Does low DHEA-S with normal morning cortisol indicate reduced adrenal androgen reserve?

Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant circulating steroid hormone and serves as the primary clinical marker of adrenal androgen reserve. As individuals age, a distinct biochemical dissociation often occurs where adrenal androgen production declines while glucocorticoid production remains intact.

Clinical evidence

• An isolated low DHEA-S level accompanied by a normal morning cortisol level indicates a selective reduction in adrenal androgen reserve rather than a broad glucocorticoid or cortisol deficiency.
• A normal morning cortisol measurement effectively rules out global hypothalamic-pituitary-adrenal (HPA) axis failure, confirming that the cortisol-producing pathways remain functional.

Mechanistic explanations

• This specific pattern is primarily driven by "adrenopause," which is characterized by the progressive, age-related structural involution of the zona reticularis (the adrenal layer responsible for DHEA-S synthesis). Meanwhile, the cortisol-producing zona fasciculata remains preserved.
• DHEA-S levels decline by approximately 2% to 5% annually after peaking in early adulthood, often dropping to just 10% to 20% of peak young-adult levels by the eighth decade of life.
• Alternatively, chronic physiological stress can cause functional HPA axis dysregulation, shifting pathway prioritization to favor the synthesis of catabolic glucocorticoids (cortisol) over anabolic androgens (DHEA-S).

Bottom line

• For a 61-year-old male, finding low DHEA-S alongside normal morning cortisol reflects a selective, age-related decline in adrenal androgen reserve (adrenopause) or stress-induced pathway shifting, rather than broad cortisol deficiency or global adrenal failure.