Sex hormones drive changes in lipoprotein metabolism

George A Robinson; Junjie Peng; Hannah Peckham; Anna Radziszewska; Gary Butler; Ines Pineda-Torra; Elizabeth C Jury; Coziana Ciurtin

doi:10.1016/j.isci.2021.103257

Sex hormones drive changes in lipoprotein metabolism

iScience. 2021 Oct 11;24(11):103257. doi: 10.1016/j.isci.2021.103257. eCollection 2021 Nov 19.

Authors

George A Robinson^{1

2}, Junjie Peng², Hannah Peckham², Anna Radziszewska², Gary Butler^{3

4}, Ines Pineda-Torra⁵, Elizabeth C Jury¹, Coziana Ciurtin^{1

2}

Affiliations

¹ Centre for Rheumatology Research, Division of Medicine, University College London, Rayne Building, London WC1E 6JF, UK.
² Centre for Adolescent Rheumatology Research, Division of Medicine, University College London, Rayne Building, London WC1E 6JF, UK.
³ Department of Paediatric and Adolescent Endocrinology, UCLH and Great Ormond Street Institute of Child Health, University College London, London, UK.
⁴ Gender Identity Development Service (GIDS), Tavistock and Portman NHS Foundation Trust, London, UK.
⁵ Centre for Cardiometabolic and Vascular Science, Department of Medicine, University College London, London WC1E 6JF, UK.

Abstract

Women 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 metabolism in 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.

Keywords: Biochemistry; Biological sciences; Metabolomics.