Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study

The diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis is essential for physical and mental health. There are sex differences in this diurnal rhythm, including steeper diurnal cortisol slopes in females compared to males, and sex hormones likely contribute to this difference. While prev...

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Main Authors: Margot W.L. Morssinkhof, David Matthew Doyle, Ysbrand D. van der Werf, Martin den Heijer, Annemieke Heijboer, Birit F.P. Broekman, Dirk Jan Stenvers
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Neurobiology of Stress
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352289525000359
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author Margot W.L. Morssinkhof
David Matthew Doyle
Ysbrand D. van der Werf
Martin den Heijer
Annemieke Heijboer
Birit F.P. Broekman
Dirk Jan Stenvers
author_facet Margot W.L. Morssinkhof
David Matthew Doyle
Ysbrand D. van der Werf
Martin den Heijer
Annemieke Heijboer
Birit F.P. Broekman
Dirk Jan Stenvers
author_sort Margot W.L. Morssinkhof
collection DOAJ
description The diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis is essential for physical and mental health. There are sex differences in this diurnal rhythm, including steeper diurnal cortisol slopes in females compared to males, and sex hormones likely contribute to this difference. While previous studies found changes in HPA axis responsivity and serum cortisol in transgender people starting gender-affirming hormone therapy (GAHT), no study examined the effect of GAHT on diurnal salivary cortisol. This study examined sex differences in diurnal cortisol and changes in diurnal cortisol after three months of GAHT.We analyzed salivary cortisol levels in eleven transmasculine (TM) and seven transfeminine (TF) participants before GAHT and after three months of GAHT. Participants collected saliva samples at 30 min, 5.5 h and 10.5 h after awakening, and at bedtime. Absolute cortisol levels and diurnal cortisol slopes were compared between the groups at baseline, and in each group between baseline and three months of GAHT.Before starting GAHT, the TM group showed a steeper diurnal cortisol slope compared to the TF group. Neither the TM group nor the TF group showed any significant changes in cortisol levels or slopes after GAHT.We replicate previously reported sex differences in diurnal cortisol levels at baseline, but we find no significant changes in diurnal salivary cortisol after participants start GAHT. This could be associated with homeostatic adaptation of the HPA axis and cortisol-binding globulin concentrations. Future studies should focus on the role of bound and unbound cortisol and stress-related cortisol changes.
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spelling doaj-art-a61a8866bc5547e9999d0718fa45280b2025-08-20T03:58:37ZengElsevierNeurobiology of Stress2352-28952025-07-013710074110.1016/j.ynstr.2025.100741Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective studyMargot W.L. Morssinkhof0David Matthew Doyle1Ysbrand D. van der Werf2Martin den Heijer3Annemieke Heijboer4Birit F.P. Broekman5Dirk Jan Stenvers6Department of Medical Psychology, Amsterdam UMC, Amsterdam, the Netherlands; Department of Psychiatry, Amsterdam UMC, Amsterdam, Vrije Universiteit Amsterdam, the Netherlands; Department of Endocrinology and Metabolism, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health, Amsterdam, the Netherlands; Corresponding author. Department of Medical Psychology, Amsterdam UMC, Amsterdam, the Netherlands.Department of Medical Psychology, Amsterdam UMC, Amsterdam, the Netherlands; Amsterdam Public Health, Amsterdam, the NetherlandsDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, the NetherlandsDepartment of Endocrinology and Metabolism, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the NetherlandsEndocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Location University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the NetherlandsDepartment of Psychiatry, Amsterdam UMC, Amsterdam, Vrije Universiteit Amsterdam, the Netherlands; Amsterdam Public Health, Amsterdam, the Netherlands; Department of Psychiatry and Medical Psychology, OLVG, Amsterdam, the NetherlandsDepartment of Endocrinology and Metabolism, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the NetherlandsThe diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis is essential for physical and mental health. There are sex differences in this diurnal rhythm, including steeper diurnal cortisol slopes in females compared to males, and sex hormones likely contribute to this difference. While previous studies found changes in HPA axis responsivity and serum cortisol in transgender people starting gender-affirming hormone therapy (GAHT), no study examined the effect of GAHT on diurnal salivary cortisol. This study examined sex differences in diurnal cortisol and changes in diurnal cortisol after three months of GAHT.We analyzed salivary cortisol levels in eleven transmasculine (TM) and seven transfeminine (TF) participants before GAHT and after three months of GAHT. Participants collected saliva samples at 30 min, 5.5 h and 10.5 h after awakening, and at bedtime. Absolute cortisol levels and diurnal cortisol slopes were compared between the groups at baseline, and in each group between baseline and three months of GAHT.Before starting GAHT, the TM group showed a steeper diurnal cortisol slope compared to the TF group. Neither the TM group nor the TF group showed any significant changes in cortisol levels or slopes after GAHT.We replicate previously reported sex differences in diurnal cortisol levels at baseline, but we find no significant changes in diurnal salivary cortisol after participants start GAHT. This could be associated with homeostatic adaptation of the HPA axis and cortisol-binding globulin concentrations. Future studies should focus on the role of bound and unbound cortisol and stress-related cortisol changes.http://www.sciencedirect.com/science/article/pii/S2352289525000359CortisolHPA axisSex hormonesTransgenderEstradiolTestosterone
spellingShingle Margot W.L. Morssinkhof
David Matthew Doyle
Ysbrand D. van der Werf
Martin den Heijer
Annemieke Heijboer
Birit F.P. Broekman
Dirk Jan Stenvers
Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study
Neurobiology of Stress
Cortisol
HPA axis
Sex hormones
Transgender
Estradiol
Testosterone
title Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study
title_full Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study
title_fullStr Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study
title_full_unstemmed Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study
title_short Effects of gender-affirming hormones on diurnal cortisol concentrations: A prospective study
title_sort effects of gender affirming hormones on diurnal cortisol concentrations a prospective study
topic Cortisol
HPA axis
Sex hormones
Transgender
Estradiol
Testosterone
url http://www.sciencedirect.com/science/article/pii/S2352289525000359
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