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

Laboratory Tests for Diagnosing Polycystic Ovary Syndrome (PCOS)

The diagnosis of PCOS requires comprehensive laboratory testing including total testosterone, free testosterone, androstenedione, LH/FSH ratio, and transvaginal ultrasound with specific follicle count and ovarian volume measurements. 1

Diagnostic Criteria

PCOS diagnosis requires at least two of three criteria:

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

All testing should be performed after excluding other relevant disorders that can mimic PCOS.

Essential Laboratory Tests

Androgen Assessment

• Total testosterone (TT):

  • Most frequently abnormal biochemical marker (70% sensitivity) 1, 2
  • Should be measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for superior specificity (92%) 1

• Free testosterone (FT):

  • 89% sensitivity, 83% specificity 1
  • Should be calculated rather than directly measured
  • Methods include equilibrium dialysis, ammonium sulfate precipitation, or Free Androgen Index (FAI)

• Free Androgen Index (FAI):

  • 78% sensitivity, 85% specificity 1

• Androstenedione (A4):

  • 75% sensitivity, 71% specificity 1
  • Abnormal in 53% of PCOS cases 2

• Dehydroepiandrosterone sulfate (DHEAS):

  • 75% sensitivity, 67% specificity 1
  • Not significantly different between PCOS and control groups in some studies 2

Gonadotropins

• Luteinizing hormone (LH):

  • Elevated in only 35% of PCOS cases 2
  • Should be measured in early follicular phase 1

• Follicle stimulating hormone (FSH):

  • Often normal or slightly decreased 1

• LH/FSH ratio:

  • Elevated in 41-44% of PCOS cases 2
  • Associated with ovarian volume 3
  • Limited sensitivity as a standalone test 2

Exclusion Tests

• Thyroid-stimulating hormone (TSH) 1
• Prolactin 1
• 17-hydroxyprogesterone (to rule out congenital adrenal hyperplasia) 1
• Overnight dexamethasone suppression test or 24-hour urinary free cortisol (to rule out Cushing's syndrome) 1

Metabolic Assessment

• Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) 1
• 2-hour 75g oral glucose tolerance test (particularly in women with BMI >25 kg/m²) 1
• Fasting glucose/insulin ratio (>4 suggests reduced insulin sensitivity) 1

Imaging Evaluation

Transvaginal Ultrasound

• Should be performed between days 3-9 of menstrual cycle 1
• Diagnostic criteria:
  • ≥20 follicles (2-9mm) per ovary OR
  • Ovarian volume ≥10ml 1
• Ovarian volume is more strongly associated with androgen levels than follicle count 3

Emerging Biomarkers

• Anti-Müllerian hormone (AMH):
  • 83% sensitivity, 99% specificity with a cut-off value of 3.3 ng/mL 4
  • Not yet included in standard diagnostic criteria but shows promise

Common Pitfalls to Avoid

1. Relying solely on LH/FSH ratio for diagnosis due to its low sensitivity (41-44%) 2

2. Misdiagnosing functional hypothalamic amenorrhea with polycystic ovarian morphology (FHA-PCOM) as PCOS phenotype D 1

3. Not using standardized laboratory methods for testosterone measurement, which can lead to inaccurate results 1

4. Failing to perform testing during the appropriate phase of the menstrual cycle (early follicular phase is recommended) 1

5. Not excluding other causes of hyperandrogenism before confirming PCOS diagnosis 1

Diagnostic Algorithm

1. First-line tests:

   • Total testosterone
   • Free testosterone or FAI
   • LH and FSH (with ratio calculation)
   • Transvaginal ultrasound (days 3-9 of cycle)

2. Second-line tests (to exclude other disorders):

   • TSH
   • Prolactin
   • 17-hydroxyprogesterone
   • Dexamethasone suppression test (if Cushing's suspected)

3. Metabolic assessment:

   • Fasting lipid profile
   • Oral glucose tolerance test
   • Fasting glucose/insulin ratio

4. Confirm diagnosis if at least two of three Rotterdam criteria are present after exclusion of other disorders.