The testis, eunuchs, and testosterone: a historical review over the ages and around the world.

INTRODUCTION: Testosterone therapy for men with testosterone deficiency is widely used, yet remains controversial. The rich and fascinating history of the testicles, including human castration, provides a valuable perspective on this important topic. OBJECTIVES: This study reviewed the history of testosterone from antiquity to the modern day. METHODS: Primary sources consisted of books and relevant articles, augmented by a MEDLINE search using the key words "testis," "testicles," "castration," "eunuchs," "testosterone," and "testicular function." RESULTS: An early scientific observation was that castration reduced sexual development and activity, originating with domestication of animals approximately 10 000 years ago. Human castration appears in ancient Egyptian mythology more than 4000 years ago, in Greek mythology from 8th century BCE, and in the Bible. The history of eunuchs in China spanned 2000 years, beginning with the Hsia dynasty (2205-1766 BCE). The concept that the testicles produced some factor responsible for male sexual development and behavior was thus known throughout the world since the beginning of recorded history. Testosterone was isolated and synthesized in 1935 and was soon available as a treatment. Multiple benefits of testosterone therapy were apparent by 1940. Recent large, controlled testosterone studies have conclusively demonstrated sexual and general health benefits, with a strong safety profile. CONCLUSION: Testosterone has been a known substance for <1% of the historical timeline, yet knowledge that the testes were responsible for male sexual development and behavior has been known since the beginning of recorded history. Today, modern evidence has demonstrated the importance of normal levels of testosterone for general health as well as sexual function and desire. Yet, testosterone therapy remains controversial. We believe this historical review provides a helpful perspective on this age-old issue.

Testosterone therapy and obstructive sleep apnea: is there a real connection?

INTRODUCTION: With the recent increased recognition and treatment of hypogonadism in men, a caution has been given that testosterone replacement therapy (TRT) may cause or aggravate obstructive sleep apnea syndrome (OSA). AIM: To evaluate the scientific data behind the cautionary statements about TRT and OSA. MAIN OUTCOME MEASURES: Methodology and criteria for such studies and evaluation of documents and results based on methodology, duration, and outcome of treatment. METHODS: A review of the literature on the subject of TRT and OSA was performed. The possible mechanisms of action of TRT, on breathing and respiration during sleep were explored. RESULT: Historically, the first such caution came in 1978. Since then, a few similar incidence reports have been cited. The total number of patients in such reports was very small, very disproportional to the millions of patients treated with TRT. Also, there was a lack of consistent findings connecting TRT to OSA. In addition, different results may occur with physiologic replacement vs. supraphysiologic doses in regard to breathing and OSA. The studies showing the effect of TRT on OSA and breathing were all case studies with small numbers of subjects and showed little effect of TRT on OSA in the majority of case reports. Only one study using supraphysiologic doses was a double-blind, placebo-controlled study, which showed a development of OSA in healthy pooled subjects. The other reports were case studies with limited numbers of subjects, suggesting an inconsistent effect of supraphysiologic TRT on OSA and breathing. CONCLUSION: Cautionary statements about TRT in OSA appear frequently in the TRT literature and guidelines, despite lack of convincing evidence that TRT causes and/or aggravates OSA. Also, there is a lack of consistency in the findings connecting TRT to OSA. It is evident that the link between TRT and OSA is weak, based on methodological issues in many of the studies, and most studies involved small numbers of men. Further studies in this area are needed.