What laboratory tests should be ordered for the diagnosis and management of Polycystic Ovary Syndrome (PCOS)?

Laboratory Testing for PCOS Diagnosis and Management

Order a comprehensive metabolic and hormonal panel including: TSH, prolactin, total or free testosterone (preferably by LC-MS/MS), 2-hour oral glucose tolerance test with 75g glucose load, and fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) as your core diagnostic workup. 1

Essential First-Line Laboratory Tests

Hormonal Assessment for Diagnosis

• Measure total testosterone OR free testosterone as the primary androgen marker, with free testosterone showing superior sensitivity (89%) compared to total testosterone (74%), though both have good specificity (83-86%). 1
• Use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for testosterone measurement rather than direct immunoassays, as LC-MS/MS demonstrates superior specificity (92% vs 78%). 1
• Check TSH levels to exclude thyroid disease as an alternative cause of menstrual irregularity. 2, 1
• Measure prolactin using morning resting serum levels to rule out hyperprolactinemia as a competing diagnosis. 2, 1

Metabolic Screening (Critical for Risk Assessment)

• Perform a 2-hour oral glucose tolerance test with 75g glucose load rather than just fasting glucose, as all women with PCOS have demonstrated increased risk for type 2 diabetes and glucose intolerance. 2, 1
• Order a complete fasting lipid panel including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, since women with PCOS frequently have dyslipidemia with elevated LDL and triglycerides plus decreased HDL. 2, 1
• Calculate BMI and waist-hip ratio to assess for central obesity, with waist-hip ratio >0.9 indicating truncal obesity. 2, 1

Second-Line Tests When Clinical Suspicion Remains High

Additional Androgen Testing

• Measure androstenedione (A4) if testosterone levels are normal but clinical suspicion persists, recognizing it has lower specificity (71%) than testosterone but can capture cases missed by testosterone alone. 1
• Check DHEAS levels to help exclude non-classical congenital adrenal hyperplasia, particularly if elevated (>10.0 nmol/L suggests adrenal/ovarian tumor). 1

Ovulatory Function Assessment

• Measure LH and FSH between cycle days 3-6, with an LH/FSH ratio >2:1 supporting PCOS diagnosis (found in 55% of PCOS patients). 1, 3
• Check mid-luteal phase progesterone to confirm anovulation, with levels <6 nmol/L indicating anovulation. 1

Tests to Exclude Competing Diagnoses

Screen for Cushing's Syndrome

• Evaluate for Cushing's syndrome if the patient presents with: buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, or proximal myopathies. 2, 1

Rule Out Androgen-Secreting Tumors

• Consider androgen-secreting tumors if: rapid onset of symptoms, severe hirsutism, or very high testosterone levels are present. 1

Important Caveats and Pitfalls

AMH Testing Limitations

• Do not use serum AMH levels as a single diagnostic test for PCOS, despite elevated AMH correlating with PCOS (threshold ≥35 pmol/L shows 92% sensitivity and 97% specificity), as international guidelines explicitly state AMH should not yet replace ultrasound for detecting polycystic ovarian morphology. 2, 1

Age-Specific Considerations

• Avoid ultrasound for PCOS diagnosis in those with gynecological age <8 years (less than 8 years post-menarche) due to high incidence of multi-follicular ovaries in this life stage. 2
• In adolescents, base diagnosis on oligomenorrhea and biochemical evidence rather than ultrasound, as large multicystic ovaries are common normal findings in girls <17 years. 4

Assay Method Matters

• Recognize that direct immunoassays for testosterone produce more false positives (specificity 78%) compared to LC-MS/MS (specificity 92%), which can lead to overdiagnosis. 1

Ongoing Metabolic Surveillance

• Repeat glucose tolerance testing regularly in obese women with PCOS due to potential for rapid progression from normal glucose tolerance to impaired glucose tolerance and diabetes. 5
• Monitor lipid profiles longitudinally as insulin resistance in PCOS is associated with elevated triglycerides, increased small dense LDL, and decreased HDL. 2