Glucose Homeostasis, Diabetes Mellitus, and Gender-Affirming Treatment

The transgender (trans) population includes individuals with gender identities more fittingly aligned with the opposite sex or with an alternative that transcends the classical dipole of male/female. Hormonal treatment in transgender individuals aims to suppress the secretion of endogenous sex steroids and replace them with the steroids of the desired gender. The mainstay of gender-affirming treatment in transgender males is testosterone, whereas for transgender females it is estrogen, usually combined with an anti-androgen or a gonadotropin-releasing hormone agonist if testes are present. Testosterone and estrogen are involved in carbohydrate metabolism via direct effects on skeletal muscle, liver, adipose tissue, and immune cells and indirectly through changes in body fat mass and distribution. The effect of transgender treatment on glucose tolerance is not clear. The provided conflicting results demonstrate a positive, neutral, or even negative association between exogenous testosterone and insulin sensitivity in trans men. Studies show that feminizing hormonal therapy of trans women has mainly an aggravating effect on insulin sensitivity. The existing evidence is not robust and further research is needed to investigate the relationships between body fat distributions, muscle mass, and glycemia/insulin resistance in transgender people under hormonal therapy.