Biological Influences On Sex, Sex Differences & Preferences

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.920 | for everyday life.

00:00:05.920 | I'm Andrew Huberman,

00:00:10.800 | and I'm a professor of neurobiology and ophthalmology

00:00:13.880 | at Stanford School of Medicine.

00:00:15.960 | This podcast is separate from my teaching

00:00:17.840 | and research roles at Stanford.

00:00:19.720 | It is, however, part of my desire and effort

00:00:21.840 | to bring zero cost to consumer information

00:00:24.120 | about science and science-related tools.

00:00:27.000 | In keeping with that theme,

00:00:28.200 | I'd like to thank the sponsors of today's podcast.

00:00:31.300 | Our first sponsor is InsideTracker.

00:00:33.980 | InsideTracker is a personalized nutrition platform

00:00:36.600 | that analyzes data from your blood and DNA

00:00:39.400 | to help you better understand your body

00:00:41.080 | and help you reach your health goals.

00:00:43.240 | I'm a big believer in blood tests and DNA tests

00:00:45.880 | for the simple reason that many of the factors

00:00:48.660 | that are important for your short-term and long-term health

00:00:51.420 | and overall wellbeing can only be analyzed

00:00:54.100 | from blood and DNA tests.

00:00:55.880 | Things like metabolic factors and hormone levels

00:00:58.680 | really can only be assessed accurately from blood and DNA.

00:01:02.920 | The thing I like about InsideTracker

00:01:04.440 | is you don't just get back levels of different hormones

00:01:07.320 | and metabolic factors and so forth.

00:01:09.700 | You also get directives.

00:01:10.920 | It has a dashboard that's very easy to use

00:01:13.240 | that tells you, based on your data,

00:01:15.440 | what sorts of foods you might want to eat more of

00:01:17.720 | or less of,

00:01:18.600 | what forms of exercise you might want to do more of

00:01:21.560 | or less of.

00:01:22.640 | It's really a wonderful way to assess

00:01:24.680 | how your behaviors and lifestyle choices

00:01:27.000 | are interacting with what's going on

00:01:29.060 | deep within your biology.

00:01:31.160 | InsideTracker makes all of that super easy to understand.

00:01:34.680 | It's also really easy to get the blood tests

00:01:36.920 | and DNA tests taken.

00:01:38.160 | You can go to a local location

00:01:39.920 | or they can send somebody to your home if you prefer that.

00:01:43.240 | If you'd like to try InsideTracker,

00:01:44.760 | you can visit insidetracker.com/huberman

00:01:48.100 | to get 25% off any of InsideTracker's plans.

00:01:51.360 | Use the code Huberman at checkout.

00:01:53.440 | That's insidetracker.com/huberman

00:01:56.600 | to get 25% off any of InsideTracker's plans

00:01:59.480 | and use the code Huberman at checkout.

00:02:02.000 | Today's episode is also brought to you by Helix Sleep.

00:02:04.880 | Helix Sleep makes mattresses and pillows

00:02:07.140 | that are designed to meet your sleep needs

00:02:09.640 | in order to optimize your sleep.

00:02:11.800 | I've done several episodes of this podcast

00:02:13.840 | and there's a ton of information out there

00:02:15.860 | pointing to the fact that getting really deep,

00:02:17.880 | restful sleep each night is vital

00:02:19.920 | for mental and physical health.

00:02:21.640 | And the mattress that you sleep on and the pillow

00:02:23.780 | that you use is very important for getting optimal sleep.

00:02:27.400 | Helix Sleep has a brief two minute quiz that you can take.

00:02:30.680 | It asks you questions like, do you sleep on your side

00:02:32.800 | or your back or your stomach, or maybe you don't know,

00:02:34.920 | do you tend to run hot or cold as you sleep

00:02:37.240 | or maybe you don't know.

00:02:38.960 | That two minute quiz matches you to a mattress and pillow

00:02:42.980 | that's ideal for your sleep needs.

00:02:45.260 | I took this quiz, I matched to the mattress

00:02:47.600 | they call the Dusk D-U-S-K

00:02:49.440 | and I've been sleeping on the Dusk mattress for many months

00:02:51.740 | now and I've been sleeping better than I ever have before.

00:02:54.480 | It's really wonderful to have a really good night's sleep

00:02:57.120 | on a consistent basis, it's a total game changer.

00:02:59.900 | So if you're interested in upgrading your mattress,

00:03:01.760 | you can go to helixsleep.com/huberman,

00:03:04.960 | take their two minute sleep quiz

00:03:06.560 | and they'll match you to a customized mattress

00:03:08.880 | and you'll get up to $200 off any of their mattress orders

00:03:12.000 | and two free pillows.

00:03:13.560 | So that's helixsleep.com/huberman,

00:03:16.740 | take the two minute sleep quiz,

00:03:18.220 | they'll match you to a mattress

00:03:19.780 | and if you order one of their mattresses,

00:03:21.060 | you'll get up to $200 off any of their mattresses

00:03:23.900 | and two free pillows.

00:03:25.580 | They have a 10 year warranty

00:03:26.800 | and you get to try out the mattress

00:03:28.440 | for a hundred nights risk-free

00:03:30.220 | and if you don't like it,

00:03:31.060 | they'll pick it up and take it away.

00:03:32.680 | If you love it, then you keep it

00:03:34.540 | and I think there's a very good chance

00:03:36.140 | that you're going to love it, I certainly love mine.

00:03:38.320 | And today's episode is also brought to you

00:03:40.340 | by Athletic Greens.

00:03:41.940 | Athletic Greens is an all-in-one

00:03:43.780 | vitamin mineral probiotic drink.

00:03:46.420 | I started using Athletic Greens way back in 2012

00:03:49.980 | and so I'm delighted that they're sponsoring the podcast.

00:03:52.700 | I started using Athletic Greens

00:03:54.160 | because I found it rather confusing

00:03:56.620 | to figure out what vitamins and minerals to take.

00:03:59.580 | And Athletic Greens, I get all the vitamins and minerals

00:04:02.220 | I need to cover my bases.

00:04:04.060 | As well, probiotics are really important.

00:04:06.620 | Probiotics have been shown now in numerous studies

00:04:08.660 | to be important for the gut microbiome,

00:04:11.020 | which impacts the gut brain axis,

00:04:13.020 | as well as various aspects of bodily health.

00:04:16.060 | So in Athletic Greens,

00:04:17.460 | I get vitamins, minerals, and probiotics.

00:04:19.980 | I also really like the way it tastes.

00:04:21.820 | It's a greens drink, so you mix it with some water.

00:04:24.400 | You could mix it with something else like juice if you like.

00:04:26.380 | I mix mine with water and lemon juice

00:04:28.340 | and I drink it once or twice a day.

00:04:30.380 | If you want to try Athletic Greens,

00:04:31.840 | you can go to athleticgreens.com/huberman.

00:04:35.060 | And if you do that, you'll claim their special offer,

00:04:38.060 | which is to get a year supply of vitamin D3K2.

00:04:41.700 | There's now also a wealth of data showing

00:04:43.540 | that vitamin D3 is important for various aspects

00:04:46.360 | of brain and body health.

00:04:48.460 | So that's athleticgreens.com/huberman

00:04:51.740 | for Athletic Greens and the year supply of vitamin D3K2.

00:04:55.480 | You'll also get five free travel packets.

00:04:58.160 | The travel packets are just a really convenient way

00:05:00.780 | to take Athletic Greens when you're on the road,

00:05:03.480 | in the car, or on a plane, or just moving around.

00:05:06.340 | You just empty one of the packets into a water bottle

00:05:09.180 | or a glass and mix it up really quickly.

00:05:11.020 | It saves any kind of mess or anything of that sort.

00:05:13.860 | So once again, athleticgreens.com/huberman

00:05:17.100 | to get vitamin D3K2, that's a year supply,

00:05:19.620 | and the five free travel packs.

00:05:21.760 | It's a new month, which means it's a new topic

00:05:24.420 | here at the Huberman Lab Podcast.

00:05:26.980 | For the next four or so episodes,

00:05:29.140 | we're going to be talking all about hormone effects

00:05:32.280 | on the brain and body.

00:05:34.380 | So that's a huge number of different topics.

00:05:37.060 | We're going to talk about sex.

00:05:39.040 | We're going to talk about reproduction.

00:05:41.260 | We're going to talk about puberty a little bit more.

00:05:43.900 | We talked about that in the previous episode.

00:05:46.000 | We're going to talk about menopause.

00:05:47.660 | We're going to talk about birth control.

00:05:49.280 | We are going to talk about aggression,

00:05:52.060 | competition, winning, losing.

00:05:55.500 | Basically, we're going to cover as much about hormones

00:05:57.920 | as we possibly can in this month.

00:06:00.980 | And in doing so, we are going to go deep

00:06:03.820 | into tools and protocols.

00:06:06.140 | We are also going to talk about a lot of tools

00:06:08.800 | that relate to things that you might not want to do

00:06:11.380 | in order to optimize hormone health,

00:06:14.820 | regardless of stage of life or your goals, et cetera.

00:06:17.720 | So it's sure to be a month rich with discussion,

00:06:21.100 | rich with tools, and you're going to learn

00:06:22.980 | a lot of neuroscience and endocrinology.

00:06:26.300 | There's actually a field of neuroendocrinology.

00:06:28.700 | It's actually where I started my graduate work.

00:06:30.520 | I did a master's in it, which is only to say

00:06:32.900 | that I love the topic.

00:06:34.920 | I have a lot of friends that work on this topic,

00:06:36.540 | many of whom I've consulted for these episodes,

00:06:38.620 | and I'm really excited to share the information with you.

00:06:41.400 | Before we dive into today's episode,

00:06:43.660 | all about emotions and sex,

00:06:45.640 | I want to just have a few announcements

00:06:48.240 | that are designed to point you to some useful resources.

00:06:51.700 | Last episode, talking about the science of emotions

00:06:54.420 | and relationships, I mentioned the Mood Meter app.

00:06:57.780 | The Mood Meter app was developed by people out

00:07:00.720 | at Yale University who study the biology

00:07:03.100 | and psychology of emotions.

00:07:04.420 | It's a really wonderful app.

00:07:06.100 | However, many of you quickly told me

00:07:09.360 | that the Mood Meter app isn't available in your area.

00:07:12.920 | You went to the link we posted,

00:07:14.100 | and it just was saying not available in your area.

00:07:16.100 | The situation was actually a lot worse than that.

00:07:17.920 | The situation was that when we recorded the episode,

00:07:20.820 | the Mood Meter app was working, I know,

00:07:22.380 | 'cause I downloaded a fresh copy of it to my phone.

00:07:25.260 | And then in the ensuing weekend,

00:07:27.320 | they took the Mood Meter app down for some repairs.

00:07:30.220 | The Mood Meter app is now up.

00:07:32.460 | It is available.

00:07:33.620 | I want to be really clear.

00:07:35.460 | It's not an app I'm affiliated with.

00:07:37.780 | I'm just mentioning it to you.

00:07:38.980 | They don't know me.

00:07:39.820 | I know them, but they don't know me.

00:07:41.500 | So we don't have any kind of business relationship.

00:07:43.860 | They do charge 99 cents for the app.

00:07:46.740 | I think the free version has disappeared

00:07:48.540 | in the last year or so.

00:07:50.180 | So that's Mood Meter app.

00:07:51.360 | We'll provide the link again,

00:07:53.060 | and the link should be working.

00:07:54.620 | Hopefully they won't take it down again

00:07:56.420 | in between this announcement

00:07:57.740 | and the release of this episode.

00:07:59.620 | Also just want to take a step back for a moment

00:08:02.100 | and talk a little bit about the logic

00:08:04.500 | of how to make the most of the information

00:08:07.260 | on the Huberman Lab Podcast.

00:08:09.380 | I tend to throw out a lot of information

00:08:11.400 | about a given topic.

00:08:12.660 | Many of you have pointed out, however,

00:08:14.420 | that I don't cover certain things.

00:08:16.680 | And once again, I'll just say,

00:08:19.080 | the goal is always to be accurate,

00:08:21.440 | but there's no way I can be exhaustive.

00:08:24.140 | There's no way I can cover everything

00:08:25.500 | for a particular topic.

00:08:26.700 | The good news is we have time.

00:08:28.600 | My goal, at least in the first year

00:08:30.440 | of the Huberman Lab Podcast is to give you a basis,

00:08:33.460 | a foundation in these different topics

00:08:35.260 | of neuroplasticity, focus, sleep, hormones, et cetera.

00:08:40.260 | And of course, to provide tools along the way.

00:08:43.540 | We are going to host guests.

00:08:44.860 | I've actually started recording

00:08:45.920 | with some of these guests already.

00:08:47.620 | And even those episodes will include a little,

00:08:49.620 | what we call primer,

00:08:50.920 | a little description of the basics of a given topic

00:08:54.220 | so that you can get more information from those topics.

00:08:56.820 | My goal really is to educate you in these topics,

00:09:00.020 | give you a foundation in these topics

00:09:01.780 | and allow you to start exploring them here in the episodes

00:09:04.740 | with our future guests,

00:09:06.260 | but also in other podcasts and books

00:09:08.380 | and other sources of information.

00:09:10.180 | So for those of you that are saying

00:09:11.520 | it's too much information,

00:09:13.080 | I just encourage you to remind yourself

00:09:16.640 | that you have a pause button,

00:09:17.840 | you can return to it, everything's timestamp.

00:09:19.920 | For those of you who feel it's not enough information,

00:09:21.940 | I'm not covering enough,

00:09:23.180 | just know that this is just the beginning.

00:09:25.440 | We intend to do this for a very long time

00:09:27.460 | and we will be thorough over time.

00:09:30.140 | So thanks for your patience.

00:09:31.700 | And please be patient with yourselves.

00:09:33.220 | There's no reason why you have to digest

00:09:35.460 | all the information in one swoop.

00:09:38.160 | The other thing is that I've been told

00:09:39.660 | both that I speak too fast and speak too slow.

00:09:42.300 | So there's a wonderful solution to this.

00:09:44.440 | If I speak too fast or too slow,

00:09:46.940 | you can adjust the speed in YouTube.

00:09:49.140 | If you're listening in a different format,

00:09:50.460 | I think you also can adjust the speed of playback.

00:09:52.920 | So that's something that wouldn't be possible

00:09:55.040 | in the classroom, but you may find useful.

00:09:57.940 | And then last but not least,

00:09:59.980 | I want to point people again to this NSDR,

00:10:02.980 | non-sleep deep rest protocol

00:10:04.700 | that the folks over at Made For

00:10:06.140 | have put out as a free resource.

00:10:08.140 | It does, as many of you pointed out,

00:10:10.180 | bear resemblance to things like yoga nidra,

00:10:12.300 | other forms of meditation.

00:10:13.500 | But what we've done is we've stripped out intentions

00:10:16.380 | or any kind of the verbiage related

00:10:19.580 | to what some people might perceive

00:10:23.020 | as kind of related to the yoga community

00:10:25.420 | or specific to kind of new agey type techniques,

00:10:29.820 | not because we don't like yoga nidra.

00:10:31.300 | In fact, I've done yoga nidra daily

00:10:33.040 | for almost the last, goodness, eight years of my life.

00:10:36.660 | I love yoga nidra, but sometimes the complicated language

00:10:41.620 | can be a separator and can discourage people

00:10:43.780 | from taking on these protocols that are extremely useful.

00:10:46.460 | So NSDR is intentionally generic.

00:10:49.640 | It's designed to bring you into a state of deep relaxation

00:10:53.720 | through a combination of breathing and body scan.

00:10:56.140 | There's the YouTube script over at Made For,

00:10:58.820 | which is linked in the caption.

00:11:00.820 | And many people find that they prefer that

00:11:03.340 | to scripts like yoga nidra scripts,

00:11:05.480 | where they're doing intentions

00:11:06.880 | and they're hearing a lot of kind of unusual language

00:11:10.320 | around the process.

00:11:11.220 | This is just very basic and I hope you'll enjoy it.

00:11:14.660 | And if you prefer the more typical yoga nidra scripts,

00:11:17.060 | then go with those.

00:11:18.060 | There are many of them available

00:11:19.220 | on the internet and elsewhere.

00:11:21.340 | And last but not least, I want to point out

00:11:23.620 | that all our episodes now are subtitled

00:11:25.860 | both in English and in Spanish.

00:11:27.820 | So for those of you that prefer

00:11:29.020 | to digest this information in Spanish,

00:11:31.620 | that's now available to you in the subtitles.

00:11:34.300 | Today, we're going to talk about the science of sex,

00:11:37.420 | in particular sexual differentiation.

00:11:40.520 | Now that's a complicated topic

00:11:42.600 | because sex is both a adjective, a noun and a verb,

00:11:47.600 | depending on the context.

00:11:49.940 | Today, we're going to talk about the hormonal effects

00:11:53.500 | and the neural effects of particular events

00:11:57.060 | that happen during development

00:11:58.340 | and how those guide adolescent and adult behavior,

00:12:02.720 | including sexual preference.

00:12:04.700 | It's an area that's fascinating

00:12:06.580 | and for which there are actually

00:12:08.540 | very solid textbook findings.

00:12:10.900 | So textbook findings means that there are many studies

00:12:14.260 | that have been aggregated over decades

00:12:16.500 | that point to what we now know to be absolute truths

00:12:20.580 | in terms of how hormones affect brain development,

00:12:23.700 | how the brain impacts hormonal development

00:12:26.140 | and how those interact to control behavior, for instance.

00:12:29.760 | We are also going to talk about reproduction, the verb sex.

00:12:34.500 | And of course, sex, the verb can also be carried out

00:12:38.020 | independent of reproduction.

00:12:39.580 | It's not always in particular in humans

00:12:42.380 | just to produce offspring.

00:12:44.180 | So that's going to be covered in the next episode,

00:12:46.020 | but you absolutely need to understand the information

00:12:48.980 | in this episode in order to make sense of the information

00:12:51.980 | in the next episode.

00:12:53.420 | So today we're going to explore hormones,

00:12:56.620 | what they are, how they work,

00:12:58.040 | what leads to masculinization or feminization

00:13:01.440 | of the brain and body.

00:13:03.160 | I'll just throw out one really interesting fact

00:13:05.140 | that perhaps most of you didn't realize

00:13:07.160 | that hormones have direct effects on the body.

00:13:10.940 | Most people know that because there are hormone differences

00:13:14.420 | and sex differences in bodies in terms of genitalia

00:13:18.100 | and body hair, distribution of body hair, et cetera.

00:13:21.280 | But there are also effects of hormones on the brain directly.

00:13:25.160 | And believe it or not, there are also effects

00:13:27.060 | on the spinal cord, on the neurons and structures

00:13:30.220 | within the spinal cord that impact in a very direct way

00:13:33.920 | what sorts of behaviors are possible.

00:13:36.620 | So it's a fascinating area.

00:13:39.140 | You might notice I'm going to go a little bit more slowly

00:13:41.900 | through this topic than I normally do.

00:13:43.720 | I want to be extremely careful with my language.

00:13:46.700 | Some of these topics, some of you may be thinking

00:13:49.880 | are extremely sensitive, right?

00:13:51.940 | And of course, any discussion about sex and reproduction

00:13:54.960 | is a sensitive one,

00:13:56.180 | but today we're just talking about the biology.

00:13:58.340 | We're not getting into the cultural constraints

00:14:00.240 | or the cultural dialogue.

00:14:02.060 | What we're trying to do today is really get to the biology,

00:14:06.220 | the physiology, the endocrinology, and the behavior.

00:14:10.020 | So let's start by talking about what hormones are,

00:14:14.180 | just to remind you, and what they do.

00:14:17.060 | Hormones by definition are a substance,

00:14:20.000 | a chemical that's released in one area of the body,

00:14:22.800 | typically from something we call a gland,

00:14:25.000 | although they can also be released from neurons,

00:14:28.440 | but they're released often from glands

00:14:30.840 | that travel and have effects both on that gland,

00:14:35.160 | but also on other organs and tissues in the body.

00:14:38.480 | And that differentiates hormones

00:14:40.140 | from things like neurotransmitters,

00:14:41.880 | which tend to act more locally.

00:14:44.160 | So that's important.

00:14:45.360 | A hormone is a substance secreted at one location,

00:14:47.420 | the body travels and has impact

00:14:49.160 | on things elsewhere in the body.

00:14:51.640 | Examples of tissues that produce hormones

00:14:54.720 | would be the thyroid, the testes, the ovaries, et cetera.

00:14:59.140 | And then of course, there are areas of the brain

00:15:00.780 | like the hypothalamus and the pituitary,

00:15:03.900 | which are closely related to one another

00:15:06.620 | and release hormones that cause the release

00:15:08.680 | of yet other hormones out in the body.

00:15:10.340 | So we're going to cover all this.

00:15:11.320 | If you don't know anything about endocrinology,

00:15:13.360 | you're still going to be able to understand

00:15:15.280 | today's discussion.

00:15:16.660 | And we're going to start with a discussion

00:15:19.280 | about what hormones actually do to create this thing

00:15:23.260 | that we call masculinization or feminization.

00:15:26.240 | So let's start with development.

00:15:29.200 | Sperm meets egg.

00:15:30.480 | Everything that happens before that

00:15:31.720 | is a topic of the next episode.

00:15:34.080 | But sperm meets egg.

00:15:35.560 | This is mammalian reproduction.

00:15:37.400 | And that egg starts to duplicate.

00:15:39.040 | It starts to make more of itself.

00:15:40.740 | It makes more cells.

00:15:41.840 | And eventually some of those cells become skin.

00:15:43.660 | Some of those cells become brain.

00:15:45.200 | Some of those cells become muscle.

00:15:46.620 | Some of those cells become fingers.

00:15:48.560 | All the stuff that makes up the brain and body plan.

00:15:51.680 | In addition, there are hormones that come both

00:15:57.000 | from the mother and from the developing baby,

00:16:01.080 | the developing fetus that impact whether or not the brain

00:16:04.480 | will be what they call organized masculine

00:16:07.400 | or organized feminine.

00:16:08.780 | And as I say this, I want you to try and discard

00:16:12.160 | with the cultural connotations

00:16:13.920 | or your psychological connotations

00:16:15.700 | of what masculinization and feminization are

00:16:18.760 | because we're only centering on the biology.

00:16:22.120 | So typically people have either two X chromosomes

00:16:27.120 | and the traditional language around that

00:16:30.200 | is that person is female, right?

00:16:33.000 | Or an X chromosome and a Y chromosome.

00:16:35.620 | And that person will become male.

00:16:37.880 | Now it's not always the case.

00:16:39.600 | There are cases where it's XXY,

00:16:42.320 | where there are two X chromosomes plus a Y chromosome.

00:16:45.040 | There are also cases where it's XYY,

00:16:47.580 | where there are two Y chromosomes.

00:16:49.220 | And these have important biological

00:16:51.520 | and psychological impacts.

00:16:53.280 | So the first thing we need to establish

00:16:56.080 | is that there is something called chromosomal sex.

00:16:59.140 | Whether or not there are two X chromosomes

00:17:00.800 | or an X and Y chromosome is what we call chromosomal sex.

00:17:05.840 | But the next stage of separating out the sexes

00:17:10.120 | is what we call gonadal sex.

00:17:12.240 | Typically, not always, but typically,

00:17:15.340 | if somebody has testes for their gonads,

00:17:18.640 | we think of them as male.

00:17:21.040 | And if somebody has ovaries, we think of them as female.

00:17:24.940 | Although that's not always the case either.

00:17:27.300 | But let's just explore the transition

00:17:29.960 | from chromosomal sex to gonadal sex

00:17:32.000 | because it's a fascinating one

00:17:33.800 | that we all went through in some form or another.

00:17:37.120 | So this XY that we typically think of

00:17:40.800 | as promoting masculinization of the fetus.

00:17:44.000 | We say that because on the Y chromosome, there are genes.

00:17:50.120 | And those genes have particular functions

00:17:52.860 | that suppress female reproductive organs.

00:17:57.240 | So on the Y chromosome, there's a gene

00:18:00.400 | which encodes for something called

00:18:02.380 | a Moolerian-inhibiting hormone.

00:18:04.660 | So there's actually a hormone

00:18:06.940 | that's programmed by the Y chromosome

00:18:09.180 | that inhibits the formation of Moolerian ducts,

00:18:12.060 | which are an important part

00:18:13.200 | of the female reproductive apparatus.

00:18:15.460 | That's critical because already we're seeing the transition

00:18:19.680 | between chromosome Y chromosome and gonad.

00:18:23.140 | And other genes on the Y chromosome

00:18:26.180 | promote the formation of testes.

00:18:28.400 | So there are genes like the SRY gene

00:18:30.440 | and other genes that promote the formation of testes

00:18:33.000 | while they also inhibit the formation of the Moolerian ducts.

00:18:37.360 | So the transition from chromosomal sex to gonadal sex

00:18:40.960 | is a very important distinction.

00:18:43.320 | It's kind of a fork in the road

00:18:44.920 | that happens very early in development

00:18:46.800 | while fetuses are still in the embryo.

00:18:49.460 | Now, what's interesting as well

00:18:52.560 | is that just because there's a Y chromosome

00:18:55.440 | that can suppress Moolerian duct formation

00:18:57.500 | and there are other genes on the Y chromosome

00:18:59.500 | that promote teste development,

00:19:02.080 | the placenta itself is an endocrine organ.

00:19:05.360 | I think most people don't know this,

00:19:06.480 | but the placenta is an endocrine organ.

00:19:08.760 | As well, the mother, which of course is carrying the fetus,

00:19:12.200 | has an adrenal gland, which can produce testosterone.

00:19:16.640 | There are instances, for example,

00:19:19.160 | where a mother has either a tumor

00:19:21.400 | or for some other reason is secreting large levels

00:19:24.320 | of testosterone while carrying a fetus that is XX,

00:19:28.600 | and that leads to what we would call masculinization

00:19:31.640 | of certain aspects of the fetus.

00:19:33.040 | Typically, that would be enlarged clitoris.

00:19:35.780 | There are also some examples of other phenotypes on the body

00:19:39.100 | that are created even though

00:19:40.560 | it's a purely XX chromosomal baby.

00:19:44.080 | So we have to distinguish between chromosomal sex,

00:19:47.180 | gonadal sex, and then there's what we call hormonal sex,

00:19:51.520 | which is the effects of the steroid hormones,

00:19:55.160 | estrogen and testosterone and their derivatives,

00:19:57.940 | on what we call morphological sex

00:20:00.800 | or the shape of the baby and the human and the genitalia

00:20:03.620 | and the jaw and all these other things.

00:20:05.480 | And so it actually is quite complicated.

00:20:07.780 | So it's a long distance from chromosomes to gender identity,

00:20:11.980 | and gender identity has a lot of social influences and roles.

00:20:15.540 | This is an area that right now is very dynamic

00:20:17.760 | and in the discussion out there, as you know,

00:20:19.960 | but just getting from chromosomal sex

00:20:21.980 | to what we would call gonadal sex and hormonal sex

00:20:25.940 | and morphological sex involves a number of steps.

00:20:28.760 | So today we're going to talk about those steps

00:20:31.020 | and there's some fascinating things

00:20:32.800 | that do indeed relate to tools,

00:20:35.480 | do indeed relate to some important behavioral choices,

00:20:39.400 | important choices about things to avoid while pregnant.

00:20:43.160 | And for those of you that are not pregnant,

00:20:44.940 | things to avoid if you're thinking

00:20:46.500 | about eventually having children,

00:20:48.540 | and that is not to drive development

00:20:50.480 | in one direction or another,

00:20:51.760 | but there are examples where there are some deleterious

00:20:54.580 | things in our environment that can actually negatively

00:20:57.300 | impact what we call sexual development overall,

00:21:00.320 | regardless of chromosomal background.

00:21:02.440 | So let's get started with that.

00:21:04.100 | Let's talk a little bit more about what hormones do.

00:21:07.200 | Hormones generally have two categories of effects.

00:21:09.820 | They can either be very fast or they can be very slow.

00:21:12.500 | There are hormones like cortisol and adrenaline,

00:21:15.240 | which act very fast.

00:21:16.820 | Adrenaline can increase your heart rate very fast

00:21:20.280 | when it's secreted into the body.

00:21:21.500 | Cortisol can be a little bit slower,

00:21:23.180 | but it also can have some very fast effects.

00:21:25.140 | And then there are hormones like testosterone and estrogen,

00:21:29.100 | which we refer to as the sex steroid hormones.

00:21:32.060 | The sex steroid hormones can have quick effects

00:21:36.580 | through signaling, meaning they can attach to cells

00:21:38.980 | and make those cells do different things.

00:21:40.980 | They can have actually quite quick effects on the brain.

00:21:43.420 | A lot of people don't know this,

00:21:44.820 | but there are some very fast effects

00:21:46.580 | of estrogen and testosterone, as well as long-term effects.

00:21:50.360 | These molecules, for those of you that are interested,

00:21:53.200 | are what are called lipophilic,

00:21:54.520 | which just means that they like fatty stuff.

00:21:56.240 | They can actually pass through fatty membranes.

00:21:58.160 | And because the outside of cells,

00:22:00.480 | as well as what's called the nuclear envelope,

00:22:02.560 | where all the DNA contents and stuff are stuffed inside,

00:22:05.720 | are made of lipid, of fat,

00:22:09.240 | these steroid hormones can actually travel into cells

00:22:12.120 | and then get into the DNA,

00:22:14.720 | basically interact with the DNA of cells

00:22:16.880 | in order to control gene expression.

00:22:18.560 | So they can change the sorts of things

00:22:21.160 | that cells will become,

00:22:22.480 | and they can change the way that cells function

00:22:24.400 | in a long-term way.

00:22:25.600 | And that's actually how the presence of these genes,

00:22:28.860 | like SRY and Mullerian inhibiting hormone,

00:22:31.640 | lead to reductions or elimination, I should say,

00:22:35.800 | of things like the Mullerian ducts

00:22:37.420 | and promote instead what's called in males,

00:22:39.400 | the Wolfian ducts,

00:22:41.180 | or promote the development of testes rather than ovaries.

00:22:44.520 | So all you need to know is that hormones have short-term

00:22:47.600 | and long-term effects,

00:22:48.600 | and the long-term effects are actually related

00:22:51.000 | to their effects on genes

00:22:52.840 | and how those genes are expressed or repressed,

00:22:55.520 | not in order to prevent them

00:22:57.380 | from having particular proteins made.

00:23:00.280 | So these hormones, these steroid hormones,

00:23:03.040 | are exceedingly powerful.

00:23:05.280 | And if we're going to have a discussion

00:23:07.160 | about masculinization or feminization, et cetera,

00:23:09.960 | you also need to think about the counterpart.

00:23:11.520 | It's not just about masculinizing the body

00:23:13.480 | or feminizing the body and brain.

00:23:15.020 | It's also about demasculinizing the brain in many cases

00:23:19.260 | as a normal biological function,

00:23:21.160 | typically of XX females,

00:23:25.020 | and defeminization, the suppression of certain pathways

00:23:27.940 | that are related to feminization of the body and brain.

00:23:31.340 | But there are some really fascinating twists in this story.

00:23:35.500 | So I've just thrown a lot of biology at you,

00:23:37.980 | but this is where it all starts to get incredibly surprising.

00:23:43.620 | You would think that it's straightforward, right?

00:23:47.160 | You have a Y chromosome.

00:23:49.280 | You suppress the female reproductive pathway

00:23:53.400 | like the malaria ducts.

00:23:55.660 | You promote the development of testes,

00:23:58.400 | and then testes make testosterone,

00:24:00.440 | and then it organizes the brain male,

00:24:02.700 | and it wants to do male-like things.

00:24:04.200 | And then in females, you get estrogen,

00:24:06.720 | and it wants to do female-like things,

00:24:08.800 | and air quotes here for all of this.

00:24:11.120 | And it turns out that isn't how it works at all.

00:24:15.460 | Here's where it's interesting.

00:24:16.460 | We have to understand that there are effects

00:24:19.020 | of these hormones, testosterone and estrogen,

00:24:22.640 | on what are called primary sexual characteristics,

00:24:25.700 | which are the ones that you're born with,

00:24:28.500 | secondary sexual characteristics,

00:24:30.500 | which are the ones that show up in puberty,

00:24:32.220 | and these are happening in the brain and body

00:24:34.700 | and spinal cord.

00:24:35.860 | And so I'm going to disentangle all this for you

00:24:37.500 | by giving you some examples.

00:24:39.740 | First, let's talk about the development

00:24:41.260 | of primary sexual characteristics,

00:24:43.120 | the ones that show up at birth.

00:24:46.320 | And one of the more dramatic examples of this

00:24:49.680 | comes from the role of testosterone

00:24:53.160 | in creating the external genitalia.

00:24:56.280 | Now, you might think it's just straightforward.

00:24:58.380 | If there's testes, 'cause there was a Y chromosome,

00:25:01.240 | you've got a gene that codes for the development of testes,

00:25:05.360 | you get testosterone, and the penis grows,

00:25:08.100 | and the baby is born with a penis.

00:25:09.600 | One of the first things that happens

00:25:10.540 | when the baby comes out is they look at the genitalia

00:25:12.960 | and they try and make an assessment

00:25:14.340 | on whether or not it's a "boy" or it's a "girl," right?

00:25:18.060 | That's been done for a very, very long time

00:25:20.520 | throughout human history.

00:25:22.100 | It turns out that it's not testosterone

00:25:27.260 | that's responsible for the development of the penis

00:25:30.620 | in a baby that has an X chromosome and a Y chromosome.

00:25:34.720 | It's a different androgen.

00:25:37.600 | Androgen is just a category of hormones

00:25:40.720 | that includes testosterone,

00:25:42.960 | but testosterone is converted in the fetus

00:25:47.360 | to something called dihydrotestosterone,

00:25:50.000 | and that's accomplished through an enzyme

00:25:52.240 | called 5-alpha reductase.

00:25:53.920 | Now, dihydrotestosterone has important effects

00:25:56.880 | later in life too.

00:25:58.220 | We will talk about those.

00:25:59.160 | In fact, you just want to know dihydrotestosterone

00:26:02.440 | is what we would call the dominant androgen in males.

00:26:05.600 | It's responsible for aggression.

00:26:07.120 | It's responsible for a lot of muscular strength.

00:26:10.980 | It's involved in beard growth and male pattern baldness.

00:26:14.440 | We're going to talk about all of that.

00:26:15.840 | But dihydrotestosterone has powerful effects

00:26:19.360 | in determining the genitalia

00:26:21.340 | while the baby is still in the embryo.

00:26:23.480 | So there's testosterone that's made,

00:26:26.640 | and that testosterone gets converted

00:26:30.080 | by this enzyme, 5-alpha reductase,

00:26:32.620 | in a little structure called the tubercle.

00:26:34.920 | That tubercle will eventually become the penis.

00:26:37.920 | So you say, okay, straightforward.

00:26:39.660 | This testosterone's converted to dihydrotestosterone,

00:26:42.700 | and then if there's dihydrotestosterone,

00:26:44.960 | it controls penis growth.

00:26:46.600 | And indeed, that's the case.

00:26:48.600 | So that's a primary sexual characteristic.

00:26:51.120 | That baby will then grow up, and later, during puberty,

00:26:56.120 | there will be the release of a molecule,

00:26:58.040 | I talked about this last episode,

00:26:59.440 | called kisspeptin, K-I-S-S-P-E-P-T-I-N, kisspeptin,

00:27:04.160 | which will cause the release of some other hormones,

00:27:06.120 | canadotropin-releasing hormone, luteinizing hormone,

00:27:08.040 | will stimulate the testes to make testosterone.

00:27:10.060 | So in puberty, testosterone leads to further growth

00:27:13.720 | and development of the penis,

00:27:15.180 | as well as the accumulation or growth of pubic hair,

00:27:19.940 | deepening of the voice,

00:27:20.920 | all the secondary sexual characteristics, okay?

00:27:24.280 | So dihydrotestosterone creates what we would call

00:27:28.400 | the typical masculine phenotype

00:27:30.780 | for primary sexual characteristics.

00:27:33.960 | And produces, testosterone, excuse me,

00:27:37.240 | produces secondary sexual characteristics during puberty.

00:27:40.400 | There's a very interesting phenomenon

00:27:43.660 | that was published in the journal "Science" in the 1970s,

00:27:46.800 | for which now there's a wealth of scientific data.

00:27:50.160 | And this relates to a genetic mutation

00:27:53.040 | where 5-alpha reductase,

00:27:55.300 | the enzyme that converts testosterone

00:27:57.740 | to dihydrotestosterone, doesn't exist.

00:28:00.580 | It's mutated in a way in a genome that it doesn't exist.

00:28:04.140 | And this actually was first identified

00:28:06.380 | in the Dominican Republic.

00:28:07.900 | It has shown up elsewhere.

00:28:09.980 | It's quite rare, but where it shows up, it's robust.

00:28:13.440 | What happens is, baby is born.

00:28:17.300 | Typically, when a baby is born,

00:28:19.060 | they don't measure chromosomes.

00:28:20.620 | They don't look at chromosomal sex, XX or XY.

00:28:22.960 | That's not typically done nowadays.

00:28:25.240 | Baby is born.

00:28:26.460 | If you were to look at that baby, it would look female.

00:28:30.080 | There would be very little or no external penis.

00:28:34.300 | And so people would say, "It's a girl."

00:28:35.760 | And they might have the celebration, "It's a girl."

00:28:38.160 | And I guess now they call them gender reveal parties

00:28:40.760 | or something like that.

00:28:41.600 | I don't know about this.

00:28:42.420 | But anyway, the baby would reveal its external genitalia

00:28:47.420 | simply by being there and being naked when it's born.

00:28:52.220 | Has nothing to do with gender.

00:28:53.600 | It has to do with genitalia and sex.

00:28:56.800 | That baby would be born.

00:28:58.580 | And what was observed is that from time to time,

00:29:02.900 | that baby, after being raised as a girl,

00:29:06.020 | perfectly happy as a girl,

00:29:08.100 | would, around the age of 11 or 12 or 13,

00:29:12.780 | would suddenly start to sprout a penis.

00:29:15.540 | There's actually a name for this.

00:29:16.700 | It's called huavedosis,

00:29:18.260 | which the translation is more or less penis at 12.

00:29:23.040 | And as strange as this might sound,

00:29:25.640 | it makes sense if you understand the underlying mutation.

00:29:28.540 | What happens in these children, these huavedosis,

00:29:32.660 | is that the child is born.

00:29:35.480 | It has testes which are not descended, so up in the body.

00:29:40.100 | They're not making a lot of testosterone early on.

00:29:44.100 | They weren't able to convert testosterone

00:29:46.500 | to dihydrotestosterone

00:29:47.700 | because they lack this enzyme, 5-alpha reductase.

00:29:50.400 | As a consequence, the primary sexual characteristic

00:29:54.440 | of external male genitalia, penis, doesn't develop.

00:29:59.440 | And then what happens is the baby grows up as a young child,

00:30:03.260 | essentially is treated as a girl.

00:30:05.760 | Generally, they report being pretty comfortable as girls,

00:30:08.860 | although not always.

00:30:10.320 | And then testosterone starts getting secreted

00:30:13.700 | from the testes 'cause kisspeptin in the brain signals

00:30:17.000 | through gonadotropin and luteinizing hormone

00:30:18.760 | travels down to the testes.

00:30:20.000 | The testes start churning out testosterone

00:30:22.120 | and there's a secondary growth of the penis

00:30:24.540 | and all of a sudden there's a penis.

00:30:25.800 | And this leads to some very complicated situations

00:30:28.640 | in families and culturally.

00:30:30.660 | And actually the outcomes in terms of whether or not

00:30:33.960 | these children decide to self-identify as males or females

00:30:37.680 | and how people treat them actually varies quite a lot.

00:30:40.540 | There's actually been a kind of an adopting

00:30:43.220 | of a third category of sex and gender in these huavedosis

00:30:48.080 | in order to just offer them the opportunity

00:30:51.040 | to explore not just what would be a typical kind of girl

00:30:55.880 | or woman or boy or man phenotype, but something in between,

00:30:59.480 | something that some people call intersex,

00:31:01.140 | although intersex and pseudo hermaphroditism

00:31:03.680 | is actually a separate thing altogether.

00:31:05.820 | So it's fascinating.

00:31:06.660 | And the point here is that dihydrotestosterone,

00:31:11.660 | not testosterone is responsible for this primary growth

00:31:15.520 | of the penis and that testosterone later is involved

00:31:19.100 | in the secondary sexual characteristics,

00:31:21.420 | deepening in the voice, et cetera.

00:31:23.920 | Now this is where the information gets even more interesting

00:31:27.160 | and applies to essentially everybody.

00:31:30.920 | You might think that testosterone,

00:31:34.040 | because it masculinizes the body

00:31:37.400 | in the secondary sexual characteristic way

00:31:40.240 | and because dihydrotestosterone, another androgen,

00:31:45.300 | masculinizes the primary sexual characteristics,

00:31:48.800 | the growth of the penis early on,

00:31:50.400 | that testosterone must masculinize the brain.

00:31:53.880 | And there are in fact aspects of masculinization

00:31:58.380 | of the brain and body that are independent of genitalia.

00:32:02.700 | Now it might be obvious to some of you,

00:32:03.940 | but some people probably don't realize that.

00:32:05.880 | Yes, indeed, the brain has receptors for testosterone.

00:32:10.880 | It also has receptors for estrogen.

00:32:14.140 | But the fascinating thing is that

00:32:18.680 | if you look at the brains of people that have Y chromosomes

00:32:22.860 | and that have testes and that make testosterone,

00:32:25.180 | and you look at the brains of people

00:32:27.080 | that don't have Y chromosomes or testes

00:32:29.760 | and therefore make far less testosterone in general,

00:32:33.360 | what you realize is that the cells in the brain

00:32:39.100 | that differ between what I'll call males and females,

00:32:42.020 | but between XY and XX,

00:32:44.380 | have receptors for testosterone,

00:32:48.900 | but the masculinization of the brain

00:32:51.440 | is not accomplished by testosterone.

00:32:54.720 | I want to repeat this.

00:32:55.560 | The masculinization of the brain

00:32:57.360 | is not accomplished by testosterone.

00:32:59.780 | It is accomplished by estrogen.

00:33:02.860 | Testosterone can be converted into estrogen

00:33:06.940 | by an enzyme called aromatase.

00:33:09.680 | This is vitally important to understand.

00:33:11.440 | Testosterone can be converted into estrogen

00:33:13.540 | by something called aromatase.

00:33:15.520 | I'll give an example of where this happens later in life

00:33:19.040 | to just illustrate the principle

00:33:20.540 | and really embed it in your mind.

00:33:22.240 | During puberty in boys, XY chromosome individuals,

00:33:28.620 | it's not uncommon for there to be transient

00:33:31.400 | or sometimes long lasting breast bud development.

00:33:34.560 | Testosterone goes up during puberty

00:33:36.840 | for the reasons we talked about before.

00:33:39.240 | And some of that testosterone gets converted into estrogen

00:33:43.060 | by an enzyme called aromatase.

00:33:46.000 | Aromatase is made by several sources in the body.

00:33:49.280 | One of the main sources is body fat.

00:33:51.880 | So it can make a lot of aromatase.

00:33:53.640 | Sometimes you'll even see a fairly dramatic

00:33:56.420 | breast development in males during puberty.

00:33:58.520 | Sometimes it's transient, sometimes it's not.

00:34:00.600 | The other place where you see this

00:34:02.080 | is in athletes and bodybuilders

00:34:04.840 | that take a lot of anabolic steroids

00:34:06.920 | that take high levels of androgens.

00:34:09.240 | So they'll be taking testosterone

00:34:11.040 | at super physiological doses.

00:34:13.660 | Sometimes not always,

00:34:15.020 | they will convert some of that testosterone into estrogen

00:34:17.820 | and they'll get what's called gynecomastia,

00:34:20.100 | which is the development of male breast tissue.

00:34:23.100 | Sometimes they'll get it cut out surgically.

00:34:25.460 | Other times they'll start trying to take estrogen blockers

00:34:27.800 | in order to try and suppress it,

00:34:29.420 | or they'll try and block prolactin.

00:34:31.140 | It's a topic that we're going to get into in more detail.

00:34:33.580 | But what's important here is to understand

00:34:35.480 | that testosterone can be converted

00:34:36.820 | into the estrogen by aromatase.

00:34:39.080 | Aromatase is not just made in body fat.

00:34:41.560 | There are neurons in the brain that make aromatase

00:34:44.880 | and convert testosterone into estrogen.

00:34:47.280 | And it is testosterone converted into estrogen.

00:34:52.280 | In other words, it's estrogen that masculinizes

00:34:55.160 | the XY individual that masculinizes the brain.

00:35:00.160 | And this has profound effects on all sorts of things,

00:35:03.560 | on behavior, on outlook in the world, et cetera.

00:35:07.800 | But I think most people don't realize

00:35:09.180 | that it's estrogen that comes from testosterone

00:35:12.100 | that masculinizes the male brain, the XY brain,

00:35:15.400 | not testosterone nor dihydrotestosterone.

00:35:19.260 | So I just want to mention some tools.

00:35:21.340 | You might be asking yourself,

00:35:22.640 | how could tools possibly come up

00:35:24.520 | at this stage of the conversation

00:35:26.000 | where we're talking about sexual development

00:35:28.240 | and we're talking about the differentiation

00:35:30.440 | of tissues in the body?

00:35:32.560 | Well, this is true both for children and parents and adults.

00:35:35.880 | I want to emphasize that there are things

00:35:39.800 | that are environmental and there are things

00:35:42.820 | that people use that in their homes sometimes

00:35:46.040 | that actually can impact hormone levels

00:35:49.060 | and can impact sexual development in fairly profound ways.

00:35:52.800 | And I want to be very clear.

00:35:54.640 | This is not me pulling from some rare journal

00:35:58.520 | I've never heard of it.

00:35:59.640 | This is pulling from textbooks.

00:36:01.880 | In particular today, I'm guiding a lot of the conversation

00:36:04.380 | on work on behavioral endocrinology.

00:36:08.540 | This is a book by Randy Nelson and Lance Crigfield,

00:36:12.220 | true experts in the field.

00:36:14.060 | I'm going to talk about some of the work from Tyrone Hayes

00:36:16.500 | from UC Berkeley about environmental toxins

00:36:20.000 | and their impacts on some of these things

00:36:21.760 | like testosterone and estrogen.

00:36:23.820 | I'm going to touch into them.

00:36:25.320 | I'm going to give some anecdotal evidence

00:36:27.320 | that's grounded in studies,

00:36:28.720 | which we will provide in the caption

00:36:30.580 | or that I'll reference here.

00:36:32.320 | One of those that's actually really interesting

00:36:34.760 | but helps illustrate the principle

00:36:36.740 | that we've been talking about is a few years ago,

00:36:39.120 | there was a lot of excitement about evening primrose oil.

00:36:41.960 | Evening primrose oil is in a lot of products

00:36:45.460 | that typically are associated with skin beauty

00:36:47.740 | and skin health.

00:36:48.720 | And so I'm generalizing here,

00:36:51.040 | but typically it was mothers or sisters that were using it.

00:36:55.360 | And there were actually examples starting to crop up

00:36:58.160 | of young boys getting accelerated breast bud development

00:37:02.460 | from skin contact with women

00:37:06.400 | who were using evening primrose oil.

00:37:08.320 | So evening primrose oil is chemically a lot like estrogen

00:37:12.600 | and it has a lot of estrogenic compounds.

00:37:14.840 | There are a number of things out there like this.

00:37:17.580 | So believe it or not, things like pine pollen

00:37:19.840 | look very much like testosterone.

00:37:21.660 | Structurally, they are more or less are testosterone.

00:37:24.760 | Their bioavailability in humans isn't as clear.

00:37:27.540 | Evening primrose oil has a lot of estrogenic elements to it,

00:37:31.900 | just structurally how it's built.

00:37:33.560 | And so there were cases where boys were understandably

00:37:37.280 | being hugged by their mom or maybe even like showering

00:37:39.700 | and using the evening primrose oil solution.

00:37:43.760 | Those things will actually change levels of estrogens

00:37:47.400 | in boys and girls.

00:37:48.880 | And so this wasn't just an issue for young boys.

00:37:50.880 | This was also an issue for young girls.

00:37:52.320 | So it's not that evening primrose oil is bad.

00:37:55.700 | It's just that many of you have probably heard

00:37:58.060 | about the dangers of soy and isoflavones

00:38:00.560 | and things like that.

00:38:01.740 | The impact of soy on estrogen levels

00:38:04.040 | is there are some decent evidence to support that.

00:38:07.400 | However, there's a lot of other factors

00:38:09.600 | that are more severe.

00:38:10.480 | And one of those is this evening primrose oil.

00:38:13.120 | So regardless of age, let's just put it this way

00:38:16.400 | because people might be wanting to drive their hormones

00:38:18.960 | more estrogenic or more androgenic.

00:38:21.600 | How could I know what your preference is?

00:38:24.360 | I don't know.

00:38:25.240 | But in any case, things like evening primrose oil

00:38:29.340 | can actually promote estrogenic pathways in the body.

00:38:32.480 | And some of it can go transdermal.

00:38:34.180 | Likewise, because testosterone replacement therapy

00:38:37.660 | is fairly widespread nowadays

00:38:39.500 | and some people accomplish that through cream,

00:38:41.480 | it's pretty well understood that if someone's taking that,

00:38:44.760 | that they want to avoid contact with anyone,

00:38:48.040 | skin contact with anyone that is trying to promote

00:38:52.600 | more estrogenic activity in their body

00:38:55.360 | and especially in children.

00:38:57.640 | So that's one.

00:38:58.520 | The other is this issue of environmental factors.

00:39:02.240 | Now this, again, I'm just going to highlight,

00:39:05.040 | when one starts talking about environmental factors

00:39:07.720 | and how they're poisoning us or disrupting growth

00:39:10.240 | or fertility rates,

00:39:11.600 | it can start to sound a little bit crazy

00:39:13.880 | except when you start to actually look

00:39:15.560 | at some of the real data,

00:39:17.080 | data from quality research labs funded by federal government

00:39:21.080 | funded not from companies or other sources

00:39:23.780 | that are really aimed at understanding

00:39:25.120 | what the underlying biology is.

00:39:26.760 | And for that, we should all be grateful to Tyrone Hayes

00:39:31.760 | at UC Berkeley.

00:39:33.400 | I remember way back when I was a graduate student

00:39:35.800 | in the late '90s, goodness, at UC Berkeley.

00:39:39.780 | And I remember him, he was studying frogs.

00:39:41.980 | He was talking about developmental defects

00:39:45.040 | in these frogs that live in different waters around,

00:39:47.920 | it was California, but also elsewhere.

00:39:50.600 | And he identified a substance which is present

00:39:53.260 | in a lot of waterways throughout this country

00:39:55.540 | and other countries, so US and beyond,

00:39:58.360 | certainly not just restricted to California,

00:40:00.400 | which is atrazine.

00:40:01.800 | This is A-T-R-A-Z-I-N-E.

00:40:04.840 | Again, this is the stuff of textbooks

00:40:06.520 | and it causes severe testicular malformations.

00:40:10.260 | So again, atrazine exposure is serious.

00:40:13.400 | And what's interesting is if you look at the data,

00:40:17.640 | what you find is that at sites in Western and Midwestern

00:40:21.160 | sections of the United States,

00:40:22.480 | 10 to 92% of male frogs, these were frogs, mind you,

00:40:27.120 | had testicular abnormalities.

00:40:29.160 | And the most severe testicular malformations

00:40:31.440 | were in the testes rather than in the sperm.

00:40:35.040 | So it's actually the organ itself, the gonad itself.

00:40:37.940 | Now, it's very well known now

00:40:41.860 | that atrazine is in many herbicides.

00:40:44.360 | And so, whereas I would say in the '80s and '90s,

00:40:47.840 | the discussion around herbicides and their negative effects

00:40:51.320 | was considered kind of like hippie-dippie stuff

00:40:53.300 | or the stuff you hear about it,

00:40:54.800 | your local community markets

00:40:57.720 | and these kind of new-agey communities,

00:40:59.520 | now there's very solid data from federally funded labs

00:41:04.360 | at major universities that have been peer reviewed

00:41:06.840 | and published in excellent journals,

00:41:09.000 | showing that indeed many of these herbicides

00:41:11.200 | can have negative effects,

00:41:13.040 | primarily by impacting the ratios of these hormones

00:41:17.680 | in either the mothers or in the testes,

00:41:22.680 | altering the testes of the fathers,

00:41:25.600 | or direct effects on developing young animals

00:41:29.260 | and potentially humans.

00:41:30.320 | And so you ask, well, what about humans?

00:41:32.160 | Frogs are wonderful, but what about humans?

00:41:35.120 | So here are the data on what's happening.

00:41:38.780 | And this isn't all going to be scary stuff.

00:41:41.400 | We're also going to talk about tools to ameliorate

00:41:43.720 | and offset some of these effects.

00:41:45.720 | One would be be cautious with evening primrose

00:41:47.700 | as well as testosterone creams,

00:41:49.200 | depending on whether or not you want to be more androgenic

00:41:51.720 | or estrogenic, depending on your needs.

00:41:54.960 | But across human populations,

00:41:57.080 | sperm counts are indeed declining, okay?

00:41:59.720 | So in 1940, the average density of human sperm

00:42:04.600 | was 113 million per milliliter of semen.

00:42:08.720 | That's how it's measured.

00:42:09.560 | How many sperm per milliliter of semen?

00:42:11.880 | In 1990, this figure has dropped to 66.

00:42:15.080 | It went from 113 million per milliliter

00:42:18.480 | to 66 million per milliliter

00:42:20.560 | in the United States and Western Europe.

00:42:22.640 | So it's not just a US thing.

00:42:24.140 | Researchers also estimated that the volume of semen

00:42:26.920 | produced by men has dropped 20% in that time,

00:42:29.680 | reduced sperm count per ejaculation even further.

00:42:32.660 | So between 1981 and 1991,

00:42:35.920 | the ratio of normal spermatogenesis

00:42:37.720 | has decreased from 56.4% to 26.9%.

00:42:42.720 | So there's a lot that's happening

00:42:46.740 | primarily because of these herbicides

00:42:49.520 | that are in widespread use to reduce sperm counts.

00:42:52.340 | And these are going to have profound effects,

00:42:54.220 | not just on sperm counts, but on development,

00:42:57.180 | sexual development at the level of the gonads and the brain

00:43:00.160 | because you need testosterone to get you

00:43:02.400 | to dihydrotestosterone for primary sexual characteristics.

00:43:05.960 | You need estrogen that's come from testosterone

00:43:08.840 | to masculinize the brain.

00:43:10.000 | And of course,

00:43:11.440 | we're not just focusing on sperm and testosterone.

00:43:14.500 | You of course also know that many of these herbicides

00:43:18.200 | are disrupting estrogens in a similar way

00:43:21.740 | or are leading to hyperestrogenic states,

00:43:26.500 | which might explain why puberty is happening

00:43:30.120 | so much earlier in young girls these days.

00:43:33.440 | So there are a lot of things that are happening.

00:43:35.240 | Now, does this mean that you have to run around

00:43:37.480 | and neurotically avoid anything that includes things

00:43:41.440 | like atrazine and should you be avoiding

00:43:44.520 | all kinds of herbicides?

00:43:46.160 | I don't know, that's up to you,

00:43:47.820 | but it does seem that these have pretty marked effects

00:43:51.000 | in both the animal studies and in the human studies.

00:43:54.640 | You can open up a textbook like the endocrinology textbook

00:43:58.080 | and find things like vinclozolin.

00:44:00.460 | This is V-I-N-C-L-O-Z-O-L-I-N,

00:44:04.840 | which is a fungicide and it's an anti-androgen.

00:44:07.860 | You give it to animals, to rats,

00:44:09.680 | and instead of forming a penis, they don't form a penis.

00:44:12.120 | They basically, it's not that they form a clitoris,

00:44:16.200 | they just don't form a penis.

00:44:17.720 | So let's talk about female sexual development.

00:44:20.960 | And as always, what we'll do

00:44:23.120 | is we'll talk about the normal biology.

00:44:24.640 | Then we'll talk a little bit about a kind of extraordinary

00:44:28.920 | or unusual set of cases, but we'll talk about them

00:44:33.160 | because they illustrate an important principle

00:44:35.700 | about how things work under typical circumstances.

00:44:39.680 | So there is a mutation

00:44:44.180 | called androgen insensitivity syndrome.

00:44:46.920 | And understanding how androgen insensitivity syndrome works

00:44:51.000 | can help you really understand

00:44:52.680 | how hormones impact sexual development.

00:44:55.760 | So here's how it works.

00:44:57.460 | There are individuals who are XY,

00:45:00.040 | so they have a Y chromosome,

00:45:01.440 | that are born, that make testosterone,

00:45:06.280 | they have testes, and they don't have Mullerian ducts

00:45:10.180 | because on the Y chromosome

00:45:12.200 | is this Mullerian inhibiting hormone.

00:45:14.360 | However, these individuals look completely female.

00:45:18.560 | And in general, they report feeling

00:45:21.720 | like girls when they're young, women when they're older.

00:45:25.280 | But there's something unusual that's happening

00:45:27.900 | in these individuals because they have an XY chromosomal type

00:45:32.900 | and not XX, so what's happening?

00:45:35.540 | Well, what's happening is the testes are making testosterone

00:45:39.940 | but the receptor for testosterone is mutated.

00:45:43.480 | And therefore the testes never descend.

00:45:46.700 | They don't have ovaries, they have testes,

00:45:49.100 | but the testes are internal.

00:45:50.920 | And so typically these individuals find out

00:45:53.920 | that they are actually XY chromosomes

00:45:55.900 | so that their chromosomal sex is male, if you will,

00:46:00.880 | and their gonadal sex is male,

00:46:03.580 | but the gonads, the testes are inside the body,

00:46:05.960 | they don't actually develop a scrotum,

00:46:07.940 | they don't make ovaries,

00:46:09.020 | and when they don't menstruate around the time of puberty,

00:46:12.180 | that's a sign that something is different.

00:46:15.180 | And so they never menstruate around puberty,

00:46:16.880 | and if they look into this deeply enough,

00:46:19.300 | what you find is that they are actually XY,

00:46:22.360 | they make testosterone,

00:46:23.360 | but their body can't make use of the testosterone

00:46:25.420 | because they don't have the receptors.

00:46:27.880 | And the receptors are vitally important

00:46:29.920 | for most all of the secondary sexual characteristics

00:46:34.140 | that we talked about, body hair, penis growth

00:46:36.740 | during puberty, et cetera.

00:46:38.880 | They live fairly happy lives as females,

00:46:42.100 | although of course they can't conceive, right?

00:46:44.060 | They don't have a uterus, they don't have ovaries.

00:46:47.260 | They also in general don't produce sperm in quantities enough

00:46:51.500 | that they could actually reproduce with somebody else,

00:46:54.020 | although sometimes they can.

00:46:55.580 | And believe it or not, and I'm not going to name names,

00:46:58.300 | but there are actually reports of several people,

00:47:02.380 | fairly prominent people throughout history

00:47:04.540 | who have had this androgen insensitivity syndrome

00:47:07.200 | or people suspected they did.

00:47:09.860 | And the reason to not name names

00:47:11.340 | is that it gets right to the heart

00:47:13.380 | of whether or not they are male or female.

00:47:16.180 | How could you say, right?

00:47:17.560 | They have XY chromosomes,

00:47:19.360 | but go Natalie, they have testes that are inside,

00:47:22.420 | and yet if you looked at their bodies,

00:47:24.740 | if you looked at their faces,

00:47:26.680 | you would say almost with certainty

00:47:29.660 | that they appeared female.

00:47:31.900 | And that naturally occurring experiment

00:47:35.160 | points to the fact that testosterone

00:47:38.700 | that shows up in the body

00:47:40.060 | and impacts the things at the levels of the receptor

00:47:42.800 | has a profound effect on phenotype,

00:47:44.740 | on the external or body plan.

00:47:47.940 | So again, we're talking about this

00:47:49.700 | in order to illustrate the principle

00:47:51.020 | that in order to have its effects,

00:47:53.160 | a hormone doesn't just have to be present,

00:47:55.560 | that hormone actually has to be able to bind its receptor

00:47:58.820 | and take action on the target cells.

00:48:01.920 | And once again, I'll just throw out the example

00:48:04.540 | of where people are using performance enhancing drugs,

00:48:08.060 | although that's a pretty broad statement.

00:48:09.700 | Nowadays, there's a lot of excitement

00:48:11.100 | about the so-called SARMs,

00:48:13.700 | which are more on the receptor side.

00:48:16.140 | And so we'll talk about this in a future episode.

00:48:18.540 | And I just say that as a teaser

00:48:20.780 | because the SARMs and what's happening right now

00:48:23.020 | in augmenting sports performance,

00:48:25.160 | both with testosterone directly,

00:48:26.660 | but also testosterone derivatives,

00:48:28.120 | and then also altering things at the level of the receptor

00:48:31.320 | is exceedingly interesting

00:48:32.780 | and is revealing to us the many ways

00:48:36.300 | in which hormones can impact brain and body

00:48:38.660 | in ways that we didn't suspect.

00:48:41.540 | Perhaps the simplest way to understand

00:48:43.980 | how estrogen and testosterone impact masculinization

00:48:48.260 | or feminization of the brain and behavior

00:48:50.700 | is from a statement.

00:48:52.620 | It's actually the closing sentence of an abstract

00:48:55.020 | that my colleague Nirav Shah

00:48:56.460 | at Stanford School of Medicine published,

00:48:59.960 | which is that estrogen, again,

00:49:02.920 | it's estrogen that is aromatized from testosterone

00:49:06.860 | by aromatase, sets up the masculine repertoire of sexual

00:49:11.860 | and in animals and in humans, territorial behaviors.

00:49:15.580 | So it sets up the circuitry in the brain.

00:49:17.900 | Estrogen does that.

00:49:19.400 | Estrogen sets up the masculine circuitry in the brain.

00:49:23.600 | And testosterone is then what controls

00:49:27.200 | the display of those behaviors later in life.

00:49:30.880 | And I find that incredibly interesting.

00:49:33.020 | You would think it was just testosterone did one thing

00:49:35.040 | and estrogen did another,

00:49:36.440 | but it turns out that nature

00:49:38.040 | is far more interesting than that.

00:49:40.340 | Okay, so what are some things

00:49:41.720 | that impact sexual development early in life

00:49:45.520 | and later in life?

00:49:47.960 | Let's talk about cannabis.

00:49:51.320 | Let's talk about alcohol.

00:49:53.580 | And dare I say, let's talk about cell phones.

00:49:56.700 | Something that I never thought I would ever do

00:49:59.400 | either in this podcast or in the classroom,

00:50:01.260 | but these days there are really interesting data

00:50:04.660 | and I think you should be aware of them.

00:50:06.340 | First of all, cannabis, marijuana, THC.

00:50:10.420 | I realize that there are now

00:50:12.900 | a lot of different variants on this.

00:50:15.720 | There are a lot of different strains of cannabis.

00:50:18.520 | I personally am not a pot smoker.

00:50:20.960 | It's just not for me.

00:50:23.040 | I'm not talking about the moral or legal implications.

00:50:25.800 | In some states it's decriminalized,

00:50:27.520 | in other places it's really illegal,

00:50:29.160 | in other places it's basically legal.

00:50:31.280 | You have to check where you live and understand the laws.

00:50:35.900 | That's not what this is about.

00:50:37.660 | What we do know, however,

00:50:39.760 | is that with the exception of one study,

00:50:43.600 | there are many studies that point to the fact

00:50:46.760 | that THC and other things in cannabis

00:50:51.080 | promote significant increases in aromatase activity.

00:50:56.080 | Now, pot smokers aren't going to like this,

00:50:58.660 | especially male pot smokers aren't going to like this,

00:51:00.840 | but it's the reality.

00:51:02.140 | Remember, what you're hearing in the background

00:51:04.960 | is Costello snoring really loud.

00:51:06.720 | Should we put him on screen?

00:51:07.880 | He's not a cannabis smoker, but you can imagine why.

00:51:10.800 | Here, come here Costello, come here buddy, come here.

00:51:13.320 | He's asleep.

00:51:14.160 | Come here, he's right, come here.

00:51:16.080 | There you go.

00:51:16.920 | This dog definitely does not need cannabis.

00:51:23.820 | This is his state for most of the time.

00:51:25.420 | He is highly, apparently he's asleep still.

00:51:27.580 | So some of you have asked to see Costello.

00:51:30.120 | If you're just listening on audio,

00:51:31.460 | maybe he'll give us something.

00:51:33.200 | That's it.

00:51:34.040 | Oh, okay, we're going to let him get back to sleep.

00:51:36.280 | He's always here.

00:51:37.200 | Some of you have asked to see him.

00:51:39.040 | Costello is not a pot smoker either.

00:51:42.440 | He did have a dog sitter that was a pot smoker years ago.

00:51:47.440 | It was his favorite dog sitter, but I'm not a pot smoker.

00:51:52.880 | Again, no judgment, but here's the deal.

00:51:55.980 | That cannabis, and it's not clear if it's THC itself

00:51:59.960 | or other elements in the marijuana plant

00:52:02.760 | promote aromatase activity.

00:52:05.860 | Now, this has been observed anecdotally

00:52:09.480 | where pot smokers have a higher incidence

00:52:12.040 | of developing something I mentioned before, gynecomastia,

00:52:14.960 | breast bud development,

00:52:15.940 | or full-blown breast development in males.

00:52:19.520 | There may be some women who want to increase

00:52:21.480 | their estrogenic activity.

00:52:24.080 | Remember, females make testosterone.

00:52:27.040 | It comes from the adrenals, right?

00:52:28.960 | They don't have testes.

00:52:30.080 | So it comes from the adrenals

00:52:31.880 | and that testosterone can also be aromatized.

00:52:34.420 | Although typically most of the aromatase activity

00:52:37.520 | that we're referring to in these examples is in males.

00:52:39.800 | So testosterone can increase estrogenic activity.

00:52:42.960 | So you might say, oh, therefore,

00:52:44.780 | does testosterone reduce sexual behavior?

00:52:49.280 | Does it create all sorts of things

00:52:51.580 | that are related to low testosterone?

00:52:54.960 | Not necessarily, not necessarily, and here's why.

00:52:58.060 | Estrogen itself in males and females

00:53:03.600 | is important for things like libido and sexual behavior.

00:53:08.940 | I'm going to repeat that.

00:53:10.120 | If estrogen is too low in males,

00:53:12.120 | it can actually inhibit libido and sexual behavior.

00:53:15.820 | So you don't want estrogen too high or too low,

00:53:19.740 | whether or not you're male or female.

00:53:21.660 | Now, of course, in females,

00:53:23.520 | estrogen levels tend to be higher than in males.

00:53:26.920 | I'm speaking very generally here.

00:53:28.600 | You just think back to the chromosomal sex.

00:53:30.440 | That's what I'm referring to when I say male or female,

00:53:33.260 | although there's nuance there, of course.

00:53:35.540 | In females, the testosterone that comes

00:53:37.920 | from the adrenals has a powerful effect

00:53:41.280 | on libido and desire to reproduce.

00:53:44.660 | And in the next episode,

00:53:45.540 | we're going to talk about how that works

00:53:47.100 | in its relationship to birth control,

00:53:48.860 | its relationship to menopause.

00:53:50.500 | We're also going to talk about

00:53:51.340 | how that whole thing works in males as well.

00:53:54.440 | But cannabis and other aspects of the marijuana plant

00:53:59.400 | can impact levels of testosterone and estrogen

00:54:02.780 | by increasing aromatase.

00:54:04.220 | And so people should be aware of that.

00:54:06.800 | As well, there are good data.

00:54:08.540 | I was able to find several studies

00:54:09.860 | on PubMed pointing to the fact

00:54:11.340 | that smoking marijuana during pregnancy

00:54:14.540 | can shift the pattern of hormones in the developing fetus

00:54:19.540 | such that it promotes more estrogenic outcomes.

00:54:24.020 | Now, earlier I said that estrogen

00:54:25.900 | is what masculinizes the male brain.

00:54:27.900 | In utero, that's true.

00:54:29.480 | But the way that cannabis seems to work,

00:54:31.420 | at least from the studies I was able to identify,

00:54:33.940 | is that it promotes circulating estrogen in the body

00:54:38.500 | and therefore can counteract

00:54:40.480 | some of the masculinizing effects

00:54:42.480 | of things like testosterone and dihydrotestosterone

00:54:46.920 | on primary and secondary sexual characteristics.

00:54:49.660 | So I mention this because, you know,

00:54:52.560 | I think nowadays marijuana use is far more widespread

00:54:55.960 | and certainly during puberty,

00:54:57.280 | it can have profound effects on these hormonal systems.

00:55:01.000 | And so we'll do another episode

00:55:03.000 | that goes really deep into this,

00:55:04.180 | but yes, cannabis promotes estrogenic activity

00:55:07.540 | by increasing aromatase.

00:55:09.840 | Most everyone can appreciate that drinking during pregnancy

00:55:13.260 | is not good for the developing fetus.

00:55:15.100 | Fetal alcohol syndrome

00:55:16.220 | is a well-established negative outcome of pregnancy.

00:55:21.220 | And it's something that there are cognitive effects

00:55:24.080 | that are really bad.

00:55:25.740 | There's actually physical malformation, et cetera.

00:55:29.040 | So drinking during pregnancy, not good.

00:55:31.700 | Probably drinking during puberty, not good either,

00:55:33.900 | because alcohol, in particular, certain things like beer,

00:55:38.280 | but other grain alcohols can increase estrogenic activity.

00:55:43.280 | Now, this isn't just about protecting young boys

00:55:49.140 | from estrogenic activity.

00:55:51.480 | It's also protecting girls from excessive

00:55:56.000 | or even hypoestrogenic effects of alcohol in puberty.

00:56:02.000 | Now, many teenagers drink, college students drink,

00:56:05.900 | and it's important to point out

00:56:07.200 | that puberty doesn't start on one day

00:56:09.180 | and end on another day.

00:56:10.960 | Puberty has a beginning, a middle, and an end,

00:56:13.280 | but development is really our entire lifespan.

00:56:16.080 | This idea that puberty has us open and close,

00:56:20.080 | that's just false.

00:56:21.480 | Okay, so we talked about cannabis.

00:56:23.100 | We talked about alcohol.

00:56:24.860 | Let's talk about cell phones.

00:56:26.860 | First of all, I use a cell phone.

00:56:29.860 | I use it very often,

00:56:32.240 | and I do not think they are evil devices.

00:56:34.380 | I think that they require some discipline

00:56:37.920 | in order to make sure

00:56:39.400 | that it does not become a negative force in one's life.

00:56:42.220 | So I personally restrict the number of hours

00:56:44.220 | that I'm on the phone and in particular on social media.

00:56:47.020 | I only answer email at particular times of day.

00:56:49.860 | But what about the cell phone itself?

00:56:52.520 | When I was a junior professor,

00:56:56.380 | that's our pre-tenure, early professor,

00:56:58.980 | I taught this class on neural circuits

00:57:01.300 | and health and disease.

00:57:02.700 | And one of the students asked me,

00:57:04.960 | are cell phones safe for the brain?

00:57:07.140 | And all the data pointed to the fact that they were,

00:57:11.840 | or at least there were no data showing that it wasn't.

00:57:14.980 | I still don't have the answer on that, frankly.

00:57:16.780 | I don't see a lot of studies about it.

00:57:18.200 | I'm not personally aware of any evidence

00:57:20.440 | in quality peer-reviewed studies

00:57:22.220 | showing that cell phones are bad for the brain

00:57:24.520 | or that holding the phone to the ear is bad

00:57:26.500 | or that Bluetooth is bad or any of that.

00:57:28.360 | I'm just not aware of any quality studies.

00:57:30.340 | If you are aware of quality studies, peer-reviewed studies,

00:57:33.360 | please reference them, put them in the comment section,

00:57:36.580 | send them to me, however you like.

00:57:38.580 | I'd love to see them.

00:57:39.800 | I'm not aware of them.

00:57:40.640 | However, I was very interested in a particular study

00:57:45.640 | that was published back in 2013 on rats.

00:57:50.680 | It was basically took a cell phone

00:57:53.200 | and put it under a cage of rats

00:57:54.800 | and looked at basically testicular and ovarian development

00:57:58.120 | in rats and saw minor but still statistically significant

00:58:03.120 | defects in ovarian and testicular development.

00:58:06.640 | Since then, and now returning to the literature,

00:58:10.080 | I've seen a absolute explosion of studies,

00:58:16.040 | some of which are in quality journals,

00:58:18.280 | some of which are in what I would call

00:58:19.920 | not blue ribbon journals, identifying defects

00:58:24.920 | in testicular and/or ovarian development

00:58:27.920 | by mere exposure to cell phone emitted waves,

00:58:32.920 | let's just call that.

00:58:34.000 | We don't know what they are.

00:58:35.000 | And this sounds almost crazy, right?

00:58:37.520 | Anytime somebody starts talking about EMFs

00:58:39.400 | and things like that, you kind of worry,

00:58:40.520 | like, is this person okay?

00:58:41.880 | But look, the literature are pointing in a direction

00:58:45.240 | where chronic exposure of the gonads to cell phones

00:58:50.240 | could be creating serious issues in terms of the health

00:58:54.200 | at the cellular level and in terms of the output.

00:58:56.880 | So the output for the testes would be sperm production.

00:59:00.900 | Swimming speed in sperm is an important feature

00:59:03.560 | of sperm health.

00:59:04.760 | In the ovaries, it would be estrogenic output,

00:59:07.640 | how regular the cycles are.

00:59:10.980 | So in animals, the cycles are a little bit different

00:59:13.120 | than in humans.

00:59:14.020 | They don't have a menstrual cycle.

00:59:15.140 | They have an estrous cycle,

00:59:16.580 | which is generally around four days.

00:59:18.440 | I think that it's fair to say based on the literature

00:59:23.420 | that there are effects of cell phone emitted waves

00:59:27.980 | on gonadal development.

00:59:29.600 | The question is, what is the proximity of the cell phone

00:59:33.000 | to the gonads?

00:59:33.840 | Now I've taken the literature as I observe it.

00:59:38.020 | And then of course, we'll point you to in the captions.

00:59:40.940 | And I don't like to have my cell phone on and in my pocket.

00:59:45.260 | I'm well past puberty, but nonetheless,

00:59:47.180 | some of these effects were seen in adult animals.

00:59:49.500 | There are effects now that have been demonstrated in humans.

00:59:52.500 | So let's just talk about a couple of those effects.

00:59:55.260 | So a paper published in the journal,

00:59:56.720 | Clinical Biochemistry from Eskander et al,

01:00:01.460 | looked at hormone profiles in people

01:00:04.140 | based on proximity to their phone and frequency of phone use

01:00:09.140 | where they stored their phone on their body,

01:00:11.480 | as well as proximity of where they lived to,

01:00:15.660 | I guess they're called these radio frequency towers,

01:00:19.140 | so the base stations.

01:00:20.760 | And they were looking at effects of radio frequency,

01:00:23.680 | radiation, RFR on human hormone profiles.

01:00:27.760 | And they show significant decreases in cortisol.

01:00:31.600 | You might say, well, that might be good,

01:00:33.060 | but you need that morning cortisol bump

01:00:35.720 | in order to wake up morning cortisol is good.

01:00:38.400 | But also thyroid hormones were significantly reduced.

01:00:41.080 | Prolactin in young females, that's definitely concerning

01:00:45.720 | and testosterone levels in males and females.

01:00:48.300 | And so there are now quite good data showing

01:00:51.340 | that being close to the phone too much of the day

01:00:55.220 | and how close is an interesting question

01:00:58.140 | or living near one of these base stations

01:01:00.620 | apparently can have effects on hormone profiles.

01:01:04.660 | And when you see a study like this, one should always ask,

01:01:08.460 | well, what are the other things

01:01:10.040 | that could also have effects on these hormone profiles?

01:01:12.660 | 'Cause you could imagine that if you ran the same study

01:01:15.660 | of people that live close to a waterway

01:01:17.660 | or close to a highway where there's a lot of exhaust

01:01:20.680 | from buses and cars, you might see similar effects.

01:01:23.360 | So you have to take these sorts of studies

01:01:24.920 | with a grain of salt, but I think it's very interesting.

01:01:27.240 | And given that the last time I looked into these data

01:01:29.620 | where way back when I was a junior professor

01:01:33.100 | and there was like one or two studies that I could find,

01:01:35.740 | one of the studies pointed to increases in testosterone

01:01:39.180 | in rats where they had close proximity

01:01:41.420 | to these radio frequency radiation waves.

01:01:45.300 | And then in the other case that showed decreases

01:01:47.780 | in testosterone, so there really wasn't any conclusion

01:01:51.980 | to take away from that.

01:01:52.820 | Now there's pretty impressive amount of data

01:01:57.220 | pointing to the fact that there are effects

01:01:59.360 | of these things on hormones.

01:02:00.920 | I don't know what to do with that information.

01:02:02.420 | I'm not going to stop using my phone,

01:02:04.020 | but in light of the work from Tyrone Hayes and others

01:02:08.500 | looking at sperm counts and looking at the decrease

01:02:13.040 | in testosterone levels in sperm counts

01:02:15.100 | and fertility over the last 20, 30 years,

01:02:18.420 | perhaps it's not surprising.

01:02:20.860 | Although there again, cell phones and smartphones

01:02:24.580 | have really been in prominent use

01:02:26.380 | mostly within the last 10 or 11 years.

01:02:28.460 | And so it's hard to explain all of those declines

01:02:31.140 | simply on the basis of cell phone use.

01:02:33.740 | There's some interesting effects of hormones

01:02:35.540 | that actually you can observe on the outside of people

01:02:38.940 | that tell you something about

01:02:41.300 | not just their level of hormones,

01:02:43.240 | but also about their underlying genetics.

01:02:45.680 | And these relate to beard growth and baldness.

01:02:48.240 | And it's fascinating.

01:02:49.440 | The molecule, the hormone dihydrotestosterone

01:02:54.120 | made from testosterone is the hormone primarily responsible

01:02:59.120 | for facial hair, for beard growth.

01:03:01.080 | As well, it's the molecule, the hormone primarily responsible

01:03:07.080 | for lack of hair on the head for hair loss.

01:03:11.320 | So how does that work?

01:03:12.560 | Well, DHT circulates in the body

01:03:15.600 | and it binds to DHT receptors in the face

01:03:19.040 | to promote hair growth.

01:03:21.340 | But it binds to DHT receptors on the scalp

01:03:24.440 | to promote hair loss.

01:03:26.160 | Not incidentally, the drugs that are designed

01:03:31.420 | to prevent hair loss are 5-alpha reductase inhibitors.

01:03:36.420 | So remember 5-alpha reductase from the huevadosis?

01:03:40.160 | Well, the people that discovered the huevadosis

01:03:42.520 | went on to do a lot of research

01:03:44.240 | on the underlying biochemistry

01:03:46.120 | of this really interesting molecule, dihydrotestosterone.

01:03:49.540 | They identified 5-alpha reductase

01:03:51.760 | and 5-alpha reductase inhibitors

01:03:55.340 | are the basis of most of the anti-hair loss treatments

01:03:59.120 | that are out there.

01:04:00.680 | And so there are some interesting things here.

01:04:02.280 | First of all, the side effect profiles

01:04:05.040 | of those treatments for hair loss

01:04:08.100 | are quite severe in many individuals.

01:04:10.240 | Remember DHT is the primary androgen for libido,

01:04:13.800 | for strength and connective tissue repair,

01:04:17.560 | for aggression, even if that aggression

01:04:21.080 | of course is held in check,

01:04:22.600 | but just sort of ambition and aggression

01:04:24.520 | is related to dopamine,

01:04:25.600 | but within the testosterone pathway,

01:04:28.000 | less so to pure testosterone,

01:04:30.100 | although pure testosterone has its effects,

01:04:31.860 | but DHT is at least in primate species, including humans,

01:04:36.360 | is the dominant androgen

01:04:38.080 | for most of those sorts of effects.

01:04:40.640 | And if you look at somebody,

01:04:43.560 | everyone can predict whether or not they're going to go bald

01:04:47.000 | based on looking at their,

01:04:48.300 | we're always taught our mother's father.

01:04:50.280 | So if your mother's father was bald,

01:04:52.640 | there's a higher probability that you're going to go bald.

01:04:55.480 | The pattern of DHT receptors on the scalp

01:04:58.960 | will dictate whether or not

01:04:59.880 | you're going to go bald everywhere

01:05:01.560 | or just in the front or so called crown type baldness.

01:05:05.200 | And the density of the beard

01:05:06.800 | tells you about the density of DHT receptors.

01:05:08.920 | Now this varies by background, by genetic background,

01:05:13.180 | and actually around the world nowadays

01:05:15.240 | because people travel and people form couples

01:05:18.100 | and have kids with so many different people

01:05:21.000 | of different mixed cultures,

01:05:22.440 | you're seeing this starting to disappear,

01:05:23.880 | but there are areas of the world

01:05:26.080 | where all the men seem to have the same pattern of baldness,

01:05:30.040 | like a strip of baldness down the center

01:05:31.760 | with hair still on the sides and full beards,

01:05:34.080 | that's because these patterns of DHT receptors

01:05:37.180 | are genetically determined.

01:05:39.020 | Elsewhere, testosterone levels can still be very high,

01:05:42.740 | DHT levels in the blood can be very high,

01:05:45.560 | and yet people will have very light beards or no beards,

01:05:48.300 | and that's because they don't have

01:05:49.940 | a lot of DHT receptors in the face.

01:05:52.260 | And still other cultures,

01:05:53.440 | you'll see people with huge beards, tons of beard go,

01:05:56.700 | like their beards are growing all the way up to their eyes

01:05:58.520 | and they have huge heads of hair,

01:05:59.780 | and that's because they have a lot of DHT receptors

01:06:01.460 | on the face and not on the scalp.

01:06:03.860 | So there are a lot of effects of DHT

01:06:06.260 | that you can just see in male phenotypes.

01:06:09.360 | And it's interesting that these hair loss drugs

01:06:12.260 | that are, or to prevent hair loss drugs,

01:06:15.920 | are directly aimed at preventing

01:06:19.300 | the conversion of testosterone into dihydrotestosterone,

01:06:22.860 | and that's why they, to some extent, prevent hair loss,

01:06:25.960 | but also to some extent have a bunch of side effects

01:06:29.380 | that are associated with low DHT.

01:06:31.820 | Along these lines, there's a particular sports supplement

01:06:35.280 | that a lot of people use called creatine.

01:06:37.780 | Creatine now, there's a lot of research

01:06:39.840 | showing that creatine can bring more water into the muscle.

01:06:43.700 | It can support strength.

01:06:45.820 | It does a number of other things.

01:06:47.700 | Might even have some important cognitive promoting,

01:06:50.180 | cognitive enhancement effects, although mild.

01:06:53.180 | The studies there show that it can be significant.

01:06:56.740 | Some people, not all, it's more anecdotal,

01:06:59.660 | report that creatine promotes hair loss.

01:07:01.980 | It differs by individual.

01:07:04.540 | For some people, that's true.

01:07:05.900 | For others, no.

01:07:07.340 | But yes, it does appear,

01:07:08.840 | based on the studies I was able to find on PubMed,

01:07:10.920 | that creatine does promote 5-alpha reductase activity,

01:07:15.320 | and therefore the conversion of testosterone

01:07:17.440 | into dihydrotestosterone.

01:07:19.160 | And so it makes sense that it might promote

01:07:21.760 | some degree of hair loss as well as beard growth,

01:07:24.980 | as well as the other effects of DHT.

01:07:27.220 | I recall in junior high school and middle school,

01:07:31.380 | going home one summer, it was seventh grade,

01:07:33.140 | coming back in the eighth grade,

01:07:34.100 | and a kid that I knew that I was friends with

01:07:36.000 | went from being like a young kid to,

01:07:38.380 | he was like a grown man, he had a full beard.

01:07:40.400 | It was amazing.

01:07:41.240 | It was like he would completely transform.

01:07:42.780 | I mean, puberty, as I've said before,

01:07:44.420 | is without a doubt the most accelerated rate of development

01:07:49.420 | that we will go through at any point in our lives,

01:07:51.660 | even faster than infancy,

01:07:53.180 | just in terms of the huge number

01:07:54.900 | of different cognitive changes and physical changes.

01:07:58.180 | Not surprisingly, that same individual

01:08:00.640 | was mostly or bald by his early 20s.

01:08:04.800 | And that's because he must've had

01:08:06.000 | just exceedingly high levels of DHT.

01:08:08.040 | I also played soccer with this kid,

01:08:09.360 | and he was basically like dribbling past everybody.

01:08:11.200 | He was like a grown man playing soccer

01:08:12.520 | with a bunch of little kids, full beard, bald at 20.

01:08:16.040 | And so the rate of maturation,

01:08:18.440 | the rate of aging is very interesting.

01:08:20.940 | It's hard to know rate of aging.

01:08:22.400 | There's some genetic tests that now can allow you to do that,

01:08:24.600 | things like Horvath clocks and things of that sort.

01:08:27.560 | Beautiful work of David Sinclair at Harvard and others

01:08:29.880 | has pointed to this.

01:08:31.480 | The speed of entry and exit from puberty might be,

01:08:36.480 | I'm putting it out there as a hypothesis,

01:08:38.400 | might be an interesting window

01:08:40.100 | into how fast one is going through

01:08:42.640 | their aging or developmental arc

01:08:44.520 | because development, of course,

01:08:46.020 | doesn't just start at birth and end after puberty,

01:08:48.440 | it continues your entire life.

01:08:50.560 | So I think it's interesting.

01:08:52.600 | You will often see that people, boys and girls,

01:08:57.520 | I should say boys or girls, will develop

01:09:01.020 | secondary sexual characteristics at different rates.

01:09:03.600 | And sometimes it's sequential.

01:09:05.320 | You might see a kid will, she'll grow very tall

01:09:09.080 | or she'll have a big growth spurt,

01:09:10.920 | but then breast development will come a little bit later.

01:09:13.920 | And then other features will come a little bit later.

01:09:16.680 | You can also see this in boys.

01:09:17.980 | The person that I referred to earlier,

01:09:19.680 | my friend that developed full beard, went bald.

01:09:22.800 | He was also quite muscular, he was a great athlete.

01:09:25.240 | So he went through puberty exceedingly fast.

01:09:27.400 | Other people go through it more slowly.

01:09:29.120 | Some people will go through puberty at age 14,

01:09:32.700 | but they won't start to accumulate facial hair

01:09:35.000 | until much, much later.

01:09:36.940 | Or their voice will change first very early,

01:09:40.040 | and then they won't get the other secondary

01:09:43.240 | sexual characteristics until much later.

01:09:45.720 | And so we don't really know how that impacts

01:09:48.280 | or relates to overall trajectory or rate of aging,

01:09:51.440 | but it's an interesting thing to think about

01:09:53.760 | for each and every one of us.

01:09:55.280 | I'm going to offer you the opportunity

01:09:56.720 | to do an experiment today while listening to the podcast.

01:10:00.200 | But first I want to tell you a story about hyenas,

01:10:05.200 | professional baseball, and clitorises the size of penises.

01:10:10.540 | So when I was a graduate student at UC Berkeley,

01:10:15.400 | we had a professor in our department,

01:10:17.720 | phenomenal scientist named Steve Glickman.

01:10:21.480 | Steve Glickman had a colony of hyenas, spotted hyenas,

01:10:26.600 | that lived within caged enclosures, of course,

01:10:30.540 | in Tilden Park behind the UC Berkeley campus.

01:10:33.180 | The enclosures are actually still there.

01:10:34.900 | I run past there fairly often.

01:10:36.940 | The hyenas are no longer there.

01:10:39.020 | This was a federally funded field station.

01:10:41.360 | These animals were brought over from Africa

01:10:44.600 | or were bred there.

01:10:46.480 | And the reason why there were hyenas in Tilden Park,

01:10:50.040 | enclosed in Tilden Park,

01:10:53.480 | was because hyenas exhibit an incredible feature

01:10:56.880 | to their body, their hormones, and their social structure.

01:11:00.600 | Hyenas, unlike many species,

01:11:05.640 | have a situation with their genitalia

01:11:08.000 | where the male penis is actually smaller

01:11:12.440 | than the female clitoris.

01:11:14.940 | And I should say that the male penis itself,

01:11:17.200 | having seen a fair number of hyena penises,

01:11:20.840 | is not particularly small,

01:11:22.700 | which means that the hyena clitorises are extremely large.

01:11:26.720 | This was well-known for some time.

01:11:30.220 | It turns out that in these spotted hyenas,

01:11:33.760 | the females are dominant.

01:11:37.020 | So after a kill, the females will eat,

01:11:39.540 | then their young will eat,

01:11:41.240 | and then the male hyenas will eat.

01:11:43.840 | As well, when the female hyena gives birth,

01:11:49.040 | she gives birth not through the vaginal canal

01:11:53.080 | that we're accustomed to seeing,

01:11:56.440 | but through a very enlarged clitoris-like phallus,

01:12:01.440 | although it's not a phallus, it's a clitoris,

01:12:05.680 | and it literally splits open.

01:12:07.660 | So many fetuses die

01:12:09.360 | during the course of hyena development and birth.

01:12:13.220 | These animals have this,

01:12:16.380 | what could only be described as a very large

01:12:18.820 | sort of giant clitoris,

01:12:19.940 | although for a hyena, it's not giant, it's normal,

01:12:22.260 | and it splits open, and the baby actually comes through.

01:12:25.240 | The baby hyena actually comes through the tissue,

01:12:29.100 | and it's a very traumatic birth.

01:12:31.620 | A lot of tissue is torn away, et cetera.

01:12:33.860 | And as I mentioned, a lot of baby hyenas die.

01:12:36.840 | It was a mystery as to how the female hyenas have this,

01:12:41.840 | we'll call it masculinization,

01:12:44.020 | but it's really androgenization

01:12:48.940 | of the periphery of the genitalia.

01:12:52.460 | And it turns out through a lot of careful research

01:12:55.460 | done by Steve Glickman, Christine Dre, and others,

01:13:00.000 | that it's androstenedione,

01:13:03.700 | what is essentially a pro-hormone to testosterone,

01:13:06.620 | it's androstenedione at very high levels

01:13:10.520 | that's produced in female hyenas

01:13:13.580 | that creates this enlargement of their genitalia.

01:13:16.640 | So if you want to read up on androstenedione,

01:13:19.300 | androstenedione is made into testosterone

01:13:22.020 | through this enzyme, 17-beta-hydroxysteroid dehydrogenase.

01:13:27.020 | It's a complicated pathway to pronounce.

01:13:32.300 | It's a fairly straightforward pathway biochemically.

01:13:35.580 | You may recall during the '90s and 2000s,

01:13:39.220 | there were a lot of performance-enhancing drug scandals,

01:13:42.580 | in particular in Major League Baseball.

01:13:45.040 | And it was purported,

01:13:47.660 | although I don't know that it was ever verified,

01:13:49.660 | but it was purported

01:13:50.740 | that the major performance-enhancing drug of abuse

01:13:54.660 | at that time in particular players,

01:13:56.940 | whose names we won't mention,

01:13:58.020 | but you can Google it if you want to find out,

01:14:00.380 | was androstenedione.

01:14:01.740 | And I actually recall long ago

01:14:03.500 | when you could buy androstenedione in the health food stores

01:14:07.540 | and so it was sold over the counter.

01:14:10.100 | So a lot's changed since then,

01:14:13.100 | but it's interesting that these hyenas

01:14:15.360 | with these highly androgenized genitalia

01:14:18.980 | accomplish that through high levels of androstenedione

01:14:24.060 | in the females.

01:14:24.900 | Now, if that's unusual,

01:14:27.140 | what might be even more unusual

01:14:28.940 | is that a graduate student

01:14:30.300 | that I was working with at the time,

01:14:32.260 | alongside, we didn't share research,

01:14:34.220 | her name was Nicola Sipka.

01:14:36.500 | She is actually a trained animal behavioral expert.

01:14:40.340 | She had trained ferrets for that show, "The Beastmaster,"

01:14:43.780 | and she would train wolves for television shows

01:14:46.660 | and was a dog trainer.

01:14:47.780 | She had these two large dogs that unlike my dog

01:14:50.260 | would actually listen to her

01:14:51.340 | when she would give them commands.

01:14:53.700 | A remarkable scientist.

01:14:55.080 | She was studying a species of mole

01:14:58.340 | that also lived in Tilden Park.

01:14:59.860 | People are going to start to wonder about Tilden Park,

01:15:01.740 | what's in Tilden Park?

01:15:03.040 | But this particular mole that lived there

01:15:06.640 | had testes for part of the year

01:15:09.060 | and had the capacity to trans-differentiate its testes

01:15:12.500 | into ovaries in order to balance out the ratio

01:15:15.400 | of males and females in the population

01:15:17.260 | to keep reproduction at appropriate levels

01:15:20.440 | for that certain population.

01:15:22.260 | So some animals are actually able to adjust

01:15:26.220 | whether or not they have androgenized

01:15:29.160 | or estrogenized gonads

01:15:32.060 | in order to adjust the ratios of offspring

01:15:36.840 | or the males and females in there for promote offspring.

01:15:39.840 | And the last little anecdote about this,

01:15:41.960 | which is also published in the scientific literature,

01:15:45.140 | which is weird, but I do find interesting.

01:15:47.360 | Hormones are so fascinating.

01:15:48.680 | They're just incredible to me,

01:15:50.480 | is going back to the marijuana plant.

01:15:54.900 | The marijuana plant has these estrogenic properties.

01:15:57.760 | And I asked a plant biologist

01:16:01.740 | whether or not this was unusual.

01:16:03.380 | And I asked because there's all this stuff out there

01:16:07.500 | about, oh, soy does this,

01:16:09.300 | and these plants are highly estrogenic, et cetera,

01:16:12.940 | although we should probably point out

01:16:13.920 | that a lot of factory meats are also estrogenic.

01:16:15.820 | So this isn't a meat versus plants thing.

01:16:18.020 | But this plant biologist told me,

01:16:19.280 | oh yeah, there are plants that make

01:16:22.620 | what is essentially the equivalent of testosterone,

01:16:26.000 | like pine pollen, it looks a lot like testosterone.

01:16:28.500 | And there are other plants that make

01:16:30.340 | what is essentially estrogen.

01:16:33.020 | And I said, well, why would they do that?

01:16:34.700 | And plants, at least as far as I know,

01:16:37.620 | don't have a consciousness, they don't have a brain,

01:16:39.540 | they don't have neurons even.

01:16:41.180 | But his answer was fascinating.

01:16:45.220 | He said that one of the reasons

01:16:48.020 | why some plants have evolved this capacity

01:16:51.080 | to increase estrogen levels in animals that smoke,

01:16:56.080 | not smoke it, but then animals that consume them,

01:16:58.680 | I'm guessing that animals aren't smoking marijuana,

01:17:00.520 | although, I don't know, send me the paper

01:17:02.180 | if you've heard of this,

01:17:04.000 | is that plants have figured out ways,

01:17:06.840 | they've adapted ways to push back on populations of rodents

01:17:10.800 | and other species of animals that eat them.

01:17:13.060 | So plants are engaged in a kind of plant to animal warfare

01:17:17.640 | where they increase the estrogen of the males

01:17:19.980 | in that population to lower the sperm counts

01:17:22.160 | to keep those populations clamped at certain levels

01:17:25.420 | so that those plants can continue to flourish

01:17:28.300 | even if those animals are reproducing very robustly.

01:17:33.140 | And I find this just fascinating.

01:17:35.180 | And hormones, therefore,

01:17:37.760 | aren't just impacting tissue growth and development

01:17:41.860 | within the individual and between the mother,

01:17:44.340 | remember the placentas and endocrine organ and the offspring,

01:17:47.360 | but plants and animals are in this communication.

01:17:49.840 | And today we're in this communication.

01:17:51.360 | I'm telling you that there are certain herbicides

01:17:53.520 | that humans are using for which there's very good data

01:17:56.000 | are disrupting the endocrine pathways.

01:17:59.360 | And so it's fascinating that humans and other animals

01:18:03.160 | were always in this interplay with plants

01:18:05.320 | and the other things in our environment.

01:18:07.880 | And hormones and adjusting the hormone levels

01:18:10.940 | of animals and plants is one way

01:18:13.040 | in which the environment kind of pushes back

01:18:15.080 | or pushes forward, if you will,

01:18:17.200 | in terms of promoting their wellbeing and longevity,

01:18:20.740 | as well as you trying to promote

01:18:21.960 | your wellbeing and longevity.

01:18:23.800 | If anyone wants to see the incredible paper

01:18:25.920 | by Steve Glickman and colleagues,

01:18:27.880 | it was published in the "Prosthetics of the National Academy"

01:18:30.020 | first in 1987, that's Glickman et al.

01:18:33.400 | That was the hypothesis that it was androstenedione.

01:18:35.880 | And then if you just Google Glickman Hyenas Science Magazine,

01:18:40.880 | there's a beautiful cover article and feature

01:18:44.200 | all about that important discovery.

01:18:45.840 | It's a fascinating one.

01:18:47.240 | And I should mention also that those discoveries,

01:18:50.320 | both the moles and the hyenas weren't just impactful

01:18:54.240 | for the world of animal behavior and endocrinology.

01:18:56.480 | They've also strongly impacted understanding

01:18:59.440 | of conditions that show up in the clinic,

01:19:01.640 | which we haven't talked about today,

01:19:03.600 | which is actually pseudo hermaphroditism.

01:19:06.040 | Occasionally babies will be born where it is unclear

01:19:09.120 | if they are boys or girls based on the genitalia.

01:19:13.200 | And this has a very important ethical and other issues.

01:19:17.900 | Do you raise them as a boy or a girl?

01:19:19.960 | It's not super uncommon for this to happen.

01:19:23.560 | And there've been terrible cases where people have gone

01:19:27.160 | against the chromosomal sex and the person was very unhappy

01:19:32.160 | with the choice that their parents had made for them.

01:19:34.920 | There were also cases where they've gone

01:19:36.620 | with the chromosomal sex and the person was very happy

01:19:39.080 | about the outcome.

01:19:39.960 | There've been cases where they've been treated with hormones

01:19:42.280 | and there've been cases

01:19:43.120 | where they have not been treated with hormones.

01:19:44.620 | It's a complicated literature and it has to be sorted out

01:19:49.620 | on kind of a case by case basis,

01:19:52.400 | but it is something that does happen.

01:19:54.040 | And the studies on androstenedione and hyenas

01:19:56.960 | and in these very interesting moles,

01:19:59.880 | pseudo hermaphroditic moles that live in Tilden Park

01:20:02.820 | have impacted not just the science,

01:20:05.040 | but the therapeutics around those important issues.

01:20:08.280 | So now last but not least,

01:20:10.520 | I want to discuss the effects of hormones

01:20:13.840 | while you and I were separately in utero

01:20:18.560 | and the effects that that had on who we are,

01:20:22.280 | who we select as mates, so mate choice, sexual preference,

01:20:28.960 | and all other aspects

01:20:31.640 | of what you would call sexual development.

01:20:35.400 | Now, this is something that's gotten a lot of popular press

01:20:38.600 | and it has to do with how exposure to androgens in particular

01:20:42.960 | while we were in utero impacted whether or not people report

01:20:47.600 | as homosexual, heterosexual, identify as male or female.

01:20:52.600 | I'm very familiar with this work

01:20:54.220 | because I was a graduate student in the department

01:20:56.120 | that first published this work

01:20:57.300 | and I'm an author on the paper.

01:20:59.580 | I was not the main driver of the work,

01:21:01.620 | but I was involved in the work

01:21:03.540 | and I certainly know the people that did this work.

01:21:06.040 | First, it starts with a story.

01:21:09.420 | There was a researcher who's still going now.

01:21:13.760 | His name is Dennis McFadden.

01:21:16.460 | I believe it was at UT Austin back then.

01:21:19.060 | And he was studying the auditory system

01:21:22.200 | and people would come into his clinic

01:21:23.560 | and he would, or his laboratory,

01:21:25.700 | and he would look at hearing

01:21:28.560 | and he would explore different aspects

01:21:30.120 | of what they call the psychophysics of hearing

01:21:31.720 | and understanding hearing thresholds

01:21:33.300 | and frequency thresholds.

01:21:34.820 | And he made several observations

01:21:36.800 | and those observations were that young males

01:21:43.260 | tended to have what are called autoacoustic emissions

01:21:47.060 | more often than young females did.

01:21:49.800 | Autoacoustic emissions, as the name suggests,

01:21:52.160 | are the ears actually making sounds.

01:21:54.620 | Now these sounds have to be picked up by a special apparatus

01:21:57.400 | 'cause they can hear into that frequency,

01:21:58.880 | but it turns out that your ears don't just take sound waves

01:22:02.440 | and convert them into these things that we,

01:22:04.200 | this thing we call hearing,

01:22:05.280 | but they also, in some cases, make sounds.

01:22:07.520 | So your ears are making sounds, strange, right?

01:22:10.360 | So it turns out that there's a sex difference

01:22:14.420 | in autoacoustic emissions.

01:22:16.740 | Turns out also that people that self-report as lesbians,

01:22:20.480 | they also have autoacoustic emissions significantly more

01:22:25.580 | than females that don't self-report as lesbian.

01:22:29.480 | And Dennis noticed this and published this,

01:22:33.520 | and it was an important discovery

01:22:35.340 | because it was one of the first discoveries

01:22:38.360 | that pointed to the fact that there are sex differences

01:22:43.360 | in biology that are independent of sex.

01:22:46.920 | I mean, this is hearing and autoacoustic emissions.

01:22:49.120 | And just to really illustrate what the former problem was

01:22:54.120 | and why this study was so important,

01:22:56.600 | a lot of people had explored, for instance,

01:22:58.640 | whether or not homosexuals had lower testosterone,

01:23:03.640 | for instance, in males.

01:23:04.720 | And actually the result often was the opposite,

01:23:06.760 | that gay men or men that self-report as gay

01:23:10.000 | often had much higher testosterone.

01:23:12.440 | And those studies then became controversial

01:23:15.040 | because people said, well, sexual behavior

01:23:17.580 | can relate to testosterone, et cetera.

01:23:19.460 | And so it became very controversial.

01:23:21.240 | And then there were some studies that attempted to look

01:23:23.420 | at the equivalent phenomenon in people

01:23:26.440 | that self-report as lesbian or self-report as heterosexual.

01:23:30.260 | And so it became very complicated,

01:23:31.820 | but this was an identification of a phenomenon,

01:23:36.160 | autoacoustic emissions, that was independent of anything

01:23:39.020 | that had to do with sexual or even social behavior.

01:23:41.520 | 1998 rolls around and I'm a graduate student at UC Berkeley

01:23:48.120 | and a guy by the name of Mark Breedlove,

01:23:50.880 | kind of an ironic name given that he worked

01:23:54.000 | and still works on sexual dimorphism in the brain

01:23:57.320 | and in the spinal cord and nervous system.

01:23:59.380 | And Mark, who's a phenomenal scientist,

01:24:02.360 | comes running down the hall, I'll never forget this,

01:24:05.600 | and he said, "Give me your hands."

01:24:06.960 | I was like, "Give me your hands."

01:24:08.200 | And he pulls out a ruler and he starts measuring my fingers

01:24:10.560 | and he takes down a couple of measurements

01:24:11.880 | and then he goes away.

01:24:13.600 | And I'm like, "What was that?"

01:24:15.500 | Well, I was in a course that Mark was teaching

01:24:18.320 | at that point, and soon after we did a study

01:24:23.320 | that Mark directed exploring the finger length ratios,

01:24:28.920 | and I'll explain what those are, of males and females

01:24:34.040 | and people that self-reported

01:24:35.780 | as homosexual or heterosexual.

01:24:38.480 | So let's just get to the basic,

01:24:40.780 | what we'll call sex differences first.

01:24:43.520 | These are averages I want to point out.

01:24:45.360 | Anytime you get into this kind of topic,

01:24:47.000 | people assume it's causal, but it's not causal.

01:24:49.360 | These are averages that I'm about to report.

01:24:51.600 | It is the case that the ratio

01:24:55.520 | of what's called the D2 to D4 digits.

01:24:58.000 | So the D2 is your index finger, so your thumb is D1,

01:25:01.100 | then D2 would be your index finger that you would point with,

01:25:03.560 | middle finger is D3, which you whatever with,

01:25:06.280 | and then D4 is the so-called ring finger, okay?

01:25:10.500 | And D5 is the pinky.

01:25:11.760 | It is the case that the D2 to D4 ratio

01:25:17.840 | is greater in self-reported females than it is in males.

01:25:23.060 | What does that mean?

01:25:24.440 | It means that digit D2 and D4 are more similar in length

01:25:29.440 | in females than in males.

01:25:31.680 | And the effect is particularly, excuse me,

01:25:34.760 | pronounced on the right hand, although not always, okay?

01:25:39.160 | And it does not have to do with handedness.

01:25:41.440 | This D2 to D4 difference has to be measured correctly.

01:25:45.800 | You can't just look at somebody's hands and say,

01:25:47.680 | oh, their ring finger and index finger are very similar

01:25:51.960 | and therefore they are female

01:25:54.280 | or they were exposed to very little testosterone in utero.

01:25:58.880 | You can't look at somebody and see that their index finger

01:26:01.560 | is much shorter than their ring finger and say,

01:26:04.040 | oh, they must've been exposed to a lot of androgen.

01:26:06.740 | You have to actually measure it

01:26:07.920 | and you have to measure it correctly.

01:26:09.880 | You have to measure it from the base of the finger

01:26:12.380 | where there's that first crease all the way to the tip,

01:26:15.240 | past the, you can't include the fingernails

01:26:17.680 | if you're growing fingernails,

01:26:18.560 | it would be logical here, folks.

01:26:20.160 | So you can't normally see it from the back of the hand.

01:26:24.940 | Although I don't know if this will show up here,

01:26:26.900 | but if you look at the back of the hand,

01:26:29.260 | sometimes you can see it.

01:26:30.600 | In my case, for instance, let me see if I can do this.

01:26:34.000 | So my D4 is a little bit longer than my D2.

01:26:37.720 | In some people it's more pronounced

01:26:39.400 | and that's on my right hand.

01:26:40.280 | On the other hand,

01:26:41.120 | the difference actually is far less pronounced.

01:26:42.640 | It's a little bit pronounced there, but not so much.

01:26:47.160 | So that's sort of the typical ratio that you would see.

01:26:50.600 | Turns out that in mice and in humans,

01:26:54.740 | the more androgen that you were exposed to in utero,

01:27:00.120 | the smaller the D4, D2 ratio,

01:27:01.980 | meaning that the ring finger tends to be slightly longer

01:27:05.780 | than the pointer finger.

01:27:07.460 | And in females,

01:27:08.440 | because they're exposed to less androgen in utero,

01:27:12.040 | typically, then those fingers tend to be more equal in length

01:27:15.320 | and these are subtle differences and these are averages.

01:27:18.040 | I invite you to look up the paper.

01:27:19.920 | This was published in Nature in 2000

01:27:21.800 | and it's been replicated six times.

01:27:26.400 | Now here's where it gets even more interesting.

01:27:30.000 | And potentially precarious,

01:27:31.540 | so we're going to step cautiously here.

01:27:33.440 | If you look at the finger length ratios

01:27:37.260 | of men that self-report as homosexual,

01:27:40.640 | they have either the typical male pattern

01:27:43.320 | of D2 to D4 ratio

01:27:45.600 | or a hyper-masculinized D4 to D2 ratio.

01:27:49.200 | Now this can't be something that's established

01:27:51.600 | or modified by behavior.

01:27:53.700 | This has to be something that was established in utero

01:27:56.040 | and in fact, it's present at birth.

01:28:00.500 | So it completely divorces the interactions

01:28:03.720 | between hormones and behavior.

01:28:05.260 | And that's an important theme that we've been talking about

01:28:07.140 | and we're going to talk about even more next episode

01:28:08.900 | is that hormones impact behavior,

01:28:10.400 | but behavior also impact hormones.

01:28:12.100 | But this is a case of hormones impacting

01:28:14.860 | what really should be considered

01:28:16.340 | a primary sexual characteristic

01:28:18.780 | because it doesn't show up in puberty,

01:28:20.260 | it shows up before puberty,

01:28:21.380 | it's actually established in utero.

01:28:23.900 | And in people that self-reported lesbians,

01:28:27.020 | and I remember going out there

01:28:28.260 | and collecting these data with these,

01:28:30.300 | with the collaborators on this work.

01:28:31.860 | Again, I wasn't the main driver on the work,

01:28:33.620 | but I participated in some of the analysis.

01:28:36.220 | People that self-report as lesbians

01:28:38.140 | also tend to have a smaller D2 to D4 ratio.

01:28:43.140 | So this is consistent with the autoacoustic emissions study

01:28:46.380 | that Dennis McFadden had published.

01:28:48.220 | And it points to the fact that early exposure to androgens

01:28:51.860 | may have an impact,

01:28:54.620 | not just on androgenization

01:28:58.180 | of the body plan,

01:28:59.540 | but also separately on sexual preference.

01:29:04.540 | Now, this raises all sorts of interesting questions

01:29:06.940 | about biological basis of sexual preference.

01:29:08.980 | I'll tell you about another study,

01:29:10.800 | a guy named Simon LeVay, who was at UCLA,

01:29:13.780 | who trained under Hubel and Wiesel.

01:29:16.540 | If any of you remember early episodes on plasticity,

01:29:18.740 | David Hubel and Torrance and Wiesel,

01:29:20.260 | my scientific great-grandparents won the Nobel Prize

01:29:22.860 | for discovery of critical periods for brain plasticity.

01:29:26.620 | They defined some of the most important aspects

01:29:28.580 | of how we see and brain plasticity.

01:29:31.620 | Simon LeVay trained with them.

01:29:33.840 | And then Simon went on to discover

01:29:36.300 | that in the brains of people that self-report homosexual,

01:29:40.620 | there is a brain difference.

01:29:42.420 | And the brain difference is in an area

01:29:43.940 | called the interstitial nucleus

01:29:45.520 | of the anterior hypothalamus.

01:29:47.580 | So it's the INAH.

01:29:50.300 | And so there are published reports

01:29:54.740 | that was published in Science.

01:29:56.340 | The other work I refer to as published in Nature

01:29:58.140 | and then replicated no fewer than six times.

01:30:00.700 | And the McFadden results

01:30:02.140 | that point to strong biological correlates

01:30:06.740 | of mate choice of sexual preference.

01:30:11.560 | And these tie directly to things like androgenization

01:30:16.560 | or estrogenization,

01:30:18.880 | meaning we could call it maleness or femaleness,

01:30:20.940 | but that's sort of tricky territory

01:30:22.620 | because of the way that we described the huge range

01:30:24.700 | in which sex can be defined earlier.

01:30:27.000 | So if you want to measure D2, D4 ratio, you're welcome to,

01:30:31.780 | but you also have to understand

01:30:33.940 | that it's not predictive of anything, right?

01:30:36.700 | It's just a window into the possible androgen exposure

01:30:39.980 | that you had early in life.

01:30:41.560 | There are plenty of men who report themselves

01:30:44.660 | as heterosexual who are out there

01:30:46.380 | who have similar or have D2, D4 ratios to females.

01:30:50.300 | And there are plenty of females whose index fingers

01:30:52.780 | are shorter than their ring fingers.

01:30:54.480 | And they're perfectly happy

01:30:55.760 | or they say they're perfectly happy

01:30:57.540 | and we are inclined to believe them being heterosexual.

01:31:00.100 | So there's variation.

01:31:01.060 | In fact, Mark tells a really good joke.

01:31:03.060 | If you want to know whether or not

01:31:05.980 | somebody is homosexual or heterosexual,

01:31:09.060 | simply look at their hands,

01:31:10.780 | look at their D2, D4 ratio and guess heterosexual

01:31:15.220 | and you'll be right 96% of the time.

01:31:17.520 | Because 96% of the time,

01:31:19.100 | people report themselves as heterosexual on average.

01:31:21.980 | Those numbers might be changing.

01:31:23.660 | So the joke really is a joke on science

01:31:26.120 | because that falls within the realm

01:31:28.420 | of statistical significance.

01:31:29.960 | And yet it really illustrates the fact

01:31:31.820 | that none of this is causal.

01:31:33.800 | But it's nonetheless very interesting

01:31:35.600 | because it means that hormones are organizing

01:31:37.840 | the brain early in development

01:31:39.280 | in ways that can potentially impact

01:31:42.340 | same or opposite sex partner choice later in life.

01:31:45.940 | Now, of course, there are other things

01:31:47.100 | that can impact opposite sex

01:31:48.780 | or same sex partner choice later in life.

01:31:51.180 | The study did not look at people who reported bisexual.

01:31:54.580 | There hasn't been a lot of studies on that yet.

01:31:57.740 | One thing that's very interesting

01:31:59.420 | for which there are some good scientific data

01:32:01.940 | but there's also some controversy

01:32:03.740 | is that it appears that the probability

01:32:07.580 | of a male human self-reporting as homosexual

01:32:11.860 | increases with the number of older brothers that he has.

01:32:16.420 | Now, that doesn't mean if you have an older brother

01:32:18.220 | or even if you have 10 older brothers

01:32:19.800 | that you are sure to self-report as homosexual.

01:32:22.860 | But statistically, it becomes more likely

01:32:26.840 | that somebody will with each successive older brother

01:32:30.360 | that they have.

01:32:31.520 | And the idea that's starting to emerge

01:32:33.160 | in the developmental neuroendocrinology landscape

01:32:37.120 | is that there's a record within the mother

01:32:41.120 | of how many male fetuses she's carried

01:32:43.380 | because male fetuses are secreting certain things,

01:32:46.380 | dihydrotestosterone, other things that can feed back

01:32:50.500 | onto the genome.

01:32:51.860 | So these could be epigenomic effects

01:32:53.380 | or onto the placenta itself

01:32:55.700 | so that there's a higher probability

01:32:57.620 | in subsequent pregnancies

01:32:59.480 | that offspring will self-report as homosexual.

01:33:02.880 | So it's a fascinating area of biology.

01:33:05.060 | And as you've noticed today,

01:33:06.500 | none of this deals with the current controversies

01:33:09.680 | around gender and how many genders and sex, et cetera.

01:33:12.980 | That's a separate conversation that is by definition grounded

01:33:17.080 | in the kind of concepts we've been talking about today

01:33:19.700 | and needs to take place,

01:33:21.400 | taking into consideration all of the aspects of sex

01:33:24.980 | and the effects of hormones, both on the body, on the brain.

01:33:28.580 | We didn't talk a lot about spinal cord,

01:33:29.980 | but we will in the next episode.

01:33:32.120 | But we can just say on the brain and the periphery,

01:33:34.700 | early effects, late effects, acute effects,

01:33:38.060 | meaning effects that are very fast

01:33:40.140 | of levels of hormones going up or down,

01:33:42.220 | something that absolutely happens

01:33:43.700 | during and across the menstrual cycle,

01:33:46.340 | as well as long-term effects,

01:33:47.920 | like the effects of these hormones on gene expression.

01:33:51.700 | So today, as always, we weren't able to cover

01:33:55.460 | all things related to sex and hormones

01:33:59.660 | and sexual differentiation or development.

01:34:02.820 | There's no way we could,

01:34:04.120 | but we have covered a lot of material.

01:34:06.340 | We talked about some effects of environmental toxins.

01:34:10.340 | We talked about potential effects of cell phone radiation,

01:34:12.900 | something I never thought that I would be talking about,

01:34:15.700 | especially not in a podcast,

01:34:17.380 | but for which there are interesting emerging data.

01:34:19.420 | We talked about considerations about evening primrose oil

01:34:23.340 | and its estrogenic effects,

01:34:24.580 | about creatine and its pro-DHT effects,

01:34:27.140 | about cannabis, alcohol,

01:34:29.140 | about plants exerting warfare on animals

01:34:31.760 | by increasing aromatase,

01:34:33.180 | the conversion of testosterone to estrogen.

01:34:35.140 | We talked about hyenas with giant clitorises,

01:34:37.380 | and we talked about moles that convert from having ovaries

01:34:41.800 | to testicles, and throughout this,

01:34:44.300 | Costello has been snoring nonstop.

01:34:46.500 | He missed all of it,

01:34:48.000 | although he might be learning it in his sleep

01:34:50.300 | for all I know.

01:34:51.820 | And I do understand it's a lot of information,

01:34:54.980 | a lot of detail.

01:34:55.800 | As always, I just want to remind you,

01:34:57.300 | you don't have to absorb all the information at once.

01:35:00.060 | Next episode, we are going to be talking about

01:35:02.660 | the science of sex, the verb, actual reproduction.

01:35:06.700 | We're also going to be talking about effects of hormones

01:35:09.500 | on various aspects of behavior

01:35:11.700 | and ways to modulate hormones

01:35:14.140 | through the use of behavior, supplementation.

01:35:19.140 | Also, we'll touch on diet and nutrition a bit,

01:35:22.020 | and we're going to talk about interactions

01:35:24.040 | between those things and behavior

01:35:26.140 | as they relate to important themes,

01:35:28.240 | like sex and reproduction, like workplace performance,

01:35:32.280 | like motivation and drive, and even anxiety.

01:35:34.860 | There's a very interesting relationship

01:35:36.820 | between hormones and anxiety

01:35:39.180 | and the desire to explore novelty.

01:35:42.400 | So just remember as we go forward

01:35:44.260 | that hormones affect behavior

01:35:46.400 | and behavior affects hormones,

01:35:48.760 | but that doesn't mean that cutting off your index finger

01:35:51.020 | will increase your testosterone.

01:35:53.140 | Many of you have asked how you can help support the podcast,

01:35:55.940 | and we thank you for the question.

01:35:57.700 | There are several ways to do that.

01:35:59.020 | The first one is to subscribe on YouTube.

01:36:01.100 | If you haven't subscribed to the YouTube channel already,

01:36:03.060 | please do so.

01:36:04.300 | As well, please hit the subscribe button

01:36:06.020 | so you're sure not to miss any of the episodes.

01:36:08.400 | We do release episodes every Monday,

01:36:10.500 | but we also occasionally release short clips in between.

01:36:14.400 | As well, if you could subscribe on Apple and/or Spotify,

01:36:17.720 | that's very helpful.

01:36:18.780 | And on Apple, you have the opportunity

01:36:20.500 | to leave us up to a five-star review

01:36:22.660 | and to leave a comment.

01:36:24.380 | On YouTube, please do leave us comments

01:36:26.580 | and suggestions for future episodes.

01:36:28.580 | We really appreciate the feedback

01:36:30.100 | and we appreciate those suggestions.

01:36:32.200 | Also ask us any questions you have

01:36:33.820 | about the material.

01:36:35.100 | Those questions help guide our office hours,

01:36:37.780 | this discussion about your questions

01:36:39.420 | that we hold from time to time,

01:36:40.860 | as well as inform future content.

01:36:43.420 | Also, if you could tell people about the podcast,

01:36:45.500 | please tell your family, your friends, your coworkers,

01:36:48.040 | anyone that you think might benefit from the material.

01:36:50.460 | That really helps us get the word out.

01:36:52.700 | As well, if you're interested in supplements,

01:36:55.180 | we've partnered with Thorne, T-H-O-R-N-E,

01:36:58.860 | and we've partnered with Thorne

01:36:59.940 | because Thorne has the highest level of stringency

01:37:02.380 | with respect to the ingredients

01:37:04.120 | that they put in their products,

01:37:05.820 | as well as the precise amounts of those contents.

01:37:09.460 | A lot of supplement brands out there

01:37:10.840 | claim to have X amount of some supplement,

01:37:13.480 | but then when people have measured the amount

01:37:15.980 | in capsules and tablets,

01:37:16.980 | it's turned out to be very different.

01:37:18.140 | Thorne is very precise about this.

01:37:19.540 | They partnered with important and stringent institutions

01:37:23.160 | like the Mayo Clinic, all the major sports teams,

01:37:25.260 | so that's why we partnered with Thorne.

01:37:27.300 | If you want to try any of Thorne's products,

01:37:29.160 | if you want to see what I take, you can go to Thorne,

01:37:31.380 | that's T-H-O-R-N-E, .com/u/huberman.

01:37:36.380 | And if you do that,

01:37:37.540 | you can see any of the products that I take,

01:37:39.060 | you can get 20% off any of those,

01:37:41.500 | as well as 20% off any of the other products

01:37:43.800 | that Thorne makes.

01:37:45.040 | So that's thorne.com/u/huberman.

01:37:48.720 | Please also check out our sponsors,

01:37:50.460 | check out the sponsor links.

01:37:51.660 | That's perhaps the best way to support us.

01:37:54.420 | And of course, I want to point out

01:37:56.060 | that any of the ways that support us,

01:37:58.160 | whether or not they are cost-free,

01:37:59.420 | like subscribing and leaving comments,

01:38:00.940 | or whether or not you're interested in the products

01:38:03.200 | that I've referred to, those all help us,

01:38:05.860 | and so we really appreciate it.

01:38:07.900 | So once again, I want to thank you

01:38:09.540 | for embarking on this journey through neuroscience,

01:38:12.140 | and today, neuroendocrinology with me,

01:38:15.140 | and as always, thank you for your interest in science.

01:38:17.760 | [upbeat music]

01:38:20.340 | (upbeat music)

Biological Influences On Sex, Sex Differences & Preferences

Chapters