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

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Abstract

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.

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The raw data collected and analysed during the present study are available from the corresponding author upon request

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Acknowledgements

This work was sponsored by the National Natural Science Foundation of China (31800952 and 31600923), Jiangsu Provincial Social Science Foundation (19JYA001) and the Fundamental Research Funds for the Southeast University (2242019s10024, 3218006405). The funding sources had no further role in the study design, data collection, analysis, interpretation, and decision to submit this manuscript for publication.

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The study was designed by Yan Wu, Yin Wu and Huihua Deng. Saliva samples were collected by Yin Wu and then were determined by Yan Wu, Liuxi Chu, Haoran Yang and Wei Wang using a developed LC-MS/MS method. The samples data were analyzed by Yan Wu, Yin Wu and Huihua Deng. The first version of the manuscript was written by Yan Wu and the draft was reviewed and edited by Huihua Deng and Yin Wu. All authors approved the final version of the manuscript for submission.

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Correspondence to Huihua Deng.

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Wu, Y., Wu, Y., Chu, L. et al. The Optimal Time-lag for Testosterone Challenge Research Based on Salivary Profiles Following Different Doses of Transdermal Testosterone Administrations. J Mol Neurosci 73, 297–306 (2023). https://doi.org/10.1007/s12031-023-02118-x

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