DHEA-S Testing in Women: Clinical Indications and Interpretation
DHEA-S should be used as a second-line test in women when first-line androgen measurements (total and free testosterone) are normal but clinical suspicion for hyperandrogenism remains high, or when signs of virilization are present. 1
When to Order DHEA-S Testing
Primary Indications
Order DHEA-S when total testosterone and free testosterone are not elevated but the patient has persistent clinical signs of androgen excess (hirsutism, acne, male-pattern baldness, menstrual irregularities). 2, 1
Measure DHEA-S alongside other androgens when virilization is present, including clitoromegaly, voice deepening, or increased muscle mass. 3
Consider DHEA-S testing in the evaluation of adrenal masses as part of comprehensive hormonal work-up for suspected adrenocortical carcinoma, measuring serum DHEA-S along with 17-OH-progesterone, androstenedione, testosterone, and 17-beta-estradiol. 2
When NOT to Use DHEA-S as First-Line
Do not use DHEA-S as the initial test for PCOS diagnosis due to poor specificity (only 67%) and inferior diagnostic accuracy compared to testosterone-based measurements. 2, 1
DHEA-S has limited utility for PCOS with pooled sensitivity of 0.75 and specificity of only 0.67, yielding an AUC of 0.77—substantially lower than total testosterone (AUC 0.87), calculated free testosterone (AUC 0.85), and free androgen index (AUC 0.87). 2, 1
Interpreting DHEA-S Results
Elevated DHEA-S Levels
Moderate elevations (above age-adjusted reference range):
- Most commonly indicate PCOS (affecting 4-6% of women) or non-classical congenital adrenal hyperplasia. 3
- Elevated DHEA-S is found in 60% of hirsute women, 34% of women with oligomenorrhea, and only 19% of infertile women with regular ovulation. 4
- When combined with unbound testosterone measurement, 82% of hirsute women show elevation in at least one of these androgens. 4
Marked elevations require imaging:
- Obtain adrenal CT or MRI to exclude adrenal tumor when DHEA-S is significantly elevated. 3
- Perform pelvic ultrasound to evaluate for ovarian pathology. 3
Low DHEA-S Levels
Low DHEA-S is characteristic of primary adrenal insufficiency, occurring alongside low cortisol, elevated ACTH, and low aldosterone. 3
Low DHEA-S levels may be associated with decreased libido in both premenopausal and postmenopausal women, suggesting a defect in adrenal steroidogenesis. 5
A low DHEA-S alone is insufficient to diagnose adrenal insufficiency and requires confirmation with dynamic testing. 1
Critical Interpretation Considerations
Age-Adjusted Reference Ranges
Always use age-specific reference ranges as DHEA-S declines progressively at approximately 2% per year, with maximum concentrations between ages 20-30 years. 1
Failure to use age-adjusted norms leads to overdiagnosis of DHEA-S elevation. 1
Assay Method Matters
Liquid chromatography with tandem mass spectrometry (LC-MS/MS) has higher sensitivity (0.82) but lower specificity (0.57) compared to direct immunoassays (sensitivity 0.67, specificity 0.70). 2, 1
The choice of assay method significantly impacts diagnostic accuracy, though differences are less pronounced for DHEA-S than for testosterone measurements. 1
Common Clinical Pitfalls to Avoid
Do not rely on DHEA-S as a standalone test for PCOS given its poor specificity and the fact that only a minority of PCOS patients have elevated levels. 1
Do not order DHEA-S without first measuring total and free testosterone, as these have superior diagnostic performance for hyperandrogenism. 2, 1
Do not interpret DHEA-S without considering the patient's age, as physiologic decline occurs throughout adulthood. 1
DHEA-S serves as a better indicator of adrenal androgen secretion than urinary 17-ketosteroids and correlates well with urinary androsterone and DHEA fractions. 6