Latest / Wellness, Actually with Emily Oster & Perry Wilson, MD / What's the deal with testosterone?

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What's the deal with testosterone? · Wellness, Actually with Emily Oster & Perry Wilson, MD

0:01
Speaker 1: Emily, I'm very excited for this episode about testosterone, as
0:06
Speaker 1: you know, we you know, we just did the Hormone
0:08
Speaker 1: replacement Therapy SOR for women episode last week, and honestly,
0:12
Speaker 1: there is a vast deference between estrogen and testosterone, and
0:18
Speaker 1: I'm excited to explore that. I think this is going
0:20
Speaker 1: to be a seminal episode.
0:24
Speaker 2: I can't even react to you, but I will say
0:27
Speaker 2: that last week you gave a whole long open about
0:31
Speaker 2: how you weren't going to talk about mint.
0:32
Speaker 3: You weren't going a man's plain. You're working a blah
0:34
Speaker 3: blah blah. I'm not giving that.
0:36
Speaker 1: I am going a woman's plain all over.
0:38
Speaker 3: I am a woman's plain. I'm not sorry.
0:40
Speaker 2: I'm going to say all kinds of feelings I have
0:42
Speaker 2: about testosterone and science, and even though I only have
0:47
Speaker 2: a little bit of it, I assume.
0:50
Speaker 1: I mean, Emily, I'm glad that you have the balls
0:53
Speaker 1: to uh to really address this. Okay, I think I
0:56
Speaker 1: have about eight more.
0:57
Speaker 2: Yeah, you know what, I think that was three was
0:59
Speaker 2: really good through vast Deeferens was.
1:01
Speaker 3: Definitely the best.
1:02
Speaker 2: The balls kind of is low, and so that's where
1:04
Speaker 2: I think we should just move forward.
1:06
Speaker 1: Okay, all right, Testosterone in a nutshell After the break.
1:13
Speaker 2: I'm Emily Astro, I'm an economist and a data expert.
1:16
Speaker 1: And I'm Perry Wilson, I'm a medical doctor.
1:19
Speaker 2: It's Thursday, April thirtieth, twenty twenty six.
1:22
Speaker 3: And this is wellness.
1:23
Speaker 1: Actually, because you're getting a staggering amount of health and
1:27
Speaker 1: wellness information nowadays from every source imaginable, and some of
1:31
Speaker 1: it is awesome and some.
1:33
Speaker 3: Of it is well actually both.
1:37
Speaker 2: Fortunately, we're both people who know how to read studies,
1:40
Speaker 2: how to parse the data, and can tell you what's
1:42
Speaker 2: worth thinking about and what you can safely ignore.
1:45
Speaker 1: But before we dig in, a note that this podcast
1:48
Speaker 1: is for educational purposes and should not be construed as
1:50
Speaker 1: medical advice. We don't know your unique situation, so talk
1:54
Speaker 1: to your doctor for personal health decisions.
1:57
Speaker 2: This week we're asking what's the deal with testosterone.
2:01
Speaker 3: It's part two of our hormone two parter.
2:04
Speaker 2: Perry and I will give the official smash or pass,
2:06
Speaker 2: and then we'll get to your question of the week.
2:08
Speaker 2: But first let's do the health news roundup after the break,
2:24
Speaker 2: and now for the health news of the week, Perry,
2:27
Speaker 2: no more flu vaccine mandates for military troops. The Department
2:32
Speaker 2: of Defense Pete Hegseth has said we will not be
2:36
Speaker 2: having required flu vaccines for the military.
2:40
Speaker 1: Your thoughts, Yeah, this is weird when it comes to
2:46
Speaker 1: combat readiness. You know, the military has long and in
2:50
Speaker 1: multiple domains, had less freedoms than the public sector or
2:57
Speaker 1: than the rest of us. Right, you know, think about
2:59
Speaker 1: like free speech, even there are limitations on that in
3:01
Speaker 1: the military because it is a job that has obviously
3:06
Speaker 1: very specific risks and is so vital to national security,
3:11
Speaker 1: and combat readiness is in part determined by the health
3:16
Speaker 1: of the troops in terms of infectious diseases. I mean,
3:18
Speaker 1: if you look at like the history of warfare, you
3:21
Speaker 1: would find that infection has killed vastly more soldiers than
3:28
Speaker 1: combat is often responsible for losing the war. I mean,
3:33
Speaker 1: one of the reasons the Americans were able to hold
3:36
Speaker 1: out during the Revolutionary War was because Washington made the
3:40
Speaker 1: rather bold and somewhat risky decision to force smallpox vaccination
3:45
Speaker 1: or inoculation really on all the Revolutionary War troops. It's
3:50
Speaker 1: hard not even speaking of just about influenza's kind of random. Obviously,
3:54
Speaker 1: there's a bunch of vaccines that the troops, get me
3:58
Speaker 1: ninjaccle disease, have a hepatitis B, pertussis, diphtheria, so many
4:04
Speaker 1: So I don't know why we're isolating influenza. And like,
4:07
Speaker 1: let's not forget that the worst influenza pandemic in history occurred.
4:13
Speaker 1: This is the Spanish flu so called Spanish flu influenza
4:16
Speaker 1: pandemic occurred after World War One because a bunch of
4:19
Speaker 1: infected troops brought brought the virus home. So a weird decision.
4:24
Speaker 1: It feels completely like brazenly sort of political to me,
4:29
Speaker 1: I see no justification for this in a rational society.
4:32
Speaker 2: Yeah, I mean, I will say I think this feels
4:34
Speaker 2: like just a complete political move to me, in the
4:37
Speaker 2: sense that it's, you know, relative to other vaccines they
4:41
Speaker 2: could have turned against. I don't know why it's they
4:45
Speaker 2: chose this one, but it's one that you know, people
4:47
Speaker 2: are having every year, and there's a lot of political
4:50
Speaker 2: resistance too, and so it feels like it's this or
4:54
Speaker 2: the COVID vaccine. I think they already don't require the
4:56
Speaker 2: covid vaccine, so that's I.
4:58
Speaker 1: Think that's that's correct. Two viruses, by the way, that
5:02
Speaker 1: just really enjoys spreading in close quarter conditions. It's pretty random. Okay,
5:12
Speaker 1: let's move on. We have some fish oil news today,
5:16
Speaker 1: but actually some bad fish oil news. So fish oil
5:19
Speaker 1: supplementation pops up every once in a while. It's a
5:22
Speaker 1: wellness trend. Like many supplement trends. The data has been
5:29
Speaker 1: rather mixed. But we've got some new headlines coming out
5:31
Speaker 1: this week that actually suggests that fish oil might hurt
5:35
Speaker 1: your brain. This is kind of the opposite of what
5:38
Speaker 1: a lot of people think about fish oil, like it's
5:40
Speaker 1: going to keep me smarter, right, probably because it has
5:43
Speaker 1: so much dolphin in it, and you know how smart
5:45
Speaker 1: they are. That's a joy. That's a Simpsons reference for
5:49
Speaker 1: the very old people. And Emily, what's going on is
5:52
Speaker 1: fish oil going to hurt my brain?
5:54
Speaker 2: Fish oil is not going to hurt your brain, or
5:57
Speaker 2: at least not. There is no strong evidence for based
6:00
Speaker 2: on this new research. And this is an example where
6:04
Speaker 2: the distinction between what the headline said, which was literally
6:08
Speaker 2: fish oil might hurt your brain, and what the actual
6:10
Speaker 2: paper said was really vast. So there is a piece
6:14
Speaker 2: of new research in which researchers took mice with traumatic
6:18
Speaker 2: brain injury, so they actually took some mice, they gave
6:21
Speaker 2: them a traumatic brain injury and then they treated them
6:24
Speaker 2: with fish oil, and they found that the treatment with
6:28
Speaker 2: fish oil did not improve the traumatic brain injury in
6:31
Speaker 2: the mice, which they had thought that it might. And
6:34
Speaker 2: so that is interesting, I guess, from the standpoint of
6:38
Speaker 2: thinking about how we treat traumatic brain injury, which is
6:40
Speaker 2: an important question, and certainly, you know, early stage mouse
6:43
Speaker 2: research might be helpful for that. To go from treating
6:47
Speaker 2: mice with traumatic brain injury with fish oil does not
6:49
Speaker 2: improve them to fish oil might hurt your brain. Feels
6:52
Speaker 2: like we took not just one, but like several very
6:56
Speaker 2: large leaps.
6:59
Speaker 1: Yeah. Yeah, well, well, obviously the mouse traumatic brain injury
7:04
Speaker 1: readership is not as large as the humans worried about
7:07
Speaker 1: their brain readership.
7:08
Speaker 3: No they're not, No, they're not.
7:10
Speaker 2: But it's I mean, it's such a strong example here
7:12
Speaker 2: of where there is a piece of evidence in data
7:16
Speaker 2: that actually is kind of interesting and I think should
7:19
Speaker 2: be something we should pursue and learn more about. And
7:22
Speaker 2: then it gets turned into some clickbait headline, because of
7:24
Speaker 2: course the headline you know, mice with traumatic brain injury
7:27
Speaker 2: don't necessarily improve with fish oil is not click is
7:31
Speaker 2: not clique, it's not okay, let's do some some good news,
7:36
Speaker 2: at least what looks to me to be good news.
7:39
Speaker 2: It seems like we have started to make a little
7:42
Speaker 2: bit of progress on pancreatic cancer, a couple of new
7:47
Speaker 2: treatments that maybe are working.
7:51
Speaker 3: Did you see this and what'd you think?
7:53
Speaker 1: So exciting? So preliminary data presented at a cancer conference
7:57
Speaker 1: out in California, so not pure reviewed yet, but still
8:02
Speaker 1: super exciting. Two new and completely different approaches for pancreatic cancer.
8:08
Speaker 1: The larger trial that was presented was of a drug
8:12
Speaker 1: that I have some difficulty pronouncing, but I'm going to
8:16
Speaker 1: go for it. It is called deraxnracib dere sonracib. This
8:23
Speaker 1: is This is a novel RAS inhibitor. It was trialed
8:28
Speaker 1: in five hundred and one patients with fairly advanced late
8:32
Speaker 1: stage pancreatic cancer. Many people know that pancreatic cancer, particularly
8:37
Speaker 1: late stage pancreatic cancer, has a very poor prognosis, with
8:42
Speaker 1: an expected life expectancy generally less than a year after diagnosis.
8:47
Speaker 1: That mortality rate at the time that they cut this
8:50
Speaker 1: data and presented it was twice as long in the
8:53
Speaker 1: patients that were randomized to receive this new therapy compared
8:55
Speaker 1: to those randomized to receive placebo, about an extra six months.
9:00
Speaker 1: This difference in life expectancy, which is very significant in
9:03
Speaker 1: a pancreatic cancer trial, and obviously that's an average, and
9:06
Speaker 1: some people are living substantially longer. So super exciting that
9:10
Speaker 1: there's that new drug. Potentially, you know, a much smaller study,
9:15
Speaker 1: but potentially even more exciting insofar as it is a
9:19
Speaker 1: totally new avenue for cancer treatment. Researchers reported on patients
9:24
Speaker 1: receiving a customized mr ANDA pancreatic cancer vaccine. So this
9:30
Speaker 1: is where you take out a piece of the actual
9:34
Speaker 1: patients pancreatic cancer, you do some genetic sequencing on it
9:38
Speaker 1: to figure out where the mutations are. You create an
9:41
Speaker 1: mRNA vaccine much like the COVID vaccine that's directed against
9:44
Speaker 1: those very specific mutations, and you give that back to
9:48
Speaker 1: the patient. This was not a randomized trial. This is
9:51
Speaker 1: phase one therapy really just testing safety. But what the
9:54
Speaker 1: researchers reported that of eight patients whose immune systems responded
10:01
Speaker 1: to the mRNA so they have signals that their like
10:03
Speaker 1: immune system got revved up to the vaccine, seven were alive.
10:08
Speaker 1: Six years or more after receiving the last treatment. So
10:13
Speaker 1: this is not necessarily a miracle. You have to respond
10:16
Speaker 1: to the therapy. There's no placebo control here, which we
10:19
Speaker 1: always talk about, but in a situation like pancreatic cancer,
10:23
Speaker 1: you know, these advances can be super promising. So phase
10:26
Speaker 1: one study Phase two will get started and give us
10:30
Speaker 1: some better efficacy data, likely with a placebo control. Yeah.
10:33
Speaker 2: I mean, this last one was really very exciting, given
10:36
Speaker 2: that six years in pancreatic cancer is really out huture
10:40
Speaker 2: on the tail and the idea that it's a sort
10:44
Speaker 2: of new approach to this. It's very cool. Hopefully hopefully
10:49
Speaker 2: more science as we go.
10:51
Speaker 1: Yeah, and just another place where mRNA technology is making
10:57
Speaker 1: an impact, and we're going to talk about this in
10:59
Speaker 1: a future episode. People know about mRNA technology because of
11:03
Speaker 1: the COVID vaccine, but what makes it so flexible is
11:06
Speaker 1: that it can essentially be programmed to do what you
11:10
Speaker 1: want it to do and to attack the specific thing
11:14
Speaker 1: you wanted to attack, whether that's a COVID spike protein
11:17
Speaker 1: or a protein on the surface of pancreatic cancer. Very cool.
11:20
Speaker 3: All right, that's it for the health news of the week.
11:22
Speaker 2: After the break what's the deal with testosterone? All right, Perry,
11:32
Speaker 2: So let's talk about testosterone. Although I said, I'm not
11:37
Speaker 2: going to be careful if I do get really out
11:39
Speaker 2: on the tail of woman's plaining, joxtrap is your safe word.
11:44
Speaker 3: Just say it and I will dial it right back in.
11:47
Speaker 1: You got it. I appreciate it, thank you.
11:49
Speaker 2: All right, So let's start with the big picture. What
11:51
Speaker 2: is testosterone and what does it do for someone who
11:56
Speaker 2: is totally unfamiliar.
11:58
Speaker 1: So, testosterone is a steroid hormone. We talked about these
12:02
Speaker 1: special types of molecules last week with the hormone replacement
12:05
Speaker 1: therapy episode. But steroid hormones are unique in that they
12:10
Speaker 1: act within the nucleus of the cell to change how
12:14
Speaker 1: DNA is transcribed. So testosterone, estrogen, progesterone, some others all
12:20
Speaker 1: work this way, and that's a function that really lets
12:23
Speaker 1: them change how cells work. It can take a cell
12:26
Speaker 1: that doesn't grow hair and change it into a cell
12:28
Speaker 1: that does grow hair. Obviously, testosterone is the hormone that
12:33
Speaker 1: makes men look like men. This is responsible for the
12:38
Speaker 1: primary and secondary sexual characteristics of men. It certainly has
12:43
Speaker 1: important roles in muscle growth. We'll get to that it's
12:46
Speaker 1: necessary for sperm to be created. It has pretty significant
12:51
Speaker 1: effects on erythropoesis or the generation of red blood cells,
12:56
Speaker 1: and this is going to come up time and time again.
12:59
Speaker 1: I don't know if we need an explicit warning on
13:01
Speaker 1: this episode or not, but libido and sexual function is
13:06
Speaker 1: clearly firmly within the testosterone wheelhouse.
13:10
Speaker 2: Right, So if you're listening with your children, this episode
13:13
Speaker 2: will discuss penises and sex, so.
13:16
Speaker 3: Just be be aware, all right.
13:18
Speaker 2: So when we start from the biggest picture here, there
13:21
Speaker 2: are things which are definitely true, which is when boys
13:25
Speaker 2: go through puberty, their.
13:27
Speaker 3: Testosterone goes up.
13:29
Speaker 2: And if that doesn't happen, if you have a medical
13:31
Speaker 2: condition in which testosterone is lacking or is very low
13:36
Speaker 2: for some reason, then you will need supplementation and that
13:41
Speaker 2: that will affect the development of secondary sex characteristics. So
13:44
Speaker 2: it's very clear that testosterone is important. Yeah, if we're
13:47
Speaker 2: going to say, you know, smash or pass, like, do
13:50
Speaker 2: we need testosterone as a species, like yes, yes, right,
13:54
Speaker 2: It's not a useless peptide. It's an actual, important or important. Also,
14:00
Speaker 2: some things that for sure are true, like if you
14:03
Speaker 2: are a person doing sports and you give yourself a
14:06
Speaker 2: bunch of extra testosterone. It will probably improve your sports performance,
14:10
Speaker 2: but also.
14:11
Speaker 3: That's cheating, so don't do that.
14:15
Speaker 2: But I think there are a bunch of open, much
14:16
Speaker 2: more interesting questions that relate to some of the wellness stuff,
14:19
Speaker 2: which is, you know, how.
14:21
Speaker 3: Much variation is there?
14:22
Speaker 2: Does that variation actually matter, like within the normal range?
14:25
Speaker 2: And if we supplement outside of a sports context, is
14:30
Speaker 2: that going to improve our various sex activities and other stuff?
14:36
Speaker 3: Are those for you the interesting sets of issues?
14:39
Speaker 1: Yeah? Absolutely. I mean when people are asking me about
14:42
Speaker 1: testosterone supplementation, they're not saying like I have a genetic
14:45
Speaker 1: condition that prevents me from synthesizing testosterone, which will be
14:48
Speaker 1: like one of the FDA indications for testosterone replacement. People
14:52
Speaker 1: are asking, you know, these two things happen in parallel.
14:56
Speaker 1: One men get older and two men's test osterone level
15:00
Speaker 1: goes down a bit. And there's a natural question to say, like, well,
15:04
Speaker 1: all these other things that happen when I get older,
15:07
Speaker 1: like decreased energy, decrease libido. Maybe I feel like I'm
15:11
Speaker 1: not quite as a top, quite as cognitively sharp as
15:14
Speaker 1: I used to be, Like is that because of testosterone
15:18
Speaker 1: or is it not? And if you go online you
15:21
Speaker 1: will get plenty of people telling you absolutely it is
15:25
Speaker 1: and please, you know, call this number to get testosterone
15:29
Speaker 1: replacement therapy. But hopefully, if you're listening to the podcast,
15:32
Speaker 1: that is not enough evidence for you. So I think
15:35
Speaker 1: it's worth noting that the FDA indications for testostereplacement therapy
15:40
Speaker 1: are quite limited. It is primary hypergonadism, which is like,
15:45
Speaker 1: as you alluded to, like very rare genetic conditions that
15:48
Speaker 1: prevent the production of testosterone in boys, you know, and
15:51
Speaker 1: you need testosterone to grow into a man. The second
15:56
Speaker 1: is pituitary hypogonadism, so your petuitary glands to creates a
16:00
Speaker 1: substance that kind of tells the testes to produce testosterone.
16:03
Speaker 1: If you have a tumor in your protuitary or you
16:05
Speaker 1: had a stroke in a certain place, that's preventing that
16:07
Speaker 1: from happening. Just the testes just won't produce testosterone. They're
16:12
Speaker 1: not getting the message from the brain to do it.
16:14
Speaker 1: Those are the only FDA approved indications, and less than
16:18
Speaker 1: one percent of men with low testosterone have one of
16:23
Speaker 1: those indications. So virtually everyone getting testosterone replacement therapy that
16:27
Speaker 1: you hear about is technically getting it. Off label, which
16:29
Speaker 1: is fine, it is legal to get drugs off label,
16:33
Speaker 1: but I think it does lead to the question of, like, Okay,
16:36
Speaker 1: why isn't there an FDA approval for age related low testosterone,
16:42
Speaker 1: which is just the fact that testosterone slowly goes down
16:45
Speaker 1: when you're aging. Caveat RFK Junior has said he wants
16:48
Speaker 1: there the FDA to investigate this and maybe there will
16:50
Speaker 1: be an improval in the future. So I think that's
16:53
Speaker 1: where we kind of have to start, is like, what's
16:55
Speaker 1: going on with testosterone in the life cycle? And it
16:59
Speaker 1: is it is their menopause, right, Is there such a
17:02
Speaker 1: thing isopause?
17:05
Speaker 2: Is there a menopause? Okay, so so yeah, let's start there.
17:08
Speaker 2: So let's start with how testosterone moves over the life cycle.
17:11
Speaker 2: And if you look at a graph, and I think
17:14
Speaker 2: I'm looking at the end. HAYNES, which is the National
17:18
Speaker 2: Health and Nutrition Examination Survey, is a nationally representative survey
17:23
Speaker 2: that the CDC runs. It's a really good source for
17:25
Speaker 2: a lot of the biometrics that we have no value
17:29
Speaker 2: over time because exactly like they they unlike many other surveys,
17:34
Speaker 2: they actually test people. They bring them into these like
17:37
Speaker 2: like drive around these mobile clinics and participants like come
17:40
Speaker 2: to the clinic and have their blood drawn anyway, So
17:43
Speaker 2: this will show you testosterone over the life cycle. And
17:47
Speaker 2: there is one really striking thing in these graphs which
17:52
Speaker 2: I'm looking at as we talk, which is, you know,
17:55
Speaker 2: between the ages of like six and you know twenty,
18:00
Speaker 2: your testosterone goes from more or less zero.
18:04
Speaker 3: To like five hundred. And this is like in what
18:07
Speaker 3: is it?
18:07
Speaker 2: Is it nanograms for nanogrator for testolator. So at any rate,
18:13
Speaker 2: you start with none, little kids have very little testosterone,
18:16
Speaker 2: and then you go up a.
18:17
Speaker 3: Lot during the period of puberty.
18:19
Speaker 2: So it's very clear testosterone is very important for driving
18:23
Speaker 2: the changes that we see in boys during puberty, the
18:26
Speaker 2: development of secondary sex characteristics, the starting of supermato genesis,
18:31
Speaker 2: et cetera. And then you see it over time. And honestly, Perry,
18:37
Speaker 2: I'm looking at this graph and.
18:39
Speaker 1: I knew you were going to say that when I
18:41
Speaker 1: put the graph in our in our research document. Yeah,
18:45
Speaker 1: you sort of. So this graph shows the uh sort
18:51
Speaker 1: of variation in testosterone levels. And let's just put some
18:53
Speaker 1: numbers on it because we'll kind of keep coming back
18:55
Speaker 1: to this in adult males. So post pubescent males. Most
19:00
Speaker 1: values tend to run between three hundred nanograms pertest leader
19:03
Speaker 1: and one thousand. Most people would draw the line at
19:07
Speaker 1: three hundred nanograms per test leader to be like low
19:10
Speaker 1: testosterone or like lower testosterone. There is no cliff. This
19:15
Speaker 1: is not estrogen for women going through menopause, which is
19:19
Speaker 1: kind of up there, and just like tanks at menopause,
19:24
Speaker 1: it is relatively flat. Now, if you mathematically model this
19:28
Speaker 1: and account for things, and you know, you can show
19:32
Speaker 1: in a large enough population that there is an age
19:35
Speaker 1: related decline in testosterone on average, this is the same
19:40
Speaker 1: and hates data using mathematical modeling, that kind of average
19:43
Speaker 1: goes from about four hundred nanograms per test leader at
19:46
Speaker 1: age twenty to about three hundred nanograms pertest at age eighty.
19:52
Speaker 1: That's a change, but it's not dramatic.
19:56
Speaker 2: So manopause, I just have to say, looking at this graph,
20:00
Speaker 2: and this graph is so obviously this is like we
20:04
Speaker 2: might need to take this out of the podcast, but
20:05
Speaker 2: this graph is so obviously driven by somebody overfitting a
20:09
Speaker 2: line to a very small amount of data on old
20:12
Speaker 2: people that I can't even much confidence.
20:14
Speaker 1: Interval.
20:15
Speaker 3: For those of you who love and overfit. This graph is.
20:17
Speaker 1: An Emily's not convinced. Okay, Emily's not convinced. How about
20:21
Speaker 1: this data does suggest across multiple populations, both in the
20:26
Speaker 1: US and abroad, that average testosterone levels in the population
20:32
Speaker 1: have decreased over time. So not only as we've gotten older,
20:36
Speaker 1: but like a fifty year old man today has a
20:39
Speaker 1: lower testosterone than a fifty year old man in nineteen eighty.
20:43
Speaker 1: Levels have been going down, they say by about one
20:45
Speaker 1: percent per year, depends how you model it. Do you
20:47
Speaker 1: buy that?
20:49
Speaker 3: Yeah?
20:50
Speaker 2: I think that's interesting and we should come and we
20:51
Speaker 2: should come back to it, because I think it's part
20:54
Speaker 2: of understanding why this has has declined. But I would say,
20:58
Speaker 2: first if we ask the question like, are is this
21:01
Speaker 2: like estrogen relative to estrogen where we talked about, there's
21:04
Speaker 2: really this period in which it declines quite a lot
21:06
Speaker 2: in which replacement is helpful.
21:08
Speaker 3: We just we're not seeing that in testosterone.
21:09
Speaker 2: So it doesn't necessarily mean you wouldn't get something from supplementation,
21:13
Speaker 2: but it doesn't. It's not the case that there's some
21:15
Speaker 2: period of your life when you're testosterone is just tanking.
21:18
Speaker 1: That's right. You can be an eighty year old man
21:20
Speaker 1: and have a testosterone level that a thirty year old
21:22
Speaker 1: man has. But like, I challenge you to find an
21:25
Speaker 1: eighty year old woman not on estrogen supplementation that has
21:28
Speaker 1: an estrogen level of a thirty year old woman like that,
21:30
Speaker 1: that does not happen.
21:32
Speaker 2: Okay, So, but we also know from this amazing enhance
21:35
Speaker 2: graph that there is a lot of variation within age. Right,
21:40
Speaker 2: So if you look at like the tenth percentile of people,
21:43
Speaker 2: say at forty to forty nine, they're at about two hundred,
21:47
Speaker 2: Then ninetieth percentile is at about I don't know, six
21:50
Speaker 2: to seven hundred, and so that's a really big range.
21:54
Speaker 2: And I think that relates to the question of, like
21:57
Speaker 2: what determines this? How do you get to be a
22:00
Speaker 2: person of a testosterone level of seven hundred and realistically,
22:05
Speaker 2: and I'm just going to channel the influencers here, how
22:08
Speaker 2: do I get the seven hundred? What do I need
22:10
Speaker 2: to do to optimize my testosterone? Parry, not me specifically,
22:15
Speaker 2: I have only a small amount of time.
22:18
Speaker 3: What do you need to do? What are you doing?
22:20
Speaker 3: What do I need, Ferry to optimize your testosterone?
22:22
Speaker 1: Yeah, And I mean they're like, all, I think.
22:26
Speaker 3: You're not doing anything.
22:30
Speaker 1: I'm actually not doing anything, but I'll give you some
22:32
Speaker 1: things that you can do to optimize yourself. Or let
22:35
Speaker 1: me let me phrase it this way. I will say
22:39
Speaker 1: that before we decide whether we should make some number higher,
22:43
Speaker 1: we should decide whether it matters to make that number higher.
22:47
Speaker 1: But because we just talked about variation, I will tell
22:51
Speaker 1: you what we know what correlates with lower levels versus
22:53
Speaker 1: higher levels in the general population. Age is one. It's
22:57
Speaker 1: not as powerful as you think, right, but there is
23:01
Speaker 1: a statistically significant correlation between age. A history of smoking
23:06
Speaker 1: lower's testosterone. Current smoking, which is really interesting, will actually
23:11
Speaker 1: increase your total testosterone level by and this actually might
23:17
Speaker 1: explain why total testosterone levels have gone down over time.
23:20
Speaker 1: Can I detour for a second, because this is very weird. Okay,
23:24
Speaker 1: So testosterone is broken down very quickly in the blood,
23:27
Speaker 1: has a half life about ten minutes to maybe sixty
23:31
Speaker 1: minutes depending, So it's carried around the blood by a
23:34
Speaker 1: chaperone protein called sex hormone binding globulin, and that kind
23:38
Speaker 1: of protects it. It like wraps testosterone in a little
23:40
Speaker 1: hug and you know, keeps it safe from being degraded.
23:43
Speaker 1: But it's also an active testosterone in that bound form
23:46
Speaker 1: can't do anything. It has to be free. Free testosterone
23:50
Speaker 1: is the active form that's about two percent of total testosterone.
23:53
Speaker 1: But most people, if you're getting your lab test measured,
23:56
Speaker 1: and all the numbers we've said so far are total
23:58
Speaker 1: testosterone numbers, because free testosterone is a very difficult test
24:02
Speaker 1: to run. It's expensive. There's a couple different essays, none
24:05
Speaker 1: of them are FDA cleared at this point in time,
24:09
Speaker 1: so most people are getting total testosterone. If you increase
24:12
Speaker 1: sex hormone binding globulin, you'll increase total testosterone because you
24:16
Speaker 1: just kind of have more that's out there stuck to
24:18
Speaker 1: the chaperone protein, but it's not actually doing anything, and
24:22
Speaker 1: current smoking does that. So there is some possibility that
24:27
Speaker 1: the reason we see this generational decline in total testosterone
24:32
Speaker 1: is actually because we're smoking less, which is a really
24:37
Speaker 1: sort of paradoxical and fascinating finding.
24:39
Speaker 2: Why would having a history of smoking make your testosterone lower.
24:43
Speaker 1: I think that's just comorbidities. So the other stuff on
24:46
Speaker 1: the list for making your testosterone lower is like higher BMI, depression, diabetes,
24:54
Speaker 1: These are all things that kind of go along with smoke. Obviously, cancer,
24:57
Speaker 1: right so I think the history of smoking is just
25:00
Speaker 1: like you've kind of if you put your body through
25:01
Speaker 1: the ringer. Testosterone also is a hormone that has a
25:05
Speaker 1: pretty fascinating response to your psychosocial state. So there's a
25:11
Speaker 1: well studied phenomenon that if a man wins something, their
25:17
Speaker 1: testosterone level goes up. So if you like measure you
25:20
Speaker 1: know soccer players before the championship game and you do
25:22
Speaker 1: their their salary testosterone and then you you know, one
25:26
Speaker 1: team wins, one team loses, the winning team will have
25:29
Speaker 1: a significantly higher testosterone after the game. This doesn't last
25:32
Speaker 1: for very long. This also carries over to men watching
25:35
Speaker 1: their favorite sports teams. So if you are, you know,
25:40
Speaker 1: an Eagles fan, Jalen Hurts runs it in for a touchdown,
25:45
Speaker 1: your testosterone might go up a little bit. So it is.
25:47
Speaker 1: It is quite a cerebral thing, don't you think.
25:50
Speaker 3: That's a that?
25:51
Speaker 2: I mean that feels like an evolutionary adaptation, right, which
25:53
Speaker 2: is like the moment that I win the fight with
25:55
Speaker 2: the other guy, that's the moment, and that a lot
25:58
Speaker 2: of the lady animals, the lady monkeys want to have
26:02
Speaker 2: sex with me, and so I want to be like
26:03
Speaker 2: in a high like tsostne environment. So I'm like ready
26:07
Speaker 2: for the lady monkeys after the soccer game.
26:09
Speaker 1: I mean, yeah, I'll buy it. I'll totally buy me.
26:11
Speaker 1: I don't know, I'm not an evolutionary biologist.
26:13
Speaker 2: Makes sense, right, I know, But I think evolutionary bology
26:15
Speaker 2: is just like telling stories like that, just some of it,
26:18
Speaker 2: some of it, some hypothesis generation. There is that kind
26:20
Speaker 2: of story, and I've asked the story I'm going with.
26:24
Speaker 1: I totally love it.
26:25
Speaker 3: Did you lose your trade of thought?
26:27
Speaker 1: No, of course not, because I have one other thing
26:29
Speaker 1: that has been shown to temporarily increase testosterone, which is
26:33
Speaker 1: watching erotica or sexually charged visual imagery. Men are simple creatures, Emily.
26:40
Speaker 2: You like to win soccer and watch porns, and those
26:42
Speaker 2: are the activities that you enjoy.
26:44
Speaker 1: As I was reading about this and comparing it to
26:46
Speaker 1: like estrogen and women, and it's like so complicated and
26:49
Speaker 1: like how you know what's what's going on? Men?
26:51
Speaker 3: Soccer and porn?
26:53
Speaker 1: Things we like, yeat, that's it doesn't take much. So
26:58
Speaker 1: but but there is a lot of between person variation
27:02
Speaker 1: and testosterone, and there is also within person variation in testosterone. Emily.
27:08
Speaker 1: One of the things that came out when I was
27:11
Speaker 1: looking at like how testosterone is measured, is this fact
27:15
Speaker 1: that the coefficient of variation of testosterone measurement is fifty
27:19
Speaker 1: percent or higher within a man. Can you, with your
27:23
Speaker 1: data hat on, explain what coefficient of variation means?
27:27
Speaker 3: So a coefficient of variation is it?
27:30
Speaker 2: Technically it's the ratio of the standard aviation to the mean,
27:34
Speaker 2: which is not that.
27:34
Speaker 3: Helpful for people.
27:36
Speaker 2: It's really a way to measure sort of how much
27:40
Speaker 2: something is varying, in this case within a person scaled
27:45
Speaker 2: to the means. So if something has a coefficient of
27:47
Speaker 2: variation of fifty percent, it varies quite a lot within
27:54
Speaker 2: a person over time. You know, many things would have
27:57
Speaker 2: like you know, your weight within a time for does
28:00
Speaker 2: not have a coefficient variation anything like that exactly.
28:03
Speaker 1: And so you know, just to put like a number
28:05
Speaker 1: on it, roughly, we could say, like, okay, if you're
28:08
Speaker 1: testosterone is kind of on average is three hundred, you
28:11
Speaker 1: get it measured one day, maybe it's four fifty, right,
28:15
Speaker 1: maybe it's one fifty another day. Let me play you
28:19
Speaker 1: an influencer that I think speaks to this potential problem
28:24
Speaker 1: with testing.
28:25
Speaker 4: I increase my testosterone by forty eight percent and only
28:28
Speaker 4: twenty one days without medication.
28:30
Speaker 1: Heer's out. I'm not even going to tell you.
28:32
Speaker 3: How is it that he tested again? Thought right?
28:35
Speaker 1: So that's the thing I want to get out. When
28:38
Speaker 1: someone says, you know, my, my, whatever it is, my
28:40
Speaker 1: testosterone might anything that went up dramatically, you have to
28:45
Speaker 1: know how variable it is at baseline, and testosterone is
28:48
Speaker 1: highly variable. We know for one thing. For example, it's
28:51
Speaker 1: about fifteen percent higher on average in the morning than
28:54
Speaker 1: in the afternoon. So like men's testosterone is just higher.
28:58
Speaker 1: But that's like averaging a cross thousands of men within
29:02
Speaker 1: a given man. If you test today and you test
29:04
Speaker 1: a week from now, you're going to get very different numbers.
29:08
Speaker 1: And that is going to have the effect because we're
29:10
Speaker 1: all human, that you will start to assign causality to
29:16
Speaker 1: things that you did to make that change when there
29:19
Speaker 1: is in fact nothing. The recommendation from endochronologists is in
29:23
Speaker 1: fact that you don't diagnose low testosterone without at least
29:27
Speaker 1: two measurements temporarily separated that are both below three hundred
29:32
Speaker 1: nanograms pertestlaer.
29:34
Speaker 2: So one of the reasons to keep I mean, I
29:35
Speaker 2: think that that influencer clip is you know, it's interesting
29:40
Speaker 2: from the coefficient a variation standpoint, but it's also interesting
29:42
Speaker 2: because of course this guy's on the internet saying how
29:45
Speaker 2: great is testosteronis And that's like as a marker of
29:49
Speaker 2: you know whatever, positive of manhood presumably, which gets to
29:55
Speaker 2: the question of whether, in fact we see like are
29:59
Speaker 2: the a symptoms of low testosterone either low or just intermediate?
30:04
Speaker 2: Like if you told me I've been tested many times
30:07
Speaker 2: at my testosterone level is five hundred, should I expect
30:11
Speaker 2: you to be better on some dimension than if your
30:14
Speaker 2: testosterone is four hundred?
30:15
Speaker 1: Yeah, that's my guys, This is the question, okay, because
30:19
Speaker 1: we're so tempted to look at numbers and be like,
30:23
Speaker 1: higher number is better. And we do this with so
30:26
Speaker 1: many things, right, We do this with like vitamins, we
30:28
Speaker 1: do it with protein to some extent, right, Like we're
30:31
Speaker 1: trying to max everything. Let me let me play another
30:34
Speaker 1: influencer clip.
30:35
Speaker 5: I'm ready, Oh, man, is normal in a three hundred
30:38
Speaker 5: testosterone range? Your quality of life is gone. And it's
30:41
Speaker 5: like you said, it's not just libido. You're not gonna
30:44
Speaker 5: be able to lose weight, You're not gonna be able
30:46
Speaker 5: to gain muscle. Just like you just said, you're gonna
30:49
Speaker 5: be feeling like you can't focus on anything, brain fog
30:53
Speaker 5: like to no end. You're also gonna ach. You know
30:56
Speaker 5: that you're gonna ache, You're not gonna be able to
30:58
Speaker 5: move well, every little thing you do going to hurt.
31:00
Speaker 1: It's going to be painful. That sounds sounds terribly, It
31:06
Speaker 1: sounds pretty bad. I don't want to have a testosterone
31:09
Speaker 1: level below three hundred, so how but is it actually true?
31:17
Speaker 1: Let's walk through the EMASS study from the New England
31:20
Speaker 1: Journal of Medicine, because I think this is the one.
31:23
Speaker 1: This is like how you would design a study to
31:26
Speaker 1: assess what the effects of differing levels of testosterone are.
31:31
Speaker 1: So, so this was a survey based study three three hundred
31:35
Speaker 1: and sixty nine men ages forty to seventy nine in Europe,
31:38
Speaker 1: and they gave them very long questionnaires asking about a
31:42
Speaker 1: wide variety of symptoms depression, confusion, brain fog, fatigue, sexual symptoms,
31:51
Speaker 1: on and on and on. After giving them all those questionnaires,
31:55
Speaker 1: they measured their testosterone level. Right, and this is what
31:57
Speaker 1: you would.
31:58
Speaker 3: Want using like for real, using a blood test.
32:01
Speaker 1: Yeah, so it's like, okay, this is you know, it's
32:04
Speaker 1: one thing to say, like I measured my testosterone and
32:08
Speaker 1: it was two hundred and fifty, and now I attribute
32:11
Speaker 1: everything that's bad in my life to that to that number.
32:14
Speaker 1: That's sort of like astrology, right, It's like it's like
32:16
Speaker 1: I'm a Libra and like, so that's why you can't
32:18
Speaker 1: trust me or whatever. I Actually, I don't know is
32:19
Speaker 1: that true about Libra's.
32:20
Speaker 3: I couldn't listeners? Not really my thing.
32:24
Speaker 1: That's probably because you're a virgo.
32:27
Speaker 3: I'm gonnaquarius.
32:28
Speaker 1: Okay, should have known no with that, Okay. So this
32:32
Speaker 1: study instead says like, look, there are gonna be people
32:35
Speaker 1: who have depression, and are there more people who with
32:39
Speaker 1: depression at a low testosterone or is it just something
32:41
Speaker 1: that yes, of course people with low testosterone have depression
32:44
Speaker 1: and people with high testosterone have depression. So, Emily, was
32:48
Speaker 1: there anything that stood out to you and the results
32:50
Speaker 1: of this study as like, what if anything? Is it
32:54
Speaker 1: clear that lower testosterone causes symptom logically symptomatically?
33:00
Speaker 2: So the statistics in this study are a little like
33:04
Speaker 2: a little tortured for the sort of basic reason that
33:08
Speaker 2: they're doing a tremendous number of different tests and running
33:11
Speaker 2: them in various ways, so the like sort of some
33:14
Speaker 2: of the key results that show up as significant. They're
33:17
Speaker 2: kind of picking a threshold and then estimating the impact
33:20
Speaker 2: as you sort of move below that that threshold. But
33:24
Speaker 2: of course there's a tremendous amount of choice that goes
33:27
Speaker 2: into like, well what is the threshold and exactly how
33:30
Speaker 2: do you structure it? And if you're kind of like,
33:33
Speaker 2: you know, messing messing around, you can get closer to significance.
33:37
Speaker 3: And they're testing many things.
33:39
Speaker 2: I will say, the thing that sort of shows up
33:43
Speaker 2: most consistently here.
33:45
Speaker 3: Is stuff about sex.
33:46
Speaker 2: So sexual thoughts, mourning, erections, erectile dysfunction, those are the
33:53
Speaker 2: key things. The effects are not that big, right, So
33:58
Speaker 2: like it's a little hard to exactly translate their number
34:02
Speaker 2: into something that would be meaningful for a person. So
34:05
Speaker 2: it's like what's the odds ratio when you move one
34:08
Speaker 2: animal per leader below the threshold?
34:10
Speaker 3: Who knows what that number means? But the effects are
34:13
Speaker 3: small and not very significant, is my read?
34:17
Speaker 1: Yeah, I mean even it's very hard to actually assign
34:20
Speaker 1: like good numbers to decrease sexual thoughts, right, It's like,
34:24
Speaker 1: what how often you thinking about sex? Like there's all
34:27
Speaker 1: those sort of urban legends and stuff like that. But yes,
34:29
Speaker 1: to me, it's very clear they looked at, you know,
34:32
Speaker 1: fifty different potential symptoms and the only things that sort
34:34
Speaker 1: of withstood, however, torture, the statistics are the only things
34:38
Speaker 1: that sort of stood out were things about sex. So yes,
34:42
Speaker 1: it does seem like if your testosterone is lower, your
34:46
Speaker 1: sex drive and things associated with sex drive is going
34:49
Speaker 1: to be lower. But notably, the psychological symptoms had no
34:52
Speaker 1: correlation with testosterone level. So these influencers who are like, oh,
34:55
Speaker 1: if you're below three hundred, you're going to be essentially
34:58
Speaker 1: on your deathbed. You're going to be in pain, and
35:00
Speaker 1: you're going to be depressed, you can't think straight, you
35:02
Speaker 1: have no energy, Like that is not born out in
35:05
Speaker 1: the data where people are blinded to their testosterone level, right,
35:10
Speaker 1: Like you can you can make the argument after the fact,
35:13
Speaker 1: you can kind of attribute it, but you're probably incorrect.
35:16
Speaker 3: Yeah.
35:16
Speaker 2: I think the other thing about this trial and even
35:18
Speaker 2: about these results is what they're looking at is sort
35:21
Speaker 2: of what is happening as you're moving down below some
35:23
Speaker 2: lower threshold. Right, So here we're like really very focused
35:26
Speaker 2: on this question of if you are like these influencers saying, okay,
35:30
Speaker 2: if you're below three hundred, what happens to you? Again,
35:33
Speaker 2: there's no cliff But most of these trials are about
35:37
Speaker 2: these lower like moving down within lower levels, not asking
35:43
Speaker 2: the question of whether seven.
35:44
Speaker 3: Hundred is better than six hundred.
35:47
Speaker 2: And oh yeah, And for that I think we just
35:49
Speaker 2: have no there's no evidence to suggest that's true.
35:52
Speaker 1: Yeah, and I would be very honestly, I'd be very
35:53
Speaker 1: surprised if it's true. And the variation within a person.
35:56
Speaker 1: You know, if you're below seven hundred, if you're six
35:58
Speaker 1: fifty today, you're seven fifty tomorrow, you're six hundred the
36:01
Speaker 1: next day. Like, you know, you're only going to see
36:04
Speaker 1: effects when things are low. And again it looks like
36:07
Speaker 1: those effects are are fairly limited. But that was an
36:11
Speaker 1: observational study, right, that didn't say anything about replacing testosterone.
36:15
Speaker 1: So there's okay, if you don't have enough testosterone, all right,
36:20
Speaker 1: you have decreased morning erections and a higher risk of
36:22
Speaker 1: rectile dysfunction. Then the question is, okay, what if we
36:26
Speaker 1: replace testosterone, do those things get better? Do other things
36:29
Speaker 1: get better too? And in this case, we really don't
36:34
Speaker 1: want influencers to tell us what their anecdotal experience was.
36:40
Speaker 1: We want to hear in the form of randomized trials, right,
36:43
Speaker 1: we want placebo controls where people don't know they're getting testosterone,
36:46
Speaker 1: because we've said a million times, if I tell you,
36:49
Speaker 1: I'm giving you testosterone, even if it's not, it's like
36:52
Speaker 1: Felix fellicis in Harry Potter, right, You're just like you
36:56
Speaker 1: feel good, and that's the power of place ebah.
36:59
Speaker 2: And this is such a a classic place where the
37:01
Speaker 2: placebo effect is going to matter, Yeah, tremendously because if
37:06
Speaker 2: you tell somebody you know, I'm giving you something and
37:08
Speaker 2: it's going to make you feel more excited about sex,
37:11
Speaker 2: Like they are going.
37:12
Speaker 3: To feel more excited about sex for sure. There's just
37:14
Speaker 3: like no question. So much of this is in your head.
37:17
Speaker 1: Yeah, yeah, yeah, that's how oysters work. So let's we
37:22
Speaker 1: can't obviously talk about every trial, but I think there's
37:24
Speaker 1: a couple that are are relevant to the discussion. The
37:27
Speaker 1: testosterone trials. The te trials enrolled seven hundred and eighty
37:31
Speaker 1: eight men above age sixty five who had total testosterone
37:34
Speaker 1: less than to seventy five.
37:35
Speaker 2: Can I just ask you before we get into the like,
37:37
Speaker 2: what do you think about focusing only on old, older
37:40
Speaker 2: men in this, do you wish that they had focused
37:43
Speaker 2: also on people like you?
37:45
Speaker 1: I think they would not find the signals that they want.
37:48
Speaker 1: I think it would be very expensive. So you know,
37:50
Speaker 1: the truth is, if you're enrolling people with normal testosterone levels,
37:55
Speaker 1: you're not going to get any signal with physiological levels
37:58
Speaker 1: of replacement. By the way, knows right that like antabolic
38:01
Speaker 1: steroids that bodybuilders use are testosterone, right, or synthetic forms
38:05
Speaker 1: of testosterone. People know that.
38:06
Speaker 2: Yeah, I'm not sure if people know that, let's tell
38:09
Speaker 2: them that anabolic steroids or a synthetic form of testosterone.
38:11
Speaker 1: Yeah, they just happen to be given in like ten
38:14
Speaker 1: times the dose of testosterone placement therapy, or even up
38:17
Speaker 1: to like thirty times the dose. So these are crazy,
38:19
Speaker 1: super physiologic doses of testosterone. And I think, in fact,
38:23
Speaker 1: some of the hesitancy to get to your point, Emily
38:26
Speaker 1: about testing and giving men testosteronal replacement therapy comes from
38:30
Speaker 1: the complications that have been seen in bodybuilders, because we
38:33
Speaker 1: know that when you're giving ten times the normal rate
38:35
Speaker 1: of testosterone, you get infertility, liver failure, roid rage, baldness,
38:42
Speaker 1: cardiovascular disease. Like all this bad stuff happens. But just
38:46
Speaker 1: because that happens at ten x the dose doesn't necessarily
38:50
Speaker 1: means it happens at one x the dose, right, like
38:52
Speaker 1: like the dose is the poison, as the toxicologists like
38:55
Speaker 1: to say. So I think that has you know, actually
38:57
Speaker 1: hampered this research a little bit.
38:58
Speaker 2: All right to getting back to this TESASA trials with
39:00
Speaker 2: the older the older men, these focus on people who
39:05
Speaker 2: have testosterone in lower levels. So I think the criteria
39:09
Speaker 2: here was below two hundred and seventy five, So people
39:12
Speaker 2: who were in the range of the you know, below
39:14
Speaker 2: three hundred and you're basically dead.
39:18
Speaker 3: And what happens.
39:20
Speaker 1: What happens is your sexual stuff gets better. So these
39:24
Speaker 1: older men that were randomizing, again placebo controlled randomized to
39:27
Speaker 1: testosterone had a forty percent increase in sexual activity sexual
39:31
Speaker 1: activity frequency, a twenty five percent increase in their libido scores,
39:35
Speaker 1: and a thirty five percent improvement in a rectile function,
39:38
Speaker 1: but no improvement in vitality or energy, and only very
39:42
Speaker 1: small improvements in mood and walking distance. And this is
39:46
Speaker 1: something that like gets repeated. I've seen this again and again,
39:51
Speaker 1: Like if you look really at if you ignore the
39:54
Speaker 1: influencers who say I started taking testosterone in placement therapy
39:57
Speaker 1: and everything was a miracle. What you hear from men
40:00
Speaker 1: is like sex sex sex. I am. I looked at
40:04
Speaker 1: a Reddit thread in.
40:05
Speaker 3: The ask Matrimonia.
40:06
Speaker 1: It's a sex serment. Okay, there's a great reddit thread
40:11
Speaker 1: in the ask Men's subreddit. It was like anyone taking
40:13
Speaker 1: testosterone placement therapy, like, how was it for you? And
40:16
Speaker 1: the basic breakdown is like twenty percent of people being like,
40:20
Speaker 1: I took it, and actually I didn't feel much. Twenty
40:23
Speaker 1: percent of people are like, I took it. My life
40:26
Speaker 1: is great now, like I feel so much more energy,
40:28
Speaker 1: I feel young again, great, And sixty percent of people
40:32
Speaker 1: are exclusively talking about like the quality of their erections
40:39
Speaker 1: and how horny they are, with one amazing comment blaming
40:44
Speaker 1: testosterone replacement therapy for the failure of his marriage because.
40:49
Speaker 3: He wanted more sex than she didn't.
40:51
Speaker 1: Exactly. Yeah, something that that has has come up on
40:56
Speaker 1: this odd podcast before. Emily has suggested that, you know,
40:59
Speaker 1: women have a lower sex drive than men. And I
41:02
Speaker 1: tried to be offended and I couldn't. And the data
41:05
Speaker 1: tends to bear Emily out.
41:06
Speaker 3: Data shows, data shows so be.
41:08
Speaker 1: Careful if you're taking testoster replacement or you might want
41:11
Speaker 1: to discuss it with your significant other.
41:13
Speaker 3: You should always talk about this stuff.
41:15
Speaker 2: Yeah, yeah, I mean, I think in a look when
41:16
Speaker 2: you look the picture here feels very clear and almost
41:23
Speaker 2: it's an example where you're in this rabbit hole of
41:26
Speaker 2: influencers and if you just pull yourself out and you're like, Okay,
41:30
Speaker 2: let me just think about, like what is likely to
41:33
Speaker 2: be true based on what we know about this.
41:35
Speaker 3: It seems likely that the thing that is going to
41:38
Speaker 3: happen is about.
41:39
Speaker 2: Sex, because that is and about feelings about sex, because
41:42
Speaker 2: that is like the core.
41:45
Speaker 3: Thing about disosterone is that.
41:47
Speaker 2: It has all these things to do with how you
41:50
Speaker 2: feel about sex and how much you want to have sex,
41:52
Speaker 2: and your ability to have sex and all these other
41:54
Speaker 2: all these other pieces. Just like it feels like that
41:56
Speaker 2: is very sensible in contrast to a claim like you
42:00
Speaker 2: won't be able to walk or move very well, which
42:05
Speaker 2: is really no reason to think testosterone would have anything
42:07
Speaker 2: to particular to do with.
42:09
Speaker 1: Yeah, and I mean, insofar as mood maybe does improve slightly,
42:15
Speaker 1: Like we can even draw a line between the sexual
42:18
Speaker 1: effects and those subjective effects on mood and energy, and whatnot.
42:24
Speaker 1: I mean, maybe not for the guy whose whole marriage
42:26
Speaker 1: fell apart because of sexual incompatibility, but you can certainly
42:31
Speaker 1: imagine that if all you do is increase sex drive,
42:34
Speaker 1: like for many men, that might be enough to feel
42:38
Speaker 1: a little bit better about things.
42:39
Speaker 2: Right, totally, So if people are not interested in taking
42:45
Speaker 2: exogenous testosterone, I mean, there are a couple of places
42:49
Speaker 2: where it seems like there are small impacts of lifestyle
42:53
Speaker 2: changes on testosterone, mainly around weight loss, is what I
42:56
Speaker 2: would say, Like, there is some evidence of small all
43:00
Speaker 2: amounts of increases in testosterone as a result of weight loss,
43:03
Speaker 2: and similar with you know, GLP ones, which is presumably
43:06
Speaker 2: for the same for the same reason. Those are again
43:09
Speaker 2: like those are actually those effects are pretty.
43:11
Speaker 3: Small, smaller than I might have thought that they would be.
43:13
Speaker 1: Actually, yeah, me too. We usually see sort of better
43:17
Speaker 1: effects with significant weight loss in other domains. Yeah, absolutely,
43:24
Speaker 1: That is actually one of the reasons as I was
43:26
Speaker 1: kind of looking through this and deciding what my feelings
43:28
Speaker 1: were about testosterone replacement therapy, I tend to constitutively be like, oh, like,
43:33
Speaker 1: let's find lifestyle things that can improve the thing first,
43:36
Speaker 1: rather than just like supplements or you know, doing it exogynously,
43:40
Speaker 1: And the truth is that there's not a slam dunk here. Again,
43:47
Speaker 1: you're gonna see some people telling you that, like there's
43:50
Speaker 1: really easy natural ways to increase your testosterone. Here's here's
43:55
Speaker 1: a guy talking about zinc.
43:57
Speaker 4: If your libido is gone and your energy is tank,
44:00
Speaker 4: you might not have a hormone problem, you have a
44:02
Speaker 4: zinc problem. Your body cannot build testosterone without zinc. Today
44:06
Speaker 4: we're libido maxing at Whole Foods.
44:10
Speaker 1: We're libido maxing. I love it.
44:12
Speaker 3: Please don't do it at whole food So why I
44:14
Speaker 3: know whole Foods.
44:15
Speaker 2: I don't want a bunch of people libido maxing while
44:17
Speaker 2: I'm just try chaper.
44:18
Speaker 1: Just to buy the testosterone.
44:21
Speaker 3: So is that true about the zinc? What what way
44:24
Speaker 3: is zinc related?
44:26
Speaker 1: This is like classic mechanism jumping to conclusion problem. So yes,
44:31
Speaker 1: zinc is a cofactor in the synthesis of testosterone, as
44:35
Speaker 1: like in the biosynthetic pathway of testosterone you need a
44:38
Speaker 1: little bit of zinc. That does not mean that getting
44:42
Speaker 1: your zinc level crazy high increases that. It's like it's
44:46
Speaker 1: a vitamin, right, or it's a mineral, but like it
44:48
Speaker 1: you know you need some amount or else you can't
44:51
Speaker 1: synthesize testosterone, but having more doesn't mean you synthesize more.
44:56
Speaker 1: About eight percent of the United States is zinc deficient,
44:59
Speaker 1: but this is lar Argually, people with significant colmorbidities, who
45:02
Speaker 1: are older and who don't have access to adequate nutrition.
45:06
Speaker 1: Your you listener are probably not sync deficient, and pumping
45:10
Speaker 1: up your zinc levels not going to really increase your testosterone,
45:12
Speaker 1: although again, if you check it a couple times, you're
45:14
Speaker 1: going to get numbers you like. It's like taking the
45:16
Speaker 1: SATs over and over again.
45:17
Speaker 2: Really, I was just thinking, it's like, and take it again, right,
45:19
Speaker 2: they only count one of.
45:20
Speaker 1: Them, and I will say that the more. If your
45:22
Speaker 1: zinc is too high, then your copper metabolism can get
45:26
Speaker 1: thrown off and maybe you don't get enough copper. I
45:28
Speaker 1: don't know, So don't don't stress about stuff like that.
45:32
Speaker 1: I think the real question for people when they're considering
45:34
Speaker 1: testosterone real placement therapy is really quite simple. Is is
45:38
Speaker 1: my indogenous testosterone low? And is it really low? Like
45:41
Speaker 1: is not? Did I get one value that was low
45:43
Speaker 1: and all the others are normal.
45:44
Speaker 3: Consistently below three hundred on multiple tests.
45:47
Speaker 1: And do I have sexual symptoms? Yeah, And if the
45:50
Speaker 1: answer to either of those is no, like there's not
45:53
Speaker 1: much to be done.
45:54
Speaker 2: I'm going to add to the to the last thing,
45:56
Speaker 2: like do I have sexual symptoms that are a problem
45:59
Speaker 2: for me? Because I think actually, when we talk about
46:01
Speaker 2: sex here, it's like, you know, we're always talking about this,
46:05
Speaker 2: like your goal is to want more sex, and like
46:08
Speaker 2: maybe that is that is your goal or I'm being
46:09
Speaker 2: bothered by not having.
46:11
Speaker 3: The libido that I want.
46:12
Speaker 2: I think that if that's true, that's absolutely a consideration.
46:15
Speaker 2: I think people should ask always ask a question like
46:18
Speaker 2: is this something that's actually a problem or.
46:21
Speaker 1: Yeah not yeah, yeah, yeah, very important.
46:25
Speaker 2: What about risks here at the kind of dosage levels
46:29
Speaker 2: So we see, obviously at very high dose levels like
46:32
Speaker 2: you would have in an anomolic steroid, there are many
46:37
Speaker 2: issues acne, weird hair in different places, or not enough hair.
46:43
Speaker 1: Strokes and heart attacks, strokes and heart attacks, liver failure.
46:46
Speaker 2: Being caught by USADA for doping. But what about for
46:50
Speaker 2: people outside of this in a normal dose.
46:54
Speaker 1: Yeah, I mean, the major concern has always been cardiovascular disease. Again,
46:58
Speaker 1: I think largely driven by the bodybuilding community in fact,
47:02
Speaker 1: the FDA mandated a trial in higher risk older adults
47:06
Speaker 1: of testosterone replacement to see This was a trial called
47:09
Speaker 1: Traverse more than five thousand people randomized trial for testosterone
47:14
Speaker 1: replacement therapy to look for cardiovascular disease as an important outcome,
47:19
Speaker 1: and actually there was no difference in major adverse coronary
47:22
Speaker 1: events in that trial. Again, you'll see influencers like who
47:26
Speaker 1: are really pushing TRT being like afraid of the cardiovascular
47:29
Speaker 1: risks the Traverse trial like repudiated this. But you know,
47:34
Speaker 1: no one trial is perfect. I mean you'll hear Traverse, Traverse, Traverse,
47:37
Speaker 1: No one trial is perfect. The follow up was thirty
47:39
Speaker 1: three months in that trial, which is you know, almost
47:42
Speaker 1: three years. But that doesn't mean that you know, stuff
47:46
Speaker 1: can be going on that gets you ten years down
47:48
Speaker 1: the line. And I will say, if you actually dig in,
47:51
Speaker 1: if you actually if you actually read the Traverse trial,
47:54
Speaker 1: what you'll find is that there was a higher rate
47:58
Speaker 1: of atrial fibrillation, which is that abnormal heart rhythm that
48:01
Speaker 1: actually endurance athletes like yourself, Emily are at higher risk
48:05
Speaker 1: for thanks and blood clots in the testosterone arm low.
48:11
Speaker 1: You know, the absolute risk was very low, but it
48:13
Speaker 1: was higher than in the placebo group. Other risks that
48:16
Speaker 1: I think are you know, worth considering. One is fertility,
48:20
Speaker 1: So so testosterone supplementation if you are trying to not
48:25
Speaker 1: become pregnant, get someone pregnant. If you're trying to get.
48:27
Speaker 3: Someone pregnant, contribute positively to pregnancy.
48:29
Speaker 1: Yeah, yeah, testosterone placement can decrease the production of sperm.
48:35
Speaker 1: There are the issues with acne and hair loss, and
48:38
Speaker 1: then prostate enlargement, but probably not prostate cancer, so benign
48:42
Speaker 1: prostatic hypert refuge is just a benign enlargement in the
48:44
Speaker 1: prostate can make it a little hard to pee. That's
48:46
Speaker 1: been shown. And then I've got a fun bit of
48:48
Speaker 1: chemistry for you, which is that testosterone is metabolized in
48:54
Speaker 1: fat cells to estrogen to a stratiol via a enzyme
49:01
Speaker 1: called aroma tase. And this is why people on very
49:06
Speaker 1: high doses of men on high doses of testosterone can
49:10
Speaker 1: develop kind of camastia, which is the development of like
49:12
Speaker 1: glandular breast tissue as popularized by Robert Paulson in Fight
49:19
Speaker 1: Club for the gen Xers, played admirably by meat Loaf.
49:24
Speaker 1: So there is a risk of gind ofcomasia from testosterone supplementation.
49:28
Speaker 1: And it is higher if you have a higher body
49:31
Speaker 1: fat percentage, because that's where that conversion to estrogen takes place.
49:37
Speaker 2: Okay, I have one last urban legend to discuss before
49:41
Speaker 2: we smash our pass, which is the ratio of index
49:45
Speaker 2: to ring finger.
49:46
Speaker 3: So there's like this idea that if you have a.
49:49
Speaker 2: Long ring finger, I think it's right that that indicates
49:55
Speaker 2: a high level of testosterone.
49:58
Speaker 1: Yeah, this is also all for Instagram. Take a listen.
50:01
Speaker 6: Your finger length reveals how much testosterone you were exposed
50:04
Speaker 6: to in the womb. Hold your right hand up. If
50:07
Speaker 6: your ring finger is longer than your index finger, you
50:11
Speaker 6: had high prenatal testosterone exposure. Is there the same length,
50:16
Speaker 6: or your index is longer you had lower exposure. This
50:19
Speaker 6: ratio is called the two D four D and it's
50:22
Speaker 6: one of the most studied markers in human biology.
50:25
Speaker 1: Okay, So, so I don't know that this is one
50:28
Speaker 1: of the most studied UH mark markers in human biology,
50:32
Speaker 1: but boy, if I didn't look at my own finger.
50:36
Speaker 3: Yeah, you your fingers seem like you're in trouble.
50:38
Speaker 1: Well, I feel like depending on kind of how I
50:40
Speaker 1: hold my hand, I can kind of make it do
50:42
Speaker 1: what now? I don't know. Maybe I didn't get enough testosterone.
50:45
Speaker 1: What does that even mean? This guy goes on, I'm
50:47
Speaker 1: not playing the whole clip, but he goes it's He
50:49
Speaker 1: goes on to say, like, oh, then you know, if
50:51
Speaker 1: you had more testosterone in the womb, you're like gonna
50:54
Speaker 1: be more aggressive in life. And I don't know, Emily,
50:57
Speaker 1: you were saying, there's.
50:58
Speaker 2: Some amount of literature. This is just a bunch of bullshit,
51:03
Speaker 2: But I like, so I happened. I'm looking at a
51:06
Speaker 2: meta analysis of this, which here is the key statement.
51:09
Speaker 2: We found no evidence of the relationship between the testosterone
51:12
Speaker 2: types and digit ratios.
51:15
Speaker 3: Furthermore, there was.
51:15
Speaker 2: No evidence and very so this is uh, there is
51:18
Speaker 2: no evidence of this. Maybe it is very highly studied,
51:21
Speaker 2: but very highly studied to conclude that it is fake
51:25
Speaker 2: that he should have added that he should have like
51:26
Speaker 2: this is very highly studyed and we've concluded it's garbage.
51:29
Speaker 1: I mean, even if true, I don't see just like
51:31
Speaker 1: how this matters aside from I don't know, making conversation
51:37
Speaker 1: of parties or something.
51:38
Speaker 3: Okay, Perry, I'm gonna ask you a personal question. Do
51:41
Speaker 3: you know your tesosterone level? No, you didn't even test
51:44
Speaker 3: it for this episode.
51:46
Speaker 2: I did.
51:46
Speaker 1: I don't how much. I don't have what I know?
51:50
Speaker 3: I know my testosterone.
51:51
Speaker 1: Oh what's your testosterone?
51:52
Speaker 3: Twenty five? Okay, it's like it's not it's below three hundred.
51:56
Speaker 3: But yeah, I don't know. It's part of this blood panel,
51:59
Speaker 3: part of some blood panel I've got. I don't know.
52:01
Speaker 3: It said it was sufficient.
52:03
Speaker 1: That seems that seems entirely normal.
52:05
Speaker 3: Sufficient.
52:06
Speaker 1: It would be low for me. No, I mean, I
52:09
Speaker 1: haven't had it tested. It's one of those things where
52:13
Speaker 1: I don't have symptoms that I would attribute to low testosterone.
52:16
Speaker 1: And so even if I had it tested and it
52:19
Speaker 1: was low, I don't know that I would necessarily want
52:22
Speaker 1: to do anything about it. And that's always our threshold
52:24
Speaker 1: for should I check something? Is the answer going to
52:26
Speaker 1: make a difference.
52:27
Speaker 2: I also feel like, what if you tested and it
52:30
Speaker 2: wasn't like it was like four hundred, and then you
52:32
Speaker 2: were like, ah, now I have to get tested again
52:35
Speaker 2: so I can try to Because you're not really like me,
52:37
Speaker 2: so you probably wouldn't do that. But I feel like
52:38
Speaker 2: that's the reaction I would have. I'd be like, oh,
52:40
Speaker 2: what can I do?
52:41
Speaker 1: Yeah, I mean sometimes just like knowledge is your ignorance
52:45
Speaker 1: is bliss.
52:46
Speaker 3: Ignorance is bliss.
52:48
Speaker 2: All right, Perry, testosterone supplementation smash your pass.
52:53
Speaker 1: I'm giving this a smash for men with low testosterone
52:57
Speaker 1: levels who have sexual symptoms. Otherwise it's a past. Emily
53:01
Speaker 1: Smasher pass.
53:02
Speaker 2: I concur smash if it is if you have low
53:06
Speaker 2: levels and it is bothering you otherwise pass.
53:11
Speaker 1: All right, That is it for testosterone. Your mailbag question
53:14
Speaker 1: of the week after the Break.
53:21
Speaker 3: Hi, Emily and Perry.
53:22
Speaker 7: This is Emily, also from Baltimore. My husband is newly sober, so.
53:27
Speaker 3: I kind of am now too.
53:29
Speaker 7: My question is what is the health impact when swapping
53:32
Speaker 7: a daily alcoholic drink for a daily soda and what's
53:36
Speaker 7: the impact of soda versus diet soda? In other words,
53:40
Speaker 7: if the choice is a daily drink of alcohol, diet
53:42
Speaker 7: soda and regular soda, is there a clear winter health wise?
53:46
Speaker 7: Love the show, Thanks so much so.
53:49
Speaker 2: You're asking the question about alcohol, diet soda versus regular soda.
53:52
Speaker 2: This feels like a fairly straightforward answer, which is, if
53:56
Speaker 2: we're kind of thinking about some kind of optimizing diet
54:00
Speaker 2: soda is the winner. It doesn't have the sugar, and
54:03
Speaker 2: it doesn't have the alcohol. That's different from saying that
54:05
Speaker 2: you can't have like a healthy lifestyle that incorporates alcohol
54:08
Speaker 2: or regular soda.
54:10
Speaker 3: In it in moderation.
54:12
Speaker 2: But if you're telling me, like I'm a difference between
54:14
Speaker 2: those three things, I'm going with the diet soda.
54:17
Speaker 1: Uh yeah, I totally agree. I mean, there is a
54:21
Speaker 1: lot of concern out there about artificial sweeteners. In fact,
54:24
Speaker 1: that is on our list of upcoming episodes somewhere our
54:28
Speaker 1: producer tomorrow can can tell us where that is happening.
54:31
Speaker 1: But much of this, as you will see in that episode,
54:35
Speaker 1: is really overblown or hypothetical concerns.
54:39
Speaker 2: Whereas mice exclusively eats sycrilos as their entire diet forever,
54:43
Speaker 2: that's not ideal, right, And.
54:46
Speaker 1: You know, but the concerns we have about alcohol and
54:49
Speaker 1: about like sugar or corn syrup as you would find
54:52
Speaker 1: in regular soda is much better documented, much higher level
54:57
Speaker 1: of evidence. So I think there's a lot of anxiety
54:59
Speaker 1: about artificial sweeteners. Diet soda water is probably better for
55:04
Speaker 1: you than drinking that stuff. But if you're purely talking
55:08
Speaker 1: about health risks, definitely diet soda over alcohol. If you
55:12
Speaker 1: get the same sort of amount of joy out of it.
55:14
Speaker 2: Yeah, I mean, I think that point about joy is
55:17
Speaker 2: important because they think, certainly, you know, I've spent a
55:20
Speaker 2: lot of time with the alcohol and health literature, and
55:23
Speaker 2: you know, occasional light drinking is I think the potential
55:27
Speaker 2: negative impacts are really quite small relative to some of
55:31
Speaker 2: what you hear. But again, if you're saying, like I'm
55:34
Speaker 2: totally indifferent, I think this is a clear call, particularly
55:38
Speaker 2: because this person has specified that like, this is what
55:41
Speaker 2: works for their relationship and is supportive of their partner,
55:44
Speaker 2: which makes it an even clearer no brainer.
55:46
Speaker 1: And also, have you tried diet doctor pepper? Amazing? It's great.
55:50
Speaker 3: It's too sweet.
55:51
Speaker 2: I find it too sweet, but diet like a nice
55:53
Speaker 2: diet coke. Like for me, that's like cannot be spot
55:57
Speaker 2: fridge cigarette. That's what gen Z calls that cigarette.
56:03
Speaker 1: Well, that's it for us today. Stick with us next
56:06
Speaker 1: week when we'll ask what's the deal with colostrum?
56:12
Speaker 2: Wellness actually is produced in association with iHeartMedia.
56:16
Speaker 3: Our senior producer is Tamar Avisheid.
56:18
Speaker 2: Our executive producer at iHeart is Jennifer Bassett. Our theme
56:22
Speaker 2: music is by Eric Deutsch. And our content is for
56:25
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56:26
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56:41
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56:44
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56:47
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56:48
Speaker 3: We'll let the influencers have the last word.
56:50
Speaker 1: Yeah.
56:51
Speaker 8: TESTOSTERM replacement therapy, hormone replacement therapy. Yeah, it makes a big.
56:54
Speaker 3: Difference, makes a big difference.
56:56
Speaker 8: Fuck Yeah, there's a stigma attached to that in a
56:59
Speaker 8: lot of people, like you know, where do you get
57:01
Speaker 8: your testosterone from? I'll get it from my balls. It's
57:06
Speaker 8: real simple. If you're fine with not feeling as good good,
57:10
Speaker 8: go ahead. Stick with that.