What is the normal range of total testosterone in women with Polycystic Ovary Syndrome (PCOS)?

Total Testosterone Range in Women with Polycystic Ovary Syndrome (PCOS)

The normal range of total testosterone in women with PCOS is typically elevated compared to women without PCOS, with diagnostic values generally above 0.75 ng/mL (2.6 nmol/L) when measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which is the most accurate method for testosterone measurement. 1

Diagnostic Accuracy of Testosterone Measurement in PCOS

Total Testosterone (TT)

• Pooled sensitivity: 74% (95% CI: 0.63-0.82)
• Pooled specificity: 86% (95% CI: 0.77-0.91)
• Area Under the Curve (AUC): 0.87 (95% CI: 0.84-0.90) 1

Calculated Free Testosterone (cFT)

• Pooled sensitivity: 89% (95% CI: 0.69-0.96)
• Pooled specificity: 83% (95% CI: 0.79-0.86)
• AUC: 0.85 (95% CI: 0.81-0.88) 1

Free Androgen Index (FAI)

• Pooled sensitivity: 78% (95% CI: 0.70-0.83)
• Pooled specificity: 85% (95% CI: 0.76-0.90)
• AUC: 0.87 (95% CI: 0.84-0.90) 1

Measurement Methods and Their Impact

The method used to measure testosterone significantly affects the results:

• LC-MS/MS (Gold Standard):

  • Higher specificity for TT: 92% (95% CI: 0.81-0.97)
  • AUC: 0.90 (95% CI: 0.87-0.92) 1
  • Recommended by the 2023 International PCOS Guidelines due to superior accuracy

• Direct Immunoassays:

  • Lower specificity: 78% (95% CI: 0.67-0.86)
  • AUC: 0.82 (95% CI: 0.79-0.86) 1
  • More widely available but less accurate

• Immunoassay after extraction:

  • Specificity: 93% (95% CI: 0.80-0.98) 1

Clinical Relevance and Interpretation

When interpreting testosterone levels in PCOS:

• A baseline testosterone level of approximately 0.75 ng/mL (2.6 nmol/L) is common in untreated PCOS patients 2
• In one study, total testosterone was the most frequently abnormal biochemical marker for PCOS, present in 70% of cases 3
• Calculated testosterone indices (bioavailable testosterone, FAI, free testosterone) showed better discrimination between PCOS patients and healthy controls than total testosterone alone 4

Important Considerations and Pitfalls

1. Diagnostic Context: Testosterone measurement should be interpreted within the Rotterdam Criteria for PCOS diagnosis, which requires at least two of: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovary morphology 5

2. Measurement Variability:

   • Different assay methods produce significantly different absolute values
   • Reference ranges should be established for each laboratory's specific assay 3

3. Alternative Androgens:

   • If TT or cFT are not elevated, androstenedione (A4) and DHEAS could be considered, though they have poorer specificity 1
   • Recent research has identified novel androgen pathways that may contribute to hyperandrogenism in PCOS 6

4. Diagnostic Accuracy:

   • No single hormonal test is sufficient for PCOS diagnosis
   • A combination of testosterone, androstenedione, or LH was elevated in 86% of women with PCOS 3

5. Phenotypic Variation:

   • Different PCOS phenotypes may have varying testosterone levels
   • Phenotype D (non-hyperandrogenic PCOS) may have normal testosterone levels despite meeting other diagnostic criteria 7

Recommended Approach for Testosterone Assessment

1. Use LC-MS/MS for testosterone measurement whenever possible
2. Interpret results using laboratory-specific reference ranges
3. Consider calculated indices (FAI, cFT) for improved diagnostic accuracy
4. Evaluate testosterone in conjunction with other diagnostic criteria for PCOS
5. Consider testing additional androgens if clinical suspicion is high but TT is normal

By following these guidelines, clinicians can more accurately assess testosterone levels in women with PCOS and improve diagnostic precision.