What is DHEA (Dehydroepiandrosterone) sulfate?

DHEA Sulfate: An Important Adrenal Androgen

DHEA sulfate (DHEAS) is the sulfated form of dehydroepiandrosterone (DHEA), the most abundant circulating steroid hormone in humans produced primarily by the adrenal glands, serving as a precursor to both estrogen and testosterone. 1

What is DHEAS?

• DHEAS is the storage form of DHEA in the bloodstream, with the majority of DHEA in circulation present as DHEAS
• It is produced by the zona reticularis of the adrenal cortex in response to adrenocorticotropic hormone (ACTH) 2
• DHEAS is formed when DHEA undergoes sulfation by the enzyme sulfotransferase in the liver and adrenal glands 3
• It serves as a reservoir for DHEA, as tissues containing steroid sulfatases can convert DHEAS back to active DHEA 4

Age-Related Changes and Production

• DHEAS levels follow a characteristic age-related pattern:
  • Peak plasma levels occur at approximately age 25 years 4
  • Levels progressively decline thereafter at a rate of about 2% per year 3
  • By age 85, levels diminish by approximately 95% compared to young adults 4
• This age-associated decrease has been termed "adrenopause" 5

Clinical Significance and Diagnostic Uses

DHEAS serves important diagnostic functions:

• Marker for adrenal function: Abnormal levels can indicate adrenal disorders
• Diagnostic marker for hyperandrogenism: Used in the evaluation of conditions like polycystic ovary syndrome (PCOS) 6
  • DHEAS has moderate sensitivity (0.75) but lower specificity (0.67) compared to other androgen markers 6
  • Age-specific reference ranges are important when interpreting DHEAS levels:
    • Age 20-29: >3800 ng/ml is considered abnormal
    • Age 30-39: >2700 ng/ml is considered abnormal 7

Potential Therapeutic Applications

DHEAS/DHEA has been investigated for several therapeutic uses:

• Female sexual function: May improve sexual satisfaction and vaginal atrophy in postmenopausal women 7
• Adrenal insufficiency: Replacement therapy in patients with primary adrenal insufficiency (PAI) who are deficient in adrenal androgens 7
  • Typically administered as oral DHEA tablets (10-50 mg), often 25 mg as a single daily dose
  • Dosing guided by serum DHEAS, androstenedione, and testosterone levels 7
• Quality of life improvements: May benefit female patients with persistent lack of libido and/or low energy levels despite optimized glucocorticoid and mineralocorticoid replacement 7

Measurement and Monitoring

• DHEAS is typically measured using direct immunoassays
• More accurate measurements can be obtained using liquid chromatography-tandem mass spectrometry (LC-MS/MS) 6
• When monitoring DHEA supplementation, levels should be measured in the morning prior to DHEA ingestion 7

Cautions and Limitations

• Limited objective evidence of clinical benefit from large studies 7
• Long-term effects of DHEA or testosterone replacement therapy in patients with adrenal insufficiency are not well established 7
• DHEA should be used with caution in cancer survivors receiving aromatase inhibitor therapy, as vaginal DHEA increases levels of circulating androgens 7
• Common pitfalls in interpreting DHEAS levels include:
  • Relying solely on one androgen marker
  • Not accounting for age-related changes in DHEAS levels
  • Using inappropriate assay methods 6

DHEAS testing provides valuable information about adrenal function and androgen status, particularly in the evaluation of reproductive disorders and adrenal insufficiency, but results must be interpreted in the context of age, gender, and clinical presentation.