How Hormones Shape Sexual Development of the Brain and Body

High-Level Overview

In this solo episode, Andrew Huberman opens a month-long series on hormones by explaining sexual differentiation: how the brain and body become masculinized or feminized during development. He walks through the layers that separate chromosomal sex from gonadal, hormonal and morphological sex, and he corrects a common assumption: it is estrogen, made from testosterone, that masculinizes the brain, and dihydrotestosterone (DHT), not testosterone itself, that forms male genitalia before birth. He then turns to practical concerns: environmental and lifestyle factors that can alter hormones, including evening primrose oil, the herbicide atrazine, cannabis, alcohol and even cell phones, before ending with DHT's role in beards and baldness, the strange biology of spotted hyenas, and research linking prenatal androgen exposure to finger-length ratios and sexual orientation.

The tone is educational and deliberately careful. Huberman says he is going more slowly than usual and choosing his language with care because the topic is sensitive, and he stresses that he is covering biology, not the cultural debate. The episode moves from textbook endocrinology to rare natural experiments, then to everyday tools, with lighter moments from his sleeping bulldog Costello.

The Discussion Explores:

• The difference between chromosomal, gonadal, hormonal and morphological sex
• How steroid hormones act quickly on cells and slowly through gene expression
• Why DHT builds male genitalia in the womb and testosterone drives puberty's changes
• The surprising fact that estrogen, converted from testosterone by aromatase, masculinizes the brain
• Androgen insensitivity syndrome and why hormones only work if their receptors do
• Environmental influences: evening primrose oil, atrazine, cannabis, alcohol and cell phones
• DHT, beard growth, baldness, hair-loss drugs and creatine
• Hyenas, sex-switching moles, finger-length ratios and prenatal hormones and sexual orientation

Deep Dive into Main Ideas

From Chromosomes to Gonads to Hormones

Huberman begins with definitions. A hormone is a chemical released in one part of the body, usually from a gland, that travels and acts on tissues elsewhere, unlike neurotransmitters, which act locally. Glands like the thyroid, testes and ovaries make hormones, and brain regions like the hypothalamus and pituitary release hormones that trigger the release of others. He asks listeners to set aside cultural connotations of "masculine" and "feminine" and focus only on biology.

He separates several layers of sex. Chromosomal sex is typically XX or XY, though XXY and XYY also occur. Gonadal sex refers to whether someone has testes or ovaries. On the Y chromosome, genes such as SRY promote the formation of testes, and another gene encodes Müllerian inhibiting hormone, which suppresses the Müllerian ducts that would otherwise form part of the female reproductive tract. Hormones don't come only from the fetus: the placenta is an endocrine organ, and if a mother's adrenal gland produces unusually high testosterone, for example because of a tumor, an XX fetus can show some masculinized features. Hormonal and morphological sex (the body plan, genitalia, jaw and so on) add further steps, making it "a long distance from chromosomes to gender identity."

How Steroid Hormones Work

Huberman explains that hormones can act fast, like adrenaline raising heart rate, or slowly. The sex steroids, testosterone and estrogen, do both. They can signal quickly at cells, including in the brain, but because they are lipophilic (fat-loving), they can pass through cell membranes and the nuclear envelope and interact with DNA to turn genes on or off. That long-term gene regulation is how processes like suppressing the Müllerian ducts and promoting testes unfold.

He also notes that sexual development isn't only about adding masculine or feminine traits. It also involves demasculinization and defeminization, actively suppressing certain pathways. And hormones affect not only the body but the brain and spinal cord, shaping which behaviors are possible. He distinguishes primary sexual characteristics present at birth from secondary ones that appear at puberty.

DHT, Genitalia and the "Penis at 12" Condition

Contrary to what many assume, Huberman explains, testosterone isn't what builds the penis before birth. In the fetus, testosterone is converted by the enzyme 5-alpha reductase into dihydrotestosterone (DHT) in a structure called the tubercle, and DHT drives penis development. He describes DHT as the dominant androgen in males, involved in aggression, strength, beard growth and male pattern baldness. At puberty, the brain releases kisspeptin, which triggers gonadotropin-releasing hormone and luteinizing hormone, stimulating the testes to produce testosterone, which then drives secondary characteristics like further genital growth, pubic hair and a deeper voice.

A natural experiment shows this clearly. A rare mutation that eliminates 5-alpha reductase, first identified in the Dominican Republic and described in Science in the 1970s, means XY babies are born with little or no external penis and are often raised as girls. Around age 11 to 13, when puberty's testosterone surge arrives, a penis develops. The condition is known locally by a name meaning roughly "penis at 12" (guevedoces). Huberman says outcomes vary widely in how these children identify and how families and communities treat them, and some communities have adopted something like a third category. The key lesson: DHT drives primary genital development, while testosterone drives the later secondary changes.

Estrogen Masculinizes the Brain

Huberman's central surprise is that "The masculinization of the brain is not accomplished by testosterone. It is accomplished by estrogen." Neurons in the brain contain aromatase, an enzyme that converts testosterone into estrogen, and it is that locally made estrogen that organizes the XY brain in a masculine pattern. He quotes the conclusion of a paper by his Stanford colleague Nirao Shah: estrogen sets up the masculine repertoire of sexual and (in animals) territorial behaviors in the brain, and testosterone later controls the display of those behaviors.

He illustrates aromatase with examples later in life. Body fat is a major source of aromatase, which is why some boys develop temporary or lasting breast tissue during puberty as rising testosterone is partly converted to estrogen. Bodybuilders taking very high doses of androgens can develop gynecomastia for the same reason, sometimes resorting to surgery or estrogen blockers. He also stresses that estrogen matters in males: if it's too low, libido and sexual behavior can suffer, so neither sex wants estrogen too high or too low.

Androgen Insensitivity: Hormones Need Receptors

Huberman describes androgen insensitivity syndrome to show that a hormone must bind its receptor to have an effect. People with this condition are XY, have internal testes that produce testosterone, and lack Müllerian structures, but their testosterone receptors are mutated, so their bodies can't respond to it. They look female, generally report feeling like girls and later women, and often discover the condition only when they don't menstruate at puberty. They lack a uterus and ovaries and generally can't conceive.

He declines to name historical figures rumored to have had it, because doing so gets at the heart of an unanswerable question of whether they were "male or female." He notes that this receptor-level principle is also relevant to performance-enhancing compounds like SARMs, which act on the receptor side, a topic he promises for a later episode.

Environmental Influences: Primrose Oil, Atrazine and Sperm Counts

Huberman says his discussion draws on textbooks, particularly Behavioral Endocrinology by Randy Nelson and Lance Kriegsfeld, and on the work of Tyrone Hayes at UC Berkeley. He cites evening primrose oil, popular in skin products, which has estrogen-like compounds; he says there were cases of young boys developing breast buds from skin contact with mothers or sisters who used it. Likewise, people using testosterone creams should avoid skin contact with others, especially children. He mentions pine pollen as a plant compound structurally similar to testosterone, though its bioavailability in humans is unclear, and says the effects of soy on estrogen have some decent evidence but that other factors may be more significant.

Hayes studied frogs and identified atrazine, an herbicide found in waterways across the US and beyond, as a cause of severe testicular malformations; at some Western and Midwestern sites, up to 92% of male frogs had testicular abnormalities. Huberman cites human data on declining sperm counts: average sperm density fell from 113 million per milliliter of semen in 1940 to 66 million in 1990 in the US and Western Europe, semen volume dropped about 20%, and the proportion of normal sperm production reportedly fell from 56.4% to 26.9% between 1981 and 1991. He attributes much of this to widely used herbicides, suggests similar disruption of estrogen pathways might help explain earlier puberty in girls, and mentions the fungicide vinclozolin, an anti-androgen that prevents penis formation in rats. He leaves it to listeners how cautious to be.

Cannabis, Alcohol and Cell Phones

Huberman, who says he isn't a cannabis user and isn't making a moral or legal argument, reports that with one exception, many studies show THC or other cannabis compounds significantly increase aromatase activity, converting more testosterone to estrogen. Anecdotally, he says, male users have a higher incidence of gynecomastia, and studies he found suggest cannabis use during pregnancy shifts fetal hormones toward more estrogenic outcomes, potentially counteracting masculinizing effects on sexual characteristics. Given how common cannabis use is during puberty, he calls this important. Alcohol, especially beer and other grain alcohols, can also increase estrogenic activity, so drinking during pregnancy is clearly harmful and drinking during puberty is probably unwise for both boys and girls. He emphasizes that puberty doesn't switch on and off, and development continues across life.

On cell phones, he says he uses his phone a lot, doesn't consider it evil, and knows of no quality evidence that phones harm the brain. But he describes a growing body of studies, some in good journals, showing effects of cell phone emissions on testicular and ovarian development in animals, starting with a 2013 rat study. In humans, a paper in Clinical Biochemistry (Eskander and colleagues) linked phone proximity, frequency of use, and living near cell base stations to lower cortisol, thyroid hormones, prolactin in young females and testosterone in both sexes. He cautions that such studies can be confounded (living near a highway might show similar effects) and that phones can't explain declines that began decades earlier, but he personally avoids keeping his phone on and in his pocket.

DHT, Beards, Baldness and Creatine

DHT binds receptors in the face to promote beard growth and receptors on the scalp to promote hair loss. The genetic pattern of DHT receptors, he says, determines both beard density and whether and where someone goes bald, which is why some populations share distinct patterns, and why people with high DHT may still have light beards if they have few facial receptors. The folk wisdom he mentions is that your mother's father's baldness predicts your own. Most hair-loss drugs are 5-alpha reductase inhibitors, developed partly from research on the guevedoces mutation, and Huberman warns that their side effects can be severe for many people because DHT supports libido, strength, connective tissue repair and drive.

He adds that creatine, a popular supplement that pulls water into muscle, supports strength and may mildly aid cognition, appears in studies he found to increase 5-alpha reductase activity. That fits anecdotal reports that it can promote hair loss in some people. He recalls a middle-school friend who returned from summer break with a full beard, dominated at soccer and was mostly bald by his early 20s, and wonders whether the speed of puberty might offer a window into how fast someone ages overall, calling it a hypothesis.

Hyenas, Moles and Plant Warfare

Huberman tells stories from his graduate days at UC Berkeley. Professor Steve Glickman kept a colony of spotted hyenas in enclosures in Tilden Park. In this species, females are dominant and eat first after a kill, and their clitoris is larger than the male penis; females give birth through it, a traumatic process that many cubs don't survive. Glickman, Christine Drea and colleagues traced this to very high levels of androstenedione, a precursor that is converted to testosterone. Huberman notes androstenedione was once sold over the counter and was allegedly used in Major League Baseball's steroid era.

A fellow graduate student, Nicole Sipka, a former animal trainer, studied a Tilden Park mole that can convert its testes into ovaries to balance the male-female ratio in its population. A plant biologist also told Huberman that some plants make estrogen-like or testosterone-like compounds, possibly as a kind of plant-to-animal warfare: raising estrogen in male animals that eat them lowers sperm counts and keeps those populations in check. Huberman says the hyena and mole research also informed clinical understanding of babies born with ambiguous genitalia, where decisions about how to raise them are ethically complex and must be made case by case.

Prenatal Hormones, Finger Ratios and Sexual Orientation

Finally, Huberman describes research on how prenatal androgen exposure relates to sexual orientation, including work he co-authored as a graduate student. Dennis McFadden found that otoacoustic emissions, sounds the ears themselves produce, differ by sex, and that women who self-report as lesbian show a pattern closer to that of men. Mark Breedlove then led a study, published in Nature in 2000 and replicated six times, on the ratio of the index finger (D2) to ring finger (D4). On average, more prenatal androgen exposure means a longer ring finger relative to the index finger. Females typically have more similar lengths, especially on the right hand, while men who self-report as homosexual show typical or even hyper-masculinized ratios, and lesbian women tend to show smaller ratios too. Because this ratio is set before birth, it can't be influenced by behavior.

Huberman repeatedly stresses these are averages, not predictors. Fingers must be measured carefully from the base crease to the tip, and many heterosexual people have ratios typical of the other sex. He shares Breedlove's joke that you could guess everyone is heterosexual and be right about 96% of the time, which shows how non-causal these findings are. He also mentions Simon LeVay's finding of a difference in a hypothalamic region called INAH in homosexual men, and research suggesting that the probability of a man identifying as homosexual rises with each older brother, possibly because of a maternal "record" of previous male pregnancies. He closes by noting none of this settles current debates about gender, which need to consider all of these layers.

Conclusion

This episode builds a foundation for understanding how hormones shape who we become. The key lessons are that sex develops in layers, from chromosomes to gonads to hormones to body shape; that DHT builds male genitalia before birth while testosterone drives puberty; that estrogen made from testosterone is what masculinizes the brain; and that hormones only work when their receptors do. Huberman pairs this with practical caution about things that can shift hormone balance, from estrogenic skin products and testosterone creams to atrazine, cannabis, alcohol and possibly how close you keep your phone, while acknowledging the uncertainty in some of that evidence. The fascinating examples, from hyenas to finger ratios, reinforce his broader theme: hormones affect behavior, behavior affects hormones, and biology is far more surprising than the simple stories we often tell about it.

This is a summary of "Essentials: How Hormones Shape Sexual Development" from Huberman Lab, giving you the GIST so you can decide if you want the REST. Listen to the full episode.