What laboratory tests should be ordered for a patient with insulin resistance and Polycystic Ovary Syndrome (PCOS)?

Laboratory Tests for Patients with Insulin Resistance and PCOS

For patients with insulin resistance and PCOS, a comprehensive laboratory panel should include total testosterone, free testosterone, TSH, prolactin, 17-hydroxyprogesterone, fasting glucose/insulin ratio, lipid profile, and 2-hour 75g oral glucose tolerance test (OGTT). 1

First-Line Laboratory Tests

Hormonal Assessment

• Androgen Profile:

  • Total testosterone
  • Free testosterone or Free Androgen Index (FAI) (sensitivity 78%, specificity 85%) 1
  • Androstenedione (sensitivity 75%, specificity 71%) 1
  • DHEAS (dehydroepiandrosterone sulfate) (sensitivity 75%, specificity 67%) 1
  • Sex hormone-binding globulin (SHBG) - often decreased in PCOS 2

• Gonadotropins:

  • LH (luteinizing hormone)
  • FSH (follicle-stimulating hormone)
  • LH/FSH ratio (>2 suggests PCOS) 2

• Other Hormones:

  • TSH (thyroid-stimulating hormone) - to rule out thyroid disorders 1
  • Prolactin - to rule out hyperprolactinemia 1
  • 17-hydroxyprogesterone - to rule out congenital adrenal hyperplasia 1
  • Progesterone (mid-luteal phase) - to assess ovulation (<6 nmol/L indicates anovulation) 2

Metabolic Assessment

• Insulin Resistance Markers:

  • Fasting glucose/insulin ratio (G/I ratio >4 suggests insulin resistance) 2
  • HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) - values ≥3.8 indicate insulin resistance 3
  • 2-hour 75g oral glucose tolerance test (OGTT) - best office-based method to assess both insulin resistance and glucose intolerance 4

• Lipid Profile:

  • Total cholesterol
  • LDL cholesterol
  • HDL cholesterol
  • Triglycerides
  • Triglyceride/HDL ratio (>3.2 has high sensitivity and specificity for metabolic syndrome in PCOS) 5

Additional Tests Based on Clinical Presentation

• Metabolic Syndrome Screening:

  • Waist circumference measurement (>83.5 cm combined with elevated FAI strongly predicts metabolic syndrome) 6
  • Blood pressure measurement
  • Fasting blood glucose

• Cardiovascular Risk Assessment:

  • HbA1c - to assess long-term glycemic control
  • High-sensitivity C-reactive protein (hs-CRP) - inflammatory marker

Testing Algorithm

1. For all patients with suspected insulin resistance and PCOS:

   • Complete hormonal profile (testosterone, LH, FSH, TSH, prolactin)
   • Fasting glucose/insulin ratio or HOMA-IR
   • Lipid profile

2. For patients with BMI >25 kg/m²:

   • Add 2-hour 75g OGTT 1
   • Consider more extensive cardiovascular risk assessment

3. For patients with waist circumference >83.5 cm and elevated FAI:

   • Prioritize metabolic syndrome screening 6
   • Consider more frequent monitoring of metabolic parameters

Clinical Pearls and Pitfalls

• The OGTT is considered the best simple office-based method for assessing insulin resistance in PCOS patients as it provides information about both insulin resistance and glucose intolerance 4

• Approximately 50-70% of women with PCOS have some degree of insulin resistance, making metabolic screening essential 4

• There is no significant difference in the frequency of insulin resistance and metabolic syndrome between the four PCOS phenotypes defined by the Rotterdam criteria, so all phenotypes should undergo metabolic screening 3

• Waist circumference combined with Free Androgen Index offers the most efficient combination to identify PCOS women who should be screened for metabolic syndrome and insulin resistance 6

• Ethnic variations exist in PCOS presentation, with East Asian women having the highest prevalence of metabolic syndrome despite lower BMI 2

• Testing should be performed during days 3-6 of the menstrual cycle for accurate hormone assessment, particularly for LH, FSH, and testosterone measurements 2