Overview of #374 - The evolutionary biology of testosterone: how it shapes male development and sex-based behavioral differences | Carole Hooven, Ph.D.
This episode of The Drive (host Peter Attia, MD) features Carole Hooven, evolutionary biologist and author of The Story of Testosterone. They review how sex chromosomes trigger hormonal cascades in embryonic development, how testosterone and its metabolites (notably DHT) shape genital and brain development during critical windows, how those developmental differences underlie many average behavioral sex differences (e.g., play style, aggression, competitiveness), and the clinical and social implications for hormone therapy, aging, parenting, and contemporary debates about sex and masculinity. Hooven also discusses personal experience with surgical menopause and the cultural aftermath she faced after public statements about biological sex.
Key biological mechanisms explained
- Sex determination basics
- Egg always donates X; sperm donates X or Y → XX (female) or XY (male).
- SRY gene on Y triggers testicular differentiation from an initially bipotential gonad.
- Gonadal hormones and ducts
- Leydig cells in developing testes produce testosterone; Sertoli cells produce anti-Müllerian hormone (AMH).
- Testosterone stabilizes Wolffian ducts (male internal tract); AMH causes regression of Müllerian ducts (female internal tract).
- DHT and 5‑alpha‑reductase
- 5‑alpha‑reductase converts testosterone → DHT locally in genital tissue.
- DHT (higher androgen receptor affinity) is critical for masculinization of external genitalia and prostate; it can act locally without high systemic exposure.
- 5‑alpha‑reductase deficiency is a natural experiment: XY individuals with testes but undervirilized external genitalia at birth who typically masculinize at puberty; evidence shows DHT is not necessary for brain masculinization.
- Androgen receptor and downstream effects
- Testosterone/androgens act as transcriptional regulators, altering expression of thousands of genes during development.
- Androgen receptor variability (e.g., CAG repeat length and receptor density) alters sensitivity to a given testosterone level; a single T concentration can produce different phenotypes between individuals.
- Estrogen in males
- Testosterone aromatizes to estradiol; estrogen has physiological roles in men (bone, libido, body composition).
- Rodents use aromatization in brain masculinization, but human evidence differs (e.g., aromatase deficiency / androgen insensitivity phenotypes highlight species differences).
Developmental timing — critical windows and “mini‑puberty”
- Fetal testosterone surge
- Male fetal testosterone rises in the early second trimester (peaking roughly mid‑pregnancy) and can reach very high concentrations compared to female fetuses; this is a critical window for organizing male-typical body and brain development.
- Mini‑puberty (postnatal surge)
- Males experience a postnatal testosterone peak around ~1–3 months (declining by ~6 months). This “mini‑puberty” appears influential for aspects of brain development, activity levels, growth, and genital development.
- Multiple critical periods
- Different tissues/behaviors can have distinct sensitive windows (genital development vs sexual/aggressive behavior), so timing of hormone exposure matters.
- Lifelong effects
- Early organizational (developmental) effects differ from activational effects of circulating hormones in adulthood. Low T in a 5‑year‑old is not the same explanatory factor as the developmental exposure that shaped brain circuitry.
Behavioral and evolutionary implications
- Sex differences on average
- Across many mammals (and in humans), males on average show higher levels of rough‑and‑tumble play, physical competition, direct confrontation; females more often use indirect/relational tactics in social competition.
- Hooven argues testosterone exposure in development is a principal proximate mechanism explaining many of these average differences, while emphasizing wide individual variation and strong cultural modulation.
- Play and learning
- Rough play among boys can serve adaptive functions: practicing physical competition, learning dominance signaling/submission rules, and reducing later serious aggression via status hierarchies.
- Aggression and crime
- Men are disproportionately represented in violent crime statistics; biology (testosterone-driven development and male physical strength) provides part of the explanation, but culture, law, and social context strongly mediate outcomes.
- Parenting and testosterone
- Male testosterone commonly decreases with pair-bonding and paternal caregiving in humans and other species; lower T is associated with greater paternal investment (adaptive in contexts where male care improves offspring survival).
Clinical implications & hormone therapy insights
- Interpreting testosterone levels
- Single serum T measurements are limited: developmental exposure, androgen receptor sensitivity, sex hormone binding globulin, and individual context matter. Symptoms and function are as important as labs.
- Testosterone replacement therapy (TRT)
- TRT in middle‑aged/older men can improve body composition, bone health, muscle mass, subjective wellbeing in symptomatic hypogonadal men.
- Important risks/considerations: suppression of endogenous spermatogenesis (infertility risk), potential behavioral changes (dose‑dependent; physiological replacement vs supraphysiologic abuse), blood pressure effects, and the need to preserve estrogen via aromatization (estradiol contributes to male libido/body composition).
- For younger men, TRT risks (infertility, suppression of the HPG axis) and the possibility of dependency/abuse argue for caution; HCG or selective strategies can be used to preserve testicular function if treatment is needed.
- Estrogen in men
- Adequate aromatization to estradiol appears important for libido, mood, and body composition; overuse of aromatase inhibitors in men on TRT is often counterproductive.
- Clinical studies show combinations of normal/high T plus physiological estrogen produce favorable outcomes versus low estrogen states.
- Rare conditions informing biology
- Complete androgen insensitivity syndrome (CAIS): XY individuals with nonfunctional androgen receptor develop typical female phenotype despite male chromosomes and high T (converted to estrogen), illustrating androgen receptor necessity for masculinization.
- Aromatase deficiency and other natural experiments highlight divergences between species and complex hormonal roles.
Social, cultural and policy topics raised
- Masculinity and modernity
- Hooven is writing a book on changing cultural views of masculinity, the “masculinity crisis,” and the interplay between biological sex differences and social expectations (education, workforce, parenting roles).
- Denial of sex differences
- She emphasizes the factual reality of two gamete‑based sexes and warns that denial of average biological differences complicates fair policy responses; she also stresses biology is not destiny and individuals vary widely.
- Academic and public fallout
- Hooven described traumatic professional consequences after public statements about biological sex, framing a broader conversation about academic freedom, public debate, and civility.
- Regulation and abuse
- Testosterone is a scheduled/regulated drug due to abuse potential; Hooven argues for particular caution with younger users and broader clinical prudence to avoid unnecessary long‑term fertility loss.
Notable quotes / succinct insights
- “We start out with a gonad that can become either testis or ovary — that’s evolution’s way of not wasting energy.” (on bipotential gonads and SRY)
- “DHT is necessary for full prostate development and masculinization of external genitalia, but it is not what masculinizes the brain.”
- “You cannot judge someone by their current testosterone level — developmental exposure and receptor sensitivity matter far more for many behavioral traits.”
- “Biology is not destiny — there’s huge variation — but understanding sex differences is critical to shaping workable social policy.”
Practical takeaways and recommendations
- For clinicians and patients
- Evaluate symptomatic context first (sleep, nutrition, exercise, obesity, stress) before TRT, particularly in younger men.
- Consider fertility goals before initiating exogenous testosterone; use HCG or other fertility‑preserving strategies if needed.
- Avoid reflexive aromatase inhibition in men on TRT — estradiol has important roles.
- Be aware of individual variability (androgen receptor sensitivity, SHBG, developmental history) when interpreting labs.
- For parents and educators
- Recognize that sex‑typical play styles (e.g., rough play in boys) can be developmentally adaptive; supervised physical play fosters social learning and conflict resolution.
- Monitor but avoid over‑pathologizing normative sex‑differences; prioritize safety and teaching social-emotional skills.
- For policy and cultural conversations
- Ground debates about sex differences, sports, education, and workplace policy in scientific nuance (averages vs variance, developmental mechanisms) rather than ideological absolutes.
- Protect spaces for reasoned disagreement and evidence‑based debate.
Episode context & personal notes
- Carole Hooven’s background: PhD in Human Evolutionary Biology (Harvard), former lecturer, author. Research emphasis: testosterone, sex differences, behavior.
- Hooven’s recent experience: removal from her academic position following public controversy over statements about sex; she’s now writing a book on masculinity and affiliated with a DC think tank.
- Practical anecdote: Hooven reported personal benefit from hormone replacement after surgical menopause — an illustration that small residual ovarian hormones can still affect functioning and that individual experience should be respected in clinical decisions.
This summary highlights the episode’s core scientific explanations, developmental timing, behavioral consequences, and the clinical/social ramifications of testosterone biology as discussed by Peter Attia and Carole Hooven.