Can a young woman have Polycystic Ovary Syndrome (PCOS) with high Dehydroepiandrosterone (DHEA) and normal testosterone levels?

PCOS with High DHEA and Normal Testosterone Levels

Yes, a young woman can have Polycystic Ovary Syndrome (PCOS) with high dehydroepiandrosterone (DHEA) or DHEAS levels and normal testosterone levels, as biochemical hyperandrogenism in PCOS can manifest through elevated levels of various androgens, not just testosterone. 1

Diagnostic Criteria for PCOS

PCOS diagnosis requires at least two of three criteria:

• Chronic anovulation (oligomenorrhea or amenorrhea)
• Hyperandrogenism (clinical or biochemical)
• Polycystic ovaries on ultrasound

Biochemical hyperandrogenism can be confirmed through various androgen measurements:

1. Primary androgen markers:

   • Total testosterone (TT): Sensitivity 74%, Specificity 86%
   • Free testosterone (FT): Sensitivity 89%, Specificity 83%
   • Free Androgen Index (FAI): Sensitivity 78%, Specificity 85% 1

2. Secondary androgen markers:

   • Androstenedione (A4): Sensitivity 75%, Specificity 71%
   • DHEAS: Sensitivity 75%, Specificity 67% 1

DHEAS in PCOS

DHEAS elevation occurs in a subset of PCOS patients:

• Approximately 8-33% of women with PCOS have elevated DHEAS levels 2, 3
• DHEAS elevation is more common in non-classic (phenotypes B and C) PCOS compared to classic phenotype A 3
• DHEAS levels correlate with other androgens but not significantly with ovarian, pituitary, or metabolic markers 2

The 2025 Human Reproduction Update guidelines note that DHEAS can be considered a secondary diagnostic androgen marker when primary markers (testosterone, FAI) are normal 4.

Clinical Implications

When evaluating a young woman with suspected PCOS who has normal testosterone but elevated DHEAS:

1. Consider PCOS phenotype:

   • Non-classic phenotypes (B and C) more commonly present with elevated DHEAS 3
   • Phenotype B: Hyperandrogenism + polycystic ovaries (with regular cycles)
   • Phenotype C: Anovulation + hyperandrogenism (without polycystic ovaries)

2. Rule out other causes of adrenal hyperandrogenism:

   • Non-classic congenital adrenal hyperplasia
   • Cushing's syndrome
   • Adrenal tumors 1

3. Comprehensive testing should include:

   • Total testosterone and free testosterone (or FAI)
   • DHEAS
   • Androstenedione
   • 17-hydroxyprogesterone
   • Thyroid function tests
   • Prolactin 1

Age Considerations

DHEAS levels are strongly age-dependent:

• Peak between ages 20-30
• Decline by approximately 40% from twenties to thirties 3

Therefore, age-specific reference ranges should be used when interpreting DHEAS levels 2.

Clinical Significance of DHEAS in PCOS

The role of elevated DHEAS in PCOS remains somewhat unclear:

• It may reflect a generalized exaggeration in androgen biosynthesis 5
• DHEA appears to have protective effects against metabolic abnormalities in PCOS women 6
• Some research suggests DHEA is a better predictor of abnormal anthropometric and biochemical parameters in PCOS than DHEAS 6

Conclusion

While testosterone remains the primary diagnostic marker for biochemical hyperandrogenism in PCOS, elevated DHEAS with normal testosterone can still support a PCOS diagnosis when other diagnostic criteria are present. This pattern appears more common in non-classic PCOS phenotypes and warrants comprehensive evaluation to exclude other causes of adrenal hyperandrogenism.