Adrenocortical tissue dynamics and corticosteroid perturbation upon the experimental male estrogenization: reflections from animal and <i>in vitro</i> data about human treatment

The current topic of sex reassignment is often under strong ideological influence and requires an impartial scientific approach. Considering the importance of corticosteroid status during male-to-female transition for numerous health aspects, here we focus on the 'transitional' functional histology of the hypothalamic-pituitary-adrenal (HPA) axis and corticosteroid output, from the perspective of our experimental experience and the available literature, both experimentally and clinically oriented. In a model of orchidectomized, estradiol-treated adult male rats we observed an increase in aldosterone secretion, as well as in corticosterone synthesis and secretion, but also a decrease in DHEA secretion, all of which were accompanied by expansive changes in adrenal tissue. Available experimental and clinical literature data support our findings. It is known that glucocorticoid excess increases the risk of metabolic complications, elevated blood aldosterone levels may underlie systemic hypertension, while reduced DHEA secretion is associated with various physical and mental issues. These health risks should be kept in mind before possibly starting the male-to-female transition through orchidectomy and estradiol administration.