What laboratory tests are used to diagnose Polycystic Ovary Syndrome (PCOS)?

Laboratory Tests for Diagnosing Polycystic Ovary Syndrome (PCOS)

The essential laboratory tests for diagnosing PCOS include total testosterone or free testosterone levels, thyroid-stimulating hormone, prolactin, and a two-hour oral glucose tolerance test, with additional tests to rule out other causes of androgen excess. 1

Core Diagnostic Laboratory Tests

Androgen Assessment (First-line)

• Total testosterone (TT) - Preferred first-line test 1
• Free testosterone (FT) - Should be calculated using:
  • Equilibrium dialysis or ammonium sulfate precipitation
  • Free Androgen Index (FAI) calculation 1
• Method recommendation: Liquid chromatography with tandem mass spectrometry (LC-MS/MS) due to superior sensitivity and specificity compared to immunoassay methods 1

Other Essential Tests

• Thyroid-stimulating hormone (TSH) - To exclude thyroid disorders 1
• Prolactin level - To rule out hyperprolactinemia 1
• Two-hour oral glucose tolerance test - Using 75g glucose load to screen for insulin resistance and diabetes 1
• Fasting lipid profile including:
  • Total cholesterol
  • LDL cholesterol
  • HDL cholesterol
  • Triglycerides 1

Secondary Androgen Tests

If total testosterone or free testosterone are not elevated, consider:

• Androstenedione (A4) - Less specific but may detect hyperandrogenism missed by testosterone testing 1
• Dehydroepiandrosterone sulfate (DHEAS) - May be elevated in some cases of PCOS 1, 2

Tests to Rule Out Other Causes of Androgen Excess

• 17-hydroxyprogesterone - To exclude non-classic congenital adrenal hyperplasia 1
• Cortisol studies - If Cushing's syndrome is suspected based on physical examination findings (buffalo hump, moon facies, abdominal striae) 1
• Sex hormone-binding globulin (SHBG) - Often decreased in PCOS, particularly with insulin resistance 2

Additional Helpful Tests

• LH/FSH ratio - May be elevated in PCOS (>1.0), though not diagnostic on its own 3, 4
• Fasting insulin - To assess insulin resistance 3
• HOMA-IR calculation - For quantifying insulin resistance 4

Diagnostic Algorithm

1. Start with androgen assessment:

   • Measure total testosterone or bioavailable/free testosterone
   • If using calculated free testosterone, also measure SHBG

2. Screen for common endocrine disorders that mimic PCOS:

   • TSH and prolactin testing

3. Assess metabolic health:

   • Two-hour oral glucose tolerance test
   • Fasting lipid profile
   • Calculate BMI and waist-hip ratio

4. If initial androgen tests are negative but clinical suspicion remains high:

   • Test additional androgens (androstenedione, DHEAS)
   • Consider LH/FSH ratio

5. If clinical features suggest other disorders:

   • Test 17-hydroxyprogesterone if congenital adrenal hyperplasia suspected
   • Screen for Cushing's syndrome if characteristic features present

Important Caveats

• Ultrasound findings alone are not sufficient for diagnosis, particularly in adolescents less than 8 years post-menarche due to high incidence of multi-follicular ovaries in this age group 1

• Laboratory values must be interpreted in context of clinical presentation (irregular menses, hirsutism, acne, obesity)

• Androgen measurement accuracy is highly dependent on the laboratory method used, with LC-MS/MS being superior to immunoassays 1

• Ethnicity and age may affect normal reference ranges for androgens, requiring careful interpretation 1

• Timing of tests: Ideally perform hormone measurements in the early follicular phase (days 2-5) of the menstrual cycle for most accurate results

By following this systematic laboratory approach, clinicians can accurately diagnose PCOS while excluding other conditions that may present with similar symptoms, ultimately leading to appropriate management and improved patient outcomes.