Plasma metabolome study reveals metabolic changes induced by pharmacological castration and testosterone supplementation in healthy young men

• Published in: Scientific reports Vol. 12; no. 1; p. 15931
• Main Authors: de Siqueira Guedes, Jéssica, Pla, Indira, Sahlin, K. Barbara, Monnerat, Gustavo, Appelqvist, Roger, Marko-Varga, György, Giwercman, Aleksander, Domont, Gilberto Barbosa, Sanchez, Aniel, Nogueira, Fábio César Sousa, Malm, Johan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45; 692/163; Amino acids; Basic Medicine; Carbohydrate metabolism; Carnitine; Castration; Comorbidity; Diabetes mellitus (non-insulin dependent); Fat metabolism; Follicle-stimulating hormone; Fysiologi; Humanities and Social Sciences; Indoles; Lipid metabolism; Lipids; Liquid chromatography; Luteinizing hormone; Mass spectrometry; Mass spectroscopy; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Metabolic disorders; Metabolic pathways; Metabolic syndrome; Metabolism; Metabolomics; multidisciplinary; Physiology; Plasma levels; Protein deficiency; Protein turnover; Science; Science (multidisciplinary); Sphingolipids; Supplements; Testosterone
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-19494-w

Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of pharmacologically induced castration and, subsequently, testosterone supplementation in healthy young males. Thirty subjects were submitted to testosterone depletion (TD) followed by testosterone supplementation (TS). Plasma samples were collected three times corresponding to basal, low, and restored testosterone levels. An untargeted metabolomics study was performed by liquid chromatography–high resolution mass spectrometry (UHPLC–HRMS) to monitor the metabolic changes induced by the altered hormone levels. Our results demonstrated that TD was associated with major metabolic changes partially restored by TS. Carnitine and amino acid metabolism were the metabolic pathways most impacted by variations in testosterone. Furthermore, our results also indicated that LH and FSH might strongly alter the plasma levels of indoles and lipids, especially glycerophospholipids and sphingolipids. Our results demonstrated major metabolic changes induced by low testosterone that may be important for understanding the mechanisms behind the association of testosterone deficiency and its comorbidities.