Abstract
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.
Highlights
It is already known that cross-sex hormone treatment (CSH) results in impressive changes in the physical appearance towards the target-sex[12,13] as well as in classical cardiovascular risk factors, such as the HDL-/LDL cholesterol ratio, triglycerides[12], fasting insulin levels, blood pressure[14] or arterial stiffness[15]
Sex hormones are known to exert a variety of effects on metabolism[18], this technique has rarely been used in this context[19,20] so far, though it might provide a lot more information on altered metabolic processes than those provided by conventional laboratory analyses
While there was no change in anthropometric measures, such as weight or BMI, CSH led to a significant decrease in the percentage of lean body mass and corresponding increase in relative fat mass (p < 0.001)
Summary
It is already known that CSH results in impressive changes in the physical appearance towards the target-sex[12,13] as well as in classical cardiovascular risk factors, such as the HDL-/LDL cholesterol ratio, triglycerides[12], fasting insulin levels, blood pressure[14] or arterial stiffness[15]. Sex hormones are known to exert a variety of effects on metabolism[18], this technique has rarely been used in this context[19,20] so far, though it might provide a lot more information on altered metabolic processes than those provided by conventional laboratory analyses It has been demonstrated in epidemiological samples that the majority of metabolites measured seem to be differentially regulated between men and women[21]. To what extent these differences can be attributed to a genetic basis or to the different sex hormonal milieu has not yet been investigated Applying this technique to a sample of transgender persons before and after initiation of CSH treatment may shed light on the general sex-hormone-accountable effect of sex-specific metabolite levels. We are reporting the results of a prospective study in transgender persons investigating the effects of the initiation of CSH treatment by applying a targeted-metabolomics approach
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