Author: Fuss, J.; Claro, L.; Ising, M.; Biedermann, S. V.; Wiedemann, K.; Stalla, G. K.; Briken, P. & Auer, M. K.
Description: Studies in mammals indicate a role for sex hormones in the regulation of hypothalamic-pituitary-adrenal (HPA)-axis reactivity. However, in humans, experimental paradigms investigating long-term exposure to sex hormones are sparse, limiting the understanding of the influence of sex hormones on HPA-axis activity. Gender-affirming hormone therapy (GAHT) in transgender persons enables to study the physiological role of sex steroids partially uncoupled from the distinct genetic background of men and women. Ten transwomen (male genotype and female gender identity) and 15 transmen (female genotype and male gender identity) were investigated at baseline and following three months of GAHT by means of the combined dexamethasone (dex)/CRH-test. Linear mixed-effects model analysis was used to assess changes over time and to identify determinants of HPA-axis reactivity. In response to CRH, overall ACTH (+18%) as well as cortisol (+15%) output were increased in transwomen after 3-months of estrogen and antiandrogen treatment, while the opposite was the case for transmen after testosterone treatment (-15% and -58%, respectively). The ACTH/Cortisol-ratio indicated that testosterone attenuated sensitivity for ACTH at the adrenal level in transmen. Interestingly, copeptin levels before CRH administration were a strong predictor of overall cortisol secretion. This is the first study demonstrating long-term effects of a complete reversal of the sex-hormonal milieu on HPA-axis activity in humans. Our findings hereby expand the current knowledge of the physiology of HPA-axis regulation. and may be particularly relevant for transgender and cisgender people undergoing hormonal suppression or substitution therapies.
Subject headings: Adrenocorticotropic Hormone, analysis; Adult; Corticotropin-Releasing Hormone, pharmacology; Dexamethasone, pharmacology; Estradiol, metabolism, pharmacology; Female; Gender Identity; Gonadal Steroid Hormones, analysis; Humans; Hydrocortisone, analysis; Hypothalamo-Hypophyseal System, drug effects, metabolism, physiology; Longitudinal Studies; Male; Pituitary-Adrenal System, drug effects, metabolism, physiology; Sex Characteristics; Steroids, metabolism, pharmacology; Stress, Psychological, drug therapy, metabolism; Testosterone, metabolism, pharmacology; Transgender Persons, psychology; Cortisol; Estradiol; Gender dysphoria; Gender incongruence; Sex steroids; Testosterone
Publication year: 2019
Journal or book title: Psychoneuroendocrinology
Volume: 104
Pages: 228-237
Find the full text: https://www.sciencedirect.com/science/article/pii/S0306453018312307
Find more like this one (cited by): https://scholar.google.com/scholar?cites=7444578518116069840&as_sdt=5,26&sciodt=0,26&hl=en
Type: Journal article
Serial number: 3049