ESPEYB17 6. Differences/Disorders of Sex Development and Transgender Medicine Transgender Medicine: Brain and Psychology (3 abstracts)
6.19. Does sex hormone treatment reverse the sex-dependent stress regulation? A longitudinal study on hypothalamus-pituitary-adrenal (HPA) axis activity in transgender individuals
Fuss J , Claro L , Ising M , Biedermann SV , Wiedemann K , Stalla GK , Briken P & Auer MK
To read the full abstract: Psychoneuroendocrinology. 2019, Jun; 104: 228–37. doi: https://www.sciencedirect.com/science/article/pii/S0306453018312307?via%3Dihub
The effect of sex hormones on long-term regulation of the hypothalamic-pituitary-adrenal (HPA) axis was studied in 25 transgender individuals (10 trans-female) at baseline and after 3 months of gender-affirming hormonal therapy. After estrogen and antiandrogen treatment, both ACTH and cortisol increased in response to CRH in transfemale persons, but decreased in transmale subjects after testosterone treatment.
Previous studies observed sex differences in HPA axis activity, but complex and mixed results in various clinical and animal studies failed to explain the direct influence of sex hormones on the reactivity of the HPA axis, mostly due to methodical limitations. Here, Fuss et al. provide evidence in transgender people that sex hormones alone (albeit out of their cis-context and corresponding genetic background) affect the stress response in different directions. The study also confirms previous results showing that testosterone attenuates adrenal ACTH sensitivity and that copeptin measurements (as a surrogate of vasopressin, the second stimulant of ACTH secretion) are able to predict the HPA axis response to a dexamethasone/CRH test.
Overall, HPA axis response studies are often difficult to interpret as they may be influenced by many confounding factors. Most relevant to transgender might be changes observed in HPA axis activity with concomitant mental disorders such as depression and anxiety disorders, which are frequent in these individuals. Thus, long-term gender-affirming hormonal treatments affecting HPA axis reactivity may directly modulate mental health.
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