Serum Testosterone and Cortisol Concentrations After Single-Dose Administration of 100-Mg Transdermal Testosterone in Healthy Men

Andrei A Puiu; Sina Radke; Mikhail Votinov; Ute Habel; Beate Herpertz-Dahlmann; Bruce Turetsky; Kerstin Konrad

doi:10.3389/fphar.2019.01397

Serum Testosterone and Cortisol Concentrations After Single-Dose Administration of 100-Mg Transdermal Testosterone in Healthy Men

Front Pharmacol. 2019 Nov 21:10:1397. doi: 10.3389/fphar.2019.01397. eCollection 2019.

Authors

Andrei A Puiu^{1

2}, Sina Radke³, Mikhail Votinov^{3

4}, Ute Habel^{3

4}, Beate Herpertz-Dahlmann⁵, Bruce Turetsky², Kerstin Konrad^{1

6}

Affiliations

¹ Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
² Brain-Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
³ Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
⁴ Institute of Neuroscience and Medicine: JARA-Institute Brain Structure Function Relationship (INM 10), Research Center Jülich, Jülich, Germany.
⁵ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
⁶ JARA-Brain Institute II Molecular Neuroscience and Neuroimaging, Research Centre Jülich, Jülich, Germany.

Abstract

The growing interest in testosterone's effects on men's social behaviors, in particular aggressive, risk-taking, or status maintenance behaviors, is accompanied by a paucity of dose-dependent pharmacokinetic data. Examining the neurophysiological effects of transdermal testosterone typically includes a 4h delay before further brain-behavior measurements. Nevertheless, high heterogeneity regarding the timing of follow-up measurements and dosage remains. In a double-blind placebo-controlled design, we examined the short-term pharmacokinetic profile of 100-mg transdermal testosterone (Testotop^®) to determine the optimal time for detecting testosterone-mediated effects. Across two studies, 35 healthy men received a single dose of testosterone and placebo in two separate sessions. In study one (n = 16), serum testosterone and cortisol were assessed serially every 30 min up to 2 h posttreatment. In study two (n = 19), we assessed serum testosterone and cortisol at baseline, 2 h, and 4.15 h (255 min) posttreatment. Relative to baseline and placebo, transdermal testosterone significantly increased total serum testosterone concentrations 90 min posttreatment, reaching maximum concentration between 2 h and 3 h posttreatment. Albeit elevated, serum testosterone levels gradually decreased between 2 h and 4 h following treatment. Transdermal testosterone did not suppress cortisol release. Instead, cortisol concentrations decreased according to cortisol's known circadian rhythm. Unlike previous findings showing significant testosterone concentration increases as soon as 60 min and as late as 3 h post 150-mg testosterone treatment, our 100-mg testosterone manipulation significantly increased testosterone concentrations 90 min following treatment. These pharmacokinetic data are important in facilitating the optimization of timing parameters for future testosterone challenge studies.

Keywords: cortisol; men; optimization; pharmacokinetics; testosterone; transdermal.