Why 1935 Ended Fifty Years of Surgery Without Refuting Any of It

From 1935 onwards, rejuvenation operations gradually lost their appeal due to the introduction of artificial androgens.[1] Not because a study exposed them. Because something that worked arrived, and the alternative stopped being interesting.

In that same year, Laqueur's Amsterdam group isolated testosterone, and Butenandt and Ruzicka synthesised it. Since then, testosterone has been available for clinical use.[2]

What ended

An international industry. Voronoff had performed monkey-tissue transplants on 300 patients within five years of starting in 1920. Steinach's vasoligation, first performed in 1918, triggered a vasectomy boom lasting two decades, with patients including Freud and W. B. Yeats.[1]

All of it built on a correct premise and delivering nothing: testes used in organotherapy and transplanted at scale for hypogonadism, with only placebo effects.[2] The full account is in the monkey-gland craze.

Why "superseded" is more common than "disproved"

This is the part worth generalising. Ineffective medicine usually does not end with a decisive negative trial. It ends when something better becomes available and attention moves.

The consequence is uncomfortable: an ineffective treatment can persist indefinitely if nothing displaces it. Seventeen years of rejuvenation surgery ran on a plausible mechanism, distinguished patients and enormous publicity, and none of that generated the trial that would have stopped it. What stopped it was a chemistry breakthrough in an unrelated field.

What 1935 did not solve

Having the molecule was not having a therapy. Given orally, testosterone is inactivated in the liver, so parenteral forms of administration or modifications of the molecule had to be found.[2]

Everything after 1935 is that problem: injectable esters, implants, patches, gels, sprays. And the pace was not fast. Over 85 years the preparations have been slowly improved, so that physiological serum levels can now be achieved.[2]

Eighty-five years to get from "we can make it" to "we can deliver it at physiological levels." That is the real timeline of testosterone medicine.

What it means for reading modern evidence

The drug is ninety years old. The good evidence about it is not.

TRAVERSE, the largest randomised testosterone trial ever conducted, reported its cardiovascular findings in 2023.[4] Its sub-studies on mood and sexual function followed in 2024.[5] Nine decades of clinical use preceded the trials that answered the basic questions about benefit and safety.

That asymmetry is worth holding onto whenever someone speaks confidently about long-term testosterone effects. Long use is not the same as long study.

Frequently asked questions

Was 1935 the discovery of testosterone? It is the year of isolation and synthesis.[2] The existence of a testicular secretion acting at a distance was established much earlier, by Berthold.[6]

Why did it take until the 2020s to run the big safety trial? Large cardiovascular outcome trials are expensive and slow, and were driven in part by regulatory concern following earlier signals. TRAVERSE reported in 2023.[4]

Are any pre-1935 treatments still used? No. The organotherapy and transplantation approaches had only placebo effects and were superseded by synthetic androgens.[1][2]

Next in this series

The prize for that work was awarded in 1939 — and one of the two laureates was not permitted to accept it.

Continue with the Nobel Prize nobody talks about.

References

6 sources

1. 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
2. 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
3. Cussons AJ, Bhagat CI, Fletcher SJ, et al. Brown-Séquard revisited: a lesson from history on the placebo effect of androgen treatment. Med J Aust. 2002;177(11-12):678–679. doi:10.5694/j.1326-5377.2002.tb05014.x · PMID 12463999
4. 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
5. Pencina KM, Travison TG, Cunningham GR, et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. J Clin Endocrinol Metab. 2024;109(2):569–580. doi:10.1210/clinem/dgad484 · PMID 37589949
6. 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