In the zona reticularis layer of the adrenal cortex, DHEA-sulfate is generated by SULT2A1. This layer of the adrenal cortex is thought to be the primary source of serum DHEA-sulfate. DHEA sulfate levels decline as a person ages as the reticularis layer diminishes in size.
Dehydroepiandrosterone sulfate levels above 1890 micromol/L or 700-800 µg/dL are highly suggestive of adrenal dysfunction because DHEA-S is made exclusively by the adrenal glands. Presence of DHEA-S is therefore used to rule out ovarian or testicular origin of excess androgen.
The Endocrine Society recommends against the therapeutic use of DHEA sulfate in both healthy women and those with adrenal insufficiency, as their role is not clear from studies performed so far. The routine use of DHEAS and other androgens is discouraged in the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, menopause due to ovarian surgery, glucocorticoid use, or other conditions associated with low androgen levels; this is because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk.
In otherwise elderly women, in whom an age-related fall DHEA sulfate may be associated with menopausal symptoms and reduced libido, DHEA sulfate supplementation cannot currently be said to improve outcomes.
^ abWierman, Margaret E.; Arlt, Wiebke; Basson, Rosemary; Davis, Susan R.; Miller, Karen K.; Murad, Mohammad H.; Rosner, William; Santoro, Nanette. "Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 99 (10): 3489–510. doi:10.1210/jc.2014-2260. PMID25279570.
^Elraiyah, Tarig; Sonbol, Mohamad Bassam; Wang, Zhen; Khairalseed, Tagwa; Asi, Noor; Undavalli, Chaitanya; Nabhan, Mohammad; Altayar, Osama; Prokop, Larry; Montori, Victor M.; Murad, Mohammad Hassan. "The Benefits and Harms of Systemic Dehydroepiandrosterone (DHEA) in Postmenopausal Women With Normal Adrenal Function: A Systematic Review and Meta-analysis". The Journal of Clinical Endocrinology & Metabolism. 99 (10): 3536–42. doi:10.1210/jc.2014-2261. PMID25279571.