12-Months metabolic changes among gender dysphoric individuals under cross-sex hormone treatment: a targeted metabolomics study
Open accessAbstract
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.
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Five longitudinal studies investigated the muscular strength of transwomen.
“Five longitudinal studies16 17 37 40 41 investigated the muscular strength of transwomen.”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [37]
The Patient population section describes transwomen assessed at baseline and after 12 months, supporting the longitudinal-study aspect. The Methods describe body-composition and laboratory measurements, but not a muscular-strength assessment; muscle mass discussed elsewhere is not the same as strength. No page numbers are available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredEight of the nine studies found that hormone therapy led to a significant decrease in Hgb/HCT of 4.6%-14.0% (p<0.01).
“Eight of these studies,16 19 36–38 43 48 49 including the large (n=239) ENIGI study,19 found that hormone therapy led to a significant (4.6%–14.0%) decrease in Hgb/HCT (p<0.01)”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [37]
The Results (General characteristics; page unavailable) report that hematocrit decreased after 12 months of hormone treatment in transwomen (p = 0.002), supporting a significant decrease for this study. Our copy does not give the claimed 4.6%–14.0% range or establish the finding across eight studies. The Methods (Patient population; page unavailable) describe 20 participants per group, not an n=239 cohort. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNine studies reported Hgb or HCT levels in transwomen before and after GAHT, with follow-up from a minimum of 3 to a maximum of 36 months post hormone therapy.
“Nine studies16 19 36–38 43 47–49 reported the levels of Hgb or HCT in transwomen before and after GAHT, from a minimum of three to a maximum of 36 months post hormone therapy.”
Two ENIGI studies found no significant strength differences, although one of these studies was carried out on adolescents who failed to reach typical female testosterone levels (8.8 nmol/L after GAHT).
“Two ENIGI studies37 40 found no significant strength differences, although one of these studies40 was carried out on adolescents who failed to reach typical female testosterone levels (8.8 nmol/L after GAHT).”
From How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation (2021) · cites this paper as [37]
The Patient population section identifies this as an ENIGI study, but the Methods and Results passages describe metabolite, body-composition, and hormone measurements, not strength outcomes. Searches for strength differences, adolescents, and 8.8 nmol/L found no passage supporting the cited claim; pages are not specified in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Mittelstrass K.. Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers. PLoS Genet. 7, e1002215 (2011). 21852955 PMC3154959
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Self-citation
- Authors
- Auer, M. K., Cecil, A., Roepke, Y., Bultynck, C., Pas, C., Fuss, J., Prehn, C., Wang-Sattler, R., Adamski, J., Stalla, G. K., & T’Sjoen, G.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Helmholtz Munich (DE)
- Ghent University Hospital (BE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Auer, Matthias K.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-11-11
- Volume
- 6
- Issue
- 1
- Pages
- 37005-37005
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5105120
- OpenAlex
- W2549318335
- Cited by
- 54
- References
- 52
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 5 · 2017: 4
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Social Sciences › Psychology › Social Psychology › LGBTQ Health, Identity, and Policy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- transgender people, serum metabolites, sexual dimorphism, metabolite ratios, asymmetric dimethylarginine, amino acids, sex steroids, body composition, transgender men, transgender women, gender differences
- MeSH terms
- Gender Dysphoria, Adult, Amino Acids, Anthropometry, Arginine, Body Composition, Energy Metabolism, Fasting, Female, Humans, Male, Middle Aged, Sex Characteristics, Gonadal Steroid Hormones, Principal Component Analysis, Lipid Metabolism, Metabolic Networks and Pathways, Metabolomics, Sex Reassignment Procedures, Gender-Affirming Procedures
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