Welcome to The Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I’m Andrew Huberman, a professor of Neurobiology and Ophthalmology at Stanford School of Medicine. This podcast is separate from my teaching and research roles at Stanford, but is part of my desire and effort to bring zero cost to consumer information about science and science related tools.

In keeping with that theme, I’d like to thank the sponsors of today’s podcast. Our first sponsor is Inside Tracker, a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I’m a big believer in blood tests and DNA tests for the simple reason that many of the factors that are important for your short-term and long-term health and overall wellbeing can only be analyzed from blood and DNA tests.

The thing I like about Inside Tracker is you don’t just get back levels of different hormones and metabolic factors and so forth, you also get directives.

Inside Tracker is a health and wellness platform that makes it easy to assess how your behaviors and lifestyle choices are interacting with what’s going on deep within your biology. It has a dashboard that is easy to use and provides information on what sorts of foods and forms of exercise you should be doing more of or less of. Additionally, it is easy to get blood tests and DNA tests taken, either at a local location or they can send someone to your home if you prefer. To try Inside Tracker, visit insidetracker.com/huberman and use the code Huberman at checkout to get 25% off any of Inside Tracker’s plans.

Helix Sleep makes mattresses and pillows that are designed to meet your sleep needs, in order to optimize your sleep. Getting deep, restful sleep each night is vital for mental and physical health. The mattress and pillow you use are very important for getting optimal sleep. Helix Sleep has a two minute quiz that asks questions such as what position you sleep in, whether you run hot or cold as you sleep, or if you don’t know. This quiz matches you to a mattress and pillow that’s ideal for your sleep needs. I took the quiz and matched to the mattress they call “The Dusk.” I’ve been sleeping on this mattress for many months now and I’ve been sleeping better than ever before. It’s a total game changer.

If you’re interested in upgrading your mattress, head over to helixsleep.com/huberman and take their two minutes sleep quiz. They’ll match you to a customized mattress and you’ll get up to $200 off any of their mattress orders and two free pillows. Not only that, they have a 10 year warranty and you get to try out the mattress for 100 nights risk-free. If you don’t like it, they’ll pick it up and take it away. If you love it, then you keep it. Today’s episode is also brought to you by Athletic Greens.

Athletic Greens is an all-in-one vitamin, mineral, and probiotic drink. I started using it back in 2012 and am delighted that it is sponsoring the podcast. I chose Athletic Greens because I found it confusing to figure out what vitamins and minerals to take, and with Athletic Greens I get all the vitamins and minerals I need to cover my bases, as well as probiotics. Probiotics have been shown in numerous studies to be important for the gut microbiome, which impacts the gut-brain axis and various aspects of bodily health. I also really like the taste of Athletic Greens – it’s a greens drink that you mix with water.

You can mix Athletic Greens with something else, like juice, if you like. I mix mine with water and lemon juice and drink it once or twice a day. If you want to try Athletic Greens, you can go to athleticgreens.com/huberman to claim their special offer of a year’s supply of Vitamin D3 K2. There is now a wealth of data showing that Vitamin D3 is important for various aspects of brain and body health. You’ll also get five free travel packets which are a convenient way to take Athletic Greens when you’re on the road, in the car or on a plane. You just empty one of the packets into a water bottle or glass and mix it up quickly, avoiding any mess.

For this month’s episode, we’re offering our listeners a special deal. Head over to athleticgreens.com/huberman to get a year’s supply of Vitamin D3 K2 and five free travel packs.

This month at the Huberman Lab Podcast, we’re discussing the effects of hormones on the brain and body. We’ll be covering a wide range of topics, such as sex, reproduction, puberty, and menopause. In our previous episode, we discussed puberty and the changes it brings. We hope our listeners will join us for this exciting discussion.

We’re going to talk about birth control, aggression, competition, winning, and losing. We will cover as much about hormones as possible in this month, including tools and protocols. We will also discuss tools that relate to optimizing hormone health, regardless of stage of life or goals. This month is sure to be rich with discussion, tools, neuroscience, and endocrinology. I have a lot of experience in this field, having done a masters in neuro-endocrinology, and I have consulted many friends on this topic for these episodes.

But, by the time the episode actually posted, the Mood Meter App had been taken down from the app store.

I want to let you know that the Mood Meter App is now back up in the app store. So, if you’d like to download it, you can go to the link that we’ve provided and you can get access to the app. Additionally, I want to let you know that I’ve also created a resource page that points to some other useful resources that you can use to learn more about emotions and relationships.

Over the weekend, the Mood Meter app was taken down for repairs. It is now available again. I want to be clear that I am not affiliated with the app in any way. They do not know me, although I know them. We do not have any kind of business relationship. The app does cost 99 cents.

I think the free version of the Mood Meter app has disappeared in the last year or so. We’ll provide the link again and hopefully they won’t take it down again in between this announcement and the release of this episode.

I want to take a step back for a moment and talk a little bit about the logic of how to make the most of the information on the Huberman Lab Podcast. I tend to throw out a lot of information about a given topic, but many of you have pointed out that I don’t cover certain things.

Once again, I’ll just say the goal is always to be accurate, but there’s no way I can be exhaustive and cover everything for a particular topic. The good news is we have time.

My goal, at least in the first year of the Huberman Lab Podcast, is to give you a basis, a foundation in these different topics of neuro-plasticity, focus, sleep, hormones, et cetera. To do this, we are going to host guests and I have already started recording with some of these guests. Each episode will include a primer, a description of the basics of a given topic, so that you can get more information from those topics. My goal is to educate you in these topics, give you a foundation and allow you to start exploring them in the episodes with our future guests, but also in other podcasts, books, and other sources of information.

For those of you that feel it’s too much information, I encourage you to remind yourself that you have a pause button and everything is timestamped. For those of you that feel it’s not enough information, just know that this is just the beginning.

We didn’t intend to do this for a very long time and we will be thorough over time. So, thanks for your patience and please be patient with yourselves. There’s no reason why you have to digest all the information in one swoop.

I’ve been told both that I speak too fast and speak too slow. So, there’s a wonderful solution to this. If I speak too fast or too slow, you can adjust the speed in YouTube. If you’re listening in a different format, I think you also can adjust the speed of playback. This is something that wouldn’t be possible in the classroom, but you may find useful.

Lastly, I want to point people again to this NSDR (non-sleep deep rest protocol) that the folks over at Madefor have put out as a free resource. It does, as many of you pointed out, bear resemblance to things like yoga nidra and other forms of meditation.

We have stripped out intentions or any kind of verbiage related to what some people might perceive as related to the yoga community or specific to new age-y type techniques. This is not because we don’t like yoga nidra; in fact, I have done yoga nidra daily for almost the last eight years of my life and I love it. However, the complicated language can be a separator and can discourage people from taking on these protocols that are extremely useful.

NSDR is intentionally generic and designed to bring you into a state of deep relaxation through a combination of breathing and body scan. There is a “you too” script over at Madefor which is linked in the caption. Many people find that they prefer this to scripts like yoga nidra, which involve doing intentions and hearing a lot of unusual language around the process. This is just very basic and I hope you’ll enjoy it.

Today we’re going to talk about The Science of Sex. In particular, sexual differentiation. Sex is both a adjective, a noun, and a verb, depending on the context. We’ll discuss the hormonal and neural effects of particular events that happen during development, and how those guide adolescent and adult behavior, including sexual preference. This is an area that’s fascinating, and for which there are very solid textbook findings, meaning there are many studies that have been aggregated over decades. If you prefer more typical yoga nidra scripts, there are many available on the internet and elsewhere. Lastly, all our episodes now are subtitled both in English and in Spanish, so those who prefer to digest this information in Spanish can do so in the subtitles.

Today, we are going to explore hormones: what they are, how they work, and what leads to masculinization or feminization of the brain and body. Hormones have direct effects on the body – most people know this since there are hormone differences and sex differences in terms of genitalia and body hair. However, hormones also have direct effects on the brain and even the spinal cord. We will also discuss reproduction and sex, which can be carried out independent of reproduction in humans. It is essential to understand the information in this episode in order to make sense of the information in the next episode. Finally, we will discuss how hormones affect brain development, how the brain impacts hormonal development, and how these interact to control behavior.

Neurons and structures within the spinal cord have a direct impact on the behaviors that are possible. As this is a sensitive topic, the speaker will be going more slowly and being careful with their language. They won’t be getting into any cultural dialogue, but rather focusing on the biology, physiology, endocrinology, and behavior.

To begin, the speaker will remind the audience what hormones are and what they do. Hormones are a chemical released in one area of the body that can have an effect on another area.

Hormones are substances secreted at one location in the body that travel and have effects on other organs and tissues. This is different from neurotransmitters, which tend to act more locally. Examples of tissues that produce hormones include the thyroid, the testes, the ovaries, and areas of the brain like the hypothalamus and pituitary. These hormones cause the release of other hormones out in the body. Today’s discussion will cover what hormones actually do to create masculinization or feminization.

Sperm meets egg, and the egg begins to duplicate itself. This process of duplication is known as mammalian reproduction. As the egg continues to duplicate, some of the cells become skin, some become brain, and some become muscle. This is the start of the development of an embryo. The events that occur before the sperm meets the egg will be discussed in the next episode.

Some of those cells become fingers. All the stuff that makes up the brain and body plan, in addition to hormones that come both from the mother and from the developing baby, the developing fetus, impact whether or not the brain will be what they call organized masculine or organized feminine. As I say this, I want you to try and discard with the cultural connotations or your psychological connotations of what masculinization and feminization are, because we’re only centering on the biology. Typically, people have either two X chromosomes and the traditional language around that is that person is female, or an X chromosome and a Y chromosome and that person will become male. However, it’s not always the case.

There are cases where it’s XXY, where there are two X chromosomes plus a Y chromosome. There are also cases where it’s XYY, with two Y chromosomes. These have important biological and psychological impacts.

We need to establish that there is something called chromosomal sex, which is determined by the presence of two X chromosomes or an X and Y chromosome. The next stage of separating out the sexes is called gonadal sex. Typically, if someone has testes for their gonads, they are thought of as male, and if they have ovaries, they are thought of as female. However, this is not always the case.

Let’s explore the transition from chromosomal sex to gonadal sex, as it is a fascinating one that we all experienced in some form or another. We typically think of XY as promoting masculinization of the fetus due to the genes found on the Y chromosome. These genes have particular functions that suppress female reproductive organs. For example, the Y chromosome encodes for something called Mullerian Inhibiting Hormone, which is a hormone programmed by the Y chromosome that inhibits the formation of Mullerian Ducts, an important part of the female reproductive apparatus. Additionally, genes on the Y chromosome such as the SRY gene promote the formation of testes, while also inhibiting the formation of the Mullerian Ducts. This transition from chromosomal sex to gonadal sex is a very important distinction, as it is a fork in the road that happens very early in development while fetuses are still in the embryo.

The Y chromosome can suppress Mullerian Duct formation and promote testes development. The placenta is an endocrine organ, and the mother carrying the fetus has an adrenal gland which can produce testosterone. In some cases, a mother secreting large levels of testosterone while carrying a fetus that is XX can lead to masculinization of certain aspects of the fetus, such as an enlarged clitoris. In addition to chromosomal sex and gonadal sex, there is also what we call hormonal sex.

The effects of steroid hormones, such as estrogen and testosterone and their derivatives, on morphological sex (or the shape of the baby and the human, and the genitalia, jaw and other features) is complex. It is a long journey from chromosomal sex to gender identity, with social influences and roles playing a large part. Currently, this area is very dynamic and the discussion around it is ongoing. To understand the journey from chromosomal sex to gonadal sex, hormonal sex and morphological sex, involves a number of steps. Today, we will be looking at these steps and the fascinating implications that relate to tools, behavioural choices, and things to avoid when pregnant or considering having children.

These hormones can have both short-term and long-term effects.

Hormones play an important role in sexual development. They can drive development in one direction or another, and there are examples of deleterious things in our environment that can negatively impact sexual development, regardless of chromosomal background. To understand the role of hormones further, we can divide them into two categories: those that act very fast, such as cortisol and adrenaline, and those that act more slowly, such as testosterone and estrogen, which are known as the sex steroid hormones. These hormones can have both short-term and long-term effects.

The sex steroid hormones can have quick effects through signaling, attaching to cells and making them do different things. They can also have quick effects on the brain. These molecules are lipophilic, meaning they like fatty stuff, and can pass through fatty membranes. This enables them to travel into cells and interact with the DNA to control gene expression. Additionally, these hormones have both short-term and long-term effects.

Hormones have both short-term and long-term effects on the body and brain. Short-term effects are related to their effects on proteins, while long-term effects are related to their effects on genes and how they are expressed or repressed. Steroid hormones, such as SRY and Mullerian inhibiting hormone, are extremely powerful and can lead to masculinization and feminization of the body and brain. In the case of females, it can also mean demasculinization of the brain. Additionally, de-feminization can occur, which is the suppression of certain pathways related to feminization of the body and brain.

But they don’t determine what is male and female.

So I’ve just thrown a lot of biology at you, but this is where it all starts to get incredibly surprising. You would think that it’s straightforward, right? You have a Y chromosome, you suppress the female reproductive pathway like the Mullerian Ducts, you promote the development of testes and then testes make testosterone. And then it organizes the brain male and it wants to do male-like things. And then in females, you get estrogen and it wants to do female-like things. It turns out that isn’t how it works at all. Here’s where it’s interesting: we have to understand that there are effects of these hormones, testosterone and estrogen, but they don’t determine what is male and female.

Primary sexual characteristics are the ones that you’re born with. Examples of this include the development of external genitalia, which is largely determined by testosterone. Secondary sexual characteristics are the ones that show up in puberty and are the result of changes in the brain, body, and spinal cord. An example of this is the development of facial hair, which is caused by an increase in testosterone during puberty.

Testosterone and dihydrotestosterone are both androgens, but dihydrotestosterone has a key role in the development of the penis in a baby with an X chromosome and a Y chromosome. It is converted to dihydrotestosterone through an enzyme called 5-alpha-reductase. Dihydrotestosterone has important effects later in life, and is considered the dominant androgen in males. When a baby is born, the genitalia is examined to determine if it is a “boy or girl”. This practice has been done for a long time throughout human history.

Dihydrotestosterone is responsible for a lot of things. It’s responsible for aggression, muscular strength, beard growth and male pattern baldness. We’ll talk about all of these effects. It also has powerful effects in determining the genitalia of a baby while it is still an embryo. Testosterone is made and then converted by an enzyme called 5-alpha-reductase in a structure called the tubercle. This tubercle will eventually become the penis.

Dihydrotestosterone controls penis growth and is a primary sexual characteristic. During puberty, the release of Kisspeptin molecule causes the release of other hormones such as Connatural releasing hormone and Luteinizing hormone which stimulate the testes to make testosterone. This leads to further growth and development of the penis, as well as the accumulation of pubic hair, deepening of the voice and other secondary sexual characteristics. In the 1970s, a phenomenon was published in the Journal of Science which now has a wealth of scientific data.

A mutation in the gene for the enzyme 5-alpha-reductase results in the enzyme not existing. This mutation was first identified in the Dominican Republic, but has since been observed elsewhere, although it is quite rare. When a baby is born, their chromosomes are not typically measured to determine their sex, as is commonly done today.

If you were to look at that baby, it would look female. There would be very little or no external penis. People would say, “It’s a girl” and have a gender reveal party. This has nothing to do with gender, it has to do with genitalia and sex. From time to time, that baby after being raised as a girl and perfectly happy as a girl, would around the age of 11 or 12 or 13 suddenly start to sprout a penis.

There is a condition called Guevedoces, which translates to “penis at 12.” It is caused by a mutation that affects the development of external male genitalia. This is because the testes don’t descend and the enzyme 5-alpha-reductase, which converts testosterone to dihydrotestosterone, is not present. As a result, the penis does not develop. These children are typically treated as girls, and they generally report being comfortable as girls, although not always.

Testosterone starts getting secreted from the testes due to kisspeptin in the brain signaling through gonadotropin and luteinizing hormone, which travels down to the testes and causes them to start churning out testosterone. This leads to the growth of the penis and very complicated situations in families and culturally. In order to offer these children the opportunity to explore something that is not just a typical girl or boy phenotype, there has been an adoption of a third category of sex and gender.

Dihydrotestosterone is responsible for the primary growth of the penis, while testosterone is involved in the secondary sexual characteristics such as deepening of the voice. This information applies to everyone as testosterone masculinizes the body in a secondary sexual characteristic way.

Testosterone and estrogen both play a role in masculinizing the primary sexual characteristics. Testosterone is responsible for the growth of the penis early on, but it is actually estrogen that masculinizes the brain and body, independent of genitalia. The brain has receptors for both testosterone and estrogen, and while cells in the brain differ between XY and XX, it is the estrogen that is responsible for the masculinization of the brain.

So, as body fat increases, aromatase activity increases, and more testosterone is converted into estrogen.

Testosterone can be converted into estrogen by an enzyme called aromatase. This process is vitally important to understand. To illustrate the principle, during puberty in boys, XY chromosome individuals, it is not uncommon for there to be transient or sometimes long-lasting breast bud development. This is due to the increase in testosterone during puberty, which is then converted into estrogen by aromatase. Aromatase is made by several sources in the body, with one of the main sources being body fat. As body fat increases, aromatase activity increases, and more testosterone is converted into estrogen.

Aromatase is an enzyme that can convert testosterone into estrogen. During puberty, males can sometimes experience fairly dramatic breast development, which may be transient or not. This is also seen in athletes and bodybuilders who take high levels of anabolic steroids and androgens, as some of the testosterone is converted into estrogen, resulting in gynecomastia. In some cases, this may require surgical removal.

Sometimes XY individuals will try to reduce their estrogen levels in order to suppress the masculinization of their brain. This can be done through taking estrogen blockers or blocking prolactin. Testosterone can be converted to estrogen by the enzyme aromatase, which is found not only in body fat but also in neurons in the brain. This conversion of testosterone to estrogen is what masculinizes the brain and has profound effects on behavior and outlook.

But I think most people don’t realize that it’s estrogen that comes from testosterone that masculinizes the male brain, the XY brain. Not testosterone nor dihydrotestosterone.

You might be asking yourself, “How could tools possibly come up at this stage of the conversation where we’re talking about sexual development and we’re talking about the differentiation of tissues in the body?” Well, this is true both for children and parents and adults. I want to emphasize that there are things that are environmental and there are things that people use in their homes sometimes that actually can impact hormone levels and can impact sexual development in fairly profound ways.

And I want to be very clear, this is not me pulling from some rare journal have never heard of it. This is pulling from textbooks. In particular, today I’m guiding a lot of the conversation on work that on “Behavioral Endocrinology,” is a book by Randy Nelson and Lance Kriegsfeld. True experts in the field.

I’m going to talk about some of the work from Tyrone Hayes from UC Berkeley about environmental toxins and their impacts on some of these things like testosterone and estrogen.

I’m going to touch into them and give some anecdotal evidence that’s grounded in studies, which we will provide in the caption or that I’ll reference here. One of those that’s actually really interesting but helps illustrate the principle that we’ve been talking about is a few years ago, there was a lot of excitement about Evening Primrose Oil.

Evening Primrose Oil is in a lot of products that typically are associated with skin beauty and skin health. But typically it was mothers or sisters that were using it. And there were actually examples starting to crop up of young boys getting accelerated breast bud development from skin contact with women were using Evening Primrose Oil.

So Evening Primrose Oil is chemically a lot like estrogen and it has a lot of estrogenic compounds. There are a number of things out there like this.

Believe it or not, things like pine pollen look very much like testosterone structurally. They are more or less the same as testosterone, although the bioavailability in humans is not clear. Evening Primrose Oil has a lot of estrogenic elements to it, just based on its structure. There have been cases where boys have been exposed to the oil through being hugged by their mom or using the solution when showering, and this has actually changed their levels of estrogens. This is not just an issue for young boys, but also for young girls.

Evening Primrose Oil is not recommended for those looking to drive their hormones more estrogenic or androgenic. There is decent evidence to suggest that soy can impact estrogen levels, but other factors, such as Evening Primrose Oil, can be more severe. People who are undergoing testosterone replacement therapy should avoid Evening Primrose Oil as it can promote estrogenic pathways in the body, even when applied topically.

It’s pretty well understood that, if someone is taking that, they want to avoid contact with anyone. Skin contact with anyone that is trying to promote more estrogenic activity in their body, especially in children. The other issue is environmental factors. When one starts talking about environmental factors and how they’re poisoning us or disrupting growth or fertility rates, it can start to sound a little bit crazy. Except when you start to look at some of the real data from quality research labs funded by Federal government, not from companies or other sources, that are really aimed at understanding what the underlying biology is. We should all be grateful to Tyrone Hayes at UC Berkeley for this. I remember way back when I was a graduate student in the late nineties at UC Berkeley.

I remember a professor I had in college. He was studying developmental defects in frogs that live in different waters around California and elsewhere. He identified a substance, atrazine (A-T-R-A-Z-I-N-E) present in many waterways throughout the US and beyond, which causes severe testicular malformations. According to the data, at sites in Western and Midwestern sections of the US, 10 to 92% of male frogs are affected.

These were frogs mind you, had testicular abnormalities. And the most severe testicular malformations were in the testes rather than in the sperm. So it’s actually the organ itself, the gonad itself. Now it’s very well known now that atrazine is in many herbicides.

Whereas in the 80’s and 90’s the discussion around herbicides and their negative effects was considered kind of like hippy-dippy stuff or the stuff you hear about at your local community markets and these kind of new age communities, there’s now very solid data from Federally funded labs at major universities that have been peer reviewed and published in excellent journals, showing that indeed many of these herbicides can have negative effects, primarily by impacting the ratios of these hormones in either the mothers or in the testes, altering the testes of the fathers or direct effects on developing young animals and potentially humans.

And so you ask, “Well, what about humans? Frogs are wonderful, but what about humans?” So here are the data on what’s happening and this isn’t all going to be scary stuff. We’re also going to talk about tools to ameliorate and offset some of these effects. One would be, be cautious with Evening Primrose as well as testosterone creams, depending on whether or not you want to be more androgenic or estrogenic depending on your needs.

Sperm counts are declining across human populations. In 1940, the average density of human sperm was 113 million per milliliter of semen. By 1990, this figure had dropped to 66 million per milliliter in the United States and Western Europe. Not only this, but the volume of semen produced by men has also decreased by 20% in the same time period, further reducing sperm count per generation. Between 1981 and 1991, the ratio of normal spermatogenesis decreased from 56.4% to 26.9%. This is believed to be primarily due to the widespread use of herbicides which have been linked to reduced sperm counts.

The use of herbicides such as atrazine is having profound effects, not only on sperm counts, but on development, particularly sexual development at the level of the gonads and the brain. Testosterone is necessary to produce dihydrotestosterone for primary sexual characteristics, and estrogen, derived from testosterone, is needed to masculinize the brain. Herbicides are also disrupting estrogens, which may explain why puberty is happening earlier in young girls. It is up to individuals to decide whether to neurotically avoid herbicides, but animal and human studies have shown that they have marked effects.

You can open up a textbook like the endocrinology textbook and find things like Vinclozolin, which is a fungicide and an anti-androgen. When given to animals, such as rats, it prevents them from forming a penis. Instead, they don’t form a penis, nor do they form a clitoris.

Let’s talk about female sexual development. We’ll discuss the normal biology and then move on to a more unusual set of cases, which illustrate an important principle about how hormones impact sexual development. For example, there is a mutation called androgen insensitivity syndrome. Understanding how androgen insensitivity syndrome works can help us better understand how hormones affect sexual development.

Individuals who are XY but have a mutated testosterone receptor are born looking completely female. They typically report feeling like girls when they are young and women when they are older. The unusual factor is that they have an XY chromosomal type instead of XX. The reason for this is because their testes are making testosterone, but the receptor for testosterone is mutated and the testes never descend. As a result, they do not have ovaries, but instead have internal testes.

Individuals with XY chromosomes typically find out that their chromosomal sex is male, but their gonadal sex is male too. The testes are inside the body, and they don’t develop a scrotum or ovaries. This is usually noticed when they don’t menstruate around puberty. Upon further investigation, it is found that they are XY and make testosterone, but their body cannot use it due to the lack of receptors.

Receptors for androgens are vitally important for the development of most secondary sexual characteristics, such as body hair and penis growth during puberty. People with Androgen Insensitivity Syndrome (AIS) live fairly happy lives as females, although they cannot conceive due to not having a uterus or ovaries. In general, they also do not produce sperm in quantities that would allow them to reproduce with somebody else, although it is possible. There have been reports of several prominent people throughout history who have had AIS, or were suspected of having it. The reason for not naming them is that it gets to the heart of whether they are male or female. People with AIS have XY chromosomes but gonadally they have testes that are inside.

Humans have long been fascinated by the effects of hormones on the body. Two examples of this are the natural experiment of individuals who have a male genetic code, but appear female due to lower levels of testosterone, and the use of performance enhancing drugs. Testosterone and its derivatives can have a profound effect on phenotype, and this is due to the hormone binding to its receptor and taking action on target cells. The use of SARMs, which are more on the receptor side, are becoming increasingly popular in augmenting sports performance. What is currently being revealed is the many ways hormones can impact brain and body, which were not previously known.

Estrogen and testosterone play an important role in the masculinization or feminization of the brain and behavior. This is according to a statement by my colleague, Neuronal Shaw at Stanford School of Medicine, which states that estrogen, which is aromatized from testosterone by aromatase, sets up the masculine repertoire of sexual and territorial behaviors in animals and humans. Testosterone then controls the display of these behaviors later in life. This is an interesting phenomenon, as it shows that nature is far more complex than simply testosterone doing one thing and estrogen doing another.

Cannabis is one of the many things that can impact sexual development early and later in life.

Let’s talk about alcohol and cell phones. Alcohol and cell phones have become increasingly intertwined in our society, with data showing that more and more people are using their phones to order alcohol and track their drinking habits. Cannabis, marijuana, and THC have also become more prevalent, with a variety of different strains available. While I’m not a pot smoker myself, I recognize that there are different moral and legal implications depending on the state. It’s important to be aware of these implications and make informed decisions.

Checking the laws of where you live is important, but that is not the focus of this discussion. With the exception of one study, there are many studies that point to the fact that THC and other cannabinoids in cannabis promote significant increases in aromatase activity. Male pot smokers may not like this reality, but it is the truth. In the background, you can hear Costello snoring loudly. We should not put him on screen, as he is not a cannabis smoker. Come here Costello, come here buddy. He is asleep.

Costello is a beloved family pet and does not need cannabis. He is usually asleep and he is always here for us. Today, he let out a grunt when we asked him to come out and say hi. We decided to let him get back to sleep.

He did have a dog sitter that was a pot smoker years ago. It was his favorite dog sitter, but I’m not a pot smoker. Again, no judgment. But here’s the deal: that cannabis, and it’s not clear if it’s THC itself or other elements in the marijuana plant, promote aromatase activity. This has been observed anecdotally where pot smokers have a higher incidence of developing something I mentioned before: gynecomastia, or breast bud development, or full-blown breast development in males. There may be some women who want to increase their estrogenic activity. Remember, females make testosterone, and it comes from the adrenals, right?

They don’t have testes, so it comes from the adrenals and that testosterone can also be aromatized. Although typically most of the aromatase activity that we’re referring to in these examples is in males. So testosterone can increase estrogenic activity. This can lead to the question: does testosterone reduce sexual behavior? Does it create all sorts of things that are related to low testosterone? The answer is not necessarily. Estrogen itself in males and females is important for things like libido and sexual behavior. If estrogen is too low in males, it can actually inhibit libido and sexual behavior. Therefore, it is important that estrogen is not too high or too low.

Whether you’re male or female, estrogen and testosterone levels play an important role in libido and desire to reproduce. In females, estrogen levels tend to be higher than in males, and testosterone from the adrenals has a powerful effect on libido and desire. In the next episode, we will discuss how these hormones relate to birth control and menopause, as well as their effects on males. Additionally, cannabis and other components of the marijuana plant can influence levels of testosterone and estrogen by increasing aromatase. People should be aware of this when considering marijuana use.

There are good data pointing to the fact that smoking marijuana during pregnancy can shift the pattern of hormones in the developing fetus, such that it promotes more estrogenic outcomes. Earlier, I said that estrogen is what masculinizes the male brain in utero, but the way that cannabis seems to work, at least from the studies I was able to identify, is that it promotes circulating estrogen in the body and therefore can counteract some of the masculinizing effects of things like testosterone and dihydrotestosterone on primary and secondary sexual characteristics.

Nowadays, marijuana use is far more widespread and certainly during puberty it can have profound effects on these hormonal systems. Cannabis promotes estrogenic activity by increasing aromatase.

Almost everyone can appreciate that drinking during pregnancy is not good for the developing fetus. Fetal alcohol syndrome is a well-established negative outcome of pregnancy, with cognitive effects that are really bad, physical malformation, et cetera. We will do another episode that goes really deep into this.

Drinking during pregnancy and puberty is not good. Certain alcohols, such as beer and other grain alcohols, can increase estrogenic activity. This not only affects young boys but girls as well, as it can cause excessive or even hypo estrogenic effects. Many teenagers and college students drink, but it is important to note that puberty doesn’t start and end on one day, but rather is an entire period of development that lasts throughout our lifespan.

I used a cell phone that was very basic. It was able to make calls and send texts. Today, cell phones are much more advanced.
They can do all sorts of things, from playing music to taking pictures. I think that cell phones are a great tool for communication and productivity. However, they can also be a source of distraction and can be used to waste time.
Therefore, it is important to use cell phones responsibly and to be mindful of how much time is spent on them.

I was a pre-tenure early professor and taught a class on neural circuits in health and disease. One of the students asked me if cell phones were safe for the brain. All the data I had seen pointed to the fact that they were or, at least, there was no data showing that they weren’t. I still don’t have an answer to this question, frankly. I’m not aware of any quality, peer-reviewed studies that show that cell phones are bad for the brain or that holding the phone to the ear is bad, or that Bluetooth is bad or any of that. If anyone is aware of such studies, please reference them in the comment section.

I’m interested in seeing these studies.

I’m interested in seeing the studies that have been published since 2013 on cell phone emitted waves and their effects on testicular and ovarian development. I was previously not aware of these studies, however I was interested in a particular study published in 2013 on rats. This study took a cell phone and put it under a cage of rats and looked at testicular and ovarian development, finding minor but still statistically significant defects. Since then, there has been an explosion of studies, some in quality journals and some in not so blue ribbon journals, all identifying defects in testicular and ovarian development by mere exposure to cell phone emitted waves. I find this almost crazy and would love to see these studies.

Anytime somebody starts talking about EMS and things like that, you kind of worry like, is this person okay? But, according to the literature, chronic exposure of the gonads to cell phones could be creating serious issues in terms of the health at the cellular level and the output of these cells. For the testes, this would be sperm production and swimming speed, which are important features of sperm health. In the ovaries, the output would be estrogenic output and regularity of the cycles. In animals, these cycles are a little bit different than in humans and they have an estrous cycle, which is generally around four days. It is safe to say, based on the literature, that there are effects of cell phone emitted waves on gonadal development.

The proximity of a cell phone to the gonads is an important question. I have taken the literature as I observe it and have pointed to it in the captions. I personally do not like to have my cell phone on and in my pocket, even though I am well past puberty. Studies have shown that there are effects of cell phones on both adult animals and humans.

One paper published in the journal Clinical Biochemistry, from S. Gander et al., looked at hormone profiles in people based on proximity to their phone and frequency of phone use, where they stored their phone on their body, as well as proximity of where they lived to radio-frequency towers.

The base stations were looking at the effects of radio frequency radiation (RFR) on human hormone profiles. Significant decreases in cortisol were observed, which could be problematic since morning cortisol is needed to wake up. Additionally, thyroid hormones, prolactin in young females, and testosterone levels in males and females were all significantly reduced. This suggests that being close to a phone too much of the day, or living near one of these base stations, can have effects on hormone profiles. However, it is important to consider other factors that could also have effects on these hormone profiles, such as living close to a waterway or highway with exhaust from buses and cars.

We should take studies on the effects of radio-frequency radiation waves on hormones with a grain of salt. However, the amount of data pointing to effects is impressive. In the past, there were one or two studies that suggested increases and decreases in testosterone in rats. Now, work from Tyrone Hayes and others have shown decreases in testosterone levels and sperm counts, as well as decreases in fertility over the past 20 to 30 years. Cell phones and smartphones have been in prominent use for the last 10 to 11 years, so this could be a contributing factor. Ultimately, I’m not sure what to do with this information, but I’m not going to stop using my phone.

There is a strong connection between testosterone levels and beard growth, as well as hair loss. The hormone dihydrotestosterone (DHT) is primarily responsible for both facial hair growth and lack of hair on the head. DHT circulates in the body and binds to DHT receptors in the face to promote hair growth, but binds to DHD receptors on the scalp to promote hair loss. Drugs that are designed to prevent hair loss are 5-alpha-reductase inhibitors.

The research on the Güevedoces led to a better understanding of the biochemistry of dihydrotestosterone (DHT) and the discovery of 5-alpha-reductase. As a result, 5-alpha-reductase inhibitors are now the basis of most anti-hair loss treatments. However, these treatments can have severe side effects, as DHT is the primary androgen for libido, connective tissue repair, and aggression. Additionally, DHT is usually the dominant androgen for ambition and aggression in humans, and it is possible to predict baldness based on looking at one’s mother’s father.

There is a higher probability that you’re going to go bald if your mother’s father was bald. The pattern of DHT receptors on the scalp will determine where you will go bald, such as just in the front or the so called crown type baldness. The density of the beard can tell us about the density of DHT receptors, which varies by genetic background. However, due to people travelling and forming couples with different cultures, these patterns of baldness are starting to disappear. In certain areas of the world, baldness is more common, such as a strip of baldness down the center with hair still on the sides and a full beard. This is because of genetically determined DHT receptors. Testosterone levels can be high and DHT levels in the blood can be high, but some people still have very light beards or none at all. This is because they don’t have a lot of DHT receptors in the face.

In many cultures, men have beards that grow all the way up to their eyes and huge heads of hair. This is due to a higher number of DHT receptors on the face compared to the scalp. Hair loss drugs are designed to prevent the conversion of testosterone to dihydrotestosterone, which can help prevent hair loss but also has side effects related to low DHT. Creatine is a popular sports supplement that can bring more water into the muscle, support strength, and do a number of other things.

Creatine may have cognitive enhancing effects, although these effects are mild. Studies have shown that it can be significant, although some people report that creatine promotes hair loss. It differs from individual to individual, with some people experiencing this effect and others not. PubMed studies have shown that creatine does promote 5-alpha-reductase activity, which can lead to the conversion of testosterone into dihydrotestosterone. This can lead to hair loss, beard growth, and other effects of DHT. I remember a friend in junior high school who went from being a young kid to having a full beard over the summer. It was amazing.

He had completely transformed in puberty. This is without a doubt the most accelerated rate of development that we will go through at any point in our lives, even faster than infancy in terms of the huge number of different cognitive and physical changes. Not surprisingly, this same individual was mostly bald by his early twenties due to his exceedingly high levels of DHT. I played soccer with this kid, and he was like a grown man dribbling past everybody. He had a full beard and was bald at 20, which illustrates the interesting rate of maturation and aging. It is hard to know the rate of aging.

There are some genetic tests that can now allow you to assess the speed of entry and exit from puberty. This work has been pioneered by David Sinclair at Harvard and others. I hypothesize that this could be an interesting window into how fast one is aging or developing. Development does not just start at birth and end after puberty, but continues throughout one’s life. It is often seen that boys or girls will develop secondary sexual characteristics at different rates.

Sometimes it’s sequential: You might see a kid grow very tall or have a big growth spurt, but then breast development will come a little bit later, followed by other features. This can also be observed in boys. For example, my friend developed a full beard, went bald, and was quite muscular and a great athlete, going through puberty exceedingly fast. Others may take longer; for instance, someone may go through puberty at age 14, but not start to accumulate facial hair until much later, or their voice may change first, very early.

Steve Glickman was interested in the role of hormones in determining the behavior of the hyenas. He had a colony of hyenas, spotted hyenas, that lived within caged enclosures in Tilden Park behind the UC Berkeley campus. He was interested in the role of hormones in determining the behavior of the hyenas. He noticed something very interesting about the hyenas. The female hyenas, which were larger than the male hyenas, had clitorises the size of a male hyena’s penis. He realized that the female hyenas were exposed to higher levels of testosterone in the womb and then they wouldn’t get the other secondary sexual characteristics until much later. This led him to question how this impacted or related to overall trajectory or rate of aging. It is an interesting thing to think about for each and every one of us. He offered us the opportunity to do an experiment while listening to the podcast.

A Federally Funded field station brought over animals from Africa or bred them there. The reason why they were hyenas in Tilden Park, enclosed in the park, is because hyenas exhibit an incredible feature to their body, hormones, and social structure. Unlike many species, the male penis of a hyena is actually smaller than the female clitoris, though the penis itself is not particularly small. This means that the hyena clitoris’ are extremely large. It is well known that in spotted hyenas, the females are dominant. After a kill, the females will eat first, and then their young will eat.

When female hyenas give birth, they do not use the vaginal canal that we are accustomed to seeing. Instead, they give birth through a large clitoris-like phallus. This is not a phallus, but a clitoris. It splits open, and many fetuses die during the course of hyena development and birth. This large clitoris is normal for a hyena, and the baby comes through the tissue. This is a very traumatic birth, and a lot of tissue is torn away.

Female hyenas have a masculinization of the genitalia due to very high levels of androstenedione, a prohormone to testosterone. This was discovered through careful research done by Steve Glickman, Christine Drey and others. Androstenedione is made into testosterone through the enzyme 17-beta-hydroxy steroid dehydrogenase. This complicated pathway helps explain why a lot of baby hyenas die.

It’s a fairly straightforward pathway biochemically. You may recall during the 90’s and 2000’s there were a lot of performance enhancing drug scandals, in particular in Major League Baseball. It was purported, although I don’t know that it was ever verified, that the major performance enhancing drug of abuse at that time, in particular players whose names we won’t mention but you can Google it if you want to find out, was androstenedione.

I actually recall long ago, when you could buy androstenedione in the health food stores. And so it was sold over the counter. So a lot’s changed since then. But it’s interesting that these hyenas, with these highly androgenized genitalia accomplish that through high levels of androstenedione in the females.

Now if that’s unusual, what might be even more unusual is that a graduate student that I was working with at the time.

Nicola Sitka was a trained animal behavioral expert who had trained ferrets for the show “BeastMaster” and wolves for television shows. She also had two large dogs that would listen to her commands, unlike my dog. She was studying a species of mole that lived in Tilden Park, which had the capacity to trans differentiate its testes into ovaries in order to balance out the ratio of males and females in the population and keep reproduction at appropriate levels. This ability of some animals to adjust the androgenized or estrogenized gonads in order to adjust the ratios of offspring is remarkable.

This plant biologist told me that plants make hormones like estrogen and testosterone to help them survive and reproduce. For example, pine pollen looks a lot like testosterone, which helps to attract pollinators. Furthermore, marijuana plants have estrogenic properties, which may help them to survive in certain environments. Interestingly, factory meats are also estrogenic. Therefore, this isn’t a plant versus meat thing.

Plants don’t have a brain or neurons, yet they have adapted ways to push back on populations of rodents and other species of animals that eat them. This adaptation includes increasing the estrogen levels of the males in that population to lower the sperm counts, thereby keeping the population levels in check and allowing the plants to continue to flourish. This plant to animal warfare is fascinating and shows that plants are capable of adapting in creative ways.

Hormones are not only impacting tissue growth and development within individuals, but also between the mother and offspring. The placenta is an endocrine organ, and this communication is not exclusive to humans and animals, but also plants. Humans are using certain herbicides which have been shown to disrupt endocrine pathways. This interplay between humans, animals, and plants is one way in which the environment can promote well-being and longevity. An important paper was published in the Proceedings of the National Academy in 1987 by Steve Glickman and colleagues which hypothesized that it was androstenedione. A feature article about this discovery can be found by Googling Glickman hyenas science magazine.

The discoveries of moles and hyenas have had a strong impact on animal behavior and endocrinology. They have also had a significant impact on understanding conditions that show up in the clinic, such as pseudo hermaphroditism. Pseudo hermaphroditism is when a baby is born and it is unclear if they are a boy or a girl based on their genitalia. This can cause ethical and other issues, such as deciding whether to raise the baby as a boy or a girl. It is not uncommon for this to happen, and there have been cases where people have gone against the chromosomal sex, with the person being very unhappy with the outcome, and cases where they have gone with the chromosomal sex and the person being very happy with the outcome. Additionally, there have been cases of people being treated with hormones and cases of people not being treated with hormones.

It is complicated to understand the effects of hormones on sexual development, however studies on androstenedione in hyenas and pseudo-hermaphroditic moles have had a great impact on the science and therapeutics around these issues. Last but not least, I want to discuss how exposure to androgens while we were in utero impacted our sexual preferences and other aspects of sexual development. This has been widely discussed in popular press and I was involved in the work as a graduate student in the department that first published this work. I am an author on the paper and I know the people that did this work.

Dennis McFadden was a researcher at UT Austin who studied the auditory system. People would come into his laboratory and he would explore different aspects of the psychophysics of hearing, such as hearing thresholds and frequency thresholds. He observed that young males tended to have auto acoustic emissions more often than young females did. Auto acoustic emissions are sounds made by the ears that can only be picked up by a special apparatus as they are in a very low frequency.

Your ears are making sound! It turns out there is a sex difference in auto acoustic emissions; those who self-report as lesbians have significantly more than those who do not. Dennis discovered this, which was an important discovery that pointed to the fact that there are biological sex differences independent of sex. This was illustrated by the fact that your ears are actually making sound.

This study was important because it identified a phenomenon – auto acoustic emissions – that was independent of anything related to sexual or social behavior. Previously, people had explored whether homosexuals had lower testosterone than heterosexuals and the result was often the opposite – gay men often had higher testosterone. This became controversial as people argued that sexual behavior could be related to testosterone. This study attempted to look at the equivalent phenomenon in people who self-reported as lesbian or heterosexual, making it a complex issue.

It was a seminar on sexual dimorphism
in the nervous system.

In 1998, I was a graduate student at UC Berkeley, studying under Mark Breedlove, a scientist who specialized in sexual dimorphism in the brain, spinal cord, and nervous system. I’ll never forget the day Mark came running down the hall, asking me to give him my hands. He pulled out a ruler and started measuring my fingers, taking down a couple of measurements before leaving. I was confused, until I remembered I was in a course Mark was teaching at that point – a seminar on sexual dimorphism in the nervous system.

The D4 is your ring finger. In males, the average ratio, the D2 is shorter than the D4. In females, the D2 and D4 are about the same size.

Mark directed a study exploring finger length ratios of males and females, as well as people who self-reported as homosexual or heterosexual. The study found that, on average, the ratio of the index finger (D2) to the ring finger (D4) was shorter in males than in females. It is important to note that this study did not attempt to explain the cause of this difference.

Your thumb is D1, your index finger is D2, your middle finger is D3, your ring finger is D4, and your pinky is D5. The ratio of D2 to D4 is greater in self-reported females than in males, meaning that the length of digits D4 and D5 are more similar in females than in males. This effect is particularly pronounced on the right hand, although not always.

The D2 to D4 difference has to be measured correctly. You can’t just look at somebody’s hands and assume their level of testosterone exposure in utero. You have to actually measure it from the base of the finger where there’s that first crease, all the way to the tip past the fingernails. It is not normally visible from the back of the hand, although sometimes you can see it.

In my case, my D4 is a little bit longer than my D2. On my right hand, the difference is more pronounced, while on my left hand the difference is far less pronounced. In general, the ratio of the length of the ring finger to the pointer finger is slightly longer. It has been found that the more androgen an individual is exposed to in utero, the smaller this ratio becomes.

Females tend to have more equal finger lengths due to less androgen exposure in utero. This subtle difference has been found to be an average, and has been replicated six times since it was first published in Nature in 2000. Furthermore, men who self-report as homosexual tend to have either the typical male pattern of D2 to D4 ratio, or a hyper-masculinized D4 to D2 ratio. This suggests that this trait is established in utero, and not modified by behavior.

A primary sexual characteristic present at birth is the interaction between hormones and behavior. This is an important concept that we have been discussing and will discuss further. Our next episode will explore how hormones impact behavior, but also how behavior impacts hormones. This specific case is of hormones impacting a primary sexual characteristic, which does not show up during puberty, but rather is established in utero. I remember collecting this data with my collaborators on this work.

Simon LeVay, who trained under them, went on to do a studyon the hypothalamus in homosexual versus heterosexual men.

I wasn’t the main driver on the work, but I participated in some of the analysis. People that self-report as lesbians also tend to have a smaller D2 to D4 ratio, which is consistent with the auto acoustic emission study that Dennis McFadden had published. This points to the fact that early exposure to androgens may have an impact, not just on androgenization of the body plan, but also separately on sexual preference.

This raises all sorts of interesting questions about the biological basis of sexual preference. Another study conducted by Simon LeVay, who trained under Hubel and Wiesel (who won the Nobel Prize for discovery of critical periods for brain plasticity) looked at the hypothalamus in homosexual versus heterosexual men.

The pioneering research of Simon LeVay and his colleagues defined some of the most important aspects of how we see and understand brain plasticity. Simon LeVay trained with them and then went on to discover that in the brains of people who self-report homosexual, there is a brain difference in an area called the Interstitial Nucleus of the Anterior Hypothalamus (INAH). This was published in Science, and then replicated no fewer than six times, as well as the McFadden results that point to strong biological correlates of mate choice and sexual preference, which tie directly to things like androgenization or estrogenization.

He says that the only thing that we know for sure about sex is that it’s not binary.

We could call it maleness or femaleness, but that’s sort of tricky territory due to the huge range in which sex can be defined. If you want to measure your D2 D4 ratio, you’re welcome to, but you also have to understand that it’s not predictive of anything. It’s just a window into the possible androgen exposure that you had early in life. There are plenty of men who report themselves as heterosexual who have similar D2 D4 ratios to females, and there are plenty of females whose index fingers are shorter than their ring fingers and are perfectly happy where they say they are. We are inclined to believe them being heterosexual. Mark tells a really good joke that the only thing we know for sure about sex is that it’s not binary.

If you want to know whether somebody is homosexual or heterosexual, simply look at their hands and their D2 D4 ratio – you’ll be right 96% of the time. This is because, on average, people report themselves as heterosexual. However, these numbers may be changing. This falls within the realm of statistical significance, but it does not necessarily mean that hormones are causing same or opposite sex partner choice. Other factors can also impact partner choice later in life. The study did not look at people who reported being bisexual, as there haven’t been many studies on that yet.

It appears that the probability of a male human self-reporting as homosexual increases with the number of older brothers that he has. This does not mean that having an older brother, or even 10 older brothers, guarantees that someone will self-report as homosexual. However, statistically, the likelihood increases with each successive older brother. This phenomenon may be due to the mother’s record of carrying male fetuses, as male fetuses secrete certain hormones, such as dihydrotestosterone, that can have epigenomic or placental effects. This conversation is separate from the current controversies around gender and sex, which are grounded in the concepts discussed today and need to take into account the effects of hormones on the body and brain, both in terms of early and late effects, as well as acute effects, such as those that occur across the menstrual cycle.

We discussed the long-term effects of hormones on gene expression, as well as the many topics we were unable to cover related to sex and hormones, sexual differentiation, and development. We discussed the potential effects of environmental toxins and cell phone radiation, something I never expected to talk about in a podcast. Additionally, we discussed Evening Primrose Oil and its estrogenic effects, and Creatine and its pro DHT effects.

Cannabis and alcohol were discussed. Plants have been found to use aromatase to increase warfare on animals, by converting testosterone to estrogen. We also discussed the interesting case of hyenas with giant clitorises, and moles that can revert from having ovaries to testicles. Throughout the conversation, Costello has been snoring non-stop and has missed all of it, although he may be learning it in his sleep. I understand that this is a lot of information and detail, but I want to remind everyone that you don’t have to absorb all the information at once.

In the next episode, we are going to be talking about the science of sex, the verb, and actual reproduction. We’ll also be discussing the effects of hormones on various aspects of behavior and the ways to modulate hormones through the use of behavior, supplementation, diet, and nutrition. We’ll explore the interactions between hormones, behavior, and important themes such as sex and reproduction, workplace performance, motivation, drive, and anxiety. There is a very interesting relationship between hormones, anxiety, and the desire to explore novelty. It’s important to remember that hormones affect behavior and behavior affects hormones, but that doesn’t mean that cutting off your index finger will increase your testosterone. Lastly, we’ll be discussing how listeners can help support the podcast.

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