How to Optimize Your Hormones for Health & Vitality | Dr. Kyle Gillett

1. 0:00 – 3:10

   Dr. Kyle Gillett, MD, Hormone Optimization

   1. AHAndrew Huberman0:00

      (uptempo music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. Kyle Gillett. Dr. Gillett is dual board certified in family medicine and obesity medicine, and practices out of a clinic in Kansas and via telemedicine. He provides full-spectrum medicine, including hormone health, preventative medicine, obstetrics, which is the branch of medicine and surgery concerned with childbirth and the care of women giving birth, and pediatrics. I first learned about Dr. Gillett from a podcast, of all things, and was immediately struck by the breadth and depth of his knowledge on all things hormones and hormone optimization. As you'll see very soon today, Dr. Gillett can teach you how to optimize your hormones using behavioral tools, nutrition, exercise-based tools, supplementation, and hormone therapies if those are appropriate for you. There are many professionals out there, including many medical doctors, of course, talking about hormone health. What really sets Dr. Gillett apart from the pack is his ability to understand how the different factors that I described before, nutrition, supplementation, exercise, and hormone therapies, how those interact with one another and the safest and most rational ways to approach hormone optimization. During today's episode, you will learn how to optimize your hormones, not just testosterone and estrogen, but also prolactin and other hormone pathways that impact your mood, mental health, and physical health. Dr. Gillett is also an avid educator about hormones and other aspects of health. He does this on zero-cost-to-consumer platforms such as Instagram and other social media. On Instagram, he is kylegillettmd. That's K-Y-L-E-G-I-L-L-E-T-T, no E at the end, M-D, so kylegillettmd on Instagram. And he is gillettehealth on all other platforms, including LinkedIn, Twitter, YouTube, TikTok, and Facebook. If you go to his Instagram or his other social media, you will learn a lot about hormone health, about the latest science impacting obesity and metabolic health. He is a wealth of knowledge, and again, he's providing all that information at zero cost to you, the consumer. What you are soon to hear is a conversation between me and Dr. Gillett about all things hormones and hormone health and hormone optimization. We dive deep into mechanisms, but we are clear to establish what each word or set of concepts mean. So, if you have no background in biology, or even if you do, I'm sure that you'll come away with a wealth of valuable knowledge. We also talk about specific protocols related, again, to lifestyle factors, nutrition, supplementation, and where appropriate, hormone replacement therapy. I know there's a lot of interest about these topics. Dr. Gillett is very thorough about addressing both male and female issues and addressing hormone health for people at all stages of life. I'm sure that you will come away from this episode with the same impression that I did, which is that Dr. Gillett is an extraordinarily clear communicator and that he has tremendous compassion for his patients and that he has a deep love of understanding biology and medicine in ways that can benefit

2. 3:10 – 4:10

   The Brain-Body Contract

   1. AHAndrew Huberman3:10

      you. I'm pleased to announce that I am hosting two live events in May 2022. The first live event will take place in Seattle, Washington on May 17th. The second live event will take place in Portland, Oregon on May 18th. Both are part of a lecture series entitled The Brain-Body Contract, during which I will talk about science and science-based tools, many of which overlap with the topics covered on the Huberman Lab Podcast, but most of which will not and will be completely new topics and tools never discussed publicly before. Both live events will also include a question and answer period during which you, the audience, can ask me questions directly about any aspect of science or science-based tools, and I will attempt to answer them. Tickets for the two events, again, Seattle on May 17th and Portland on May 18th, are both available at hubermanlab.com/tour. Before we begin with today's episode, I want to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer

3. 4:10 – 8:24

   Thesis, InsideTracker, ROKA

   1. AHAndrew Huberman4:10

      information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Thesis. Thesis makes nootropics. In fact, they make custom nootropics. Now, what is a nootropic? Technically, nootropic means smart drug. Frankly, I'm not a big fan of the word nootropics, because what is smart? I mean, there's creativity. There's focus. There's task switching. Different aspects of our brain and body engage different aspects of cognition, many of which we can call smart. There's emotional intelligence. There's analytic intelligence. There's logic. There's creativity. Thesis understands this and has designed custom nootropics designed to bring your body and brain into the specific state that you want. So for instance, they have specific nootropics for creativity, other nootropics for focus, other nootropics for motivation, and so on and so forth. In addition to that, each nootropic is custom designed for you. They use only the highest quality ingredients, things like Alpha-GPC and phosphatidylserine, which I've talked about on this podcast before. They also use ingredients like ginkgo biloba, which many people use, like, and benefit from. However, there are also people like me, who can't take ginkgo biloba because it gives me terrible headaches. I learned that a long time ago, and so I simply can't take any nootropic or any supplement for that matter that includes ginkgo biloba.I'm sure I'm not alone in the fact that some ingredients work for me and others do not. Thesis has solved this problem of individual variation by creating a brief quiz. So if you go online to takethesis.com/huberman and take a three-minute quiz, and then Thesis will send you to four different formulas that match your specific preferences. Again, that's takethesis.com/huberman, and if you use the code Huberman, you'll get 10% off your first box of custom nootropics. Today's episode is also brought to us by InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test. There are a lot of blood and DNA tests out there, but a major issue with many of them is that you get numbers back about levels of hormones, metabolic factors, lipids, et cetera, but you don't know what to do with that information. InsideTracker has solved that problem by creating a personalized dashboard. So you take your blood and/or your DNA test, you get the results back, and where certain values might be too high or too low for your preference, you can click on that and it will direct you immediately to lifestyle factors, nutrition, supplementation, et cetera, that can help you bring those numbers back into the ranges that are ideal for you. So it not only gives you information about where your health stands, it gives you directives as to how to improve your health. If you'd like to try InsideTracker, go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. That's insidetracker.com/huberman to get 20% off. Today's episode is also brought to us by ROKA. ROKA makes eyeglasses and sunglasses that are of the absolute highest quality. I've spent a lifetime studying the visual system and I can tell you that your visual system is incredibly sophisticated. It allows you to do things like move from a shady area outside to a sunny area outside and to adjust your visual system so you don't even notice that transition. A lot of sunglasses and eyeglasses are not designed with those sorts of biological transitions in mind. ROKA sunglasses and eyeglasses are different. Every one of their glasses is designed with the biology of the visual system in mind. First of all, they're incredibly lightweight, so you don't even notice that they're on your face. Second of all, they were designed to be worn during activities like running and cycling, et cetera, and they won't slip off your face, even if you get sweaty, and they have a terrific aesthetic. So even though they were originally designed as active eyewear, they look great, so you can wear them out to dinner, to school, at work, et cetera. If you'd like to try ROKA sunglasses or eyeglasses, you can go to ROKA, that's roka.com, and enter the code Huberman to save 20% on your first order. Again, that's ROKA, roka.com, and enter the code Huberman at checkout. And now for my discussion about hormone health and optimization with Dr. Kyle Gillett.

4. 8:24 – 14:17

   Preventative Medicine & Hormone Health

   1. AHAndrew Huberman8:24

      Dr. Gillett, welcome.

   2. KGDr. Kyle Gillett8:26

      Thank you for having me.

   3. AHAndrew Huberman8:27

      Well, I'm super excited to talk to you because I found out about you on a podcast, uh, and it immediately became clear that you are an encyclopedia of knowledge about hormone health for men and for women across the lifespan, so I have many, many questions. But before we dive into those questions, I'd love to just get a little bit of your background in terms of your medical training and what your particular orientation is toward treating your patients and how do you think about this whole landscape that we call hormone health? What is a hormone? Uh, how do you envision, uh, people managing their hormones? If you could just kind of fill in a few of those blanks for us, I think a lot of people would appreciate it.

   4. KGDr. Kyle Gillett9:12

      Absolutely. So I'm dual board certified in family medicine and obesity medicine. I've kind of tailored my training in order to provide what I call a balanced approach to total health, which includes body, mind, and soul. I recently saw a podcast with Joe Rogan and MrBeast, and Joe asks, uh, MrBeast, "How do you become such an amazing YouTuber and have all these, uh, you know, great clickbait videos and how did you become good at it?" And it turns out he just became obsessed when he was a teenager, and that's essentially how I've tailored my education a-, as well. I've become obsessed with optimal human performance, their body, their mind, and even their spirit. So I attended med school at the University of Kansas, which is, um, one of the few med schools that still emphasizes full spectrum care. They emphasize exercise as medicine, they emphasize food as medicine, of which I was active in both of those interest groups. In residency, I was active in a lot of, uh, mindfulness curriculum and then also things like Walk with a Doc, where you emphasize preventative medicine. That's something that we've kind of got away from, and that niche led me to hormone health. It didn't really start as hormone health, but it's a very important component of health in general that many people don't emphasize.

   5. AHAndrew Huberman10:33

      Great. Well, this idea of preventative medicine, I think, is starting to really take hold in the general population, especially given the events of the last few years. People realize that they are showing up to health challenges at a bunch of different levels and with some people feeling very robust, other people feeling back on their heels. When someone comes to you as a patient, uh, what are some of the first things that you want to know about them? I mean, obviously you want to know their blood pressure, you want to know, um, something about their mental health and family history, but in terms of hormone health, wh- what are the sorts of probe questions that you ask and, and what are you looking for? And I ask this because I'd like people to be able to ask some of these very same questions for themselves.

   6. KGDr. Kyle Gillett11:13

      Yeah. So when you do a physical exam and a history, you have a lot of different parts. You have your history of present illness, if they have a complaint. Maybe the patient doesn't have a complaint. In that case, things like their social history and their family history are extremely important because that gives you a- an insight in their- into their genetics and an insight into their hormone health. So patients will tell me, "Oh, I'm doing okay, but..."... it helps to ask them, "Well, how are you now?" Let's say the patient is 50. "How are you now versus when you were 20, and what has changed?" So, I've got the question a lot, "How do you get your doctor to order a better lab workup or to even include your basic hormones?" And there's no magic answer to that, but what really helps is you tell them, you know, "My energy is not as good as it used to be. My focus is not as good as it used to be. My athletic performance is not as good as it used to be." So you don't have to have a pathology in order for a lab to be indicated. You just need to have that pertinent symptom.

   7. AHAndrew Huberman12:14

      I think that's going to be really helpful, because for many people, the, the idea of getting a blood test to look at their homo- hormones se- just seems like such an enormous hurdle to get over, and many doctors won't prescribe them. Um, and would you say that it's, using the approach you just described, that it's, um, equally effective for men and women, or do you find that, um, for one reason or another that men and women have different challenges in, and advantages in trying to access their deeper hormone data?

   8. KGDr. Kyle Gillett12:44

      Yeah, it's slightly different, um, with women there's a lot more objective data. So if they're having menstrual irregularities, or, um, you know, if they're going in, if they're not having a period, if they're having too heavy of periods, then those are things that they talk about very frequent- frequently with their doctor. Men are more hesitant. So men really want to know what their testosterone is. But they r- at the same time, they really don't want to tell their doctor how their libido is, or how their energy is, because it, it's almost like, um, they feel less masculine or they feel less like a guy when they say that, even if they're just talking to their doctor about it.

   9. AHAndrew Huberman13:21

      Yeah, I think that that raises a really important point, which is that the whole discussion around hormone health is a bit of a barbed wire topic, because in many ways when we hear the word hormone we think...

   10. KGDr. Kyle Gillett13:32

       Yeah.

   11. AHAndrew Huberman13:33

       ... testosterone and estrogen. We think notions of masculinity and femininity, and of course testosterone and estrogen are present in all sexes, right, all chromosomal backgrounds. (laughs)

   12. KGDr. Kyle Gillett13:44

       Yeah.

   13. AHAndrew Huberman13:44

       Um, and just to varying degrees and ratios. But it also raises all these issues about sexual health that, uh, it's kind of interesting because I'm surrounded by medical doctors in my lab at Stanford, and the more physicians that I surround myself with, the more open is the discussion around sexual health and reproductive health. But in the general population, I think some of these topics are a little bit, um, taboo or, again, it's kind of barbed wire, and so I think that people are seeking a lot of this information on YouTube and through communities that may or may not be very educated a- about the actual biology. So along those lines,

5. 14:17 – 17:14

   The Six Pillars of Hormone Health Optimization

   1. AHAndrew Huberman14:17

      you know, we could probably assume that hormones are changing across the lifespan, I think, right? Uh, certainly from, from childhood up, and puberty and onward. If, if you would, um, I'd love to just kind of take a snapshot of what you think everybody should be thinking about or doing to optimize their hormone health, male or female, in the, let's say in their 20s. And then maybe we can migrate that to their 30s and 40s. But before that, could you just tell us what everyone should be doing for their hormone health a- from puberty onward?

   2. KGDr. Kyle Gillett14:51

      Yeah. The law of diminishing returns applies. So doing a little amount of what I call lifestyle interventions over a long period of time is going to be far more helpful or efficacious than doing a lot and then doing nothing, or doing a lot and then doing nothing. So I talk about the big six pillars. The two strongest ones are likely diet and exercise. For hormone health, specifically resistance training is particularly helpful. For, um, diet, caloric restriction can be particularly helpful, especially with the epidemic of metabolic syndrome that is continuing to ongo in this country and in developed countries in general. So those are the two most powerful, so number one and number two are diet and exercise. For the last four, I have a little bit of alliteration. So there's stress and stress optimization. That has to do with cortisol. That has to do with your mental health. That has to do with societal health and collective health of your family as well. Um, when you're a member of a family, or even a very close friend, um, trying to achieve optimal health together is very important. It's the same thing with nicotine cessation. It's the same thing with hormone optimization. If you do it as a household unit, it's far more helpful. So after stress, you have sleep optimization. Sleep is extremely important, um, especially for mitochondrial health as well, and then you have sunlight, which encompasses anything that's outdoors, so you move more, you have cold exposure, you have heat exposure. Um, that's sunlight. And then the last one is spirit. So, um, that's kind of the body, mind, and soul. If you have all the other five in, uh, they're dialed in completely, but you don't have your spiritual health, whatever you believe, then that's going to profoundly impact your body and your mind as well.

   3. AHAndrew Huberman16:44

      And we're definitely going to touch into this notion of spiritual health, because I think for some people that might, um, draw connotations of, of, um, certain things that may or may not be accurate. But, uh, I know a number of academic laboratories that are focused on this, and a number of, of not just, um, functional medicine clinics, but, um, research clinics and hospitals throughout the country that are ar- achieving some really interesting data, not just in, in people that are quite sick, but in healthy people who are trying to further optimize health. So we will definitely touch back to that.

6. 17:14 – 20:21

   Diet for Hormone Health, Blood Testing

   1. AHAndrew Huberman17:14

      If, if you, um, would be so kind as to maybe give us a little bit more detail about some of these other areas. So when people hear diet, I immediately think, okay, now we get into the, um, the combat around...

   2. KGDr. Kyle Gillett17:26

      Yeah.

   3. AHAndrew Huberman17:26

      ... vegan, plant based, carnivore, et cetera. But I think that my general view of this is that most people should probably be eating as few highly processed foods, highly palatable foods as possible, which doesn't mean eating foods that don't taste good, of course. But what other sorts of things d- do you recommend in the realm of diet?Um, and then I also want to know about caloric restriction, because my understanding is that a caloric surplus can actually support certain hormones like testosterone. So how does one combine caloric restriction and still optimize our hormones? But what would you say is a, a really terrific way to think about and approach diet?

   4. KGDr. Kyle Gillett18:04

      Yeah. Diet should be an individualized approach. So if you have a, a car, each car is made different and requires a different sort of fuel. Whether it's a race car, whether it's a diesel truck, they have different fuels for different performance outcomes. So if you're trying to tow something or if you're trying to go fast. So it's the same way with athletes. It's, uh, pretty well studied, the more inter-workout carbs ultra-long distance athletes take, in general they do better. I think they've studied this in cyclists quite often. It also depends on your genetics. So you can have a genetic polymorphism and you metabolize carbs and sugar better even when they're unopposed by fiber.

   5. AHAndrew Huberman18:44

      How does one d- determine whether or not i- they have such a polymorphism? I mean, I'm an omnivore, so I eat, I do eat some high quality meats, not in huge quantities, but I also eat vegetables and starches. I feel fine. I've never done an elimination diet. Uh, ma- I think I did a very low carb diet once and all it gave me was a lot of psoriasis and poor sleep, so I backed off. I probably didn't do it correctly, um, but I know a lot of people that do quite well on, on a very low carb or zero carb diet.

   6. KGDr. Kyle Gillett19:10

      Yeah. Particularly those who are at risk of cancer, because you have less, uh, glucose that can be easily uptaken into cells, and then also people with autoimmune diseases. Um...

   7. AHAndrew Huberman19:22

      They tend to do well on auto- on...

   8. KGDr. Kyle Gillett19:23

      On lower carb diets, yeah. But yeah, as far as the, uh, how do you know? Basically you can use your biofeedback, how you're feeling, to guess what you tolerate well, or you can just get genetic testing, which can be fairly expensive, but most of all it requires a physician or someone who knows how to interpret the test accurately.

   9. AHAndrew Huberman19:43

      And if someone had the means or the, uh, would you say that getting regular blood testing is a good idea? And if so, what is regular blood testing? Is it every three months, is it every six months? Of course the backdrop of, of life is changing too. Stress levels, etc.

   10. KGDr. Kyle Gillett19:57

       Yeah. Every three to six months for preventative purposes. At times you need blood tests at, uh, faster frequencies than that. And then you should also get a blood test when you're fasting and when you're not fasting. So if you're looking for damage to the beach, you wanna... You don't just look at low tide, you look at high tide and you see what's happening at high tide as well.

   11. AHAndrew Huberman20:17

       It's a great way to put it. And in terms of, uh, general recommendations

7. 20:21 – 21:06

   Exercise for Hormone Health

   1. AHAndrew Huberman20:21

      around exercise, I mean, I'm of the mind, based on the data that I've seen, that almost everybody should, or everybody should be getting 150 to 180 minutes minimum of zone two cardio per week that kind of could continue, uh, while having a conversation, but with, uh, if one were to exert any more effort, it would have a hard time getting the words out. At least that, right? For cardiovascular health and general brain health and...

   2. KGDr. Kyle Gillett20:47

      Yeah.

   3. AHAndrew Huberman20:47

      ... musculoskeletal health, plus resistance exercise. Is that more or less the contour of what you recommend?

   4. KGDr. Kyle Gillett20:52

      Yeah, that's more or less the contour. The more you're doing your zone two cardiovascular exercise, the slightly less important a long duration of caloric restriction is.

   5. AHAndrew Huberman21:05

      Interesting.

8. 21:06 – 23:55

   Caloric Restriction, Obesity & Testosterone

   1. AHAndrew Huberman21:06

   2. KGDr. Kyle Gillett21:06

      Yeah.

   3. AHAndrew Huberman21:06

      And that brings us to caloric restriction.

   4. KGDr. Kyle Gillett21:08

      Yeah.

   5. AHAndrew Huberman21:08

      So it's very clear that caloric restriction can allow one to lose weight, right?

   6. KGDr. Kyle Gillett21:14

      Yeah.

   7. AHAndrew Huberman21:14

      This is the classic CICO, C-I-C-O, calories in, calories out. We are not disputing calories in, calories out.

   8. KGDr. Kyle Gillett21:20

      Yeah.

   9. AHAndrew Huberman21:20

      Somehow that always has to be stated 50 times, um, in any forum because of whatever follows, people I think, uh, will anchor to and assume that we don't mean that. But I know you and I both agree on calories in, calories out as a fundamental law of thermodynamics.

   10. KGDr. Kyle Gillett21:33

       Yeah.

   11. AHAndrew Huberman21:34

       But it's clear to me that, based on what I've read, that when one is in a slight caloric surplus, that hormones like testosterone can be optimized. But is that true for somebody who's showing up with excessive body fat? How does this all work? Because body fat is manufacturing enzymes that convert testosterone to estrogen. So in other words, how does someone know if they should u- use caloric restriction or avoid caloric restriction?

   12. KGDr. Kyle Gillett21:59

       Yeah. Here's how to parse that out. So before I delve into the details a bit more, I should say as a board certified obesity medicine physician, obviously the laws of thermodynamics apply and then, in addition to that, there is nothing special about intermittent fasting or caloric restriction or exercise when it pertains to losing body weight in general. When you do lose weight, about 33% of that is lean body mass and about 10% of fat cells, you know, adipose cells are actually lean body mass as well because it has proteins and water and things like that in it too. So the reason for exercise and the reason for caloric restriction in general, including intermittent fasting, is health reasons. That's how you increase your health span. It's not necessarily going to make the weight on the scale change, but that doesn't matter as much. It's been fairly well studied in both mice and humans. It's much easier to study in mice, so that's a precursor to our six types of people, the ones that care about mice studies and the ones that care about human studies. But if you calorically restrict mice by 40%, then, um, they can have improved testosterone parameters, but only if they're obese to start. And it appears to be that same way in humans as well. So the easy way to think about it is if you're obese or you have metabolic syndrome, caloric restriction will improve your testosterone. There has been a study, and they talk about all these studies in a systematic review from the Mayo Clinic proceedings in March of last year, and, um, they note that there is a study in young, healthy men and they calorically restrict them, and their testosterone does decrease. So if you're young and healthy and you don't have metabolic syndrome, then caloric restriction will likely decrease your testosterone.

   13. AHAndrew Huberman23:51

       Th- that clarifies a lot for me, and I, I believe it will clarify

9. 23:55 – 29:08

   Intermittent Fasting, Growth Hormone (GH), IGF-1

   1. AHAndrew Huberman23:55

      a lot for other people as well. And I'm...... delighted that you pointed out this distinction about intermittent fasting not being the only way to achieve caloric restriction. There are a number of, uh, young, uh, healthy, or older healthy, uh, people I know who like using intermittent fasting, even if they're not trying to lose weight-

   2. KGDr. Kyle Gillett24:15

      Mm-hmm.

   3. AHAndrew Huberman24:15

      ... for a couple of reasons. Some believe that it might extend lifespan. I think there's still, that's still a bit of an open question. It's a bit of a hard experiment to do, because the control group is-

   4. KGDr. Kyle Gillett24:24

      Yeah. (laughs) Yeah.

   5. AHAndrew Huberman24:24

      (laughs) No one wants to be in the control group, as I say. Um-

   6. KGDr. Kyle Gillett24:26

      It does in mice.

   7. AHAndrew Huberman24:27

      Right. Right, exactly.

   8. KGDr. Kyle Gillett24:28

      Captive audience. (laughs)

   9. AHAndrew Huberman24:29

      Exactly. And the other, uh, feature of it that's a little bit tricky is that many people like intermittent fasting because of the mental effects, the clarity of mind that they feel during fasting, the increased pleasure in eating when they finally do eat. Um, and here I'm referring to intermittent fasting of the sort where eating windows are anywhere from eight to 12 hours a day, not extended fasts of 24 hours or more. So the question, therefore, is for the healthy, um, lean enough person, right, non-obese, uh, person, is intermittent fasting a bad idea in terms of hormone health? Is oscillating between this period of, of kind of feast and famine within a 24 hours a problem if one is getting sufficient calories to maintain weight?

   10. KGDr. Kyle Gillett25:14

       Yeah, so if they're in a caloric maintenance, then it's not going to be, uh, it's not gonna be deleterious. It's not gonna be bad for their hormone health. There's a couple different hormones that we can talk about. We can talk about testosterone. We can talk about DHEA, which usually go hand in hand, and then we can also talk about growth hormone, which is not a steroid hormone, but it's a peptide hormone. So it's um, a chain of proteins, amino acids that are put together instead of a sterol. Think of sterol hormones as coming from cholesterol. So intermittent fasting, you do get a little spike in growth hormone after you eat, but you also get a huge spike in growth hormone, a more significant, less negligible spike overnight, and that is improved if you are intermittent fasting. So it's probably gonna help your growth hormone, and subsequently IGF-1 levels, which will help more in older age groups than younger age groups.

   11. AHAndrew Huberman26:15

       And, uh, I like to eat dinner, so for me that means sometime around six or seven o'clock, sometimes eight o'clock. I confessed last night, 'cause I was working late, I ate, I ate pretty big. I, it was basically my only meal of the day. At 10 o'clock, that's a rare thing for me. Can I still achieve a high degree of growth hormone output if I, let's say I avoid food in the two to three hours before going to sleep? Or does one have to be very deep into a fast in order to achieve this, the increase in growth hormone?

   12. KGDr. Kyle Gillett26:44

       There's still pretty good growth hormone output even if you eat two or three hours before you sleep. It's just the law of diminishing returns. The longer you go, you get slightly more and slightly more.

   13. AHAndrew Huberman26:55

       Right. Um, and I know a number of people think of growth hormone, uh, in the context of the exogenous growth hormone, um, and the fact that that can, in some cases, be associated with cancers. Um, I've been asked many times before, can the increase in growth hormone from things like saunas or intermittent fasting cause levels of growth hormone that are so high that they cause cancers? I- I, my impulse is to say no, that doesn't, that seems-

   14. KGDr. Kyle Gillett27:21

       (laughs) .

   15. AHAndrew Huberman27:21

       ... like it's not, um, likely to happen, but I, I should probably verify that statement with you.

   16. KGDr. Kyle Gillett27:27

       Yeah, so quite unlikely. I think about growth hormone, and especially IGF-1, and there's actually an IGF-1 and IGF-2, but I think about it in terms of endocrine IGF-1, mostly IGF-1 that's, uh, synthesized in the liver and released in the r- in the liver, versus IGF-1 that's released, um, classically. An example of this would be your IGF-1 levels increase after resistance training or exercise. And that's more of, like, paracrine or autocrine, and they have more local action. So that IGF-1, it's pretty well studied that if you just give people IGF-1, it's not going to, at, uh, physiologic levels, it's not gonna improve their body composition. However, that IGF-1 that's autocrine and paracrine just working in those local tissues and muscles is likely part of the reason why you get a improved body composition response after exercise.

   17. AHAndrew Huberman28:21

       I see. And, um, just to clarify for me and for, for others, uh, what can we say are the major functions of IGF-1 and IGF-2 that are distinct from just growth hormone? Are they just kind of the active form of growth hormone, the kind of the, the, um, the pickax end of the, of the w- of the assembly line?

   18. KGDr. Kyle Gillett28:39

       Yeah. (laughs) So they have a much longer duration of action. I believe the half-life of IGF-1 is several days, almost a week, whereas growth hormone has an extremely fast half-life of only hours. So growth hormone acts, uh, significantly on the liver to produce IGF-1. So it's, uh, hmm, it's around in the serum, in the blood long enough to where it's producing an effect, uh, pretty much all the time.

10. 29:08 – 35:03

    Sleep Quality & Hormones

    1. KGDr. Kyle Gillett29:08

    2. AHAndrew Huberman29:08

       Very interesting.

    3. KGDr. Kyle Gillett29:10

       Yeah.

    4. AHAndrew Huberman29:10

       Well, and then your other pillars, um, stress, uh, you know, we've talked a lot about stress on this podcast before, and tools for managing stress. Um, sleep obviously is a big one. I'm, I think, uh, you know, if, if nothing else, I will, um, either put people to sleep with my podcast, um, certainly not this one, but my, my solo episodes, or, um, hopefully convince people that sleep is the foundation of mental and physical health and, and performance. Are there any aspects of hormone optimization that can improve sleep? I know sleep can improve hormone optimization, but are there any aspects of hormone optimization that can improve sleep? And for people that, uh, are suffering from this common syndrome of going to sleep and then waking up at 3:00 or 4:00 in the morning, we know that can be associated with depression, but are there any hormo- hormonal indications that might lead to that kind of situation?

    5. KGDr. Kyle Gillett29:57

       Yeah.There's three big ones. The first one is not super common, but it's a very direct correlation. If you have a growth hormone deficiency, a true deficiency, whether you're an adult or a child, then your sleep is likely going to be affected. And, uh, let's say you're a child with growth hormone deficiency, once that is replaced with therapy, your sleep is gonna get significantly better. The second one that's a very common scenario is if you're having what's called vasomotor symptoms of menopause or vasomotor symptoms of andropause, which are also applicable, and that's where your progestogenic activity, so your, uh, pro- main progestogens are progesterone and then pregnenolone and then 5-alpha, 3-alpha progesterone, which is a slight-

    6. AHAndrew Huberman30:46

       Where are those manufactured in the body?

    7. KGDr. Kyle Gillett30:48

       So they're manufactured in a few places. In men, they're manufactured some in the testes, in the Leydig cells. In women, they're manufactured in the ovaries until menopause, and then they're also manufactured in the adrenal glands. So, um, if you're in- if you're pre-adrenopausal, where your adrenal glands are still working fairly well, you usually still have a decent amount of progesterone around, and this can be measured too. So, um, after menopause, women make progesterone from their, uh, ovaries, or sorry, from their adrenal glands. If that progesterone crosses the blood-brain barrier, especially if it's 5-alpha and 3-alpha reduced, so it's modified a little bit, then it is both a GABA agonist, um, which helps sleep just like GABA does, gamma-Aminobutyric acid, the main inhibitory neurotransmitter of which lots of things work on. Alcohol works on GABA as well. Gabapentin also works on GABA. Migraine medicines, many of them work on GABA. Benzodiazepines and also non-benzos. Uh, so an example of a benzo would be Xanax. An example of a, um, non-benzo would be Ambien. So those all work on GABA. So GABA is also helped by the progestogenic activity as well. That's why a lot of women in menopause feel like their sleep is much worse, is because they have lower activity of those progestogens.

    8. AHAndrew Huberman32:15

       Is that... And for men in so-called andropause, um, low testosterone, is that also one of the causes of poor sleep?

    9. KGDr. Kyle Gillett32:24

       Low testosterone can lead to poor sleep, but my third scenario, uh, is actually if a man begins TRT, then they develop a poor sleep because of sleep apnea. It drastically raises the risk that somebody is going to have sleep apnea, and then a lot of people, especially when they first start it in the first month or two, it puts them into this hyper sympathetic state, because they have, uh, overactive androgen receptors, especially after a long time of being hypogonadal. Then they have, uh, a physiologic dose of TRT, and that causes the sleep issue itself.

    10. AHAndrew Huberman33:00

        Interesting. Uh, I have a lot of questions about TRT, testosterone replacement therapy. Um, I should just mention that when you say, uh, it increases sympathetic activity, uh, uh, you don't mean, uh, that taking testosterone increases sympathy for others. It may in fact do the opposite, although it's very clear from my discussions with, uh, my colleagues in- on the- in the endocrinology side and also with, um, the great Dr. Robert Sapolsky that- that increasing testosterone merely exacerbates existing features of people. So the jerks become bigger jerks, kind people become even more kind, in general. Um, but we will- I want to get into TRT in depth, but it's very interesting to me to hear that testosterone replacement therapy, um, increases the risk of sleep apnea, and I want to make sure that I ask that, is that also the case in people that are using TRT who are not hypogonadal? Because in the classic situation, if somebody isn't making enough testosterone, they're below 300 nanograms per deciliter on the chart, they go in and take TRT. But many people nowadays, let's be honest, are- are taking doses of- of testosterone even though they are in the sort of standard range because the range is so large because of other symptomatology. Is that right?

    11. KGDr. Kyle Gillett34:11

        Yeah. I do love the analogy that Dr. Sapolsky had about monks taking testosterone and making them more and more generous.

    12. AHAndrew Huberman34:19

        Mm-hmm.

    13. KGDr. Kyle Gillett34:19

        So that does appear to be what testosterone usually does, is it exacerbates, if you will, what you were previously like. So it's not gonna change you as a person. But, uh, if you're eugonadal before you start testosterone, you s-

    14. AHAndrew Huberman34:34

        Meaning your- meaning?

    15. KGDr. Kyle Gillett34:35

        Meaning you have normal testosterone, and then you start TRT or, um, self-administered TRT, steroids, whate- however you want to look at it, then your risk of sleep apnea still goes up in a dose-dependent fashion. So the higher the dose, the more risky. With the sympathetic and the parasympathetic nervous system, the sympathetic is the fight or flight nervous system. The parasympathetic is the rest and digest. So if you have too much fight or flight, and stress can cause that too, then you're not gonna rest

11. 35:03 – 38:55

    Testosterone in Women

    1. KGDr. Kyle Gillett35:03

       as well at night.

    2. AHAndrew Huberman35:04

       I want to touch on testosterone in women, because there is testosterone in women. I'd like to know where that testosterone comes from, which tissues. I'd like to know whether or not testosterone replacement therapy makes sense in women. I'm hearing more and more about women using testosterone. And I'd like to know whether or not knowing a woman's testos- for her to know her testosterone is of equal, less than, or more value than knowing, uh, for instance, progesterone and estrogen levels, because I think there are a lot of misconceptions about the roles of testosterone in women.

    3. KGDr. Kyle Gillett35:38

       For health optimization, testosterone is just as important to know. For pathology prevention, for example, breast cancer, osteoporosis, estrogen and progesterone are more important to know. So when you're thinking about women, women think that they have such a tiny amount of testosterone, because you could... You test it. Most people test a free testosterone, so testosterone that's unbound, which is by far the-... the smallest proportion of testosterone. Any androgen is bound by lots of different steroid-binding proteins, but the ones that are most pertinent are called SHBG or sex hormone-binding globulin, and that binds the androgenic steroid, for example, DHT or dihydrotestosterone, it's associated with prostate enlargement, it's associated with male pattern baldness, it binds that the most strongly, and then it binds testosterone next most strongly, and then it binds things like androstenedione or DHEA, dehydroepiandrosterone, and then it binds the estrogens, the weakest, like estradiol. So if you look at the total amount of testosterone, women actually have, um, almost all women, not all women, but almost all of them have significantly more testosterone than estradiol, but it's because it's in different, um, measurements. So estradiol, a lot of time, is, you know, picograms per mL as opposed to nanograms per deciliter. So women have more testosterone than estrogen, and significantly more DHEA than either.

    4. AHAndrew Huberman37:14

       Interesting. Do women make dihydrotestosterone?

    5. KGDr. Kyle Gillett37:16

       Yeah.

    6. AHAndrew Huberman37:18

       And where does it, where does this testosterone come from? Because they don't have testes.

    7. KGDr. Kyle Gillett37:22

       Yeah, so most testosterone in women that are premenopausal can come from theca cells, T-H-E-C-A. So theca cells are cells in the ovaries that can produce testosterone, and a lot of people, um, have actually heard about hyperthecosis, not the term itself, but a lot of Olympians that are, uh, their chromosomes are XY, they're females, and they are not taking any-

    8. AHAndrew Huberman37:47

       Wait, they're XY but they're females?

    9. KGDr. Kyle Gillett37:48

       Or sorry, they're XX.

    10. AHAndrew Huberman37:49

        Oh, okay.

    11. KGDr. Kyle Gillett37:50

        Yeah. Thank you. (laughs) So they're XX, they are not XY.

    12. AHAndrew Huberman37:53

        Mm-hmm.

    13. KGDr. Kyle Gillett37:54

        And they have never transitioned or been on any sort of, uh, hormone replacement or testosterone, but they naturally produce a huge amount of testosterone, as much as many men, and some of these women, I believe they were from Botswana, were banned from competing in the Olympics in certain distances. I believe they were banned from the 400 meter and 800 meter because their natural testosterone was deemed to be too high.

    14. AHAndrew Huberman38:19

        So they mistakenly thought that they were using steroids?

    15. KGDr. Kyle Gillett38:22

        They actually knew they were not using steroids. They knew it was their theca cells were just genetically gifted, I suppose, and they still made them change distances.

    16. AHAndrew Huberman38:31

        Wow.

    17. KGDr. Kyle Gillett38:31

        So one or two of these athletes changed to, I believe it was the 3K or the 5K, and they still did quite well, but it was not their best event.

    18. AHAndrew Huberman38:40

        Interesting.

    19. KGDr. Kyle Gillett38:41

        Yeah.

    20. AHAndrew Huberman38:41

        Yeah, that's turning out to be a very interesting and controversial area of this notion of hormone therapies and natural variation in hormones on different chromosomal backgrounds. Fascinating, we should probably do a whole episode about that 'cause it's very much of the times. Um,

12. 38:55 – 43:46

    Dihydrotestosterone (DHT), Hair Loss

    1. AHAndrew Huberman38:55

       so men and women both make DHT. I'd like to ask about DHT in men. Uh, so often we hear about testosterone in men and free testosterone in, uh, being the unbound form, of course, but dihydrotestosterone, uh, where does it come from in men? Uh, what is the cascade of, of events that takes testosterone to dihydrotestosterone, and what are some of the, quote-unquote, "positive and negative effects" of, of... uh, here I'm only referring to endogenous di- uh, dihydrotestosterone, and in fact, I'll, I'll make it very clear whether or not, uh, I'm talking about taking something or one's own natural production. Here, we're just, I think up until now, we've just been talking about natural production. So w- tell us about DHT in men, uh, it's such a powerful hormone during development, obviously.

    2. KGDr. Kyle Gillett39:43

       Yeah.

    3. AHAndrew Huberman39:43

       Um, but what's it, what is it doing?

    4. KGDr. Kyle Gillett39:46

       DHT is a very androgenic hormone, so whether you're talking about DHEA, which is a mild, a weak androgen, or testosterone, which is a relatively strong androgen, or DHT, which is a very strong androgen, they bind to the androgen receptor in both men and in women. So the, uh, effect of all three of those is mediated by the androgen receptor. There's a couple different beta estradiol receptors and a- alpha estradiol receptors, but there's only one androgen receptor. Intriguingly, it is on the X chromosome, so men get their androgen receptor gene from their mother. Women get one androgen receptor gene from their father, one from their mother. Often, the one that is more sensitive to androgens in p- people with PCOS, that's the one that's active. The other one is methylated and inactive.

    5. AHAndrew Huberman40:38

       Can I just pause you one second? Sorry to interrupt, but I have to ask this question, uh, before I forget, and I know a number of people are probably wondering. I've heard that whether or not one develops male pattern baldness, whether or not a, uh, male develops male pattern baldness, (laughs) just to be very precise, uh, you could get some information about that by looking at your mother's father, and that would, b- in keeping with what you just described, that the X chromosome, which of course is handed off through the mother, is carrying the, uh, genes that encode for the number and distribution of these D- of these androgen receptors that DHT will bind to, 'cause of course, I think as you'll probably tell us, that DHT is responsible for male pattern baldness and beard growth, is that right? Should I look at my grandfather on my mother's side to determine what I'm likely to look like in terms of my DHT-ness? Is that a word?

    6. KGDr. Kyle Gillett41:26

       Yeah. It's the best guess that you can make purely from phenotypes. Now, you can measure your genotype, and, um, you know, get a better idea of that. Assuming that it's true male pattern baldness, it's related to the gene transcription of the androgen receptor. So I like to think of it as how much of this androgen receptor gene is activated by any androgen. So if you have an extremely sensitive gene, which usually means you have very few CAG repeats, which is basically just a, a certain, CAG encodes for a certain, uh, amino acid, and if you have very few of the repeats, then your androgen receptor gene works better. Think of it as a corollary to Huntington's disease, where if you have very few of, called trinucleotide repeats, then it's not as severe of a disease. But after you get more and more CAG repeats, which, by the way, are, um-... in a population, you're getting more and more CAG repeats. Um, so that's a, a natural selection process that has been ongoing for a, a variety of number of reasons. But anyway, if you have more repeats, then that gene activates in the cytoplasm and moves to the nucleus and causes gene transcription more often and hair loss more often.

    7. AHAndrew Huberman42:42

       Does that mean we're seeing more hair loss now due to elevated levels of DHT than we were 50 years ago?

    8. KGDr. Kyle Gillett42:49

       Um, probably not. Um, the hair loss 50 years ago, well, not 50 years ago, but 500 years ago, was probably more significant, because on average, 500 years ago, people were more sensitive to androgens. So there's a syndrome called androgen insensity- insensitivity syndrome, AIS, and that syndrome is related to when men who have the copy from their mother, who is a carrier, their AR gene, or androgen receptor gene, is completely insensitive. So think of it, it doesn't have a, it's not related to the CAG repeats, but think of that, uh, receptor as just not working at all. So there's a continuum, so everybody's receptor works a little bit better or a little bit worse, and the better your receptor works, the more likely you are to have male pattern baldness.

    9. AHAndrew Huberman43:40

       To zoom out from this, but still keeping a, uh, an eye on DHT,

13. 43:46 – 50:10

    DHT in Men and Women, Turmeric/Curcumin, Creatine

    1. AHAndrew Huberman43:46

       what do you like to see all women and all men do to optimize DHT? And here, I'm talking about regardless of age. So we're still in this fr- from puberty onward phase. We haven't yet, uh, microdissected out decade by decade, which we will do. But, uh, what do you like to see people do to keep DHT in check? But before you tell us that, could you tell us what positive things DHT does when it's in the proper range?

    2. KGDr. Kyle Gillett44:13

       Yeah. So DHT helps a lot for, uh, same reason why testosterone helps. It activates the androgen receptor gene. It helps effort feel good, so it can be motivating. So that's how it's active in the CNS. It also is active in cardiovascular tissue. So if you look at, um, someone that has heart failure or if someone has cardiac hypertrophy, the level of DHT can matter, because it's also binding to the androgen receptor in the myocardium or in the heart itself. So you think of the classic bodybuilder heart. That's an easy example to make. They have very thickened muscle. Their muscle is very strong, because they're pumping blood often with high blood pressure, and that DHT, and the testosterone, and any DHT derivatives like masterone or, uh, oxandrolone, primobolan also bind to the heart, and they cause even more hypertrophy or enlargement of that muscle tissue. So then let's say the person stops and they're recovering, and they're trying to have cardiac remodeling, which is where you take a very thick heart, and cardiac remodeling's important in a lot of different, um, cardiac pathologies. But if you give them finasteride or dutasteride, which inhibit the enzyme that converts testosterone to DHT, so making less activity at the androgen receptor gene, they have cardiac remodeling, and their heart health improves.

    3. AHAndrew Huberman45:40

       I see. So for the non-bodybuilder, the typical woman or man or, uh, young- younger or older, uh, what sorts of things support DHT and thereby heart health? Um, presumably DHT is involved in some of the other things that testosterone is famous for in both men and women, things like libido, as you mentioned, um, making effort feel good, so motivation, drive, and, um, vitality, it's, uh, I guess could be the...

    4. KGDr. Kyle Gillett46:04

       Yeah.

    5. AHAndrew Huberman46:04

       ... the general phrase. Uh, what, what sorts of things support DHT? What sorts of things, uh, create problems for DHT?

    6. KGDr. Kyle Gillett46:11

       There's lots of dietary changes and supplementation that you're probably doing right now that's affecting your DHT.

    7. AHAndrew Huberman46:17

       You mean me personally?

    8. KGDr. Kyle Gillett46:18

       So, well, every- everybody. A- all of the listeners, um, because let's say you have a diet high in plant polyphenols. Many of those inhibit the enzyme that converts testosterone to DHT.

    9. AHAndrew Huberman46:30

       Could, um, w- could you give us an example of, of one of those, um, either in supplementation form or in food form?

    10. KGDr. Kyle Gillett46:39

        Curcumins. Certain curcuminoids, depending on the structure, will inhibit the enzyme called 5-alpha-reductase that converts testosterone to DHT.

    11. AHAndrew Huberman46:48

        Turmeric.

    12. KGDr. Kyle Gillett46:49

        Yeah, turmeric.

    13. AHAndrew Huberman46:49

        Yeah.

    14. KGDr. Kyle Gillett46:50

        Black pepper extract. So if you, it's used often to increase bioavailability. It's also called Bioperine. It's also a 5-alpha-reductase inhibitor. So, uh, and on top of that, people have different genetics too. So some people, their 5-alpha-reductase enzymes, there's three of them, um, they're on chromosome two, three, and four, I believe. But, uh, some of them are active in the prostate. Some of them are active in the brain, and some of the- so it depends on which tissue. They're tissue-specific enzymes that depend on how much DHT you convert.

    15. AHAndrew Huberman47:26

        Do you recommend that people avoid curcumin and turmeric for that reason? Um, and is there any specific recommendations for men versus women?

    16. KGDr. Kyle Gillett47:34

        If a man or a woman... By the way, in women, a lot of times, if you just ask your doctor for a DHT check, it's the same units as in men, so it's essentially undetectable. So, uh, you have to, um, you know, especially if they're on oral contraceptives, which is a different topic, their DHT is very likely undetectable, especially if it's free DHT. You can measure both the DHT and the free DHT. But if someone's DHT is already low or if they have somewhat insensitive androgen receptor via genetics or via lifestyle, then I recommend they avoid bioavailable curcuminoids, like bioavailable turmeric, black pepper extract, and they might be a good candidate for creatine. Creatine...... uh, like creatine monohydrate can significantly increase the conversion of testosterone to DHT.

    17. AHAndrew Huberman48:23

        Interesting. There's also a lot of really interesting data coming out now about the, um, the role of, of creatine as a brain fuel and maybe even as a cognitive enhancer over time. The data are still, uh, ongoing, but, uh, some of the studies in humans are pretty impressive, at least to me. I- I'm glad you mentioned this thing about curcumin and black pepper. I wish we'd had this conversation six years ago, because I had the experience of, um, jumping on the bandwagon of the excitement around turmeric, and I took a turmeric supplement. It was a couple capsules of what I l- thought to be h- and I think was high-quality turmeric, and I've never felt as poor as I did in the subsequent few days. Flat line of, let's just say, everything that one would want to have in life, energy, vitality, just it was a cliff. And, um, a friend somehow knew, uh, that curcumin could inhibit 5-alpha-reductase that converts testosterone to DHT as you pointed out. I stopped taking it. It was the only new addition to my diet and supplementation, and things bounced back within about three, four days. But it was remarkable.

    18. KGDr. Kyle Gillett49:25

        Yeah.

    19. AHAndrew Huberman49:25

        I mean, I felt like garbage, and it was actually kind of frightening to, to experience the, the, uh, sharpness of that cliff. But, um, I know that some people like turmeric for its, uh, i- anti-inflammatory, uh, properties, et cetera. Sounds like people either need to experiment or, um, and if they do obviously to approach that with caution, any time you add or remove something, you need to talk to your, to your doctor. You're a doctor, and I'm guessing that, um, if one were to experiment, um, would you say that most of these effects of things like curcumin are reversible as they were in me, or is there any potential of permanent damage if people have been taking them for a long time?

    20. KGDr. Kyle Gillett50:04

        The effects are nearly always reversible. When you're talking about 5-alpha-reductase inhibition, so what

14. 50:10 – 52:30

    5-Alpha Reductase, Finasteride, Saw Palmetto

    1. KGDr. Kyle Gillett50:10

       turmeric does but stronger, um, the most common story that we hear is regarding a supplement known as saw palmetto, which a lot of older men take for their prostate health, or finasteride, which you can take for your prostate or your heart or your hair, or dutasteride. So if you're having side effects on these, then it's probably because of a couple different reasons. One can be your ratio of androgens to estrogens is off, and that needs addressed. Another one can be it's inhibiting the conversion of your progesterone to that other type of progesterone, the 5-alpha, 3-alpha that we talked about earlier that's helping with your sleep and your brain and your calmness, and, um, th- that's definitely an effect. Another one is depending on the type of supplement or med, they inhibit different isoenzymes of that 5-alpha-reductase. So if it's- if they're just inhibiting one and two, then that's gonna be a different effect than if they're inhibiting two and three. So finasteride does two and three, saw palmetto does one and two, and then dutasteride does all three. The third one is active in the brain, and dutasteride inhibits that third one a little bit weaker in vivo but strongly in vitro. So it's really hard to parse out. You can use biofeedback and experimentation. I do think with supplements it's safe to experiment. The time that it takes to set in is usually about three months. So the risk of, and this is anecdotally, there's been lots of research published about if post-finasteride, post-finasteride syndrome is real or fake, and it is real, but it's one of those things that's a combination of organic and inorganic disease, almost kinda like fibromyalgia, where it's definitely real and there's lots of things that you can do to help with it, but it's very unlikely to occur if you stop taking your supplement or medication after you have side effects.

    2. AHAndrew Huberman52:05

       Interesting. Well, I certainly feel better when I'm taking five grams of creatine monohydrate per day. I know most people take it for muscle growth and tissue repair and things of that sort, mainly I think brings water into the muscle tissue, et cetera. But I, I take it for the brain effects and also because I like to think that it gives me a b- little bit of a DHT bump, um, that I can actually see in my, my blood charts when I've done them. Uh, I know many

15. 52:30 – 55:07

    Hair loss, DHT, Creatine Monohydrate

    1. AHAndrew Huberman52:30

       people want to avoid the hair loss that can sometimes be associated with DHT levels going too high, and so I've been asked many times, "Does creatine monohydrate cause hair loss?" It would make sense that if creatine increases DHT and DHT binding to the androgen receptor on the scalp can induce hair loss that that would be the case. Is that true, or, um, is- are people just overly concerned about something that's trivial or nonexistent?

    2. KGDr. Kyle Gillett52:57

       Each male and f- so yes, it can potentially add it. I don't like to say it causes it, but it's a- it can be a little bit more fuel to the fire. So just like everybody has a different sensitivity of their androgen receptor, they have a different amount of gene transcription that is going to cause death of the follicle. That's an arbitrary threshold, so you don't really know until you start losing hair.

    3. AHAndrew Huberman53:20

       And if somebody takes a little bit of creatine for the m- uh, to increase their DHT maybe for the cognitive enhancing effects or for whatever reason and they notice a little bit more hair falling o- out in the sink, um, and they stop taking it, w- you just said death of the follicle, which sounds very dramatic.

    4. KGDr. Kyle Gillett53:34

       Yeah.

    5. AHAndrew Huberman53:35

       Are those folli- are those little stem cell niches that reside in the follicle which hairs grow from, are those then abolished, like there's- there's no going back, or can you, one rescue the- the hair?

    6. KGDr. Kyle Gillett53:45

       It takes months. If they're still there, the hair will come back. So the loss of the hair itself is a normal part of the hair cycle. So you have your anagen phase, your catagen phase, your telogen phase, and then your hair loss, and then a new follicle-

    7. AHAndrew Huberman54:00

       Of the stem cell niche in the-

    8. KGDr. Kyle Gillett54:01

       Yeah.

    9. AHAndrew Huberman54:02

       ... in the hair follicle?

    10. KGDr. Kyle Gillett54:02

        Yeah. Think of, think of it like sharks have teeth. So a shark loses a tooth and they have a new one that comes through, or losing your baby tooth and you have a new one, but your hair just always keeps coming through, so it's natural for it to die and lose. That's why, that's why when you start 5-alpha-reductase inhibitors, often you have a big shed. So what happens during that big shed is all of these cells that are unhealthy-... they immediately jettison that hair and then they start making a much healthier new follicle. So a lot of the hairs that are i- at the end of their telogen phase, then, uh, they have what's called telogen effluvium, which also happens after pregnancy, also happens in, uh, thyroid pathologies. So you shed it, a new one comes in place, and you think that you're having a, a horrible hair loss caused by your finasteride or whatever e- whatever you're doing. And minoxidil does this too, but you're really just having a new healthier follicle. If you go a really long time, if you go a year, then those hairs might come back and they might not.

    11. AHAndrew Huberman55:02

        Mm-hmm. So for, um, simplicity's sake, if somebody is concerned about

16. 55:07 – 58:12

    Hair Regrowth, Male Pattern Baldness

    1. AHAndrew Huberman55:07

       or is experiencing hair loss, male or female, what are their options of, uh, ways to offset that hair loss that are not going to negatively impact other tissues sensitive to DHT? And, and what I'm re- what I'm basically saying here is, uh, I could imagine taking a D- a DHT inhibitor, um, a pill of some sort or an injection of some sort, and offsetting hair loss, maybe even stimulating more hair growth. Um, it's clear that I'm not doing that, but, but I know people that do, but then experience some of the other negative effects of b- of blunting DHT; reduced affect, reduced libido, reduced drive, um, disruptions in, uh, prostate function or, or even, um, sexual function g- generally. So what could, can people do if they want to maintain or grow back hair, but they don't want all those other effects? What should they a- avoid and what should they perhaps consider talking to their doctor about?

    2. KGDr. Kyle Gillett55:59

       Yeah, there's a whole host of options. I, I try to separate alopecia or hair loss into two different categories; male pattern baldness or androgenic alopecia, also known as androgenetic alopecia, versus other types of alopecia, usually telogen effluviums. And if it's androgenetic alopecia or mal- male pattern baldness, even if they're a female, perhaps they have PCOS, something like that, then you want some sort of strategy to decrease the activity of that androgen receptor in that follicle.

    3. AHAndrew Huberman56:31

       So women can get male pattern baldness?

    4. KGDr. Kyle Gillett56:33

       Absolutely.

    5. AHAndrew Huberman56:34

       Okay, I'm going to have to wrap my head around that one, but okay.

    6. KGDr. Kyle Gillett56:37

       Yeah. So there's a lot of different things that you can do that are topical. The most promising is called dutasteride mesotherapy. Essentially what it is, is it's very localized injections in areas that are prone to male pattern baldness, um, whether they're a female or a male, and it acts locally only and you repeat these injections from time to time. It decreases the conversion of testosterone to DHT just in the scalp.

    7. AHAndrew Huberman57:04

       So that can avoid prostate effects and... What are some of the negative effects of, of blocking DHT in, uh, females in the periphery? Meaning not in the- not on the scalp or in the brain, but w- where is DHT doing its stuff?

    8. KGDr. Kyle Gillett57:18

       Yeah, so it's both DHT and then also that 5-alpha, 3-alpha progesterone, which is called, uh, THP or dihydroprogesterone or tetrahydro, trihydroprogesterone. So they're active in the central nervous system, but it's also just active, again, binding to the androgen receptor in a female as well, causing them to have that effort, feel good motivation. A lot of women that are sensitive to DHT, 'cause women can be sensitive to DHT as well, feel very different when they start an oral contraceptive. Not because it alters their DHT to a huge amount, it does to some degree, because the negative feedback inhibition in the pituitary and less produced in the ovaries, but it increases SHBG really high. So because their SHBGs are significantly higher, their free DHT is way lower.

17. 58:12 – 1:04:00

    Polycystic Ovary Syndrome (PCOS), Inositol, DIM

    1. KGDr. Kyle Gillett58:12

    2. AHAndrew Huberman58:12

       I see. H- how does a woman know if she has PCOS, polycystic ovarian syndrome? What are the issues with polycystic ovarian syndrome? What can be done about PCOS? I confess, I was naive to PCOS, um... That wasn't supposed to rhyme, but since it does, I do confess, I was completely naive to it, um, and I started getting a lot of questions about it in various forums, and I think that's just, that's actually the reason why I initially approached you. I know you, uh, have treated a lot of PCOS. Uh, what age women, um, should be thinking about PCOS? What's PCOS? Teach us about PCOS, please.

    3. KGDr. Kyle Gillett58:49

       Yeah. (laughs) So PCOS is polycystic ovarian syndrome, and this is one of those conditions which is underdiagnosed. So its prevalence is much higher than we think it is. There's been a lot of studies, and some, some studies say prevalence of 10%, some say 20%. It's not completely clinically penetrant, so most people don't know they have PCOS until they have infertility or subfertility.

    4. AHAndrew Huberman59:16

       And is this, is PCOS happening at this frequency in 20-year-old women, in 30-year-old women, and 40 and onward?

    5. KGDr. Kyle Gillett59:22

       Most women find out they have PCOS in their 30s, especially, it's on a spectrum or a continuum like a lot of things, where you can have a weaker version or a very severe version.

    6. AHAndrew Huberman59:32

       What are the symptoms?

    7. KGDr. Kyle Gillett59:33

       There's a criteria called the Rotterdam Criteria, and in the Rotterdam Criteria, there's a couple different ways that you can diagnose it. You're looking for androgen excess, insulin resistance, and you could also look for polycystic ovaries. You don't actually have to have polycystic ovaries or get an ultrasound of your ovaries to be diagnosed. If you have androgen excess, for example, androgenic acne or hormonal acne, if you have hair growth, like a hair growth on the chin, it's called, uh, hirsutism, or if you have, uh, you know, like deepening of the voice, um, uh, any symptom of too much andro- uh, male pattern baldness, if you're a female, that's a, a symptom of PCOS as well. Then you can also have insulin resistance, so this is obesity, it's pre-diabetes, a high fasting insulin, a HOMA-IR over two, eh, a fasting insulin of over six. So if you have significant insulin resistance-And also, uh, androgen dominance, that's a sign of it. Androgen dominance often leads to what's called oligomenorrhea. So if you're having more than 35-day intervals in between a period, or if you have less than nine per year, then that can be a sign that you have oligo, which means too little, menorrhea, which means menses. So that's a very common sign of PCOS. If you have infertility, so if you're under the age of 35 and you've been trying for more than a year, or if you're over the age of 35 and you've been trying for more than six months, then that can also be, it's a very common presenting complaint when somebody presents with PCOS.

    8. AHAndrew Huberman1:01:12

       And assuming that, uh, a woman is doing, uh, the, all these other things, is paying attention to the six pillars that we, you talked about earlier, diet, exercise, caloric restriction in some cases, right? Not everyone needs to be caloric restricted. Uh, stress, sleep, and sunlight, spirit. Um, assuming that they're doing all those things, uh, what other things in the realm of diet or supplementation can help them avoid PCOS if they have subclinical PCOS or they have not developed it but don't want to develop it 'cause it doesn't sound like a good thing?

    9. KGDr. Kyle Gillett1:01:42

       Yeah. So depending on where they are, if they're very strong on the insulin resistance spectrum, then, uh, optimizing their body composition, decreasing their body fat, and treating that metabolic syndrome can help. So, uh, a lot of people ask, "Well does everybody that's on, uh, like does everybody need to be on metformin as PCOS?" Not necessarily, but metformin is one of the tools that can help with insulin sensitization. Other tools that can help are anostolol. So myo-inositol is an insulin sensitizer. Its, uh, cousin, D-chiro-inositol, is a, a weak anti-androgen. A lot of types of inositol have both of those in it, so depending on if you're, um, a female or a male and you're on inositol, the type of inositol does matter.

    10. AHAndrew Huberman1:02:33

        Yeah, this is a very important point. I- I, just today I said, "I'm trying this new, um, supplement, inositol, um, for its role in p- help perhaps enhancing sleep even further." My sleep's generally pretty good. Lately it's been a little bit off for a number of reasons, so I took it for the first time last night and, and I said, "I th- I thought it helped and, um, just subjectively..." And you said, "Uh, what kind of inositol is it? Because inositol is a very potent androgen inhibitor." It turns out I was taking myo-inositol, which is not an androgen inhibitor. The type, the other type that you mentioned which is an androgen inhibitor is...

    11. KGDr. Kyle Gillett1:03:09

        D-chiro-inositol.

    12. AHAndrew Huberman1:03:10

        Mm-hmm.

    13. KGDr. Kyle Gillett1:03:11

        It's usually in a ratio of 1 to 25 or 1 to 40, in a much lower amount compared to myo-inositol.

    14. AHAndrew Huberman1:03:18

        In a b- in a supplement or in the body?

    15. KGDr. Kyle Gillett1:03:20

        In a supplement to help induce ovulation.

    16. AHAndrew Huberman1:03:23

        But for women who have PCOS who might want to try and reduce androgen, then they would perhaps want to take a form of inositol...

    17. KGDr. Kyle Gillett1:03:32

        Yeah.

    18. AHAndrew Huberman1:03:32

        ... that reduce the androgen receptor activity, correct?

    19. KGDr. Kyle Gillett1:03:35

        Yeah. They want both. So if you're a woman and you've ever talked to your doctor about getting on a oral contraceptive or spironolactone, which is also an anti-androgen but it happens to be a potassium-sparing diuretic blood pressure medicine as well, um, D-chiro-inositol might be a better option. DIM or diindolylmethane is other, another kind of weak anti-estrogen, anti-androgen that a lot of women should consider as well.

18. 1:04:00 – 1:10:31

    Oral Contraception, Perceived Attractiveness, Fertility

    1. KGDr. Kyle Gillett1:04:00

    2. AHAndrew Huberman1:04:00

       You mentioned oral contraception. Um, I've done a few posts, uh, on these, uh, let's just call them, th- they really are perceptual effects whereby, uh, it's been demonstrated in humans several times now and, and what I, what appear to me to be very solid studies, where, uh, women that take, uh, oral contraceptives, there is both a shift in their perception of men, 'cause th- these studies only looked at heterosexual, uh, uh, the sort of arrangements here, um, where women who are on oral contraception, because it blunts some of the peaks and valleys of ho- of hormone output...

    3. KGDr. Kyle Gillett1:04:39

       Yeah.

    4. AHAndrew Huberman1:04:39

       ... no longer, uh, experience the same peaks and valleys in their assessment of other men's attractiveness, so it sort of flattens the, the, their perception, so to speak. They still find m- certain men attractive and certain men unattractive, but the, the, the h- the degree of difference has kind of mellowed out.

    5. KGDr. Kyle Gillett1:04:55

       Yeah.

    6. AHAndrew Huberman1:04:55

       Um, and likewise, men perce- th- these datas say that men perceiving women's attractiveness, they still see women on oral contraceptives as attractive, but they're, a woman taking oral contraception eliminates this kind of peak in her attractiveness that men would otherwise perceive. In other words, oral contraceptives are changing the way that we perceive each other, at least in terms of these m- uh, male/female, um, experiments. What is going on with that? Is that because oral contraceptives blunt the increase in testosterone that occurs just before ovulation, or is it because of a complex cascade? What, what is going on? I find this fascinating.

    7. KGDr. Kyle Gillett1:05:37

       Yeah. So there's differences in how your... And I wouldn't use the word change necessarily, but alter the severity or alter the, uh, peak, as you said. So it's n- just like TRT is not gonna change you as a person, an oral contraceptive will not change you as a person. It will just change your, um, day-to-day peaks and troughs in, um, libido and attractiveness. So one of the main effects of oral contraceptives, almost all of them have a synthetic estrogen and a synthetic progestogen in them. One common type of synthetic estrogen is ethinyl estradiol. There is another new, uh, synthetic estrogen that's out there as well, but that, anecdotally that seems to have even more side effects. So this ethinyl estradiol is 100 times more potent than endogenous or bioidentical estradiol in the liver. So it binds to the estrogen receptor in the liver, and it's going to increase sex hormone binding globulin which secondarily, as you mentioned, decreases your free testosterone and especially your free DHT. So that little testosterone hump that you get when you're a female that's ovulating......that's really flat-lined. And it's already, uh, it's a pretty insignificant difference. It's not negligible, but it's a little bit of a hump, and you have significantly less of that when you're on a oral contraceptive.

    8. AHAndrew Huberman1:07:03

       And does that blunt the associated increase in libido that normally would occur from that increase in, in androgen?

    9. KGDr. Kyle Gillett1:07:10

       Yes.

    10. AHAndrew Huberman1:07:10

        Yeah. Interesting. Um, what about other forms of contraception, right? 'Cause there are, uh, there's copper IUD. There's, um, various implants. There's rings. There's a, a huge number of, of different, um, forms of these.

    11. KGDr. Kyle Gillett1:07:23

        Yeah.

    12. AHAndrew Huberman1:07:23

        So what we're talking about is, uh, as I understand it, is only the effect of, um, uh, oral contraception that impacts hormone output. Is that, is that correct?

    13. KGDr. Kyle Gillett1:07:34

        Yeah, there's a lot of other effects as well. For example, your choice of synthetic progestin will alter how high your platelets and SHBG go. It appears to be the higher your platelets and the higher your SHBG, the higher your risk of a blood clot. So a lot of women know that if they're on a oral contraceptive, and they're already predisposed to a blood clot or a venous thromboembolism, in their vein, they have a blood clot in either their leg or their lung, then it can increase that chance. So you can choose a synthetic progestin that is not going to have as high of a response. Um, but there's, there's various pros and cons. Some synthetic progestins are weak anti-androgens as well. For example, the- there's one known as Slend, which is made from spironolactone. So some women are on spironolactone and that as well, which is made from spironolactone, which probably isn't particularly necessary unless they need it for a diuretic or a hypertensive effect.

    14. AHAndrew Huberman1:08:32

        I see. I, I, I'm just gonna, uh, um, intentionally interrupt, and I apologize. But, um, specifically because I wanted to ask about, uh, there is this notion that, um, you know, that oral contraception taken over long periods of time can disrupt fertility in ways that are independent of just the, uh, age-related decrease in infertility. Is that true?

    15. KGDr. Kyle Gillett1:08:56

        It depends on what you mean by a long time. Six to 12 months, it's possible. Past that, it seems very unlikely. However, the persistently elevated SHBG can be present for quite some time.

    16. AHAndrew Huberman1:09:08

        Wait, so if a, if a woman takes oral contraception for six to 12 months and then stops, will she essentially be where she would have been anyway in terms of her fertility at that age? Or are you saying that it can cause permanent damage?

    17. KGDr. Kyle Gillett1:09:22

        Her fertility would be equitable as if she had never taken it if she's certainly 12 months, but probably six months off.

    18. AHAndrew Huberman1:09:29

        And what if she, uh, wha- I know of women that have taken an oral contraception for many years. Are, in addition to the age-related decline in fertility that occurs, that's inevitable, um, of course the slope is gonna be different depending on, um, the individual, but i- i- are they, uh, quickening the, uh, the transition to infertility?

    19. KGDr. Kyle Gillett1:09:50

        Probably not. Um, you could make a case that because they've been on a oral contraceptive, they may have been slightly more predisposed to insulin resistance and/or lower lean body mass. But that's n- probably gonna be a negligible difference compared to their resistance training and also their caloric restriction or caloric maintenance. So-

    20. AHAndrew Huberman1:10:13

        And of course, there are also effects of having children. Uh-

    21. KGDr. Kyle Gillett1:10:16

        Yeah.

    22. AHAndrew Huberman1:10:16

        Yeah. Right? (laughs) I mean, on all these parameters, right? 'Cause it's a severe, it's a major lifestyle shift-

    23. KGDr. Kyle Gillett1:10:21

        Yeah.

    24. AHAndrew Huberman1:10:21

        ...right?

    25. KGDr. Kyle Gillett1:10:22

        Yeah.

    26. AHAndrew Huberman1:10:23

        Um, that obviously w- people contend with and have for since the beginning of, uh, human time anyway. Um,

19. 1:10:31 – 1:14:27

    Testosterone & Marijuana or Alcohol

    1. AHAndrew Huberman1:10:31

       I want to ask some questions about male hormone therapy and male hormones generally. But before I do that, I, I have a couple of burning questions that I get very often that I'm just gonna insert now. Um, marijuana. I've heard that it can decrease testosterone in men and women. I've heard that it can increase testosterone. Alcohol, I think there's general consensus that high alcohol intake, high barbiturate intake can re- does in fact reduce testosterone. What about modest increase of alcohol? I'm not a drinker so that I'm not asking these questions for me. I don't smoke pot. I'm quite open about it. I've just never really liked, you know, marijuana or alcohol. They're not my thing. But many people want to know the answers to these. And the, the data that I've seen are very confused and conflicting. So what about marijuana? Does it reduce testosterone to a significant degree or not?

    2. KGDr. Kyle Gillett1:11:23

       Cannabinoids itself, whether it's THC or CBD, are not going to reduce testosterone by themself. If it's smoked marijuana, then it's very likely to increase your aromatase, which increases your estrogen. And, uh, you know, that's gonna, it's aromatizing from testosterone, so that is going to decrease testosterone. When you have an increased estrogen, like estradiol, that's gonna work on your pituitary to make less hormones that cause re- the release of p- of testosterone, so you're gonna have less LH and less FSH. So it's almost kind of like, uh, you know, opiates are well known to, um, opiate agonists. Uh, um, they're going to decrease LH and FSH, and subsequently testosterone. Smoked marijuana will as well. As far as alcohol, high alcohol will decrease testosterone, as will any very potent GABA agonist. Whether it's a barbiturate or a benzodiazepine or a non-benzo or alcohol, they're definitely going to. Um, moderate alcohol, I guess it depends on what your definition of that is. The Am- the American Heart A-

    3. AHAndrew Huberman1:12:29

       I guess I'm thinking of like a, like, I, some people I know that don't seem to be alcoholics, at least by my, you know, uh, assessment will have a, a glass or two of wine four nights a week, which to me seems like-

    4. KGDr. Kyle Gillett1:12:42

       Yeah.

    5. AHAndrew Huberman1:12:42

       ...a tremendous amount only because I don't like alcohol. I, I don't have a problem with other people liking alcohol, but, but I think many pe- for many people, that would be considered low or-... or moderate intake.

    6. KGDr. Kyle Gillett1:12:52

       Yeah. I, I would consider that low intake. The American Heart Association for men recommends beli- between one and two drinks a day on average. So around-

    7. AHAndrew Huberman1:13:02

       They recommend it?

    8. KGDr. Kyle Gillett1:13:03

       Yeah. So around one per week.

    9. AHAndrew Huberman1:13:04

       Wait, so I'm making my heart less healthy by not drinking alcohol?

    10. KGDr. Kyle Gillett1:13:07

        Yeah. They, they recommend a very low amount of alcohol intake for men. For women, they recommend zero to one, so that's kind of hard to interpret, zero to one. Um, but the protective effect of alcohol, especially if it's a red wine, um, with polyphenols in it, uh, outweighs the deleterious effect.

    11. AHAndrew Huberman1:13:28

        Interesting, 'cause I've seen some studies that point to the idea that even low intake of alcohol over a prolonged period of time might actually decrease brain volume, or at least volume of particular brain areas. But of course, we don't know the consequence of, of decreasing the volume of a gi- of a given brain a- area either. I mean, one could imagine it's decreasing the size of one's amygdala and making them less stressed, although there's no evidence to support that. I've been told that I need a drink many, many times, but I always reply that I don't need to drink anything in order to speak my mind, so again, uh, individual differences. Uh, very interesting. So it sounds like smoked marijuana may, in fact, reduce testosterone, or at least increase the conversion of testosterone to estrogen. Correct?

    12. KGDr. Kyle Gillett1:14:07

        Yeah.

    13. AHAndrew Huberman1:14:07

        Okay.

    14. KGDr. Kyle Gillett1:14:08

        And with alcohol and GABA agonists, it's important to remember that it shouldn't be daily. So one drink of alcohol a day is actually very mildly immunosuppressive. So it's better to have two drinks of alcohol one day of the week, and then two more drinks of alcohol another day of the week, and then no alcohol the rest of the time. The

20. 1:14:27 – 1:15:34

    Sleep Supplement Frequency

    1. KGDr. Kyle Gillett1:14:27

       same could be said even for supplements that have GABA in them. A lot of sleep supplements have gamma-Aminobutyric acid, which is GABA, so-

    2. AHAndrew Huberman1:14:33

       I occasionally take... Oh, sorry to interrupt. I occasionally take 100 to 200 milligrams of GABA-

    3. KGDr. Kyle Gillett1:14:38

       Mm-hmm.

    4. AHAndrew Huberman1:14:39

       ... um, in order to enhance sleep, but I do it maybe every third or fourth night, no more than three or four nights a week.

    5. KGDr. Kyle Gillett1:14:44

       Yeah.

    6. AHAndrew Huberman1:14:45

       Yeah.

    7. KGDr. Kyle Gillett1:14:45

       That's perfect.

    8. AHAndrew Huberman1:14:46

       Okay.

    9. KGDr. Kyle Gillett1:14:47

       So there's a lot of sleep supplements that should not be taken daily, and GABA is one of them. Um, another one of them is Trazodone, and, and melatonin is kind of arguable, and it depends on the situation, but in general, if you're taking a sleep supplement, it should not be taken every night.

    10. AHAndrew Huberman1:15:05

        The, the sleep supplements that I understand are okay to take every night or nearly every night are things like magnesium threonate-

    11. KGDr. Kyle Gillett1:15:11

        Yes.

    12. AHAndrew Huberman1:15:11

        ... apigenin. Uh, um, if that's not true, correct me. I, are those are... I certainly take them every night unless I forget them, uh, in the-

    13. KGDr. Kyle Gillett1:15:18

        Yeah.

    14. AHAndrew Huberman1:15:18

        ... back home when I'm traveling.

    15. KGDr. Kyle Gillett1:15:20

        Magnesium is one of the exceptions. L-theanine is also another exception.

    16. AHAndrew Huberman1:15:24

        Great. Well, then at least I haven't put anything into the world that's, uh-

    17. KGDr. Kyle Gillett1:15:27

        (laughs)

    18. AHAndrew Huberman1:15:27

        ... that's wrong in that category, uh, yet. Um, and hopefully I won't. But if I do, I'll correct myself.

21. 1:15:34 – 1:20:24

    Testosterone Supplementation & Prostate Cancer

    1. AHAndrew Huberman1:15:34

       So let's talk about testosterone in, in males. There, you see these, um, headlines all the times now that testosterone levels are dropping. Um, sperm counts are dropping. Um, phenotypes of men are changing over time, and, and I can't quite follow the literature on that, because, uh, obviously those are hard-controlled experiments to do, because techniques change over time and sensitivity of techniques change over time. But regardless, I, I'm aware that a lot of people are considering increasing their testosterone by taking testosterone that a, a few years ago that was considered, you know, steroid use, and it was really extreme kind of stance. Nowadays, it seems like there's more discussion about it. First off, I'd like to know, does testosterone supplementation, and here I'm talking about prescription from a doctor, does it make one more prone to prostate cancer? That seems to always be the first question that comes out.

    2. KGDr. Kyle Gillett1:16:31

       Yeah, and there is a huge amount of misinformation about this too. So testosterone is not going to cause a prostate cancer. However, normal aging causes prostate cancer, and testosterone will grow your prostate cancer. So if you're a 80-year-old male and you have an autopsy, then there's at least a 50% chance that you have a prostate cancer. If you're 90 or 100 years old, there's at least a 90% chance. So for humans with a prostate, it's only a matter of time until you get a prostate cancer. So that begs the question, do you want to take something that's going to grow it for sure once you have it? So it's an individual assessment, and it's important to follow things like PSAs as well.

    3. AHAndrew Huberman1:17:18

       So a PSA of, of four or less, I mean, ideally you wouldn't be at four, 'cause that's kind of the upper threshold, is, um, the simplest readout of whether or not there's, um, excessive prostate growth. There's benign prostate hyperplasia where the prostate is, is growing, but, um, it's non-cancerous, correct? And then, of course, there are the symptomologies, like people who have challenges with urination, they have sexual difficulties, et cetera. I'm always struck by the, um, correlation that people draw between testosterone and prostate health, and the fact that, or the, I should say the claim that testosterone makes prostate health worse, because if you think about it, young males have high testosterone often, if not always. Um, certainly often, and you don't see a lot of prostate overgrowth and cancer in young males. So something's going on here. How, how should we conceptualize this?

    4. KGDr. Kyle Gillett1:18:10

       So if you have a PSA of 3.9 and you're a 25-year-old male versus a 75-year-old male and you have a PSA of 5.9, the 3.9 PSA is significantly more concerning. So think of your prostate as taking cumulative damage from not only testosterone, but also estrogen, and also growth hormone. So that's why obese individuals have higher incidences of prostate cancer as well, is because they don't have those cell checkpoints where, uh, your immune system takes a second and says, "All right. Stop, uh, replicating as fast, prostate cells. Let's see if there's any atypical ones," and then it finds those, and it prevents them from reproducing. That's why immunotherapy in cancer is so promising, is because they can target these certain things.So the older male is going to have that cumulative damage happen already. And arguably, prostate cancer is a normal, uh, you know... It... With aging, you know, fast aging is abnormal, very slow aging is normal. There's a fine line to walk between those two. But there's a lot of things that can be done to decrease the turnover, decrease the inflammation, and decrease the congestion of the prostate over time. There's also a lot more than just PSAs that can be done. There's prostate MRIs and things like that, that can look at the structure and the function of the prostate.

    5. AHAndrew Huberman1:19:41

       So what should every male do to maintain the health of their prostate? And I realize that younger males probably aren't thinking about it at all, although it seems like nowadays, I get these kind of what I call, um, cryptic questions, you know. Um, I think women are more comfortable talking about their hormone and sexual health because of they, they cycle, you know, because of menstrual cycles, they're used to fluctuations that all- it sort of give them the experience of what it's like to have different levels of progesterone, estrogen, testosterone, et cetera. But I get these kind of cryptic questions often in my direct messages, where what I think people are asking is, um, wha- you know, "Wha- is there something wrong (laughs) with my prostate? What should I do for my prostate?" These are often indirect questions for other aspects of their life where they're suffering, but, um... And I don't say that, uh, in jest. I, I, I think,

22. 1:20:24 – 1:24:05

    Prostate Health, Dietary Fiber, Saw Palmetto, C-Reactive Protein

    1. AHAndrew Huberman1:20:24

       um, more direct discussion would be great. So, uh, what should all males do to main- to maintain, uh, prostate health throughout the lifespan?

    2. KGDr. Kyle Gillett1:20:34

       Maintaining prostate health can be looked at similarly how you can maintain a good natural optimal testosterone. So you look for things that can hurt it, you don't necessarily look for one thing that can improve it or boost it. So for young males, those are prostatitis, so, uh, it goes hand in hand with epididymitis, so different infections of the prostate. The younger the male is, the more likely it is related to something that could be sexually transmitted. But another very common cause is what we call gram-negative and anaerobic bacteria. The prostate is right by the end of the colon, so if you have chronic constipation or if you have colitis or, uh, if you ha- you know, even just an E. coli overgrowth in the colon is very likely to cause an infection of the prostate as well.

    3. AHAndrew Huberman1:21:27

       What should males do to, to prevent that?

    4. KGDr. Kyle Gillett1:21:30

       Have a diet that has good healthy prebiotic fiber, probiotics as well. Um, make sure that they're having regular bowel movements, that they don't have chronic constipation. Have good sources of dietary fiber, which is also known as soluble fiber, and enough insoluble fiber. Most people get enough insoluble or non-dietary fiber. So that can help prevent the chance of diverticulitis, which is another type of infection. It can also decrease the chance of colitis and decrease the chance of prostate infections as well.

    5. AHAndrew Huberman1:22:02

       Uh, are there any foods and/or supplements that men should take or avoid? What about... You hear about saw palmetto, um, yeah, supplements for or agai- uh, supplements that support or cause issues for the prostate?

    6. KGDr. Kyle Gillett1:22:18

       Yeah. If there's a strong genetic predisposition to enlarged prostates, or even just really early prostate cancers that grow fast, then they can consider taking saw palmetto or even curcumin as an anti-androgen, as long as they're able to tolerate it. It's an individualized basis and depends on their history. As far as, um, making sure that their prostate is not congested, there's an interesting correlation between having girls and having prostate cancer.

    7. AHAndrew Huberman1:22:48

       Having girl offspring.

    8. KGDr. Kyle Gillett1:22:49

       Yeah. So if your, if your offspring are females, then you're slightly more likely to have prostate cancer. There is some, uh, there's hypotheses that link estrogen to prostate cancer rather than testosterone. So if you have hyperestrogenism, your prostate, uh, has more atypical cells. In general, the higher your C-reactive protein, which is a general marker of inflammation in your body, we call it CRP, and the test to order is hsCRP or high-sensitivity CRP. If your CRP, uh, raises up very high if you have an autoimmune disease, like if you have a Crohn's flare, or if you have, uh, lupus or an infection or a sexually transmitted infection or even, uh, colitis or even the flu, your CRP is gonna raise significantly.

    9. AHAndrew Huberman1:23:40

       That you would detect in a blood test, of course.

    10. KGDr. Kyle Gillett1:23:42

        Correct. Yeah.

    11. AHAndrew Huberman1:23:42

        Yeah.

    12. KGDr. Kyle Gillett1:23:43

        So you want to get a baseline CRP when you haven't had any of those things recently. And if your CRP is higher, you also have more female offspring. If your CRP is higher, then your reactive oxygen species, which are causing mutations and atypical cell turnover in the prostate, are also likely higher. So you want to keep a very low CRP.

23. 1:24:05 – 1:30:54

    Prostate Health & Pelvic Floor, Viagra, Tadalafil

    1. KGDr. Kyle Gillett1:24:05

    2. AHAndrew Huberman1:24:05

       Interesting. And, uh, what about blood flow and pelvic floor in general? We should probably do a whole episode on pelvic floor. You know, there's so much interesting, um, data coming out of the, the fields of clinical and research urology. I realize it's kind of the Netherlands of, of, uh, biology and medicine. People probably aren't thinking so much about this. But pelvic floor is obviously a, um, a confluence of a ton of bl- of vasculature, of nerves, and of course the prostate resides there, and of course the genitals and, uh, reside there as well. So I would imagine that the, one of the six pillars, you know, exercise, being able to maintain adequate blood flow to those regions is key. What about just postural things, people sitting too much, um, not, um, hydrating well enough? Um, you mentioned avoiding constipation. Uh, what are some other things, including medications, that can serve to support the prostate over time, and maybe even support pelvic floor in general, both in males and females over time?

    3. KGDr. Kyle Gillett1:25:01

       Absolutely, and this is something that's rightfully getting more and more attention. The way I explain the pelvic floor is, your abdominal cavity, which includes your peritoneum or where most of your organs are, your retroperitoneum, your pelvic space, think of it as a box, and your abs are the front of the box. Your back muscles are the back. Your diaphragm is the top of the box. And your pelvic floor, that's where your port is to the outside world. Especially important, it has muscles as well, and you can do exercises. Pelvic floor physical therapists are becoming more and more utilized, especially after childbirth, but in other situations as well, including by men getting care from urologists.So, you want to both strengthen that pel- pelvic floor and make sure that the tubes that are docked to the outside world are working well enough, but they're not too loose, they're not working too well. So, there's a lot of medications that can be, uh, positives or negatives for your pelvic floor. We kind of talked about your gut and colon health in general. As far as your prostate health and as far as your, um, bladder and urinary system health, you think a- about a couple different classes. So, you have your phosphodiesterases, you have your tadalafil, um... Basically, this is gonna help decrease congestion in the prostate. A lot of people take it for ED, but it can actually help you decrease your-

Episode duration: 2:59:21