Dehydroepiandrosterone sulfate (DHEA-S) is a steroid hormone synthesized in the adrenal cortex’s reticular zone under the influence of adrenocorticotropic hormone (ACTH). Like other steroids, DHEA-S is synthesized from cholesterol. DHEA-S is considered a prohormone. It is hormonally inert but can be converted into other, more potent androgens and estrogens. It is an important marker of adrenal function and is useful for diagnosing various endocrine disorders, as well as for evaluating premature adrenarche in children.
During fetal development, DHEA-S is produced in the adrenal glands; its level rapidly decreases during the first year of life and then rises again at adrenarche (around 6–8 years old), gradually increasing during puberty and reaching its peak between the ages of 20–30. After that, DHEA-S levels steadily decline.
In males, the adrenal glands contribute only a small portion of total androgen production, while in women of reproductive age, the adrenal glands play a more significant role in androgen production.
In women, elevated DHEA-S levels may cause signs of hyperandrogenism (hirsutism, acne, virilization). Men are usually asymptomatic, but due to peripheral conversion of androgens to estrogens, a mild excess of estrogens may sometimes be observed.
Common causes of elevated DHEA-S levels include:
1. Androgen-secreting adrenal tumors (adenomas or carcinomas), especially when DHEA-S is markedly elevated (more than 5 times above normal).
2. Congenital adrenal hyperplasia.
3. Polycystic ovary syndrome (PCOS), often with mild to moderate elevation.
Common causes of low DHEA-S levels include:
1. Adrenal insufficiency, such as Addison’s disease or secondary adrenal insufficiency due to hypopituitarism.
2. Subclinical or overt hypercortisolism.
3. Severe systemic illnesses, acute stress, or chronic conditions such as anorexia.
DHEA-S affects immune modulation, inflammation, and neuronal protection; low levels are associated with cognitive decline and mood disorders.