Up to the maximum—testosterone dose‐dependent effects on anabolic and androgen responsive tissues in orchiectomized rats

Abstract

BackgroundDespite the high number of synthetic androgenic–anabolic steroids, testosterone is still misused for doping in amateur and professional sports.However, only few studies investigated the dose–response effects of testosterone beyond its physiological concentrations and in over 90 years of research, no saturation dosage has been experimentally described for exogenous testosterone administration.ObjectivesWe want to elucidate the physiological and pathophysiological effects of supra‐physiological testosterone application and close this gap in testosterone dose–response data.Materials and methodsMale orchiectomized rats were treated with different testosterone doses ranging from 0.1 to 50 mg/kg body weight for 3 weeks. Several physiological endpoints (e.g., body weight, organ and muscle weight, muscle strength, muscle fiber size) were examined during and after the termination of the treatment with an adjusted Hershberger assay, open‐field‐test, and (immuno‐)histologic.ResultsThe wet weights of androgen responsive organs (penis, prostate, seminal vesicle) showed a significant increase in a dose‐dependent manner. Histological evaluation of the prostate showed a significant higher percentage of KI67 positive prostate nuclei in the highest dosage group and an increasing hyperplasia with increasing testosterone administered. A significant anabolic effect was only observed in Levator ani wet weight, and to minor degree for the cardiac muscle. Regarding other skeletal muscles (Musculus soleus and Musculus gastrognemicus), no significant testosterone effects were observed. We showed a significant increasing dosage–response effect for testosterone in androgen responsive organs with saturation at the two highest concentration of 10 and 50 mg/kg body weight.Discussion and conclusionThe dose‐dependent androgenic effects of testosterone were well observable and the anabolic effects on muscle tissue were visible although to a lesser degree, without the support of aerobic exercise and a protein rich diet. Future studies should investigate a combinatorial effect of testosterone and training. Nevertheless, with the chosen range of applied testosterone, we showed a saturation of testosterone effects in prostate, seminal vesicle, penis, and Levator ani.

Annual banned‐substance review 16th edition—Analytical approaches in human sports drug testing 2022/2023

“…Here, Derwand et al provided first insights using a rat model, where up to 50 mg of testosterone per kg bodyweight was administered daily for up to 3 weeks, suggesting a ceiling of the dose-response of various organs at daily testosterone dosages of 10 mg/kg. 53 Also blood parameters such as serum erythropoietin (EPO) concentrations and percentage of reticulocytes were corroborated to be affected under supraphysiological AAS use, 54 and health risks observed in humans appear to outreach physical effects, with personality disorders and clinical psychiatric syndromes in males and females having recently been attributed to AAS misuse, too. [120][121][122][123] In the light of the 2021 anti-doping testing figures, where anabolic agents (and in particular AAS) represented 40% of reported AAFs, the extensive efforts that resulted in various publications within the past 12 months (aiming at faster and orthogonal strategies as well as more comprehensive and extended analytical retrospectivity for AAS in sports drug testing) appear warranted.…”