In 1935, working with their teams, Ernst Laqueur in Amsterdam isolated testosterone, and Adolf Butenandt in Gdansk and Leopold Ruzicka in Zürich synthesised it.[1] Three groups, one year, after decades of detours. From that point testosterone has been available for clinical use.[1]
The effect on everything that came before was swift. From 1935 onwards, rejuvenation operations gradually lost their appeal due to the introduction of artificial androgens.[2] An international surgical industry did not collapse under criticism — it was simply superseded.
Why it took so long
The search was not casual. In reaction to the malpractice of the organotherapy and transplantation era, science and the young pharmaceutical industry initiated a deliberate hunt for the male hormone.[1]
The obstacle was quantity and chemistry. Testosterone circulates in minute amounts, and identifying, isolating and then building a molecule of that complexity required analytical methods that were themselves new. "After several detours" is how the definitive history describes the path.[1]
Isolating and synthesising are different achievements
Worth separating, because they get conflated.
Isolation — getting the actual substance out of biological material and proving what it is. That was Laqueur's Amsterdam group.[1]
Synthesis — building the molecule from other chemicals, which is what makes a drug manufacturable rather than harvested. Butenandt and Ruzicka, independently.[1]
Isolation answers what is it. Synthesis answers can we make enough of it to treat anyone. The second is what turned a laboratory finding into medicine.
The perfume chemist
Leopold Ruzicka's route to testosterone is the strangest detail in the story. He shared the 1939 Nobel Prize in Chemistry — awarded to Adolf Butenandt "for his work on sex hormones" and to Ruzicka "for his work on polymethylenes and higher terpenes."[3]
Terpenes are the chemistry of scent. Ruzicka had been working on the active components of natural musk perfumes, and it was from that structural work that he proposed a connection between the terpene family and the sex hormones Butenandt was characterising.[3] The insight that made industrial testosterone possible came out of the fragrance industry.
What still had to be solved
Having the molecule was not the same as having a usable treatment, and the problem showed up immediately: given orally, testosterone is inactivated in the liver. Parenteral forms of administration, or modifications of the molecule, had to be found.[1]
That single sentence sets up the next eighty years. Every delivery route that follows — the injectable esters, the patches, the gels, the sprays — exists because of it. The history of testosterone after 1935 is not the history of the hormone. It is the history of getting it into the body.
Nieschlag and Nieschlag's summary of that work is measured: over 85 years, preparations have been slowly improved, so that physiological serum levels can now be achieved.[1] Eighty-five years, and "slowly" is their word.
The consequences of that constraint are still live: the dosing-interval question in daily vs weekly dosing, and the transfer risk that comes with putting a hormone on skin in gel transfer risk.
Why the date matters to a patient today
Because it sets the age of the evidence base. Testosterone has been clinically available since 1935, but the large randomised outcome trials — the ones that answer whether treatment helps and whether it is safe — are recent. TRAVERSE, the largest, reported in 2023.[4]
Nine decades of clinical use, and the definitive cardiovascular safety answer arrived in the last few years. That is worth knowing when weighing any confident claim about long-term effects: the drug is old, and much of the good evidence about it is not.
Frequently asked questions
Who discovered testosterone? No single person. Laqueur's group isolated it; Butenandt and Ruzicka synthesised it; all in 1935.[1] The groundwork — that the testes secrete an active substance — was Berthold's, in the previous century.[5]
Did they know what to do with it straight away? No. Oral testosterone is inactivated in the liver, so the delivery problem had to be solved before it was broadly useful.[1]
Why did rejuvenation surgery stop? It was displaced rather than refuted — the operations lost their appeal from 1935 with the arrival of artificial androgens.[2]
Was the Nobel for testosterone specifically? Butenandt's citation is "for his work on sex hormones"; Ruzicka's is for polymethylenes and higher terpenes.[3] The prize recognised the broader chemistry, of which testosterone was one product.
Where the story goes next
The molecule existed. Getting it to stay in the body long enough to matter took another fifty years — injectable esters first, then patches, gels and sprays — and produced a problem men still describe today. Those seasons of The T Files are in progress.
In the meantime, the modern end of that thread is what higher doses actually buy you and how long TRT takes to work.
References
5 sources
- Nieschlag E, Nieschlag S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180(6):R201–R212. doi:10.1530/EJE-19-0071 · PMID 30959485
- Schultheiss D, Denil J, Jonas U. Rejuvenation in the early 20th century. Andrologia. 1997;29(6):351–355. doi:10.1111/j.1439-0272.1997.tb00329.x · PMID 9430441
- The Nobel Foundation. The Nobel Prize in Chemistry 1939 — Adolf Butenandt "for his work on sex hormones" and Leopold Ruzicka "for his work on polymethylenes and higher terpenes". nobelprize.org
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107–117. doi:10.1056/NEJMoa2215025 · PMID 37326322
- Freeman ER, Bloom DA, McGuire EJ. A brief history of testosterone. J Urol. 2001;165(2):371–373. doi:10.1097/00005392-200102000-00004 · PMID 11176375
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