DHEA-S Testing in Clinical Practice

Primary Clinical Indications for DHEA-S Testing

DHEA-S serves as a second-line diagnostic marker when first-line androgen tests are negative but clinical suspicion for hyperandrogenism remains high, as recommended by the Endocrine Society 1, 2.
The American College of Obstetricians and Gynecologists suggests that DHEA-S should be measured when clinical signs of virilization are present, alongside other androgens 3.

DHEA-S has limited utility for diagnosing PCOS, with pooled sensitivity of 0.75 and specificity of only 0.57, making it inferior to testosterone-based measurements, according to the American Society for Reproductive Medicine 1, 4.
The area under the curve (AUC) for DHEA-S in PCOS diagnosis is 0.77, lower than total testosterone (0.87), calculated free testosterone (0.85), and free androgen index (0.87), as reported by the Endocrine Society 1, 5.

Direct immunoassays for DHEA-S have sensitivity of 0.67 and specificity of 0.70, while LC-MS/MS methods have higher sensitivity (0.82) but lower specificity (0.57), as noted by the Clinical and Laboratory Standards Institute 6, 1.
The choice of assay method significantly impacts diagnostic accuracy, though the differences are less pronounced for DHEA-S than for testosterone measurements, according to the National Academy of Clinical Biochemistry 1, 7.

DHEA-S levels decline progressively with age at approximately 2% per year, reaching maximum concentrations between ages 20-30 years, as observed by the American Geriatrics Society 2.
Age-adjusted reference ranges are essential for accurate interpretation, as failure to use age-specific norms leads to overdiagnosis of DHEA-S elevation, as recommended by the Endocrine Society 2.

The American College of Physicians advises against using DHEA-S as a first-line test for PCOS diagnosis due to poor specificity and low prevalence of elevation 1.
A low DHEA-S alone is insufficient to establish the diagnosis of adrenal insufficiency and requires confirmation with dynamic testing, as noted by the Endocrine Society 8.

Second‑line testing for hyperandrogenism – In women whose total and free testosterone levels are within normal limits but who exhibit persistent clinical signs of androgen excess (e.g., hirsutism, acne, male‑pattern hair loss, menstrual irregularities), DHEA‑S should be measured to further evaluate the source of excess androgens. 9
Evaluation of adrenal masses – When an adrenal lesion is suspected (e.g., possible adrenocortical carcinoma), DHEA‑S should be included in a comprehensive hormonal panel that also measures 17‑OH‑progesterone, androstenedione, testosterone, and 17‑β‑estradiol. 10

Poor specificity as a primary PCOS test – DHEA‑S should not be used as the initial diagnostic test for polycystic ovary syndrome because its specificity is only ~67 %, which is substantially lower than that of testosterone‑based measurements. 9
Reduced overall accuracy – Meta‑analysis data show that DHEA‑S has a pooled sensitivity of 0.75, specificity of 0.67, and an area under the ROC curve (AUC) of 0.77 for PCOS detection—values that are inferior to total testosterone (AUC 0.87), calculated free testosterone (AUC 0.85), and free androgen index (AUC 0.87). 9

Impact of assay choice on diagnostic metrics – Liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) provides higher sensitivity (0.82) but lower specificity (0.57) for DHEA‑S measurement compared with direct immunoassays, which have sensitivity 0.67 and specificity 0.70. The selection of assay method therefore influences diagnostic accuracy, although the effect is less pronounced for DHEA‑S than for testosterone assays. 9

Measure testosterone first – Total and free testosterone should be obtained before ordering DHEA‑S, because these testosterone assays demonstrate superior diagnostic performance for hyperandrogenism. DHEA‑S is appropriate only after testosterone results are normal or inconclusive. 9