Testosterone is produced primarily in the testes, with smaller contributions from the adrenal glands and, in women, the ovaries. Once released into the bloodstream, it reaches tissues throughout the body, driving muscle growth, bone maintenance, red blood cell production, fat distribution, skin and hair changes, and shifts in mood and cognition. The story of testosterone is less about a single hormone doing a single job and more about a molecule that gets modified, transported, and interpreted differently depending on which tissue it reaches.
Where Testosterone Is Made
In men, roughly 95 percent of circulating testosterone comes from specialized cells in the testes called Leydig cells. These cells sit between the seminiferous tubules, the coiled structures where sperm develop, and they respond to a signal from the brain: luteinizing hormone, or LH. When LH docks onto receptors on a Leydig cell’s surface, it triggers a cascade that shuttles cholesterol into the cell’s mitochondria. There, an enzyme called CYP11A1 clips the cholesterol molecule into a precursor called pregnenolone, which is then converted through several steps into testosterone. The bottleneck in the whole process is simply getting cholesterol to the right spot inside the mitochondria; a set of specialized proteins forms a complex at the mitochondrial membrane to make that handoff happen.1PubMed Central. Leydig cells: formation, function, and regulation
The adrenal glands, which sit atop the kidneys, also produce androgens, though mostly weaker ones like DHEA and androstenedione. These are converted into testosterone in peripheral tissues. In women, the ovaries and adrenal glands split the work roughly evenly, producing much lower total amounts. Even the skin can convert circulating weak androgens into more potent forms locally, which matters for conditions like acne.2PubMed. Cutaneous androgen metabolism: basic research and clinical perspectives
How the Brain Runs the Show
Testosterone production does not run on autopilot. It is controlled by a feedback loop connecting the hypothalamus, the pituitary gland, and the gonads. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in pulses, which tells the pituitary to secrete LH and follicle-stimulating hormone (FSH). LH then stimulates the Leydig cells to produce testosterone, while FSH supports sperm development. When testosterone in the blood rises high enough, it feeds back to the hypothalamus and pituitary, dialing down GnRH and LH release. This negative feedback keeps levels within a relatively stable range.3PubMed. Physiology of the Hypothalamic Pituitary Gonadal Axis in the Male
This feedback system is why injecting testosterone from outside the body can paradoxically lower the body’s own production. When the brain senses an abundance of circulating testosterone, it shuts down LH, causing the Leydig cells to go quiet. The consequences of that are explored further below.
How Testosterone Travels
Testosterone does not float freely through the blood in large quantities. Once it leaves the Leydig cells and enters the bloodstream, it binds to carrier proteins. The two main ones are sex hormone-binding globulin (SHBG) and albumin. SHBG grips testosterone tightly, while albumin holds it loosely. Only about one to three percent of circulating testosterone is truly unbound, or “free.”4PubMed Central. A Reappraisal of Testosterone’s Binding in Circulation: Physiological and Clinical Implications
The balance between free and bound testosterone matters because free testosterone is the fraction that can most easily enter cells and exert effects. SHBG-bound testosterone is essentially locked up during transit, whereas albumin-bound testosterone dissociates quickly enough that some tissues can access it. This is why doctors sometimes measure free testosterone or calculate “bioavailable” testosterone (the free fraction plus the albumin-bound fraction) rather than relying solely on total testosterone.5PubMed Central. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology SHBG levels vary with age, weight, liver function, and thyroid status, so two people with the same total testosterone reading can have very different amounts of active hormone available to their tissues.
Conversion Into Other Hormones
Testosterone is not always the final product. Two enzymes convert it into distinct hormones with their own effects. The enzyme 5-alpha reductase turns testosterone into dihydrotestosterone (DHT), a more potent androgen that drives prostate growth, facial hair development, and, less welcomely, male-pattern hair loss and acne.6PubMed Central. 5alpha-reductase: history and clinical importance The prostate, skin, and hair follicles are especially rich in 5-alpha reductase, which is why those tissues are so androgen-sensitive.7PubMed Central. The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme?
The second enzyme, aromatase, converts testosterone into estradiol, the primary estrogen. This conversion happens in fat tissue, bone, brain, and other sites. It sounds counterintuitive that a “male” hormone is routinely turned into a “female” one, but estradiol is critical for male bone health. Studies of men who lack aromatase show that without this conversion, bones fail to mature properly. Pubertal bone changes that were once assumed to be purely testosterone-driven turn out to depend heavily on estradiol produced from testosterone.8PubMed. The essential role of the aromatase/p450arom
What Testosterone Does in Muscle
Skeletal muscle is one of the most testosterone-responsive tissues in the body. Testosterone increases muscle protein synthesis and activates satellite cells, which are the resident stem cells of muscle fiber. When a muscle fiber grows in response to training or hormonal stimulation, it eventually needs more nuclei to manage the larger volume of protein. Testosterone promotes the fusion of satellite cells into existing fibers, supplying those extra nuclei.9PubMed Central. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement
Research in healthy young men given graded testosterone doses has quantified this effect. At higher doses, satellite cell numbers climbed from a baseline of about 2.5 percent to 15 percent of total fiber nuclei, and the absolute satellite cell count per millimeter of fiber rose several-fold. The increase in satellite cell numbers correlated with the rise in both total and free testosterone.10PubMed. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men This mechanism explains why supraphysiological testosterone doses, like those used in performance doping, produce muscle growth even without exercise. It also explains why loss of testosterone with aging or disease leads to gradual muscle wasting.
Bone Density
Testosterone supports bone mineral density through both direct and indirect pathways. Directly, androgen receptors in bone cells respond to testosterone. Indirectly, the aromatase conversion to estradiol described earlier plays a major protective role, particularly in slowing the breakdown of old bone. In men, declining testosterone with age is associated with reduced bone density, and testosterone replacement in men with low levels has been shown to improve it.11PubMed Central. Testosterone and Bone Health in Men: A Narrative Review
The relationship is not exclusive to men. In a large analysis of women aged 40 to 60, higher testosterone levels were positively associated with lumbar spine bone density, even after adjusting for age, body mass index, and other factors.12Scientific Reports. Association between testosterone levels and bone mineral density in females aged 40–60 years from NHANES 2011–2016 Testosterone is not just a “male bone hormone.” Women’s skeletons respond to it as well, though the clinical implications for treatment remain limited.
Red Blood Cell Production
One of the more medically relevant effects of testosterone is its stimulation of red blood cell production. Testosterone boosts erythropoietin (EPO), the kidney hormone that tells bone marrow to make more red blood cells, and it suppresses hepcidin, a liver hormone that restricts iron availability. In men receiving testosterone therapy, hemoglobin rose by about 7 to 10 percent and hematocrit increased correspondingly. After the initial EPO surge, levels returned partway toward baseline even while testosterone was still being given, but EPO remained higher than expected for the elevated hemoglobin, suggesting the body resets its “thermostat” for red blood cell production.13PubMed Central. Testosterone Induces Erythrocytosis via Increased Erythropoietin and Suppressed Hepcidin: Evidence for a New Erythropoietin/Hemoglobin Set Point
This effect can be beneficial for men with anemia due to low testosterone, most of whom see hemoglobin climb back into normal range with treatment. But it can also become a side effect: if hematocrit rises too high, blood becomes thicker, which raises the risk of clotting. This is why doctors monitor blood counts in men on testosterone therapy, and it is the main reason some patients need periodic dose adjustments or blood donation.
Skin, Hair, and Sebaceous Glands
Skin is an active site of androgen metabolism. Sebaceous glands and hair follicles contain the enzymes needed to convert weaker circulating androgens into testosterone and, further, into DHT. The distribution of these enzymes varies by body site: sebaceous glands in acne-prone areas of the face show higher reductive enzyme activity than glands in areas that rarely break out. Hair follicles rely heavily on the type II isoenzyme of 5-alpha reductase, which explains why drugs that block that enzyme can slow androgenetic hair loss.2PubMed. Cutaneous androgen metabolism: basic research and clinical perspectives
The relationship between androgens and hair is paradoxical: testosterone and DHT stimulate facial and body hair growth while simultaneously promoting hair loss on the scalp. The hair follicles in different regions of the body express different receptor profiles and respond to the same hormonal signal in opposite directions. This is why a man going bald may simultaneously notice thicker body hair.
Metabolism and Body Composition
Testosterone has broad effects on how the body handles fat, sugar, and cholesterol. Men with low testosterone tend to accumulate more visceral fat (the deep abdominal fat surrounding organs), show reduced insulin sensitivity, and have less favorable cholesterol profiles. Clinical trials of testosterone replacement in these men have shown improvements in insulin resistance, reductions in body fat (especially truncal fat), and decreases in triglycerides and total cholesterol.14PubMed. Testosterone: a metabolic hormone in health and disease
Longitudinal data reinforce this connection. In one study, men with the lowest testosterone at baseline developed significantly higher insulin resistance years later, even after accounting for waist-to-hip ratio, physical activity, alcohol intake, and other metabolic risk factors. Interestingly, the reverse did not hold: high insulin resistance at baseline did not predict future low testosterone, suggesting the direction of influence runs primarily from testosterone to metabolic health rather than the other way around.15PubMed Central. The association between serum testosterone and insulin resistance: a longitudinal study
Brain and Mood
Testosterone reaches the brain, where it influences serotonin signaling, among other systems. Animal studies have shown that castration reduces serotonin receptor and transporter expression in key brain regions, and that restoring testosterone (or its aromatized product, estradiol) brings those markers back up. DHT, the non-aromatizable form, did not have the same effect, suggesting that testosterone’s mood-related actions in the brain depend at least partly on its conversion to estradiol.16PubMed. Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory Clinically, men with very low testosterone often report fatigue, low motivation, and depressed mood, and some of these symptoms improve with testosterone restoration. The relationship between testosterone and cognition is less settled and varies by age and health status.
The Daily Rise and Fall
Testosterone levels are not constant throughout the day. They follow a circadian rhythm, peaking in the early morning and reaching their lowest point in the late afternoon. In younger men, the difference is striking: levels measured at 4 p.m. can be 20 to 25 percent lower than levels measured at 8 a.m. This swing diminishes with age; by 70, the morning-to-afternoon difference shrinks to about 10 percent.17PubMed Central. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men
A more recent study of men with symptoms of testosterone deficiency found that the difference between morning and afternoon levels was actually modest on a population level, with a median morning reading of about 387 ng/dL versus 373 ng/dL in the afternoon. But individual variation was wide: about a quarter of the men had an afternoon drop exceeding 100 ng/dL, while 13 percent actually had higher afternoon values. Younger men showed more variability than older men.18PubMed Central. Analysis of Diurnal Variation in Serum Testosterone Levels in Men With Symptoms of Testosterone Deficiency Clinical guidelines therefore recommend morning blood draws, partly to catch levels at their peak and partly for consistency. A man who tests borderline low in the afternoon may be perfectly normal in the morning. In the earlier study, 17 men whose afternoon levels fell below 300 ng/dL all tested normal on three separate morning draws.
The underlying rhythm involves at least a 43 percent fall from peak to trough over 24 hours, with the acrophase (the peak time) landing around 7:00 to 7:30 a.m. in both young and middle-aged men.19PubMed. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men
Testosterone Across Life Stages
Androgen activity is low before puberty. During pubertal development, the testes ramp up testosterone production, which deepens the voice, increases muscle mass, drives genital growth, and triggers the growth spurt. Intratesticular testosterone concentrations and androgen receptor expression both rise dramatically during this period.20Endocrinology. The Role of Androgen Signaling in Male Sexual Development at Puberty
In women, testosterone levels are lower but still physiologically important. After menopause, both ovarian and adrenal androgen output decline. Randomized controlled trials have shown that exogenous testosterone in postmenopausal women can improve sexual desire, arousal, and orgasmic response, though evidence for benefits beyond sexual function (bone density, hot flashes, lean body mass) remains insufficient.21PubMed. The role of testosterone therapy in postmenopausal women: position statement of The North American Menopause Society A complicating factor is that standard laboratory assays perform poorly at the low testosterone concentrations typical in women, making it hard to establish a reliable “deficient” threshold.
In aging men, the picture often called “late-onset hypogonadism” turns out to be more nuanced than a simple age-related decline. Obesity and chronic illness are more common drivers of low testosterone than chronological age itself. The testosterone drop in these cases is usually secondary to reduced signaling from the hypothalamus and pituitary (low LH) rather than primary testicular failure (high LH), and it can improve with weight loss or treatment of the underlying condition.22PubMed Central. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment
When Outside Testosterone Shuts Down the Inside
One of the most clinically important consequences of the feedback loop is what happens when you inject testosterone. The brain reads the elevated blood levels as a signal that production is more than adequate, so it turns down GnRH and LH. Without LH stimulation, the Leydig cells shrink, intratesticular testosterone plummets, and spermatogenesis grinds to a halt.23PubMed Central. Exogenous testosterone: a preventable cause of male infertility The result can be azoospermia (zero sperm in the ejaculate) and testicular atrophy, even while blood testosterone is supranormal.24PubMed Central. Pandemic of testosterone abuse: Considerations for male fertility
This is a frequent and under-recognized problem. Many men begin testosterone therapy for fatigue or low libido without being counseled that it can effectively act as male contraception. Recovery of spermatogenesis after stopping exogenous testosterone can take months to over a year, and in some cases full recovery never occurs.25PubMed Central. Clinician’s guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids For men who want to preserve fertility, alternative treatments exist that stimulate the body’s own production rather than replacing it.
Sleep and Other Lifestyle Influences
Sleep is tightly linked to testosterone production. A meta-analysis pooling human studies found that partial sleep restriction (sleeping a few hours less than usual) did not significantly reduce testosterone, but complete sleep deprivation for 24 hours or more caused a clear drop.26Sleep Medicine. Effect of partial and total sleep deprivation on serum testosterone in healthy males: a systematic review and meta-analysis The mechanism may involve serotonin’s inhibitory effect on testosterone production: sleep deprivation raises brain serotonin levels, which in turn suppress the StAR protein that controls cholesterol delivery into the mitochondria of Leydig cells, the same rate-limiting step described earlier.27PubMed. Effects of sleep deprivation on serum testosterone concentrations in the rat
Beyond sleep, body composition and exercise both influence testosterone. Excess body fat increases aromatase activity, converting more testosterone to estradiol, while also promoting the hypothalamic suppression seen in late-onset hypogonadism. Resistance training generally raises testosterone acutely, though the long-term effect on resting levels is debated. Chronic excessive endurance exercise, especially when paired with caloric restriction, can lower levels. Alcohol has a dose-dependent suppressive effect on testicular testosterone synthesis.
Testosterone in Other Species
The testosterone system is ancient and conserved across vertebrates, but the ways animals use it are strikingly varied. In white-tailed deer, testosterone follows a dramatic seasonal cycle tied to breeding season. Mature bucks peak at around 853 ng/dL in January during the rut, compared to roughly 221 ng/dL outside breeding season. Immature bucks show a similar pattern but reach only about half the peak levels of mature animals.28PubMed Central. Patterns of testosterone in male white‐tailed deer (Odocoileus virginianus): Seasonal and lifetime variation
European badgers present an even more unusual situation. While all males show elevated testosterone during the winter mating season and low levels in autumn, two distinct endocrine profiles emerge during spring and summer. Some males drop testosterone to near-quiescent levels after the main breeding season, while others maintain high levels well into summer, suggesting the existence of two endocrinological phenotypes within the same population.29PubMed. Seasonal and inter-individual variation in testosterone levels in badgers Meles meles: evidence for the existence of two endocrinological phenotypes In Iberian ibex, researchers tested whether the autumn testosterone surge causes horn growth to stop, since horns pause growing during the mating season. It turned out that photoperiod (day length) was the primary signal; even when testosterone was blocked with an anti-androgen drug, horns only kept growing if the animals were also held under long-day light conditions.30PubMed. Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids
A Brief History of Knowing About Testosterone
People have understood that the testes do something important for a very long time. In 1849, Arnold Berthold transplanted testes into castrated roosters in Göttingen and showed that the transplants restored masculine traits, effectively founding the field of endocrinology before the word “hormone” even existed (Ernest Starling coined it in 1905).31PubMed Central. Testosterone deficiency: a historical perspective Through the late 1800s, various testicular extracts and even grafts of animal testes onto humans were marketed as rejuvenation treatments, most of which had no real effect beyond placebo.
The breakthrough came in 1935, when Ernst Laqueur in Amsterdam isolated the actual molecule from bull testes and named it testosterone. That same year, Adolf Butenandt and Leopold Ruzicka independently achieved chemical synthesis, work that earned Butenandt and Ruzicka the Nobel Prize in Chemistry in 1939.32Endocrine Abstracts. The history of testosterone Once synthetic testosterone was available, clinical androgen therapy began in earnest, eventually branching into treatments for hypogonadism, anemia, muscle-wasting conditions, and, more controversially, athletic performance enhancement.