Insulin Sensitivity and Associated Plasma Proteomics During Sex Hormone Therapy

Abstract

Purpose: Women are generally protected against insulin resistance and related comorbidities when compared with men, potentially due to the role of sex hormones. While epidemiological and animal studies suggest that sex hormones may impact insulin sensitivity, studies in humans on the effects of estradiol and testosterone treatment on insulin sensitivity assessed by gold-standard measures remain limited. The molecular mechanisms involved are also not well understood. Therefore, we aimed to investigate changes in insulin sensitivity and associated change in plasma proteome following 3 months of sex hormone therapy. Methods: This prospective, observational study included 29 individuals initiating feminizing (estradiol with GnRH analogue; n = 16) or masculinizing (testosterone; n = 13) therapy. Measurements at baseline and after 3 months included insulin sensitivity, assessed via hyperinsulinemic-euglycemic clamp (M-value: adjusted for lean body mass and M/I ratio: M-value adjusted for plasma insulin concentrations), along with plasma proteomics. Results: During feminizing hormone therapy, insulin sensitivity increased (M-value: + 23.3%, M/I ratio: + 20.2%; P