[2][6][7][8] Although DHEA-S itself is hormonally inert, it has been thought that it can be converted back into DHEA,[9] which is weakly androgenic and estrogenic, and that DHEA in turn can be transformed into more potent androgens like testosterone and dihydrotestosterone (DHT) as well as estrogens like estradiol.

[5] DHEA and DHEA-S are produced in the zona reticularis of the adrenal cortex under the control of adrenocorticotropic hormone (ACTH).

[13] Then, DHEA-S is formed by sulfation of DHEA at the C3β position via the sulfotransferase enzymes SULT2A1 and to a lesser extent SULT1E1.

[1][17][18] Approximately 10 to 15 mg of DHEA-S is secreted by the adrenal cortex per day in young adults.

[20][21] In contrast to DHEA, DHEA-S is not bound to any extent to sex hormone-binding globulin (SHBG).

[2][29] The Endocrine Society recommends against the therapeutic use of DHEA-S in both healthy women and those with adrenal insufficiency, as its role is not clear from studies performed so far.

[45] Common etiologies for hirsutism include ovarian dysfunction (polycystic ovary syndrome) and adrenal dysfunction (congenital adrenal hyperplasia, cushing's syndrome, androgen secreting tumors); 90% of these cases are caused by PCOS or are idiopathic in nature.

[45] However, severely increased DHEA-S levels (>700 μg/dL) necessitate further workup and are almost stem from benign or malignant adrenal alterations.