12-months metabolic changes among gender dysphoric individuals under cross-sex hormone treatment: a targeted metabolomics study.
Metabolomic analyses in epidemiological studies have demonstrated a strong sexual dimorphism for most metabolites. Cross-sex hormone treatment (CSH) in transgender individuals enables the study of metabolites in a cross-gender setting. Targeted metabolomic profiling of serum of fasting transmen and transwomen at baseline and following 12 months of CSH (N = 20/group) was performed. Changes in 186 serum metabolites and metabolite ratios were determined by targeted metabolomics analysis based on ESI-LC-MS/MS. RandomForest (RF) analysis was applied to detect metabolites of highest interest for grouping of transwomen and transmen before and after initiation of CSH. Principal component analysis (PCA) was performed to check whether group differentiation was achievable according to these variables and to see if changes in metabolite levels could be explained by a priori gender differences. PCA predicted grouping of individuals-determined by the citrulline/arginine-ratio and the amino acids lysine, alanine and asymmetric dimethylarginine - in addition to the expected grouping due to changes in sex steroids and body composition. The fact that most of the investigated metabolites did, however, not change, indicates that the majority of sex dependent differences in metabolites reported in the literature before may primarily not be attributable to sex hormones but to other gender-differences.
Endocrinology, Diabetology and Internal Medicine, Max Planck Institute of Psychiatry, Munich, Germany.
Matthias K
MK
Auer
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
Alexander
A
Cecil
Endocrinology, Diabetology and Internal Medicine, Max Planck Institute of Psychiatry, Munich, Germany.
Yasmin
Y
Roepke
Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium.
Charlotte
C
Bultynck
Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium.
Charlotte
C
Pas
Institute for Sex Research and Forensic Psychiatry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Johannes
J
Fuss
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
Cornelia
C
Prehn
Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Rui
R
Wang-Sattler
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
Jerzy
J
Adamski
Endocrinology, Diabetology and Internal Medicine, Max Planck Institute of Psychiatry, Munich, Germany.
Günter K
GK
Stalla
Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium.
Guy
G
T'Sjoen
D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D000886:Anthropometry; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D005260:Female; D000068116:Gender Dysphoria / Q000188:drug therapy / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics; D008875:Middle Aged; D025341:Principal Component Analysis; D012727:Sex Characteristics; D057829:Gender-Affirming Procedures
D000596:Amino Acids; D012739:Gonadal Steroid Hormones; C018524:N,N-dimethylarginine; D001120:Arginine