The Optimal Time-lag for Testosterone Challenge Research Based on Salivary Profiles Following Different Doses of Transdermal Testosterone Administrations

In recent decades, testosterone challenge research examining the effects of testosterone on human neuropsychological behaviors has rapidly grown with the development of a single-dose transdermal testosterone administration paradigm. However, the optimal time-lag between testosterone administration and behavioral measurement is not unified, partly hindering causal understanding of the “testosterone effect”. The present study aimed to investigate the optimal time-lag through LC-MS/MS-based salivary profiles of ten biomarkers among healthy males following administration of different doses of transdermal testosterone (i.e., 450- and 150-mg [Androgel®]). Results revealed that testosterone administration significantly increased salivary testosterone levels, reaching maximum levels 2 hours after 450-mg testosterone administration and 1 hour after 150-mg testosterone administration, respectively. Salivary androstenedione and DHEA increased synchronously with testosterone following administration. Moreover, the ratios of testosterone to androstenedione, DHEA, estradiol, and of androstenedione to estrone significantly elevated 1 hour after testosterone administration. In contrast, salivary cortisol and cortisone were decreased over time due to circadian rhythm rather than testosterone administration. Consistent with previous serum studies, the present salivary findings recommended 1-hour post testosterone administration as the optimal time-lag to measure the effects of testosterone on human behaviors in transdermal testosterone challenge research.