your author on a paper that was linking muscle mass, muscle quality and strength with erectile function.

28:04Dr. Michael Eisenberg:Wow. Okay.

28:05Dr. Gabrielle Lyon:And Mo was on there. Shane was on there. Lipschitz 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? Yeah.

28:39Dr. Michael Eisenberg: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.

28:56Dr. Gabrielle Lyon:And shop.

28:57Dr. Michael Eisenberg:Shop.

28:58Dr. Gabrielle Lyon:Okay, fine. No, you don't.

29:01Dr. Michael Eisenberg:Sometimes. 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, 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.

29:21Dr. Gabrielle Lyon:Maybe that would be the next one.

29:23Dr. Michael Eisenberg:Yeah.

29:24Dr. Gabrielle Lyon: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?

29:59Dr. Michael Eisenberg: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 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, coming up with less interesting study ideas. It'd be very interesting to see how that affects it.

30:35Dr. Gabrielle Lyon:Is low libido a sign of poor sperm quality?

30:41Dr. Michael Eisenberg: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 infertile men. So I think if we kind of pulled that string, I think we'd also see low libido.

31:02Dr. Gabrielle Lyon: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 say, OK, 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?

31:33Dr. Michael Eisenberg:It's all supposed to help with sex selection as well. Really? Yeah. But again.

31:38Dr. Gabrielle Lyon:See, now I don't like I'm like, am I going to turn red while I'm asking this question?

31:42Dr. Michael Eisenberg:But no, like I think 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 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.

32:02Dr. Gabrielle Lyon: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?

32:22Dr. Michael Eisenberg: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'd 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 to have sex 10, 12, 14, 16, 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.

32:56Dr. Michael Eisenberg: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 because they're sort of less there.

33:11Dr. Gabrielle Lyon:So it does a decreased volume?

33:13Dr. Michael Eisenberg: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 that are very sensitive, some that are less so. But in general, it's better to, you know, I would say every sperm you produce, you want inside your partner when you're trying to conceive.

33:38Dr. Gabrielle Lyon:So space it. It's 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 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.

34:15Dr. Michael Eisenberg:Seems to be beneficial. I would also try and time out 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 can predict when that ovulation event's going to occur so you can try and have sex around them.

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

34:41Dr. Michael Eisenberg: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. And 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 start to try.

35:02Dr. Gabrielle Lyon: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?

35:11Dr. Michael Eisenberg: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.

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

35:45Dr. Michael Eisenberg:Yes. Yes. There's a joint effort by the American Urologic Association, the American Society of Reproductive Medicine, got to assemble a 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?

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37:19Dr. Gabrielle Lyon: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? So it's a good question.

37:44Dr. Michael Eisenberg: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. 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.

38:15Dr. Gabrielle Lyon:And do certain areas of the U.S. have better fertility than others?

38:21Dr. Michael Eisenberg:Well, 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 them to give a semen sample. Not everybody did, but a lot did. And so this was four centers around the U.S.

38:54Dr. Michael Eisenberg: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 -

39:08Dr. Gabrielle Lyon:That's very counterintuitive.

39:09Dr. Michael Eisenberg: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.

39:36Dr. Gabrielle Lyon: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?

39:56Dr. Michael Eisenberg: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 you 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.

40:21Dr. Gabrielle Lyon: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.

40:37Dr. Michael Eisenberg: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.

40:54Dr. Gabrielle Lyon:Like what?

40:56Dr. Michael Eisenberg: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 and kind of, you know, you know, 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.

41:27Dr. Michael Eisenberg: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 rheumatogenesis, most men will improve a little bit. So 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 real. But, you know, most will. Most are certainly, you know, are willing to do that.

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

42:05Dr. Michael Eisenberg: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.

42:30Dr. Gabrielle Lyon: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?

42:45Dr. Michael Eisenberg: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 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, you know, given it by their, you know, psychiatrist or primary care doctor, I want to make sure they have that discussion with them.

43:16Dr. Michael Eisenberg: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.

43:36Dr. Gabrielle Lyon: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?

43:49Dr. Michael Eisenberg:You know, I think I would not be surprised if there are some blood pressure medications that are affecting things to some extent. I agree with that. 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. And if you were on a beta blocker, it was different than a calcium channel blocker, you know, than like an ARB, an angiotensical receptor blocker.

44:20Dr. Michael Eisenberg:So I think it does make a difference. Yeah, I guess, you know, time will tell if this is sort of validated in other groups as well.

44:28Dr. Gabrielle Lyon: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.

44:45Dr. Michael Eisenberg:Yeah. I think you're saying it too. Yeah. In terms of what we're talking about is, would you say that sperm is, I don't want to say metabolic, but when we evaluate the health of muscle, like a triglycerides and insulin and glucose, and that probably rides along, there's

45:02Dr. Gabrielle Lyon:probably a correlation between sperm health.

45:05Dr. Michael Eisenberg:Yeah.

45:05Dr. Gabrielle Lyon:I'm sure there's this bidirectional relationship. Would you consider sperm, again, as like a metabolic marker, perhaps, that those with diabetes seem to have this percentage of sperm? Like, do you think that there is some kind of correlate?

45:24Dr. Michael Eisenberg:Yeah, 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 disorders. It's interesting. Yeah. So there is a study where we looked at fertility and found that men that were diagnosed with male olfactory and fertility, 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 develop diabetes.

45:57Dr. Michael Eisenberg:So one in 20 of these patients that we're seeing somehow years later develop 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.

46:15Dr. Gabrielle Lyon: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 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.

46:56Dr. Michael Eisenberg: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. 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 studies showing that semen quality, like lower semen quality, is associated with a higher risk of cancers, you know, later in life.

47:28Dr. Michael Eisenberg: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 registries. So they had about 80 ,000 men. They followed them for nearly half a century. And they showed that a man, if you did check his semen analysis, you know, when he's in his thirties, that can tell you when he's going to die decades later. So if you had a 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.

48:05Dr. Michael Eisenberg:So it's amazing, right? 40 years later that you would get that information.

48:09Dr. Gabrielle Lyon:That would make me think that life insurance individuals, life insurance evaluations could probably be able to contribute to funding to be able to look at that.

48:18Dr. Michael Eisenberg:Yeah. It adds to right, actually, actuarial tables. I mean, it gives us a lot of information. And it's sort of exciting, I think, that we're getting this new data.

48:27Dr. Gabrielle Lyon: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.

48:41Dr. Michael Eisenberg:Yeah, I think it all contributes to some extent. So, you know, about 10 percent 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 know, not to blame mothers for things, but, you know, whether there's microplastic.

48:59Dr. Gabrielle Lyon:I blame my mom for everything, so go right ahead.

49:02Dr. Michael Eisenberg: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, turn out.

49:12Dr. Gabrielle Lyon:I 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.

49:21Dr. Michael Eisenberg: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 cardioprotective.

49:51Dr. Michael Eisenberg:You know, if you have kids, there are times it feels like they're trying to kill you. 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, you know, go hand in hand with reproduction, they are very important for health and longevity.

50:07Dr. Gabrielle Lyon:Male marijuana use seems to really be increasing. Younger males using marijuana.

50:12Dr. Michael Eisenberg: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'd say daily, seemed 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 used 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.

50:43Dr. Michael Eisenberg:So people use that for a lot of different things. if they use it for stress, anxiety, sleep. You know, I never want to discourage them if 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.

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

51:06Dr. Michael Eisenberg:On marijuana? No. 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.

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

51:31Dr. Michael Eisenberg: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 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. 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.

52:03Dr. Michael Eisenberg:But I'm sure he saw real benefits. but in general if we 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 at play so i tell men seven to nine hours i'd be only do

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

52:21Dr. Michael Eisenberg:you always look at so i do think like sort of um sleep hygiene is important like again when you look at men that report not even have gone to like a sleep study or 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 patterns for men that 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.

52:46Dr. Gabrielle Lyon: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. Mohawk Cara, or Dr. Lipscholz, 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?

53:17Dr. Michael Eisenberg: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.

53:34Dr. Gabrielle Lyon:You did your fellowship at Baylor?

53:35Dr. Michael Eisenberg:I did my fellowship at Baylor, yeah, which was 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. Have you done a fellowship in male reproduction? Are you an expert in the area? I think that's important.

53:59Dr. Gabrielle Lyon: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 fellows a year, you're talking about 40 fellows a year. And that's probably extra. Yeah.

54:18Dr. Michael Eisenberg:Yeah. The number of male reproductive urologists, yeah, it's in the low hundreds right now. It's really, really small.

54:26Dr. Gabrielle Lyon: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 Nandrolone, which again is a medication that's FDA approved. How do medications like that affect fertility?

54:45Dr. Michael Eisenberg:I mean, I think it would be the same pathways as just, you know, testosterone sipionate or others. You know, we're going to 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 you're going to be on these. How long does the frozen sperm last? So the longest time, interestingly, between freezing in use ever reported is about 25 years. In theory, just... And what happened?

55:14Dr. Michael Eisenberg:They actually, you like that? Yeah.

55:15Dr. Gabrielle Lyon:Okay.

55:16Dr. Michael Eisenberg: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.

55:45Dr. Gabrielle Lyon: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

56:07Dr. Michael Eisenberg: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 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.

56:40Dr. Michael Eisenberg: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 women age, fertility goes down. And so we may see some issues.

56:50Dr. Gabrielle Lyon: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?

57:07Dr. Michael Eisenberg:Yeah, that'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.

57:22Dr. Gabrielle Lyon:I think that there has to be something else.

57:24Dr. Michael Eisenberg:Yeah.

57:24Dr. Gabrielle Lyon: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.

57:32Dr. Michael Eisenberg:Yeah, maybe. But yes, I mean, it's fascinating. I think just like when people ask me how I choose urology. Right. I think there's some.

57:39Dr. Gabrielle Lyon:Did you choose urology?

57:40Dr. Michael Eisenberg:There's some randomness to it. Right. It's who you're exposed to. I mean, for me and 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 very early exposed to Larry Lipschultz.

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59:01Dr. Michael Eisenberg:I'm from Houston, yeah. You are? Okay. Yeah, born and raised. But I did a sub-internship at Baylor College of Medicine, spent time with him, And that really told me that this is the new 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.

59:21Dr. Gabrielle Lyon:And you love what you're doing.

59:22Dr. Michael Eisenberg:I love what I'm doing.

59:24Dr. Gabrielle Lyon: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?

59:36Dr. Michael Eisenberg: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.

59:55Dr. Gabrielle Lyon:A quarter to a third. Never evaluated. Never evaluated. Even now, even still.

59:59Dr. Michael Eisenberg: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, he 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.

1:00:28Dr. Michael Eisenberg: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.

1:00:35Dr. Gabrielle Lyon: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.

1:00:48Dr. Michael Eisenberg: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 going to be some opportunities.

1:01:02Dr. Gabrielle Lyon: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?

1:01:12Dr. Michael Eisenberg: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.

1:01:48Dr. Michael Eisenberg: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, 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 varicocele. And after, I think, about 18 months, they only enrolled three couples.

1:02:21Dr. Gabrielle Lyon:Oh, my gosh.

1:02:22Dr. Michael Eisenberg:And this was like eight centers around the U.S. Gosh. And when they talked to these couples, they said, well, how come you're not doing this? and they did sort of a post-mortem. And their issue was that these couples had been trying for a year. And then if a man was finally seen and to do like, like you talk about, if you're going to do anything, a surgery to fix a varicosele 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.

1:02:49Dr. Michael Eisenberg:I think it's now getting more and more pushed to the forefront or at least equal to female fertility. That's going to be an upfront evaluation that's done.

1:02:56Dr. Gabrielle Lyon:And if someone was evaluated very early on for, say, a varicocele, which is there, does that, it happens a little bit later? Is it true that it happens a little bit later?

1:03:06Dr. Michael Eisenberg:It usually starts around puberty. I mean, there are certainly adolescent ones that we see, but typically around puberty is where we see it. And, 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. And so over time, those veins can grow in size, and then they can kind of cross over to that pathology.

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

1:03:33Dr. Michael Eisenberg:So varicocils have been associated with testosterone levels. And there have been some investigators that have shown if you fix a varicocil, 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 varicocil repair.

1:03:51Dr. Gabrielle Lyon:And would you consider that clinically significant or would it depend?

1:03:55Dr. Michael Eisenberg:I guess it depends where you're starting, but generally 100 points is a lot. I think men would be happy with that.

1:04:01Dr. Gabrielle Lyon: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 standard. It's very innovative.

1:04:13Dr. Michael Eisenberg: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, you know, 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, you know, we wanted to be very thoughtful about this.

1:04:46Dr. Michael Eisenberg: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.

1:04:54Dr. Gabrielle Lyon:How common is that in general?

1:04:56Dr. Michael Eisenberg: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 going to 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 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 looked at for this at first.

1:05:26Dr. Michael Eisenberg:So they'd 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, donor sperm adoption, live without children. There's not much else medically that can be done at this point.

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

1:05:42Dr. Michael Eisenberg:Some of them did, yeah. 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 them out. And unfortunately, they didn't, you know, cryopreserve sperm beforehand.

1:05:57Dr. Gabrielle Lyon:What about blast injury?

1:05:59Dr. Michael Eisenberg: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 the 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.

1:06:23Dr. Gabrielle Lyon:And the reason I was just thinking about that is because for women, they're born with a certain amount of eggs and then they're not. But it seems like for men, it's a bit different.

1:06:34Dr. Michael Eisenberg:Yeah. So we're born with sort of sperm precursors. And after puberty, they start to, you know, self-renew and then produce sperm, over and over again, 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 we think that older men have higher rates of these kind of rare disorders compared to younger fathers.

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

1:07:02Dr. Michael Eisenberg: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 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 yesterday -

1:07:21Dr. Gabrielle Lyon:How many? Five?

1:07:22Dr. Michael Eisenberg:One in five.

1:07:23Dr. Gabrielle Lyon:That's amazing. That's the difference between having a child and not.

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

1:07:37Dr. Gabrielle Lyon:It changes legacies for people.

1:07:40Dr. Michael Eisenberg: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, you know, for all patients, you know, just with low sperm counts and have 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.

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

1:08:04Dr. Michael Eisenberg:Yeah. 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 for fertility.

1:08:11Dr. Gabrielle Lyon:What about muscle?

1:08:12Dr. Michael Eisenberg:Yeah, muscle too. You'll convert me.

1:08:15Dr. Gabrielle Lyon:I will because what happens when you lift? Don't you increase androgen receptor density?

1:08:19Dr. Michael Eisenberg:Yeah. That's only going to be good.

1:08:21Dr. Gabrielle Lyon:I mean, I think that's only a positive.

1:08:24Dr. Michael Eisenberg:Yeah.

1:08:24Dr. Gabrielle Lyon: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.

1:08:34Dr. Michael Eisenberg:I'm not sure. I'll have to get back to you. You're the expert. So I think exercise is good, but it is possible to overtrain, certainly undertrain. That certainly can be done. But for men that have very vigorous exercise too many times a week, we do see, again, this sort of reverse U-shape where benefit, benefit, benefit, and then it starts to decline a little bit. So I think that cut 0.5 varies for men. In some, obviously, you're going to have a lot more capacity than others, like Navy SEALs or things like that.

1:09:02Dr. Gabrielle Lyon:They can't find their socks. Yeah.

1:09:04Dr. Michael Eisenberg:But others may be an issue. So I do think to sort of be mindful about, you know, overtraining. 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 seamen quality.

1:09:17Dr. Gabrielle Lyon:Is that similar to the female triad?

1:09:20Dr. Michael Eisenberg:Yeah. Yeah. I think that's a great analogy.

1:09:23Dr. Gabrielle Lyon:Of amenorrhea, you know, somewhat infertility. Yeah.

1:09:29Dr. Michael Eisenberg:If you're going too hard, if there's no fat, I mean, if there's that sort of pattern, it can affect reproduction. I think it's sort of the same thing. If your body senses that you're kind of at the very peak of trying to prioritize survival, that reproduction gets deprioritized to some extent.

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

1:09:50Dr. Michael Eisenberg: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. Yeah.

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

1:10:07Dr. Michael Eisenberg:Yeah, we've seen it in 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, 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.

1:10:33Dr. Gabrielle Lyon:Your top three to five tips for increasing fertility for men. Yeah.

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

1:10:48Dr. Gabrielle Lyon:I'm curious, which is?

1:10:49Dr. Michael Eisenberg: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 foods. And, of course, proteins. Proteins, yeah. You definitely want to get all those. And then, you know, trying 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.

1:11:21Dr. Michael Eisenberg:You know, how much? Any, any can be bad.

1:11:24Dr. Gabrielle Lyon:So any sauna exposure.

1:11:25Dr. Michael Eisenberg:Yeah. So again, like, I mean, we talked about patients that like have gotten the flu or kind of have this, you know, bedbrow 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. And we have to wait.

1:11:44Dr. Gabrielle Lyon:And we know that to be true.

1:11:45Dr. Michael Eisenberg:We know that to be true. Yeah.

1:11:47Dr. Gabrielle Lyon:Sauna would not be good if you're trying to go for fertility.

1:11:50Dr. Michael Eisenberg:Yeah. Yeah, there was a very interesting attempt at a contraceptive. It was a sort of a truss 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 wore it for some period of time. And then as soon as they took it off, the sperm counts were covered. So we're very sensitive to temperature. So that's also something that we want to.

1:12:17Dr. Gabrielle Lyon:But not cold, just heat.

1:12:18Dr. Michael Eisenberg:Just heat. Yeah, I think cold is sort of interesting whether we could find ways to improve that. But like, yeah, some patients talk about, you know, cold exposure and that doesn't seem to be a negative impact. Diet, exercise, environmental exposures,

1:12:34Dr. Gabrielle Lyon:even though you can't.

1:12:36Dr. Michael Eisenberg:And then I think, 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 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, you know, one of us, seeing Dr. Lipschel, Dr. Kara, myself, so we can get screen. You know, we do a comprehensive hormone panel, do a semen analysis with 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.

1:13:13Dr. Gabrielle Lyon: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.

1:13:32Dr. Michael Eisenberg:Yeah. Yeah.

1:13:33Dr. Gabrielle Lyon:If estrogen is, say, 50 and beyond, does that affect fertility?

1:13:37Dr. Michael Eisenberg: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 leaches the testosterone, the testosterone goes down. You can sometimes get in the 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.

1:14:12Dr. Michael Eisenberg: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 semen quality.

1:14:28Dr. Gabrielle Lyon: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.

1:14:38Dr. Michael Eisenberg: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, some 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.

1:15:11Dr. Michael Eisenberg:So we want to check for those as well.

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

1:15:21Dr. Michael Eisenberg: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 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 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.

1:16:01Dr. Michael Eisenberg: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 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.

1:16:29Dr. Michael Eisenberg: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.

1:16:41Dr. Gabrielle Lyon: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?

1:16:49Dr. Michael Eisenberg: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, you know, again, as technology improves, we have sort of an omic view of everything.

1:17:19Dr. Michael Eisenberg: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.

1:17:32Dr. Gabrielle Lyon: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?

1:17:41Dr. Michael Eisenberg:Yeah, this is pretty wild. Well, 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 affected. And 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.

1:18:11Dr. Gabrielle Lyon: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. Right.

1:18:23Dr. Michael Eisenberg:Exactly.

1:18:23Dr. Gabrielle Lyon:They're also released from muscle during exercise.

1:18:25Dr. Michael Eisenberg:Oh, is that right? Okay. Yes.

1:18:26Dr. Gabrielle Lyon: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.

1:18:36Dr. Michael Eisenberg: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 improve in, 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.

1:18:52Dr. Gabrielle Lyon: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?

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

1:19:04Dr. Gabrielle Lyon:Thank you so much.

1:19:06Dr. Michael Eisenberg:This is a pleasure. Thank you so much.