{"doi":"10.1210/clinem/dgae226","title":"Impact of Distinct Antiandrogen Exposures on the Plasma Metabolome in Feminizing Gender-affirming Hormone Therapy","abstract":"CONTEXT: The plasma metabolome is a functional readout of metabolic activity and is associated with phenotypes exhibiting sexual dimorphism, such as cardiovascular disease. Sex hormones are thought to play a key role in driving sexual dimorphism. OBJECTIVE: Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender care, but longitudinal changes in the plasma metabolome with feminizing GAHT have not been described. METHODS: Blood samples were collected at baseline and after 3 and 6 months of GAHT from transgender women (n = 53). Participants were randomized to different anti-androgens, cyproterone acetate or spironolactone. Nuclear magnetic resonance-based metabolomics was used to measure 249 metabolic biomarkers in plasma. Additionally, we used metabolic biomarker data from an unrelated cohort of children and their parents (n = 3748) to identify sex- and age-related metabolite patterns. RESULTS: We identified 43 metabolic biomarkers altered after 6 months in both anti-androgen groups, most belonging to the very low- or low-density lipoprotein subclasses, with all but 1 showing a decrease. We observed a cyproterone acetate-specific decrease in glutamine, glycine, and alanine levels. Notably, of the metabolic biomarkers exhibiting the most abundant \"sex- and age-related\" pattern (higher in assigned female children and lower in assigned female adults, relative to assigned males), 80% were significantly lowered after GAHT, reflecting a shift toward the adult female profile. CONCLUSION: Our results suggest an anti-atherogenic signature in the plasma metabolome after the first 6 months of feminizing GAHT, with cyproterone acetate also reducing specific plasma amino acids. This study provides novel insight into the metabolic changes occurring across feminizing GAHT.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2024,"id":455674,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9623,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1279771,"name":"Lachlan M. Angus","orcid":"0000-0002-5842-6173","position":1,"is_corresponding":false},{"id":1279772,"name":"Toby Mansell","orcid":"0000-0002-1282-6331","position":2,"is_corresponding":false},{"id":1279773,"name":"Bridget M Arman","orcid":"0000-0003-0314-378X","position":3,"is_corresponding":false},{"id":1280183,"name":"Bo Won Kim","orcid":null,"position":4,"is_corresponding":false},{"id":320984,"name":"Katherine Lange","orcid":"0000-0002-8175-6285","position":5,"is_corresponding":false},{"id":344495,"name":"David Burgner","orcid":"0000-0002-8304-4302","position":6,"is_corresponding":false},{"id":918376,"name":"Jessica A. Kerr","orcid":"0000-0002-3150-4047","position":7,"is_corresponding":false},{"id":1279774,"name":"Ken C. Pang","orcid":"0000-0002-6881-775X","position":8,"is_corresponding":false},{"id":726814,"name":"Jeffrey D. Zajac","orcid":"0000-0003-3933-5708","position":9,"is_corresponding":false},{"id":310282,"name":"Richard Saffery","orcid":"0000-0002-9510-4181","position":10,"is_corresponding":false},{"id":1279775,"name":"Ada S. Cheung","orcid":"0000-0001-5257-5525","position":11,"is_corresponding":false},{"id":225197,"name":"Boris Novakovic","orcid":"0000-0002-5623-9008","position":12,"is_corresponding":false},{"id":14041,"name":"Rebecca Shepherd","orcid":"0000-0002-8888-305X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38609170","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}