摘要：SummaryWomen have a reduced cardiovascular disease (CVD) risk compared with men, which could be partially driven by sex hormones influencing lipid levels post puberty. The interrelationship between sex hormones and lipids was explored in pre-pubertal children, young post-pubertal cis-men/women, and transgender individuals on cross-sex-hormone treatment (trans-men/women) using serum metabolomics assessing 149 lipids. High-density lipoproteins (HDL, typically atheroprotective) were significantly increased and very-low- and low-density lipoproteins (typically atherogenic) were significantly decreased in post-pubertal cis-women compared with cis-men. These differences were not observed pre-puberty and were induced appropriately by cross-sex-hormone treatment in transgender individuals, supporting that sex hormones regulate lipid metabolismin vivo. Only atheroprotective apolipoprotein (Apo)A1 expressing lipoproteins (HDL) were differentially expressed between all hormonally unique comparisons. Thus, estradiol drives a typically atheroprotective lipid profile through upregulation of HDL/ApoA1, which could contribute to the sexual dimorphism observed in CVD risk post puberty. Together, this could inform sex-specific therapeutic strategies for CVD management.Graphical abstractDisplay OmittedHighlights•Estradiol increases typically atheroprotective HDL/ApoA1 in cis- and trans-women•Differences in HDL/ApoA1 are induced in a dose-dependent manner by estradiol•Sex differences are not identified pre-puberty and are disrupted in autoimmunity•Serum lipid metabolites could inform sex-tailored strategies for CVD risk managementBiological sciences; Biochemistry; Metabolomics
