ESPE Yearbook of Paediatric Endocrinology

iScience. 2021 Oct 11;24(11):103257. PMID: 34761181, doi: 10.1016/j.isci.2021.103257.

Brief Summary: The authors explored the relationship between sex hormones and lipids in pre-pubertal children, young post-pubertal cisgender men and women, and transgender adolescents on gender affirming hormone (GAH) treatments using serum metabolomics to assess 149 lipids. High-density lipoproteins (HDL, typically atheroprotective) were higher and very-low- and low-density lipoproteins (typically atherogenic) were lower in post-pubertal cisgender women compared with cisgender men. There were no differences seen pre-puberty.

Knowing what happens to health outcomes from sex hormone treatments is important as there are sex differences in long-term cardiovascular disease (CVD) risk. GAH treatment in transgender adolescents induced reversals of lipoprotein profiles, concluding that sex hormones regulate lipid metabolism in vivo. Thus, estradiol drives a typically atheroprotective lipid profile through upregulation of apolipoprotein (Apo)A1 expressing lipoproteins (HDL), which could contribute to the sexual dimorphism observed in CVD risk post puberty. In clinical management terms, if GAH is prescribed, this worsens CVD risk for transgender men, but likely improves CVD risk for transgender women.

In another smaller study, smaller changes in VLDL and ApoB were seen after testosterone treatment [1]. Together, this could inform sex-specific therapeutic strategies for CVD risk management, especially diet and lifestyle in transgender adolescents, and these are reviewed in Kean et al [2].

References: 1. Millington K, Chan YM. Lipoprotein subtypes after testosterone therapy in transmasculine adolescents. J Clin Lipidol. 2021 Nov-Dec;15(6):840–844. doi: 10.1016/j.jacl.2021.09.051. Epub 2021 Oct 2. PMID: 34657833; PMCID: PMC8742606. 2. Kean AC, Saroufim R, Meininger E, Fuqua JS, Fortenberry JD. Cardiovascular Health of Youth During Gender-Affirming Testosterone Treatment: A Review. J Adolesc Health. 2021 Dec;69(6):896–904. doi: 10.1016/j.jadohealth.2021.08.009. Epub 2021 Oct 7. PMID: 34627656.