The history of testosterone runs from ancient castration and animal-testis remedies to a hormone that was isolated and synthesized in 1935, and from there to today’s prescription testosterone replacement therapy (TRT). For most of that history, people knew what the testes did long before anyone could explain how. Many of the “rejuvenation” treatments sold along the way worked, at best, as placebos, a pattern worth remembering when comparing testosterone products today.
Testosterone history at a glance
| Date | Milestone | Why it mattered |
|---|---|---|
| Antiquity | Castration is widely practised; Pliny the Elder recommends eating animal testes | The effects of the testes were known by observation, with no mechanism |
| 1849 | Arnold Berthold’s rooster experiment in Göttingen | First evidence that the testes act through the blood |
| 1889 | Brown-Séquard reports injecting himself with testicular extract | Launched organotherapy; the effects were almost certainly placebo |
| 1910s–1920s | Testis grafting, the Steinach operation and Voronoff’s monkey grafts | A rejuvenation boom that was later discredited |
| 1935 | Laqueur’s group isolates and names testosterone; Butenandt and Ruzicka publish syntheses | Testosterone becomes a defined chemical that can be made and dosed |
| 1939 | Butenandt and Ruzicka share the Nobel Prize in Chemistry | Recognition for steroid and sex-hormone chemistry |
| 1941–1944 | Huggins links androgens to prostate cancer; Klinefelter and Kallmann syndromes described | Hypogonadism gets defined causes, and testosterone gets a lasting reputation for risk |
| 1950s | Long-acting testosterone enanthate injections | The main treatment for roughly half a century |
| 1990 | US Anabolic Steroids Control Act | Testosterone and other anabolic steroids become Schedule III controlled substances |
| 1990s–2000 | Skin patches, then the first testosterone gel in 2000 | Steadier, closer-to-natural blood levels |
| 2023 | TRAVERSE trial published in the New England Journal of Medicine | No increase in major cardiac events versus placebo in high-risk men |
| 2025 | FDA class-wide labeling changes | Cardiovascular boxed warning removed; blood pressure warning added |
Ancient knowledge: castration and testis remedies
People learned what the testes did mainly by seeing what happened without them. Castration was practised from antiquity for punishment, slavery and court service. In China, eunuchs are documented from about 1300 BCE, and the imperial eunuch system lasted until 1912. Aristotle described the effects of castration on animals and men, and twentieth-century examinations of former court eunuchs found missing beard growth and frequent signs of bone loss.
Treatment followed a simple logic: if losing the testes weakened a man, eating testes might restore him. The Roman author Pliny the Elder recommended animal testes, a remedy in keeping with much of Roman medicine. Physicians in Abbasid Baghdad prescribed testicular extracts, and Chinese sources recorded raw and dried testes as remedies by the twelfth century. None of these could have supplied meaningful hormone: the testes make testosterone but do not store it, and testosterone swallowed by mouth is largely broken down by the liver before it reaches the circulation.
Ayurveda gave virility a branch of its own. Vajikarana, one of the eight classical branches of ancient Indian medicine, dealt with sexual vigour and fertility through herbs, diet and conduct, and the Charaka Samhita devotes a chapter of its treatment section to it. Herbs still sold as testosterone boosters, ashwagandha among them, come from this broader tradition, although its authors knew nothing of hormones.
1849: Berthold’s roosters
The first experiment pointing to a hormone was small. In 1849, Arnold Adolph Berthold, a physiologist in Göttingen, castrated four young cockerels. Two were left as they were. In the other two he transplanted a testis into the abdomen. The birds with transplants went on crowing, fighting and courting hens, unlike the untreated capons.
Because the transplanted testis had lost its original nerve connections, Berthold reasoned that it must act through the blood. That is the core idea of an endocrine hormone. His paper ran to four pages and described four animals. A rival at the same university failed to repeat the work and dismissed it, and Berthold’s finding was largely forgotten for decades. It was a quiet start compared with the rest of nineteenth-century medicine.
1889: Brown-Séquard and the organotherapy craze
Forty years later, testes returned to medicine with far more noise. In 1889 the 72-year-old physiologist Charles-Édouard Brown-Séquard, a respected member of several scientific academies, reported in Paris and then in The Lancet that he had injected himself daily with a mixture of testicular vein blood, semen and juice extracted from dog or guinea-pig testes. He described regaining his old strength, working for hours in the laboratory and measuring stronger limbs on a dynamometer.
The improvements were almost certainly placebo effects, since the extracts could not have contained enough testosterone to matter. The public response was enormous anyway. “Extracts of animal organs by the Brown-Séquard method” were manufactured and sold across Europe and America, and worried physicians later mocked the excesses of organ-extract therapy as “endocriminology”.
The gland-grafting era
In the early twentieth century, some surgeons moved from extracts to transplants. G. Frank Lydston in Chicago transplanted human testes. At San Quentin prison, Leo Stanley implanted testicular material from executed prisoners into other inmates, and later used animal tissue. In Vienna, Eugen Steinach promoted vasoligation, the “Steinach operation”, as a way to rejuvenate ageing men. His follower Serge Voronoff grafted slices of monkey testes into wealthy patients, first in Paris and later in Algiers. In the United States, John R. Brinkley built a lucrative practice on goat-gland operations.
The claims did not survive scrutiny. In 1927 a committee sent by the Royal Society of Medicine in London to assess Voronoff’s work concluded that his claims were unfounded. The grafts could not keep producing hormone, and the reported benefits rested on patient testimony rather than measurement.
1935: testosterone becomes a chemical
Real progress came from chemistry and measurement. In 1929 researchers standardised the capon comb test, which measured male-hormone activity by the growth of a castrated rooster’s comb, echoing Berthold’s experiment. In 1931 Adolf Butenandt isolated the weaker androgen androsterone: about 15 milligrams from roughly 15,000 litres of urine.
In 1935 Ernst Laqueur’s group in Amsterdam extracted about 10 milligrams of a more potent hormone from 100 kilograms of bull testes and named it testosterone. The same year, Butenandt in Göttingen and Leopold Ruzicka in Basel each published a chemical synthesis. Testosterone was no longer a mysterious “vital principle” but a molecule that could be manufactured, purified and dosed. Butenandt and Ruzicka shared the 1939 Nobel Prize in Chemistry, Butenandt “for his work on sex hormones”. Germany’s Nazi government forced him to decline the prize at the time, and he received it after the war. The breakthrough belongs to the wider story of twentieth-century drug development and to the longer history of medication and pharmacy.
From pellets to injections: early testosterone therapy
Because swallowed testosterone was largely inactivated in the liver, doctors first used pellets implanted under the skin and short-acting injections of testosterone propionate. An oral form, 17α-methyltestosterone, was also developed in 1935, but it proved toxic to the liver and later fell out of use in Europe. From the mid-1950s, longer-acting testosterone enanthate injections became the standard treatment for about half a century.
Diagnosis developed alongside treatment. Klinefelter syndrome was described in 1942 and Kallmann syndrome in 1944, giving hypogonadism, the clinical name for deficient testicular function, defined causes. In 1941 Charles Huggins showed that prostate cancer depends on male hormones, work that later earned him a Nobel Prize and left many doctors wary of testosterone for decades. Later research has not shown that normal testosterone levels or properly monitored treatment cause prostate cancer, but prostate monitoring remains part of care.
Ancient & Modern Medicine’s take: History repeats itself in this field. In the 1920s Serge Voronoff’s monkey-gland grafts drew wealthy clients on testimony alone, much as unregulated ‘T-booster’ supplements do today. The lesson running from Berthold’s roosters to the 2023 TRAVERSE trial is the same: measure hormone levels, test treatments against placebo, and judge them on outcomes, not on how patients feel in the first weeks.
Anabolic steroids and doping
In the 1950s and 1960s, drug companies modified the testosterone molecule to try to separate its muscle-building (anabolic) effects from its masculinising (androgenic) ones. Textbooks listed 256 androgenic steroids by 1956 and more than 1,000 by 1976. A purely anabolic compound was never achieved. Medical use of these drugs declined, but they found a long second life in sport and bodybuilding. In the United States, the Anabolic Steroids Control Act of 1990 made testosterone and related anabolic steroids Schedule III controlled substances, which is why testosterone still requires a prescription.
Patches, gels and the “Low T” era
Once laboratories could measure blood testosterone reliably, from the 1970s, it became clear that existing injections produced peaks and troughs far from natural levels. A 1990 workshop sponsored by WHO, NIH and FDA concluded that treatment should aim for physiological concentrations. Transdermal patches followed in the mid-1990s, and the first testosterone gel reached the US market in 2000. Oral testosterone undecanoate, absorbed through the lymphatic system rather than the liver, had been introduced in the late 1970s, a long-acting injectable version came to Europe in 2004, and the FDA approved an oral undecanoate capsule in 2019.
Easier products and heavy marketing to ageing men drove a sharp rise in prescriptions in the 2000s and early 2010s. Concern about heart attacks and strokes followed, and in 2015 the FDA cautioned against using testosterone for low levels caused by ageing alone and required labeling about possible cardiovascular risk.
Settling the heart question: the TRAVERSE trial
The FDA asked manufacturers for a proper safety trial. TRAVERSE enrolled 5,246 men aged 45 to 80 with symptomatic low testosterone and existing heart disease or high cardiovascular risk, randomising them to daily testosterone gel or placebo at 316 US sites. Over a mean of about 22 months, major cardiac events (cardiovascular death, heart attack or stroke) occurred in 7.0% of the testosterone group and 7.3% of the placebo group. The testosterone group did have more atrial fibrillation, acute kidney injury and blood clots in the veins. The results were published in the New England Journal of Medicine in 2023.
In 2025 the FDA required class-wide labeling changes for testosterone products, adding the TRAVERSE results, removing the boxed warning about increased cardiovascular risk and adding a warning about increased blood pressure. It was the latest step in a long shift: testosterone went from quack tonic to defined drug, and its risks are now measured rather than assumed.
What this history means for testosterone treatment today
Three lessons carry over. First, feeling better is not proof that a treatment works: Brown-Séquard and Voronoff had many satisfied patients. Modern care therefore starts with a confirmed diagnosis, usually repeated morning blood tests and, where needed, LH and FSH to find the cause. Second, testosterone is a real drug with real effects, including suppressed sperm production and higher red blood cell counts, so treatment needs monitoring. Third, the market for “boosters” echoes the organotherapy boom: products range from approved prescriptions to supplements with limited or no evidence.
If you are comparing options now, our guide to the best medicine to boost testosterone sets out prescription TRT, enclomiphene, ashwagandha and homeopathic products side by side, with what the evidence does and does not show.
This article is historical and general information, not medical advice. Testosterone treatment requires a diagnosis and a prescription from a licensed clinician.
Continue to modern medicine, or step back to the global medical timeline.
Sources and further reading
- Nieschlag E, Nieschlag S. Testosterone deficiency: a historical perspective. Asian Journal of Andrology, 2014: castration, organotherapy, grafting, isolation, synthesis and preparations.
- The Nobel Prize in Chemistry 1939: Butenandt and Ruzicka.
- Lincoff AM et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine, 2023: the TRAVERSE trial.
- Cleveland Clinic, TRAVERSE trial announcement: enrolment, design and main results.
- US FDA, class-wide labeling changes for testosterone products: 2025 labeling update.
- Brown-Séquard CE. The effects produced on man by subcutaneous injections of a liquid obtained from the testicles of animals. The Lancet, 1889.
