What lab workup is recommended for a patient suspected of having Polycystic Ovary Syndrome (PCOS)?

Laboratory Workup for Suspected PCOS

The essential lab workup for suspected PCOS includes first-line androgen testing (total and free testosterone via LC-MS/MS), TSH, prolactin, 2-hour oral glucose tolerance test, and fasting lipid panel, with additional tests guided by clinical presentation. 1, 2

Core First-Line Laboratory Tests

Androgen Assessment

• Measure total testosterone (TT) and free testosterone (FT) as your primary androgen markers using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which shows superior specificity (92%) compared to direct immunoassays (78%). 1
• TT demonstrates pooled sensitivity of 74% and specificity of 86%, while FT shows superior sensitivity of 89% with specificity of 83%. 1
• If LC-MS/MS is unavailable, calculate Free Androgen Index (FAI) using equilibrium dialysis or ammonium sulfate precipitation as an alternative. 1
• Critical caveat: Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition. 1

Exclusion of Other Endocrine Disorders

• Measure thyroid-stimulating hormone (TSH) to rule out thyroid disease as a cause of menstrual irregularity. 1, 2
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia (levels >20 μg/L considered abnormal). 1, 2
• Measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 2

Metabolic Screening (Mandatory for All Patients)

• Perform a 2-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes, regardless of BMI. 1, 2
• Obtain fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides. 1, 2
• All women with PCOS require metabolic screening regardless of body weight, as insulin resistance occurs independently of BMI and affects both lean and overweight women. 2

Second-Line Laboratory Tests (When Clinical Suspicion Remains High)

Additional Androgen Testing

• If TT and FT are normal but clinical suspicion persists, measure androstenedione (A4) with sensitivity of 75% and specificity of 71%. 1
• Measure DHEAS (dehydroepiandrosterone sulfate) with sensitivity of 75% and specificity of 67%, particularly to rule out non-classical congenital adrenal hyperplasia. 1
• Important limitation: A4 and DHEAS have poorer specificity than TT/FT and should only be used as adjunctive tests, not primary markers. 1

Ovulatory Function Assessment

• Measure LH and FSH between days 3-6 of menstrual cycle (calculate based on average of three estimations taken 20 minutes apart). 1
• Pitfall: LH/FSH ratio >2 suggests PCOS but is abnormal in only 35-44% of women with PCOS, making it a poor standalone diagnostic marker. 1
• Measure progesterone in mid-luteal phase to confirm anovulation, with levels <6 nmol/L indicating anovulation. 1

Insulin Resistance Assessment

• Measure fasting glucose and insulin levels, with glucose/insulin ratio >4 suggesting reduced insulin sensitivity. 1

Anthropometric Measurements

• Calculate BMI to assess obesity (BMI >25 considered obese). 1, 2
• Measure waist-hip ratio to identify central obesity (WHR >0.9 indicates truncal obesity). 1, 2
• Look for acanthosis nigricans on physical examination (neck, axillae, under breasts, vulva), which indicates underlying insulin resistance. 2

Tests to Exclude Mimicking Conditions

When to Screen for Specific Conditions

• Screen for Cushing's syndrome with dexamethasone suppression test if patient has buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies. 1, 2
• Consider androgen-secreting tumors if rapid onset of symptoms, severe hirsutism, or very high testosterone levels (androstenedione >10.0 nmol/L). 1, 2
• Measure FSH levels to check for primary ovarian failure. 1

Tests NOT Recommended for Routine Diagnosis

• Do not use Anti-Müllerian Hormone (AMH) levels as an alternative for detecting polycystic ovarian morphology or as a single test for PCOS diagnosis. 1, 2
• While AMH ≥35 pmol/L (5 ng/mL) shows high sensitivity (92%) and specificity (97%), it lacks assay standardization, has no validated cut-offs, and shows significant overlap between women with and without PCOS. 1, 2

Critical Diagnostic Considerations

• If the patient has both irregular menstrual cycles AND clinical/biochemical hyperandrogenism, you can diagnose PCOS without ultrasound or any abnormal laboratory values beyond the androgen testing. 1
• The Rotterdam criteria require only two of three features: oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. 1, 3
• Document the specific PCOS phenotype when making the diagnosis, as each has different long-term health and metabolic implications. 4