The Evolution of Masculinity: A History of Testosterone Therapy

Dernière mise à jour : mai 11, 2026

• Facebook
• Instagram
• WordPress
• Télégramme
• WhatsApp
• LinkedIn
• Courrier

For centuries, humanity has recognized that a certain “vital spark” resides within the male anatomy. Long before we had the vocabulary of endocrinology or the precision of laboratory blood tests, it was understood that the testes held the key to male vigor, muscle mass, and sexual drive. I recently had the opportunity to be lectured by Professor Mohit Khera, a leading expert in male reproductive medicine at Baylor College of Medicine, regarding the fascinating and often misunderstood history of testosterone. It is a journey that moves from ancient rituals to radical early experiments, through a long “prohibition” based on fear, and finally into the evidence-based modern era.

This article draws on the comprehensive 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 10,000 BC, with human records appearing by 4000 BC. In animals, it was noted that this practice decreased sexual behavior and led to an increase in body fat. Human eunuchs were similarly known to lose their “power,” both sexually and in terms of physical stature.

These ancient observations made one thing clear: the testis produced a chemical substance essential for male vigor. The challenge for the next several millennia was determining exactly what that substance was — and whether it could be harvested to restore vitality.

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 hard science.

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. He claimed to have regained the strength of his younger years, noting improved “intellectual labour” and even better “expulsion of fecal matters.” While we now recognize his results were likely a powerful placebo effect — the actual concentration of testosterone in such an extract would have been negligible — his work sparked a global interest in the potential for hormonal rejuvenation.

The Steinach Procedure (1920s)

One of the more unusual chapters in urology was the Steinach Procedure, popularized by Austrian physiologist Eugen Steinach in the 1920s. The procedure involved a unilateral vas ligation (tying off one side of the vas deferens). The theory was that by blocking the exit of sperm, the “vital substances” produced by the testicles would be retained within the body rather than lost through ejaculation, leading to physical and mental rejuvenation. This procedure became a sensation, sought out by famous figures including Sigmund Freud and the poet W.B. Yeats.

The Isolation of Testosterone

The “Golden Age” of testosterone research arrived in the 1930s when scientists finally isolated and synthesized the hormone.

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 15,000 liters of urine collected from Berlin policemen.
1935	Ernest Laqueur isolated a much more potent substance from bull testes and officially named it “Testosterone”.
1939	The Nobel Prize in Chemistry was awarded to Butenandt and Leopold Ružička for the synthesis of testosterone.

Early Formulations and Challenges

The earliest forms of testosterone therapy (TTh) 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, longer-acting injections (enanthate and cypionate) were developed, which remain common today. However, a major barrier during this era was the difficulty of measurement — it was not until the 1970s and the invention of Radioimmunoassays (RIA) that testing for testosterone became accurate, reliable, and reproducible.

The Dark Ages: The Fear of Prostate Cancer

In 1941, the trajectory of TTh changed dramatically due to a study by Charles Huggins and Clarence Hodges. They concluded that prostate cancer was “activated” by androgen injections. This birthed the Androgen Hypothesis, which dominated medical thinking for the next 60 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 gasoline on a fire.”

Because of this fear, testosterone use became extremely rare by the late 1980s, restricted primarily to young men with severe conditions like pituitary tumors or Klinefelter’s syndrome. In 1990, the Anabolic Steroid Act classified testosterone as a Schedule III controlled substance, further restricting medical access due to concerns about athletic abuse.

The Modern Era: Evidence Overcomes Fear

The turn of the 21st century brought a “rediscovery” of testosterone as research began to challenge old fears.

The Cardiovascular Scare (2013)

In 2013, a study by Vigen et al. suggested an association between TTh and increased risk of heart attack and stroke. However, the study faced massive criticism after researchers were found to have misreported data — even including women in the “all-male” study population. Ultimately, 29 medical societies petitioned for the study’s retraction.

The Turning Point: Large-Scale Trials

The demand for better data led to major Randomized Controlled Trials (RCTs):

• 2016 (The T-Trials): A large multicenter RCT of 790 men over age 65 showed that testosterone gel significantly improved libido, erectile function, mood, and physical activity. Critically, cardiovascular events were similar between the testosterone and placebo groups.
• 2023 (TRAVERSE Trial): This is the largest RCT to date, involving 5,246 men. The results were definitive: there was no difference in cardiovascular risk or prostate cancer risk between the testosterone and placebo groups.

The Future: 2025 and Beyond

We are now entering an era where medical policy is finally aligning with modern evidence. In 2025, an FDA Expert Panel made several landmark recommendations:

• Remove testosterone from the controlled substances list.
• Remove prostate cancer warnings, as they are not supported by evidence.
• Remove restrictions on treating “age-related” testosterone deficiency.
• Raise the diagnostic threshold for low testosterone to 350 ng/dL.

Speculations on Care

As we look toward the future, testosterone deficiency will likely be more widely recognized as a profound medical condition affecting quality of life. We may see increased use of TTh in men with existing prostate cancer, and future studies may reveal benefits for asymptomatic men who have low lab values alone.

Conclusion

Testosterone therapy has survived a 60-year “prohibition” driven by fears that modern science has finally debunked. We now have the tools and the clinical data to show that TTh is both safe and effective for those who need it. The “vital spark” identified by our ancestors has been found, measured, and mastered, offering a path for men to reclaim their vigor and well-being.

If you are experiencing symptoms of low testosterone and would like a comprehensive evaluation grounded in the latest evidence, Dr. Soarawee Weerasopone offers specialist consultations in men’s health and testosterone therapy at Bangkok Hospital Headquarters. Prendre rendez-vous.

Frequently Asked Questions About the History of Testosterone Therapy

When was testosterone first discovered and synthesized?

Testosterone was first isolated by Ernest Laqueur in 1935 from bull testes, and a synthetic form was developed shortly after. In 1939, Adolf Butenandt and Leopold Ružička were awarded the Nobel Prize in Chemistry for the synthesis of testosterone. However, the role of the testes in male vigor had been recognized for over 10,000 years through observations of castration in animals and human eunuchs.

Why was testosterone therapy avoided for so many decades?

In 1941, Huggins and Hodges published a study suggesting testosterone “activated” prostate cancer, leading to the Androgen Hypothesis that dominated medical thinking for 60 years. This created a culture of fear in which giving testosterone to a man was considered like “pouring gasoline on a fire.” Modern evidence — including the Saturation Model and the 2023 TRAVERSE trial — has now thoroughly debunked these fears.

What did the 2023 TRAVERSE trial prove about testosterone safety?

The TRAVERSE trial is the largest randomized controlled trial of testosterone therapy to date, involving 5,246 men. It found no difference in cardiovascular risk or prostate cancer risk between men receiving testosterone therapy and those on placebo. This landmark study effectively ended the long-held safety controversies that had restricted access to TTh for decades.

What changes did the 2025 FDA Expert Panel recommend for testosterone therapy?

The 2025 FDA Expert Panel recommended four landmark changes: (1) removing testosterone from the controlled substances list, (2) removing prostate cancer warnings as they are not supported by current evidence, (3) removing restrictions on treating age-related testosterone deficiency, and (4) raising the diagnostic threshold for low testosterone to 350 ng/dL. These changes mark a significant shift toward evidence-based access to testosterone therapy.

Rédigé et révisé sur le plan médical par : Dr Soarawee Weerasopone (Dr Pom) — Urologue certifié, siège de l'hôpital de Bangkok.
Chercheur invité à l'étranger : Baylor College of Medicine (États-Unis) · Université Juntendo (Japon) · Hôpital Chang Gung Memorial (Taïwan).

Avis de non-responsabilité : Ce contenu est rédigé et revu par le Dr Soarawee Weerasopone, urologue certifié au siège de Bangkok Hospital. Il est destiné uniquement à des fins éducatives et ne constitue pas un avis médical. Consultez toujours un professionnel de la santé qualifié avant de commencer tout traitement médical.