The Oldest Evidence About Testosterone Came From Castration, Not Chemistry

The biological effects of testosterone and the testes have been known since antiquity — long before testosterone was identified as the active agent.[1] The knowledge came from castration, practised for reasons that had nothing to do with medicine: to produce obedient servants, as punishment, to preserve the prepubertal soprano voice, and even as a treatment for disease.[1]

It is the least comfortable origin story in medicine, and it is the reason so much was already known before any of it could be explained.

What was observed, and why it was reliable

Castration before puberty produces a consistent, visible set of consequences. Because the practice was carried out across many societies over a very long period, the pattern was recorded repeatedly and independently — which is, structurally, a great deal of observational data.

The observations were about voice, body composition, hair, fertility and behaviour. What nobody had was a mechanism. That the testes secreted a substance acting at a distance was not established until Berthold's transplant work in the nineteenth century.[2]

So antiquity had the outcome without the cause: an accurate description of what removing the testes does, with no concept of a hormone to explain it.

The soprano voice

Of the reasons listed, preserving the prepubertal soprano voice is the one that most clearly isolates a single effect.[1]

The voice deepens at puberty because the larynx grows under androgen exposure. Remove the source before puberty and the change does not happen. That is a clean, one-variable demonstration of an androgen-dependent process — carried out on children, for music.

Modern endocrinology has a phrase for this category: androgen-dependent processes, each with its own dose-response relationship.[3] The larynx is one. Bone, muscle, red cell production and body-hair distribution are others, and they do not all respond identically — which is why a dose that changes one may not change another.

Why "we already knew" delayed nothing and enabled nothing

There is a tempting version of this story where ancient knowledge gave medicine a head start. It did not.

Knowing that the testes matter is compatible with almost any theory of how they matter — including that they act through the nerves, which was the leading assumption until it was ruled out experimentally.[2] And knowing that they matter told nobody how to help a man whose own production was low. That gap produced two thousand years of nothing, then several decades of treatments that did not work: organotherapy and testicular transplantation used at scale, with only placebo effects.[1]

The knowledge only became useful when the molecule was isolated in 1935.[1] Before that, the accurate ancient observation and the useless Edwardian surgery sat side by side without contradiction.

What it means for reading modern claims

The pattern in this episode repeats through the whole series: a correct observation about testosterone does not license a conclusion about treatment.

Castration demonstrably changes voice, muscle and hair. That is true, ancient and well evidenced. It does not follow that giving testosterone to a man with a normal level improves those things — and where large trials have looked, several expected benefits did not appear. Testosterone treatment produced no significant improvement in cognition in older men with low testosterone and age-associated memory impairment,[4] and TRAVERSE found improvements in sexual desire and activity but not erectile function.[5]

The gap between "this hormone does something" and "adding it helps you" is the whole subject.

Frequently asked questions

Does castration history tell us what testosterone levels should be? No. It shows which processes depend on androgens, not what concentration is appropriate for an individual. Diagnosis rests on symptoms plus confirmed low levels, and treatment targets the mid-normal range.[6]

Were these effects reversible? Not for changes fixed at puberty. Laryngeal growth and skeletal development, once they have or have not occurred, are not undone later.

Is this really the earliest evidence? It is the earliest recorded observation of testicular function. The first controlled demonstration that the testes act through a secreted substance came much later, with Berthold.[2]

Next in this series

Two thousand years of accurate observation, and no mechanism. That changed with a nineteenth-century experiment involving four roosters.

Continue with the rooster that changed medicine.

References

6 sources

1. 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
2. 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
3. Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281(6):E1172–E1181. doi:10.1152/ajpendo.2001.281.6.E1172 · PMID 11701431
4. Resnick SM, Matsumoto AM, Stephens-Shields AJ, et al. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA. 2017;317(7):717–727. doi:10.1001/jama.2016.21044 · PMID 28241356
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. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364