Morssinkhof Margot W L, Doyle David Matthew, van der Werf Ysbrand D, Heijer Martin den, Heijboer Annemieke, Broekman Birit F P, Stenvers Dirk Jan
Department of Medical Psychology, Amsterdam UMC, Amsterdam, the Netherlands.
Department of Psychiatry, Amsterdam UMC, Amsterdam, Vrije Universiteit Amsterdam, the Netherlands.
Neurobiol Stress. 2025 Jun 18;37:100741. doi: 10.1016/j.ynstr.2025.100741. eCollection 2025 Jul.
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.
下丘脑-垂体-肾上腺（HPA）轴的昼夜节律对身心健康至关重要。这种昼夜节律存在性别差异，包括女性的昼夜皮质醇斜率比男性更陡，性激素可能导致了这种差异。虽然先前的研究发现，开始性别确认激素治疗（GAHT）的 transgender 人群的 HPA 轴反应性和血清皮质醇有变化，但没有研究考察 GAHT 对昼夜唾液皮质醇的影响。本研究考察了昼夜皮质醇的性别差异以及 GAHT 三个月后昼夜皮质醇的变化。我们分析了 11 名男性化 transgender（TM）参与者和 7 名女性化 transgender（TF）参与者在 GAHT 前及 GAHT 三个月后的唾液皮质醇水平。参与者在醒来后 30 分钟、5.5 小时和 10.5 小时以及就寝时采集唾液样本。比较了两组在基线时以及每组在 GAHT 基线和三个月之间的绝对皮质醇水平和昼夜皮质醇斜率。在开始 GAHT 之前，TM 组的昼夜皮质醇斜率比 TF 组更陡。GAHT 后，TM 组和 TF 组的皮质醇水平或斜率均未显示出任何显著变化。我们重复了先前报道的基线时昼夜皮质醇水平的性别差异，但发现参与者开始 GAHT 后昼夜唾液皮质醇没有显著变化。这可能与 HPA 轴和皮质醇结合球蛋白浓度的稳态适应有关。未来的研究应关注结合型和非结合型皮质醇的作用以及与压力相关的皮质醇变化。
