Introduction: Sex steroid hormones exert a wide range of effects on metabolism. New techniques such as metabolomic profiling allow for a deeper insight into metabolic regulation. In epidemiological samples it has been demonstrated that most of these metabolites show sex-specific differences. However, if these differences are attributable to the effects of sex hormones or genetics is little understood so far.
Methods: We performed targeted metabolomics profiling in serum of fasting transmen (F2M) and transwomen (M2F) at baseline and following 12 months of cross-sex hormone treatment (n=20/group). Subjects investigated in this study were part of the European Network for the Investigation of Gender Incongruence (ENIGI). The targeted metabolomics approach was based on ESILCMS/MS measurements by AbsoluteIDQTM p180 Kit (Biocrates Life Sciences AG).
Results: Several metabolites concentrations changed significantly between the two visits in the M2F group including DL-carnitine, octadecanyl-L-carnithine, threonine, alpha-amino adipic acid, hydroxyproline, phosphatidylcholine diacyl C34:3, ornithine, citrulline, and ornithine/arginine ratio (FDR <0.05, P<0.05). In the F2M group there was only a significant change in ornithine. After adjustment for age, lifestyle factors and body composition in a linear mixed effects model, these results remained significant but vanished after adjusting for sex hormone levels. This indicates a direct effect of sex hormones on metabolite levels. Opposite effects were seen, i.e. for changes in ornithine levels between the two groups. Ornithine was further strongly positively related to testosterone levels in both groups. These findings are also in line with the sex-specific dimorphism for metabolites observed in epidemiological studies.
Conclusion: In this first pilot study we could show that cross-sex hormone treatment induces several changes in serum metabolites. Our findings indicate a direct effect of sex hormones on different metabolic cycles including lipid metabolism, nitric oxide formation, and amino acid regulation.