Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females

Yael Sofer*, Esther Osher, Wiessam Abu Ahmad, Michal Yacobi Bach, Naomi Even Zohar, Dana Zaid, Nehama Golani, Yaffa Moshe, Karen Tordjman, Naftali Stern, Yona Greenman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axis of transgender subjects in an effort to throw light on this question. Methods: Ten transgender males (TM) and eight transgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30 and 40 min. Results: For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p <.05). Likewise, the overall SC response as calculated by the area under the curve was significantly lower (p =.0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p <.01) while ACTH-stimulated SC levels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p <.001). Conclusion: Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.

Original languageEnglish
Pages (from-to)164-169
Number of pages6
JournalClinical Endocrinology
Issue number2
StatePublished - Feb 2024


  • cortisol
  • gender
  • gender affirming hormonal therapy
  • hipothalamo-pituitary adrenal axis
  • transgender


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