What's the Deal with Testosterone?

Perry: [00:00:01] Emily, I'm very excited for this episode about testosterone. As you know, we, you know, we just did the hormone replacement therapy sort of for women episode last week. And, and honestly, there is a vas deferens between estrogen and testosterone. And I'm excited to explore that. I think this is going to be a seminal episode.

Emily: [00:00:23] I can't even react to you, but I will say that last week, you gave a whole long open about how you weren't going to talk about, you weren't going to mansplain, you weren't going to blah, blah, blah. I'm not giving that.

Perry: [00:00:36] I am a womansplained all over the place.

Emily: [00:00:38] I am a woman. I'm not sorry. I'm going to say all kinds of feelings I have about testosterone and science. And even though I only have a little bit of it, I assume.

Perry: [00:00:50] I mean, Emily, I'm glad that you have the balls to to really address this.

Emily: [00:00:55] Okay, I think we're done here.

Perry: [00:00:56] I have about eight more.

Emily: [00:00:57] Testosterone. You know what? I think that was three was really good. [00:01:00] Three Vas deferens was definitely the best. The balls kind of is the low end. So that's where I think we should just move forward.

Perry: [00:01:06] Okay. All right. Testosterone in a nutshell. After the break.

Emily: [00:01:13] I'm Emily Oster. I'm an economist and a data expert.

Perry: [00:01:16] And I'm Perry Wilson. I'm a medical doctor.

Emily: [00:01:19] It's Thursday, April 30th, 2026. And this is Wellness, Actually.

Perry: [00:01:24] Because you're getting a staggering amount of health and wellness information nowadays from every source imaginable. And some of it is awesome.

Emily: [00:01:32] And some of it is, well, actually bullshit. Fortunately, we're both people who know how to read studies, how to parse the data, and can tell you what's worth thinking about and what you can safely ignore.

Perry: [00:01:45] But before we dig in a note that this podcast is for educational purposes and should not be construed as medical advice. We don't know your unique situation, so talk to your doctor for personal health decisions.

Emily: [00:01:57] This week we're asking, what's the deal with testosterone? [00:02:00] It's part two of our hormone two parter. Perry and I will give the official smash or pass, and then we'll get to your question of the week. But first, let's do the health news roundup after the break. And now for the health news of the week. Perry, no more flu vaccine mandates for military troops. The Department of Defense. Pete Hegseth has said we will not be having required flu vaccines for the military. Your thoughts?

Perry: [00:02:42] Yeah, this is weird. When it comes to combat readiness, you know, the military has long and in multiple domains had less freedoms than the public sector or than the rest of us. Right. Um, you know, think about like free speech even. [00:03:00] Um, there are limitations on that in the military because it is a job that has obviously very specific risks, um, and is so vital to national security and combat readiness is in part determined by the health of the troops in terms of infectious diseases. I mean, if you look at like the history of warfare, you would find that infection has killed vastly more soldiers than combat. Um, is often responsible for losing the war. I mean, one of the, one of the reasons Americans were able to hold out during the Revolutionary War was because Washington made the rather bold and somewhat risky decision to force smallpox vaccination or inoculation, really, on all the Revolutionary War troops. It's hard not even speaking of just about influenza is kind of random. Obviously, there's a bunch of vaccines that the troops get meningococcal disease, hepatitis [00:04:00] A, hepatitis B, pertussis, diphtheria, um, so many. So I don't know why we're isolating influenza. And like, let's not forget that the worst influenza pandemic in history occurred. This is the Spanish flu. So-called Spanish flu. Influenza pandemic occurred after World War One because a bunch of infected troops brought brought the virus home. So a weird decision. It feels completely like brazenly sort of political to me. I see no justification for this in a rational society.

Emily: [00:04:32] Yeah. I mean, I will say I think this feels like a just a complete political move to me in the sense that it's, you know, relative to other vaccines they could have turned against. I don't know why they chose this one, but it's one that that, you know, people are having every year and there's a lot of political resistance to. And so it feels like it's this or the Covid vaccine. I think they already don't require the Covid vaccine.

Perry: [00:04:58] So that's I think that's that's correct. [00:05:00] Two, two viruses, by the way, that just really enjoy spreading in close quarters conditions, particularly unsanitary.

Emily: [00:05:07] It's their favorite.

Perry: [00:05:08] It's pretty random. Okay. Um, let's move on. We have, uh, some fish oil news today, but actually some bad fish oil news. So fish oil supplementation pops up every once in a while as a wellness trend. Um, like many supplement trends, the data has been rather mixed, but we've got some new headlines coming out this week that actually suggest that fish oil might hurt your brain. This is kind of the opposite of what a lot of people think about fish oil. Like it's going to keep me smarter, right? Probably because it has so much dolphin in it and you know how smart they are. Um, uh, that's a joke. That's a Simpsons reference for the very old people. And, Emily. What's going on? Is fish oil going to hurt my brain?

Emily: [00:05:54] Uh, fish oil is not going to hurt your brain. Or at least not. There is no strong evidence for that [00:06:00] based on this new research. And this is an example where the distinction between what the headline said, which was literally fish oil, might hurt your brain and what the actual paper said was really vast. So there is a piece of new research in which researchers took mice with traumatic brain injury. So they actually took some mice. They gave them a traumatic brain injury, and then they treated them with fish oil. And they found that the treatment with fish oil did not improve the traumatic brain injury in the mice, which they had thought that it might. And so that is interesting, I guess, from the standpoint of thinking about how we treat traumatic brain injury, which is an important question. And certainly, you know, early stage mouse research might be helpful for that to go from treating mice with traumatic brain injury with fish oil does not improve them, to fish oil might hurt your brain. Feels like we took not just one, but like several very large leaps.

Perry: [00:06:58] Yeah, yeah. Well, obviously [00:07:00] the, the, the mouse traumatic brain injury, uh, readership is not as large as the humans worried about their brain readership.

Emily: [00:07:08] No they're not. No they're not. But it's I mean, it's such a strong example here of where there is a piece of evidence in data that actually is kind of interesting and I think should be something we should pursue and learn more about. And then it gets turned into some clickbait headline because of course, the headline, you know, mice with traumatic brain injury don't necessarily improve with fish oil is not is not clicky. It's not, it's not. Um, okay, let's do some, some good news at least what looked to me to be good news. It seems like we have started to make a little bit of progress on pancreatic cancer. A couple of new Treatments that maybe are working. Uh, did you see this? And what did you think?

Perry: [00:07:52] Um. So exciting. Uh, so preliminary data presented at a cancer conference out in California. So, um, not peer [00:08:00] reviewed yet, but, uh, still super exciting. Two new and completely different approaches for pancreatic cancer. The larger trial that was presented was of a drug that I have, uh, some difficulty pronouncing, but I'm going to go for it. Um, it is called Derrickson. Derrickson Racib. This is this is a novel Ras inhibitor. It was trialed in 501 patients with fairly advanced late stage pancreatic cancer. Many people know that pancreatic cancer, particularly late stage pancreatic cancer, has a very poor prognosis. Um, with, you know, an expected life expectancy generally less than a year after diagnosis, that mortality rate at the time that they cut this data and presented, it was twice as long in the patients that were randomized to receive this new therapy compared to those randomized to receive placebo. About an extra six months [00:09:00] difference in life expectancy, which is very significant in a pancreatic cancer trial. And obviously, that's an average and some people are living substantially longer. So super exciting that there's that new drug potentially, you know, a much smaller study, but potentially even more exciting insofar as it is a totally new avenue for cancer treatment.

Perry: [00:09:21] Researchers reported on patients receiving a customized mRNA pancreatic cancer vaccine. So this is where you take out a piece of the the actual patients pancreatic cancer. You do some genetic sequencing on it to figure out where the mutations are. You create an mRNA vaccine, much like the Covid vaccine that's directed against those very specific mutations. And you give that back to the patient. Um, this was not a randomized trial. This is phase one therapy really just testing safety. But what the researchers reported that of eight patients whose immune systems responded [00:10:00] to the mRNA. So they have signals that their immune system got revved up to the vaccine. Seven were alive six years or more after receiving the last treatment. So this is not necessarily a miracle. You have to respond to the therapy. There's no placebo control here, which we always talk about. But in a situation like pancreatic cancer, you know, these advances can be super promising. So phase one study, phase two will get started and give us some better efficacy data, likely with a placebo control.

Emily: [00:10:33] Yeah. I mean, this last one was really very exciting, given that six years in pancreatic cancer is really out on the tail. Um, And the idea that it's a sort of new approach to this. It's it's very cool. Hopefully, hopefully more science as we go.

Perry: [00:10:51] Yeah. And just another place where mRNA technology is making an impact. And we're going to talk about this in a future episode. [00:11:00] People know about mRNA technology because of the Covid vaccine. But what makes it so flexible is that it can essentially be programmed to do what you want it to do and to attack the specific thing you wanted to attack, whether that's a Covid spike protein or a protein on the surface of pancreatic cancer. Very cool.

Emily: [00:11:20] All right. That's it for the health news of the week after the break. What's the deal with testosterone? All right, Perry. So let's talk about testosterone. Although I said I'm not going to be careful if I do get really out on the tale of women women's planning. Uh, jockstrap is your safe word. Just say it, and I will dial it right back in.

Perry: [00:11:46] Okay. You got it, I appreciate it, thank you.

Emily: [00:11:49] All right, so let's start with the big picture. What is testosterone and what does it do for someone who is totally unfamiliar?

Perry: [00:11:58] So testosterone is [00:12:00] a steroid hormone. We talked about these special types of molecules last week with the hormone replacement therapy, uh, episode. But steroid hormones are unique in that they act within the nucleus of the cell to change how DNA is transcribed. So testosterone, estrogen, progesterone, some others all work this way. And that's a function that really lets them change how cells work. It can take a cell that doesn't grow hair and change it into a cell that does grow hair. Obviously, testosterone is the hormone that makes men look like men. This is, uh, you know, responsible for the primary and secondary sexual characteristics of men. It certainly has important roles in muscle growth. We'll get to that. It's necessary for sperm to be created. It has pretty significant effects on Erythropoiesis or the generation of red blood cells. And this is going to come up time and time again. I don't know if we [00:13:00] need an explicit warning on this episode or not, but libido and sexual function is clearly firmly within the testosterone wheelhouse, right?

Emily: [00:13:11] So if you're listening with your children, this episode will discuss penises and sex. So just be be aware. All right, so when we start from the, the biggest picture here, there are things which are definitely true, which is when boys go through puberty, their testosterone goes up. And if that doesn't happen, if you have a medical condition in which testosterone is, is lacking or is very low for for some reason, then you will need supplementation and that that will affect the development of secondary sex characteristics. So it's very clear that testosterone is important. If we're going to say, you know, smash or pass. Like, do we need testosterone as a species? Like, yes, yes. Right. It's not it's not a useless peptide. It's an actual important hormone. There are [00:14:00] also some things that for sure are true. Like if you are a person doing sports and you give yourself a bunch of extra testosterone, it will probably improve your sports performance. But also that's cheating. So don't do that. Um, but I think there are a bunch of open, much more interesting questions that relate to some of the wellness stuff, which is, you know, how much variation is there? Does that variation actually matter? Like within the normal range? And if we supplement outside of a sports context, is that going to improve our various sex activities and other stuff. Are those for you, the interesting sets of issues?

Perry: [00:14:39] Yeah, absolutely. I mean, when people are asking me about testosterone supplementation, they're not saying like, I have a genetic condition that prevents me from synthesizing testosterone, which would be like one of the FDA indications for testosterone replacement. People are asking, you know, these two things happen in parallel. One, men get older and two men's testosterone [00:15:00] level goes down a bit. And there's a natural question to say like, well, all these other things that happen when I get older, like decreased energy, decreased libido, maybe I feel like I'm not quite as on top, not quite as cognitively sharp as I used to be. Like, is that because of testosterone or is it not? And if you go online, you will get plenty of people telling you absolutely it is. And please, you know, call this number to get testosterone replacement therapy. But hopefully if you're listening to the podcast, that is not enough evidence for you. So I think it's worth noting that the FDA indications for testosterone replacement therapy are quite limited. It is primary hypogonadism, which is like, as you alluded to, like very rare genetic conditions that prevent the production of testosterone in boys. And you need testosterone to grow into a man. The second is pituitary hypogonadism.

Perry: [00:15:58] So your pituitary gland secretes [00:16:00] a substance that kind of tells the testes to produce testosterone. If you have a tumor in your pituitary or you had a stroke in a certain place, that's preventing that from happening, you just the testes just won't produce testosterone. They're not getting the message from the brain to do it. Those are the only FDA approved indications, and less than 1% of men with low testosterone have one of those indications. So virtually everyone getting testosterone replacement therapy that you hear about is technically getting it off label, which is fine. It is legal to get drugs off label, but I think it does lead to the question of like, okay, why isn't there an FDA approval for age related low testosterone, which is just the fact that testosterone slowly goes down when you're aging. Caveat RFK Jr has said he wants the FDA to investigate this, and maybe there will be an approval in the future. So I think that's where we kind of have to start is like, what's going on with testosterone in the life cycle? And is it is it is [00:17:00] there menopause? Right? Is it is it is there such a thing as.

Emily: [00:17:03] Manopause.

Perry: [00:17:04] For men?

Emily: [00:17:05] Is there a manopause? Okay. So so yeah, let's start there. So let's start with how testosterone moves over the life cycle. And you know, if you look at a graph and I think I'm looking at the, the Nhanes, which is the National Health and Nutrition Examination Survey, is a nationally representative survey that the CDC runs. It's a really good source for a lot of the biometrics that we have.

Perry: [00:17:28] Normal.

Emily: [00:17:28] Values over time because Is exactly like they. They. Unlike many other surveys, they actually test people. They bring them into these like, like drive around these mobile clinics and, and participants like come to the clinic and have their blood drawn anyway. So this will show you testosterone over the life cycle. And there is one really striking thing in these graphs, which I'm looking at as we talk, which is between the ages of like six and, you know, 20, your [00:18:00] testosterone goes from more or less zero to like 500. And this is like in what is it? Is it nanograms for.

Perry: [00:18:09] Nanograms per deciliter? Yeah.

Emily: [00:18:11] For deciliter. So at any rate, you start with none. Little kids have very little testosterone. And then you go up a lot during the period of puberty. So it's very clear testosterone is very important for driving the changes that we see in boys during puberty. The development of secondary sex characteristics. Starting of sperm, spermatogenesis, etc. and then you see it over time. And honestly, Perry, I'm looking at this graph and it looks.

Perry: [00:18:38] I knew, I knew I knew you were going to say that when I put the graph in our, in our research document. Um, yeah, you sort of. So, so this graph shows the, um, uh, sort of variation in testosterone levels. And let's just put some numbers on it because we'll kind of keep coming back to this in adult males. So post-pubescent males, uh, most [00:19:00] values tend to run between 300 nanograms per deciliter and 1000. Most people would draw the line at 300 nanograms per deciliter to be like low testosterone or like lower testosterone. Um, there is no cliff. This is not estrogen for women going through menopause, which is kind of up there. And just like tanks at, at, at menopause, it is relatively flat. Now, if you mathematically model this and account for things. And, you know, you can show in a large enough population that there is an age related decline in testosterone on average, this is the same Nhanes data using mathematical modeling, the kind of average goes from about 400 nanograms per deciliter at age 20 to about 300 nanograms per deciliter at age 80. That's a change, but it's not dramatic. So Manopause.

Emily: [00:19:57] Also.

Perry: [00:19:57] Um.

Emily: [00:19:58] I just have to say, I'm looking [00:20:00] at this graph and this graph is so obviously this is like we, I mean, we might need to take this out of the podcast, but this graph is so obviously driven by somebody over fitting a line to a very small amount of data on old people that I can't even.

Perry: [00:20:14] There's confidence intervals.

Emily: [00:20:15] For those of you who love an overfit, this graph is not convinced. Okay.

Perry: [00:20:19] Emily's not convinced. Um, how about this data does suggest across multiple populations, both in the US and abroad, that test average testosterone levels in the population have decreased over time. So not only is we've gotten older, but like a 50 year old man today has a lower testosterone than a 50 year old man in 1980. Levels have been going down, they say, by about 1% per year. Depends how you model it. Do you buy that?

Emily: [00:20:49] Yeah, I think that's interesting. And we should come and we should come back because I think it's part of understanding why this has has declined. But I would say first, if we ask the question like are [00:21:00] is this like estrogen relative to estrogen, where we talked about there's really this period in which it declines quite a lot in which replacement is helpful. We just we're not seeing that in testosterone. So it doesn't necessarily mean you wouldn't get something from supplementation, but it doesn't. It's not the case that there's some period of your life when your testosterone is just tanking.

Perry: [00:21:18] That's right. You can be an 80 year old man and have a testosterone level that a 30 year old man has. But like, I challenge you to find an 80 year old woman not on estrogen supplementation that has an estrogen level of a 30 year old woman like that. That does not happen.

Emily: [00:21:32] Okay. So but we also know from this amazing Nhanes graph that there is a lot of variation within age, right? So the if you look at like the 10th percentile of people say at 40 to 49, they're at about 200, the 90th percentile is at about, I don't know, 6 to 700. Mhm. And so that's a really big range. And I think that that relates to the question of like, what, what determines this? How do [00:22:00] you get to be a person of a testosterone level of 700? And realistically, and I'm just going to channel the influencers here. How do I get the 700? What do I need to do to optimize my testosterone? Perry. Not me specifically. I have only a small amount of time. What do you need to do? What are you.

Perry: [00:22:19] Doing? What do I.

Emily: [00:22:20] Need to optimize your testosterone?

Perry: [00:22:22] Yeah. And I mean, they're like all.

Emily: [00:22:26] Things to you. You're not you're not doing anything.

Perry: [00:22:29] Um, I'm actually not doing anything, but I'll give you some things that you can do to optimize your or let me, let me phrase it this way. I will say that before we decide whether we should make some number higher, we should decide whether it matters to make that number higher. But because we just talked about variation, I will tell you what we know. What correlates with lower levels versus higher levels. In the general population, age is one, it's not as powerful as you think, right? [00:23:00] But there is a statistically significant correlation between age. Um, a history of smoking lowers testosterone. Current smoking, which is really interesting, will actually increase your total testosterone level by and, and this actually might explain why total testosterone levels have gone down over time. Can I detour for a second? Because this is very weird.

Emily: [00:23:23] Detour.

Perry: [00:23:23] That's weird. Okay, so testosterone is broken down very quickly in the blood. It has a half life of about ten minutes to maybe 60 minutes depending. So it's carried around the blood by a chaperone protein called sex hormone binding globulin. And that kind of protects it like wraps testosterone in a little hug and keeps it safe from being degraded. But it's also inactive testosterone, and that bound form can't do anything. It has to be free. Free testosterone is the active form. That's about 2% of total testosterone. But most people, if you're getting your lab tests measured and all the numbers we've said so far are total testosterone numbers, because [00:24:00] free testosterone is a very difficult test to run. It's expensive. There's a couple different assays. None of them are FDA cleared at this point in time. So most people are getting total testosterone. If you increase sex hormone binding globulin, you'll increase total testosterone because you just kind of have more that's out there stuck to the chaperone protein, but it's not actually doing anything. And current smoking does that. So there is some possibility that the reason we see this generational decline in total testosterone is actually because we're smoking less, which is a really sort of paradoxical and fascinating finding.

Emily: [00:24:39] Why would having a history of smoking make your testosterone lower?

Perry: [00:24:43] I think that's just comorbidities. So the other stuff on the list for making your testosterone lower is like higher BMI, depression, diabetes, uh, these are all things that kind of go along with smoking, obviously cancer, right. So, so I think the history of smoking is just like [00:25:00] you've kind of, if you put your body through the wringer, testosterone also is a hormone that has a pretty fascinating response to your psychosocial state. So there's a well-studied phenomenon that if a man wins something, their testosterone level goes up. So if you like measure, you know, soccer players before the championship game and you do their, um, their salivary testosterone and then you, you know, one team wins, one team loses, the winning team will have a significantly higher testosterone after the game. This doesn't last for very long. This also carries over to men watching their favorite sports teams. So if you are, you know, an Eagles fan Jalen Hurts runs it in for a touchdown. Your testosterone might go up a little bit. So it is it is quite a cerebral thing.

Emily: [00:25:49] But don't you think that's a that I mean that feels like an evolutionary adaptation right. Which is like the moment that I win the fight with the other guy. That's the moment that a lot of the lady animals, [00:26:00] the lady monkeys, want to have sex with me. And so I want to be like in a high testosterone environment. So I'm like, ready for the lady monkeys after the soccer game?

Perry: [00:26:09] I mean, yeah, I'll buy that. I'll totally buy. I mean, I don't know, I'm not an evolutionary biologist. Makes sense.

Emily: [00:26:13] Right? I know, but I think evolutionary biology is just like telling stories like that. Some of it, some of it, some hypothesis generation. There is that kind of story and I that's the story I'm going with.

Perry: [00:26:23] Um, I totally love it. Um, did.

Emily: [00:26:26] I, did you lose your train of thought?

Perry: [00:26:27] No, of course not. Because I have one other thing that has been shown to temporarily increase testosterone, which is, um, watching, uh, erotica or sexually charged visual imagery. Men are simple creatures, Emily.

Emily: [00:26:40] You like to win soccer and watch porn, and those are the activities that you enjoy.

Perry: [00:26:44] As I was reading about this and comparing it to like, estrogen in women. And it's like so complicated and like how, you know, what's what's going on.

Emily: [00:26:51] Men, soccer and porn. It's things we like.

Perry: [00:26:54] That's it doesn't take much.

Emily: [00:26:57] Um, no.

Perry: [00:26:57] So, but, but there is a lot [00:27:00] of, uh, between person variation and testosterone. And there is also within person variation in testosterone. Emily. Um, one of the things that came out when I was looking at like how testosterone is measured is this fact that the coefficient of variation of testosterone measurement is 50% or higher within a man? Can you, with your data hat on, explain what coefficient of variation means?

Emily: [00:27:27] So a coefficient of variation is the. Technically, it's the ratio of the standard deviation to the to the mean, which is not that helpful for people. It's it's really a way to measure sort of how much something is varying. In this case, within a person's scaled to the to the mean. So if something has a coefficient of variation of of 50%, it varies quite a lot within a person. Over time, many things would have like, you know, your weight within a time period [00:28:00] does not have a coefficient of variation, anything like that.

Perry: [00:28:02] Exactly. And so, you know, just to put a number on it roughly, we could say like, okay, if your testosterone is kind of on average is 300, you get it measured one day. Maybe it's 450, right? Maybe it's 150 another day. Let me play you, um, an influencer that, uh, I think speaks to this potential problem with testing.

Influencer: [00:28:25] I increase my testosterone by 48% and only 21 days without medication. Here's how.

Perry: [00:28:30] I'm not even going to tell you how.

Emily: [00:28:32] Is it that he tested again, though? Is that is that right?

Perry: [00:28:35] So that's the thing I want to get out. Um, when someone says, you know, my, my, whatever it is, my testosterone, my, uh, anything that went up dramatically, you have to know how variable it is at baseline. And testosterone is highly variable. We know for one thing, for example, it's about 15% higher on average in the morning than in the afternoon. So like men's testosterone is just higher. But that's like averaging across [00:29:00] thousands of men within a given man. If you test today and you test a week from now, you're going to get very different numbers. And that is going to have the effect because we're all human, that you will start to assign causality to things that you did to make that change when there is, in fact, nothing. The recommendation from endocrinologists is, in fact, that you don't diagnose low testosterone without at least two measurements temporarily separated that are both below 300 nanograms per deciliter.

Emily: [00:29:34] So one of the reasons to keep I mean, I think that that influencer clip is, you know, it's interesting from the coefficient of variation standpoint, but it's also interesting because of course, this guy is on the internet saying how great his testosterone is. And that's like as a marker of, you know, whatever positive manhood, presumably. Which gets to the question of whether, in fact we see like, are there [00:30:00] symptoms of low testosterone, either low or just intermediate? Like if you told me, I've been tested many times and my testosterone level is 500. Should I expect you to be better on some dimension than if your testosterone is 400? Yeah, that's my guys.

Perry: [00:30:16] This is the question. Okay. Because we're so tempted to look at numbers and be like, higher number is better. And we do this with so many things, right? We do this with like vitamins. We do it with protein to some extent, right? Like we're trying to max everything. Let me let me play you another influencer clip.

Emily: [00:30:35] I'm ready.

Influencer: [00:30:36] No man is normal in a 300 testosterone range. Your quality of life is gone. And it's like you said, it's not just libido. You're not going to be able to lose weight. You're not going to be able to gain muscle, just like you just said, you're going to be feeling like you can't focus on anything brain fog like to no end. You're also going to ache, you know, that you're going to ache. You're not going to be able to move. Well, every little thing you do is [00:31:00] going to hurt. It's going to be painful.

Perry: [00:31:01] That sounds.

Emily: [00:31:03] Sounds terrible. It's sounds terrible.

Perry: [00:31:05] It sounds pretty bad. I don't want to have a testosterone level below 300. So how? But but is it actually true? Um, let's walk through the study from the New England Journal of Medicine because I think this is the one. This is like how you would design a study to assess what the effects of differing levels of testosterone are. So so this was a survey based study of 3369 men, ages 40 to 79 in Europe, and they gave them very long questionnaires asking about a wide variety of symptoms depression, confusion, brain fog, fatigue, sexual symptoms, on and on and on. After giving them all those questionnaires, they measured their testosterone level, right? And this is what you would want.

Emily: [00:31:58] Using a blood like for real, using a blood [00:32:00] test. A blood test.

Perry: [00:32:00] Yeah. So it's like, okay, this is, you know, it's one thing to say, like, I measured my testosterone and it was 250. And now I attribute everything that's bad in my life to that, to that number. That's sort of like astrology, right? It's like, it's like I'm a Libra and like, so that's why you can't trust me or whatever. I actually, I don't know, is that true about Libras?

Emily: [00:32:20] I could not.

Perry: [00:32:22] So listeners.

Emily: [00:32:23] Not really my thing.

Perry: [00:32:24] That's probably because you're a Virgo.

Emily: [00:32:27] I'm an Aquarius.

Perry: [00:32:28] Okay. I should have known. No. But. Okay. So this study instead says like, look, there are going to be people who have depression and are there more people with depression at a low testosterone, or is it just something that. Yes, of course, people with low testosterone have depression and people with high testosterone have depression. Um, so, Emily, was there anything that stood out to you in the results of this study as like, what, if anything, is it clear that lower testosterone causes symptoms logically, symptomatically?

Emily: [00:33:00] So [00:33:00] the, the statistics in this study are a little like a little tortured, um, for the, the sort of basic reason that they're doing a tremendous number of different tests and running them in various ways. So the like sort of some of the key results that that show up as significant. They're kind of picking a threshold and then estimating the impact as you sort of move below that, that threshold. But of course, there's a tremendous amount of choice that goes into like, well, what is the threshold and exactly how do you structure it? And if you're kind of like, you know, messing, messing around, you can get closer to, to significance. Um, and they're testing many things. I will say the thing that sort of shows up most consistently here is stuff about sex. So sex.

Perry: [00:33:47] Hundred percent.

Emily: [00:33:49] Morning erections, erectile dysfunction, those are the key things. The effects are not that big. Right? So like, it's a little [00:34:00] hard to exactly translate their number into something that would be meaningful for a person. So it's like, what's the odds ratio when you move one nanomole per liter below the threshold? Who knows what that number means, but the effects are small and not very significant. Is my read.

Perry: [00:34:16] Yeah. I mean, even it's very hard to actually assign good numbers to decrease sexual thoughts, right? It's like what?

Emily: [00:34:25] How often are.

Perry: [00:34:25] You thinking about sex? Like there's all those sort of urban legends and stuff like that. But yes, to me, it's very clear. They looked at, you know, 50 different potential symptoms. And the only things that sort of withstood what however tortured the statistics are the only things that sort of stood out were things about sex. So yes, it does seem like if your testosterone is lower, your sex drive and things associated with sex drive is going to be lower. But notably, the psychological symptoms had no correlation with testosterone level. So these influencers who are like, oh, if you're below 300, you're going to be essentially on your deathbed, you're going to be in pain, you're [00:35:00] going to be depressed. You can't think straight. You have no energy. Like that is not borne out in the data where people are blinded to their testosterone level, right? Like you can you can make the argument after the fact. You can kind of attribute it, but you're probably incorrect.

Emily: [00:35:16] Yeah. I think the other thing about this trial and even about these results is what they're looking at is sort of what is happening as you're moving down below some lower threshold, right? So here we're like really very focused on this question of if you are like these influencers saying, okay, if you're below 300, what happens to you? Again, there's no cliff, but most of these trials are about these lower, like moving down within lower levels, not asking the question of whether 700 is better than 600.

Perry: [00:35:47] Yeah.

Emily: [00:35:47] And for that, I think we just have no there's no evidence to suggest that's true.

Perry: [00:35:51] Yeah. And I would be very honestly, I'd be very surprised if it's true. And the variation within a person, you know, if you're below 700, if you're 650 today, you're 750. [00:36:00] Tomorrow you're 600 the next day. Like, you know, you're only going to see effects when things are low. And again, it looks like those effects are are fairly limited. But that was an observational study, right? That didn't say anything about replacing testosterone. So there's okay if you don't have enough testosterone. All right. You have decreased morning erections and a higher risk of erectile dysfunction. Um, then the question is, okay, what if we replace testosterone? Do those things get better? Do other things get better, too? And in this case, we really don't want influencers to tell us what their anecdotal experience was. Um, we want to hear in the form of randomized trials, right? We want placebo controls where people don't know they're getting testosterone because we've said a million times, if I tell you I'm giving you testosterone, even if it's not, it's like Felix Felicis in Harry Potter, right? You're just like, you feel good. And that's the power of placebo.

Emily: [00:36:59] And this is such [00:37:00] a classic place where the placebo effect is going to matter tremendously. Because if you tell somebody, you know, I'm giving you something and it's going to make you feel more excited about sex, like they're going to feel more excited about sex, for sure. There's just like, no question. So much of this is, is in your head. Yeah, yeah, yeah.

Perry: [00:37:18] That's how oysters work.

Emily: [00:37:20] Um, so.

Perry: [00:37:21] Let's, let's talk. We can't obviously talk about every trial, but I think there's a couple that are relevant to the discussion. Um, the testosterone trials, the T trials enrolled 788 men above age 65 who had total testosterone less than two. 75.

Emily: [00:37:35] Can I just ask you before we get into like, what do you think about focusing only on old older men in this? Do you wish that they had focused also on people like you?

Perry: [00:37:44] Uh, I think they would not find the signals that they want. I think it would be very expensive. So, you know, the truth is, if you're enrolling people with normal testosterone levels, you're not going to get any signal with physiologic levels of replacement. By the way, everyone [00:38:00] knows that like anabolic steroids that bodybuilders use are testosterone or synthetic forms of testosterone. People know that. Yeah.

Emily: [00:38:07] So I'm not sure if people know that. Let's tell them that anabolic steroids are a synthetic form of testosterone.

Perry: [00:38:11] Yeah. They just happen to be given in like ten times the dose of testosterone replacement therapy or even up to like 30 times the dose. So these are crazy supraphysiologic doses of testosterone. And I think, in fact, some of the hesitancy to get to your point, Emily, about testing and giving men testosterone replacement therapy comes from the complications that have been seen in bodybuilders, because we know that when you're giving ten times the normal rate of testosterone, you get infertility, liver failure, roid rage, baldness, cardiovascular disease, like all this bad stuff happens. But just because that happens at ten x, the dose doesn't necessarily mean that it happens at one x the dose, right? Like like the dose is the poison as the toxicologists like to say. So I think that has, you know, actually hampered this research a little bit.

Emily: [00:38:58] All right. So getting back to the testosterone [00:39:00] trials with the older the older men, uh, these focus on people who have testosterone in lower levels. So I think the correct criteria here was below 275. Um, so people who are in the range of the, you know, below 300 and you're basically dead. Um, and, and what happens.

Perry: [00:39:20] Um, what happens is your sexual stuff gets better. So these older men that were randomized and placebo controlled, randomized to testosterone had a 40% increase in sexual activity, sexual activity frequency, a 25% increase in their libido scores, and a 35% improvement in erectile function, but no improvement in vitality or energy, and only very small improvements in mood and walking distance. Um, and this is something that like gets repeated. I've seen this again and again. Like if you look really at. If you ignore the influencers who say, I started taking testosterone replacement therapy and everything was a miracle, what you hear from men [00:40:00] is like sex, sex, sex I am. I looked at a Reddit thread in the, there's a great Reddit thread, uh, in the AskMen subreddit. It was like anyone taking testosterone replacement therapy. Like, how was it for you? And the basic breakdown is like 20% of people being like, I took it. And actually I didn't feel much. 20% of people are like, I took it. My life is great now. Like I feel so much more energy. I feel young again. Great. And 60% of people are exclusively talking about like the quality of their erections and how horny they are. Um, with one amazing comment blaming testosterone replacement therapy for the failure of his marriage because.

Emily: [00:40:49] He wanted more sex. And she didn't.

Perry: [00:40:51] Exactly. Yeah. Something that, uh, that has, uh, has come up on this podcast before. Emily has suggested that, you know, women have [00:41:00] a lower sex drive than men. Um, and I tried to be offended and I couldn't. And the data tends to bear Emily out.

Emily: [00:41:06] Data shows. Data shows it.

Perry: [00:41:08] So be careful if you're taking testosterone replacement. You might want to discuss it with your significant other.

Emily: [00:41:13] You should always talk about this stuff. Yeah. Yeah. I mean, I think, you know, look, when you look at the picture here feels very clear and, and almost it's an example where you're in this rabbit hole of influencers. And if you just pull yourself out and you're like, okay, let me just think about like, what is likely to be true based on what we know about this, it seems likely that the thing that is going to happen is about sex, because that is and about feelings about sex, because that is like the core thing about testosterone is that it Has all of these things to do with how you feel about sex and how much you want to have sex, and your ability to have sex and all of these other all these other pieces, just like it feels like that is very sensible. In contrast to a claim, [00:42:00] like you won't be able to walk or move very well, which is really no reason to think testosterone would have anything to, to particular to do with.

Perry: [00:42:09] Yeah. And I mean, insofar as mood maybe does improve slightly, like we can even draw a line between the sexual effects and those subjective effects on mood and energy and whatnot. I mean, maybe not for the guy whose whole marriage fell apart because of sexual incompatibility, but but you can certainly imagine that if all you do is increase sex drive, like for many men, that might be enough to feel a little bit better about things, right?

Emily: [00:42:40] Totally. Um, so if people are not interested in taking exogenous testosterone, I mean, there are a couple of places where it seems like there are small impacts of lifestyle changes on testosterone, mainly around weight loss, is what I would say. Like there is some evidence of small [00:43:00] amounts of increases in testosterone as a result of weight loss and similar with GLP one, which is presumably for the same, for the same reason. Those are again, like those are actually those effects are pretty small, smaller than I might have thought that they would be, actually.

Perry: [00:43:14] Yeah. Me too. We usually see sort of better effects with significant weight loss in other domains. Um, yeah, absolutely. That is actually one of the reasons, as I was kind of looking through this and deciding what my feelings were about testosterone replacement therapy, I, I tend to constitutively be like, oh, like, let's find lifestyle things that can improve the thing first rather than just like supplements or, you know, doing it. Exogenously. And the truth is that there's not a slam dunk here. Again, you're going to see some people, uh, telling you that like there's really easy natural ways to increase your testosterone. Here's, um, here's a guy, uh, talking about zinc.

Influencer: [00:43:57] If your libido is gone and your energy is [00:44:00] tanked, you might not have a hormone problem. You have a zinc problem. Your body cannot build testosterone without zinc. Today we're libido maxing at Whole Foods.

Perry: [00:44:10] We're libido maxing, I love it.

Emily: [00:44:12] Please don't do it at Whole Foods though. Why? I know Whole Foods. I don't want a bunch of people libido maxing while I'm just trying to buy salmon.

Perry: [00:44:18] Just buy the testosterone. Um.

Emily: [00:44:21] So is that true about the zinc? What? What way is zinc related?

Perry: [00:44:26] This is like classic mechanism jumping to conclusion problem. So yes, zinc is a cofactor in the synthesis of testosterone. Like in the biosynthetic pathway of testosterone. You need a little bit of zinc. That does not mean that getting your zinc level crazy high increases that it's like it's a vitamin, right? Or it's a mineral, but like, you know, you need some amount or else you can't synthesize testosterone. But having more doesn't mean you synthesize more. About 8% of the United States is zinc deficient. But this is largely [00:45:00] people with significant comorbidities who are older and who don't have access to adequate nutrition. You, listener, are probably not zinc deficient, and pumping up your zinc levels is not going to really increase your testosterone. Although, again, if you check it a couple times, you're going to get numbers you like. It's like taking the SATs over and over again.

Emily: [00:45:17] I was just thinking, it's like, take it again. They only count one of them.

Perry: [00:45:21] And I will say that the more if your zinc is too high, then your copper metabolism can get thrown off. And maybe you don't get enough copper. I don't know. So don't don't stress about stuff like that. Um, I think the real question for people when they're considering testosterone replacement therapy is, is really quite simple. Is, is my endogenous testosterone low and is it really low? Like, is it not? Did I get? One value that was low and all the others were normal.

Emily: [00:45:44] Is it consistently below 300 on multiple tests?

Perry: [00:45:47] And do I have sexual symptoms? Yeah. And if the answer to either of those is no, like there's not much to be done.

Emily: [00:45:54] I'm going to add to the to the last thing, like, do I have sexual symptoms that are a problem for me? Because [00:46:00] I think actually when we talk about sex here, it's like, you know, we're always talking about this. Like your goal is to want more sex and like, maybe that is that is your goal. Or I'm being bothered by not having the libido that I want. I think that if that's true, that's absolutely a consideration. I think people should ask. Always ask the question like, is this something that's actually a problem or not?

Perry: [00:46:22] Yeah, yeah, yeah. Um very important.

Emily: [00:46:25] What about, uh, risks here, uh, at the kind of dosage levels that we see, obviously at very high dose levels, like you would have in an anabolic steroid. Uh, there are many issues acne, weird hair in different places. Or not enough hair.

Perry: [00:46:43] Strokes and heart attacks.

Emily: [00:46:44] Strokes and heart attacks.

Perry: [00:46:45] Liver failure.

Emily: [00:46:46] Being caught by USADA for doping. But what about for people outside of this at a normal dose?

Perry: [00:46:54] Yeah. I mean the major concern has always been cardiovascular disease. Again I think largely driven by the [00:47:00] bodybuilding community. In fact, the FDA mandated a trial in higher risk older adults of testosterone replacement to to see this was a trial called traverse. More than 5000 people randomized trial for testosterone replacement therapy to look for cardiovascular disease as an important outcome. Um, and actually, there was no difference in major adverse coronary events in that trial. Again, you'll see influencers like who are really pushing TRT being like afraid of the cardiovascular risks, the traverse trial, like repudiated this, but, you know, no one trial is perfect. I mean, you'll hear traverse, traverse, traverse, no one trial is perfect. The follow up was 33 months in that trial, which is, you know, almost three years. But that doesn't mean that, you know, stuff can be going on that gets you ten years down the line. And I will say, if you actually dig in, if you actually if you actually read the traverse trial, what you'll find is that there was a higher rate of atrial fibrillation, which is [00:48:00] that abnormal heart rhythm that actually endurance athletes like yourself, Emily, are at higher risk for.

Emily: [00:48:06] Yes, thanks.

Perry: [00:48:07] And, and blood clots in the testosterone arm low. You know, the absolute risk was very low, but it was higher than in the placebo group. Um, other risks that I think are, you know, worth considering. One is fertility. So, so testosterone supplementation, if you are trying to become not become pregnant, get someone pregnant. If you're trying to get someone pregnant.

Emily: [00:48:28] Contribute positively to pregnancy.

Perry: [00:48:29] Yeah, yeah. Testosterone replacement can decrease the production of sperm. Um, there are issues with acne and hair loss and then prostate enlargement, but probably not prostate cancer. So benign prostatic hypertrophy, which is just a benign enlargement of the prostate, can make it a little hard to pee. That's been shown. And then I've got a fun bit of chemistry for you, which is that testosterone is metabolized in fat cells to estrogen, to estradiol via a [00:49:00] enzyme called aromatase. And this is why people on very high doses of test men on high doses of testosterone can develop gynecomastia, which is the development of glandular breast tissue as popularized by Robert Paulson in Fight Club for the Gen Xers, um, played admirably by meatloaf. So there is a risk of gynecomastia from testosterone supplementation. And it is higher if you have a higher body fat percentage, because that's where that conversion to estrogen takes place.

Emily: [00:49:37] Okay, I have one last urban legend to discuss before we smash or pass, which is the ratio of index to ring finger. So there's like this idea that if you have a long ring finger, I think it's right that that indicates a high level of testosterone.

Perry: [00:49:57] Uh, yeah, this is this is also all over [00:50:00] Instagram. Take a listen.

Influencer: [00:50:01] Your finger length reveals how much testosterone you were exposed to in the womb. Hold your right hand up. If your ring finger is longer than your index finger. You had high prenatal testosterone exposure. If they're the same length or your index is longer, you had lower exposure. This ratio is called the 2D 4D, and it's one of the most studied markers in human biology.

Perry: [00:50:25] Okay. So so I don't know that this is one of the most studied markers, markers in human biology, but boy, if I didn't look at my own fingers.

Emily: [00:50:36] Did you? Your fingers seem like you're in trouble.

Perry: [00:50:38] Well, I, I feel like depending on kind of how I hold my hand. I can kind of make it. Do what? No, I, I don't know, maybe I didn't get enough testosterone. What does that even mean? This guy goes on. I'm not playing the whole clip. But he goes, it's he goes on to say like, oh, then, you know, if you had more testosterone in the womb, you're like, gonna be more aggressive in life. And I don't know, Emily, you, you were saying there's some there's a fair. [00:51:00]

Emily: [00:51:00] Amount of literature. This is just a bunch of bullshit, but I like, so I haven't I'm looking at a meta analysis of this, which here is the key statement. We found no evidence of the relationship between the testosterone types and digit ratios. Furthermore, there was no evidence in various. So this is there is no evidence of this. Maybe it is very highly studied, but very highly studied to conclude that it is fake, that he should have added that he should be like, this is very highly studied and we've concluded it's garbage.

Perry: [00:51:29] I mean, even if true, I don't see just like how this matters. Aside from, I don't know, making conversation at parties or something.

Emily: [00:51:38] Okay, Perry, I'm going to ask you a personal question. Do you know your testosterone level?

Perry: [00:51:42] No.

Emily: [00:51:43] You didn't even test it for this episode?

Perry: [00:51:46] I don't. How much? I don't have whatever it is.

Emily: [00:51:49] I know $50. I know my testosterone.

Perry: [00:51:51] Oh. What's your testosterone?

Emily: [00:51:52] 25.

Perry: [00:51:54] Okay.

Emily: [00:51:55] It's like. It's not. It's below 300, but I don't know. It's part of this blood panel. It's part of some blood [00:52:00] panel I've got. I don't know. It said it was. It was sufficient.

Perry: [00:52:03] That seems that seems entirely normal.

Emily: [00:52:05] Sufficient?

Perry: [00:52:06] Uh, it would be low for me. Um, no, I mean, I, I haven't had it tested. It's one of those things where I don't have symptoms that I would attribute to low testosterone. And so even if I had it tested and it was low, I don't know that I would necessarily want to do anything about it. And that's always our threshold for should I check something? Is, is the answer going to make a difference?

Emily: [00:52:27] I also feel like, what if you what if you tested and it wasn't like it was like 400. And then you were like, ah, now I have to get it tested again so I can try to because you're not really like me. So you probably wouldn't do that. But I feel like that's the reaction I would have. I'd be like, oh, what can I do?

Perry: [00:52:41] Yeah. I mean, sometimes just like knowledge is, um, your ignorance is bliss.

Emily: [00:52:46] Ignorance is bliss. All right. Perry. Testosterone supplementation, smash or pass?

Perry: [00:52:52] Uh, I'm giving this a smash for men with low testosterone levels who have sexual symptoms. Otherwise, it's a pass. [00:53:00] Emily, smash or pass.

Emily: [00:53:02] I concur, smash if it is. If you have low levels and it is bothering you. Otherwise, pass.

Perry: [00:53:11] All right. That is it for testosterone. Your mailbag. Question of the week after the break.

Mailbag: [00:53:21] Hi, Emily. I'm Perry. This is Emily, also, from Baltimore. My husband is newly sober, so I kind of am now, too. My question is what is the health impact when swapping a daily alcoholic drink for a daily soda? And what's the impact of soda versus diet soda? In other words, if the choice is a daily drink of alcohol, diet soda, and regular soda, is there a clear winner health wise? Love the show. Thanks so much.

Emily: [00:53:49] So you're asking the question about alcohol diet soda versus regular soda. This feels like a fairly straightforward answer, which is if we're kind of thinking about some kind of optimizing diet [00:54:00] soda is the winner. It doesn't have the sugar and it doesn't have the alcohol. That's different from saying that you can't have a healthy lifestyle that incorporates alcohol or regular soda in it in moderation. But if you're telling me like I'm indifferent between those three things, I'm going with the diet soda.

Perry: [00:54:17] Yeah, I totally agree. I mean, there is a lot of concern out there about artificial sweeteners. In fact, that is on our list of upcoming episodes somewhere, our producer Tamar Can can tell us where that is happening. But, um, much of this, as you will see in that episode is, is really overblown or hypothetical concerns. Um, whereas.

Emily: [00:54:40] Mice exclusively eat sucralose as their entire diet forever, that's not ideal.

Perry: [00:54:44] Right? And, you know, but the concerns we have about alcohol and about like sugar or corn syrup, as, as you would find in, uh, regular soda is much better documented and much higher level of evidence. So I think there's a lot of anxiety about [00:55:00] artificial sweeteners. Diet soda water is probably better for you than drinking that stuff. But if, if you're purely talking about health risks, definitely diet soda over alcohol, if you get the same sort of amount of joy out of it.

Emily: [00:55:14] Yeah. I mean, I think that point about joy is, is important because I think certainly, you know, I've spent a lot of time with the alcohol and health literature and, you know, occasional light drinking is. I think the potential negative impacts are really quite small relative to some of what you hear. But again, if you're saying like, I'm totally indifferent, I think this is this is a clear call, particularly because this person has specified that like, this is what works for their relationship and is supportive of their, of their partner, which makes it an even clearer and no brainer.

Perry: [00:55:46] And also, have you tried Diet doctor Pepper? Amazing. It's great.

Emily: [00:55:50] Uh, it's too sweet. I find it too sweet, but like a nice Diet Coke. Like for me that's like cannot beat it. Fridge cigarette. That's what Gen Z calls that. The fridge cigarette. [00:56:00]

Perry: [00:56:03] Well, that's it for us today. Stick with us next week when we'll ask what's the deal with colostrum?

Emily: [00:56:12] Wellness actually is produced in association with iHeartMedia. Our senior producer is Tamar Avishai. Our executive producer at iHeart is Jennifer Bassett. Our theme music is by Eric Deutsch, and our content is for educational purposes only.

Perry: [00:56:26] If you like the show, help other people find us. Leave a rating and review on Apple Podcasts or your podcatcher of choice and help us spread the word about the show. You can follow us on Instagram at wellness. Actually, pod. And don't forget, we want to hear from you. Head over to wellness.fm and leave us a question for our mailbag or suggest a topic for a future show.

Emily: [00:56:48] We'll let the influencers have the last word.

Joe Rogan: [00:56:50] Yeah. Testosterone replacement therapy. Hormone replacement therapy. Yeah. It makes a big difference.

Rogan guest: [00:56:55] Makes a big difference.

Joe Rogan: [00:56:56] Yeah. There's a stigma attached to that. And a lot [00:57:00] of people like, you know, where do you get your testosterone from? I get it from my balls. It's real simple. If you're fine with not feeling as good. Good. Go ahead. Stick with that.