From antiquity, Man has been fascinated by at least two processes of testicular function: virility and reproduction; their biological basis was uncovered beginning in the mid-19th century. We have divided the search into 3 epochs: the speculative and observational, the experimental, and the biochemical/physiological. The first begins with Susruta, approximately 3,000 years ago and winds its way through the Greek, Roman, the Christian Bible, Arabic, Chinese, and Indian pathways before coalescing in Europe at the dawn of the Renaissance. The second began withThomas Willis who postulated a virilizing factor from the testis. A century later de Bordeu hypothesized a neurosecretory function for the hypothalamus/pituitary. After John Hunter began to study testis implantation, it was Berthold who showed a secretory function of the testis following implantation. Charles-Éduard Brown-Séquard focused the medical and lay communities on the testis secretion with self-experimentation with animal testis extracts leading to more than four decades of uncertainty in the newly-launched science of endocrinology. Multiple series of testicular implants and vas deferens ligations for the purposes of rejuvenation of older men followed. The medical experimentation continued in the biochemical/physiological epoch where androgenic steroids were isolated, purified, identified, synthesized and used in clinical trials. The effects of castration, some known from antiquity were placed on a modern scientific basis with studies of the Skoptzy, a self-castrating sect from Russia and the castrati opera singers. Details of hypothalamic-pituitary-gonadal axis function as well as the embryology of male sexual differentiation and spermatogenesis were defined during this epoch.

Keywords: castrati; experimental endocrinology; hypogonadism; rejuvenation; testis; testosterone.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.