The Evolution of Masculinity: A History of Testosterone Therapy

Last updated: August 29, 2026

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For centuries, humanity has recognised that a certain vital spark resides within the male anatomy. Long before the vocabulary of endocrinology or the precision of laboratory blood tests, it was understood that the testes held the key to male vigour, muscle mass and sexual drive. I recently had the opportunity to be lectured by Professor Mohit Khera at Baylor College of Medicine on the history of testosterone — a journey from ancient observation through radical early experiments, a long prohibition built on fear, and into the era of large trials.

This article draws on the 2024 historical review by Morgentaler and Hanafy, The testis, eunuchs, and testosterone: a historical review over the ages and around the world, published in Sexual Medicine Reviews.

Ancient Origins: The Lessons of Castration

The history of testosterone begins with the observation of its absence. Evidence of castration in animals dates back to around 10,000 BC, with human records appearing by 4000 BC. In animals it was noted that the practice reduced sexual behaviour and increased body fat. Human eunuchs were similarly known to lose their power, both sexually and in physical stature.

These observations made one thing clear: the testis produced something essential to male vigour. The challenge for the next several millennia was working out what.

The Rejuvenation Era: Experiments and Oddities

In the late 19th and early 20th centuries, scientists began experimenting with ways to restore lost vitality — often with results rooted more in hope than in evidence. This part of the story is worth telling honestly, because the pattern in it recurs.

The Brown-Séquard Elixir (1889)

In 1889 the 72-year-old physician Charles-Édouard Brown-Séquard reported a radical change in his own health after self-injecting a liquid obtained from the testicles of guinea pigs and dogs, claiming to have regained the strength of his younger years. We now recognise his results as a powerful placebo effect — the actual testosterone content of such an extract would have been negligible — but his report sparked global interest in hormonal rejuvenation.

The Steinach Procedure (1920s)

One of the stranger chapters in urology was the Steinach procedure, popularised by the Austrian physiologist Eugen Steinach. It involved tying off one vas deferens, on the theory that blocking the exit of sperm would retain vital substances in the body rather than losing them through ejaculation. It became a sensation, sought out by figures including Sigmund Freud and the poet W.B. Yeats. It did nothing of the kind.

Both stories are worth keeping in mind, because the appetite that drove them has not gone anywhere — it now expresses itself as unregulated products sold online, which is a modern version of the same trade.

The Isolation of Testosterone

The golden age of testosterone research arrived in the 1930s, when the hormone was finally isolated and synthesised.

Year	Milestone
1929	The first bioassay was created, showing that testicular extract could cause a capon (a castrated rooster) to grow a large red comb.
1931	Adolf Butenandt isolated the first androgen, androsterone, from thousands of litres of urine collected from Berlin policemen.
1935	Ernest Laqueur isolated a more potent substance from bull testes and named it testosterone.
1939	The Nobel Prize in Chemistry was awarded to Butenandt and Leopold Ružička for work including the synthesis of testosterone.

Early Formulations and Challenges

The earliest forms of testosterone therapy were difficult to administer. Oral testosterone was largely ineffective because the liver inactivated it too quickly. By the late 1930s doctors used pellets and daily injections of testosterone propionate; in the 1950s the longer-acting enanthate and cypionate esters arrived, and remain in use today. A major barrier throughout this era was measurement — it was not until the 1970s and the invention of radioimmunoassay that testing for testosterone became reliable. Worth pausing on that: for the first four decades of its clinical use, nobody could accurately measure the thing they were giving.

The Dark Ages: The Fear of Prostate Cancer

In 1941 the trajectory changed dramatically because of work by Charles Huggins and Clarence Hodges, who concluded that prostate cancer was activated by androgen injections. This produced the androgen hypothesis, which dominated thinking for the next sixty years:

1. High testosterone causes prostate cancer.
2. Low testosterone protects against it.
3. Giving testosterone to a man with prostate cancer is like pouring petrol on a fire.

The striking part, looking back, is how few patients that conclusion rested on. A doctrine that shaped six decades of practice grew from a very small body of observation — a reminder that confident medical positions are not always built on the evidence base people assume. The modern reassessment is set out in testosterone and prostate cancer: the saturation model.

Because of this fear, testosterone use became rare by the late 1980s, largely restricted to young men with pituitary tumours or Klinefelter’s syndrome. In 1990 the Anabolic Steroid Act in the United States classified testosterone as a controlled substance, further restricting medical access because of concerns about athletic abuse.

The Modern Era: Better Evidence, Not Final Answers

The Cardiovascular Scare (2013)

In 2013 a study by Vigen and colleagues suggested an association between testosterone therapy and increased risk of heart attack and stroke. It drew heavy criticism after errors emerged in how the data had been reported, including the presence of women in what was described as an all-male population, and a large number of medical societies petitioned for its retraction. It is a useful reminder that a frightening headline and a reliable result are not the same thing — in either direction.

The Turning Point: Large-Scale Trials

• 2016, the T-Trials: a multicentre randomised trial of 790 men over 65 found that testosterone gel improved libido, erectile function, mood and physical activity, with cardiovascular events similar between groups. The trials were not powered to settle cardiovascular safety, and they excluded men with a history of prostate cancer.
• 2023, TRAVERSE: the largest randomised trial to date, involving 5,246 men aged 45 to 80 with existing cardiovascular disease or high risk, followed for a mean of 33 months. It found no increase in major adverse cardiac events and no signal of increased prostate cancer — though it too excluded men who had already had prostate cancer.

The other half of TRAVERSE — and a correction this page has had to make about it

TRAVERSE is usually quoted only as far as the reassuring headline, and it deserves the rest. But there is more than one way to get the rest wrong, and an earlier version of this page got it wrong in a way the history above should have warned against.

That version said the trial reported higher rates of atrial fibrillation, pulmonary embolism and acute kidney injury, and left it there. Stated that way it reads as three established harms. None of those three differences reached statistical significance. They were numerically higher, the numbers moved in the same direction, and a trial of this size failing to reach significance is not proof of no effect — but presenting a difference the trial could not separate from chance as a finding is exactly the move that produced the androgen hypothesis in 1941.

What did reach statistical significance were two findings the earlier version did not mention at all:

• Erythrocytosis — a thickening of the blood — by a wide margin the clearest adverse effect in the trial, and the reason haematocrit is monitored for as long as treatment continues.
• Clinical fractures, which rose by roughly 43% in the fracture subtrial — counterintuitive, because testosterone improves bone density on a scan, and a firm reason not to prescribe it to protect bone.

So the honest summary is narrower and more useful than either half alone: the specific harm people feared did not appear; two different things did; and three others moved without the trial being able to say whether that was real. Testosterone therapy is a monitored treatment, not a settled one. The practical consequences are set out in what TRAVERSE actually found and in testosterone therapy today.

There is a small irony in having to make that correction on this particular page. The lesson of the sixty-year prohibition is that a confident claim can outrun its evidence. It turns out that applies just as much to the cautious-sounding claims as to the enthusiastic ones.

Where Policy Is Heading

Medical policy has begun to catch up with the evidence. A United States FDA advisory panel has recommended a series of changes, including removing testosterone from the controlled substances list, removing prostate cancer warnings from labelling, removing restrictions on treating age-related testosterone deficiency, and raising the diagnostic threshold for low testosterone.

Three qualifications matter here, because this section is the one most likely to be misread. An advisory panel recommends; it does not decide, and a recommendation is not a rule until a regulator adopts it. These are United States regulatory questions, and they do not govern practice or licensing in Thailand. And a change in a diagnostic threshold is a change in a definition, not a discovery about anyone’s body — it would not mean that a man previously told his level was normal has developed a deficiency. If you are wondering whether a number applies to you, that is a conversation with your own doctor rather than a reading of someone else’s regulator.

What Is Likely Next

Testosterone deficiency is likely to be recognised more widely as a condition that genuinely affects quality of life, and its treatment in selected prostate cancer survivors will probably become less controversial as longer follow-up accumulates.

One direction I would not expect, and would not welcome: treating men who have only a low laboratory value and no symptoms. Testosterone therapy is treatment of a person, not of a number — it suppresses the body’s own production and fertility while it continues, and offering it to someone who feels well in order to correct a decimal place gets that balance wrong. The lesson of the whole history above is that enthusiasm has run ahead of evidence at least as often as fear has held it back.

Conclusion

Testosterone therapy survived a sixty-year prohibition built on a foundation far narrower than its influence suggested. Modern trials have not vindicated that prohibition, and for men with a confirmed deficiency and real symptoms the treatment is reasonable, effective and reasonably well characterised — given properly, with monitoring.

What the history should leave us with is not a new certainty to replace the old one. It is a habit: check the evidence behind a confident claim, in whichever direction it points — including the claims on this page. Modern testosterone replacement therapy rests on a confirmed diagnosis, an appropriate formulation and structured monitoring — the three things that were missing for most of the story above.

If you are experiencing symptoms of low testosterone and would like a full evaluation, Dr. Soarawee Weerasopone consults at Bangkok Hospital Headquarters and at Samitivej Sriracha Hospital in Chonburi on 088-022-1445.

Bangkok Hospital Telemedicine is available for patients who cannot attend in person, including international patients — arrange it in advance by email to the Urology department at bhquro@bdms.co.th. It suits reviewing blood results and planning follow-up; the initial assessment needs an in-person visit and morning blood tests. Samitivej Sriracha is in-person only. Enquiries about cost are answered by the hospital rather than through this website.

Frequently Asked Questions About the History of Testosterone Therapy

When was testosterone first discovered and synthesised?

Testosterone was isolated by Ernest Laqueur in 1935 from bull testes, with synthetic forms developed shortly after. In 1939 Adolf Butenandt and Leopold Ružička received the Nobel Prize in Chemistry for work including its synthesis. The role of the testes in male vigour, however, had been recognised for thousands of years through observations of castration in animals and of human eunuchs.

Why was testosterone therapy avoided for so many decades?

In 1941 Huggins and Hodges published work suggesting testosterone activated prostate cancer, producing the androgen hypothesis that dominated thinking for sixty years. What is striking in retrospect is how small the body of observation was relative to the doctrine built on it. Modern evidence, including the saturation model and the TRAVERSE trial, has substantially undermined the absolute version of that fear.

What did the TRAVERSE trial actually show?

TRAVERSE is the largest randomised trial of testosterone therapy to date, involving 5,246 men aged 45 to 80 with existing cardiovascular disease or high risk. It found no increase in major adverse cardiac events and no signal of increased prostate cancer, though it excluded men with a prostate cancer history. Two adverse findings reached statistical significance: erythrocytosis, a thickening of the blood, by a wide margin the clearest; and a roughly 43% increase in clinical fractures in the fracture subtrial. Atrial fibrillation, pulmonary embolism and acute kidney injury were numerically higher but did not reach statistical significance and should not be described as established harms.

What did the FDA advisory panel recommend, and does it apply in Thailand?

A United States FDA advisory panel recommended removing testosterone from the controlled substances list, removing prostate cancer warnings from labelling, removing restrictions on treating age-related deficiency, and raising the diagnostic threshold. Three things to keep in mind: an advisory panel recommends rather than decides; these are United States regulatory matters that do not govern practice or licensing in Thailand; and a change to a diagnostic threshold changes a definition, not anyone’s physiology.

Should men with a low level but no symptoms be treated?

Not on current evidence. Testosterone therapy treats a person with symptoms and a confirmed deficiency, not a laboratory value in isolation. Therapy suppresses the body’s own testosterone and sperm production while it continues, which is a poor trade for someone who feels well. Diagnosis rests on symptoms together with more than one morning blood test.

Disclaimer: This content is written and reviewed by Dr. Soarawee Weerasopone, a board-certified urologist at Bangkok Hospital Headquarters. It is intended for general education only and does not constitute medical advice. Regulatory decisions described here relate to the United States and do not govern practice in Thailand. No advice, diagnosis or prescription is given through personal messaging channels or social media, and Dr. Soarawee operates no public social media account. Always consult a qualified healthcare professional before starting or changing any medical treatment.