What laboratory evaluations are recommended for a patient suspected of having Polycystic Ovary Syndrome (PCOS)?

Laboratory Evaluations for Suspected PCOS

For a patient with suspected PCOS, obtain total testosterone (preferably by LC-MS/MS), TSH, prolactin, a 2-hour 75g oral glucose tolerance test, and a fasting lipid panel as your core diagnostic workup. 1

Core Diagnostic Laboratory Tests

Androgen Assessment

• Measure total testosterone as the primary androgen marker, which demonstrates a pooled sensitivity of 74% and specificity of 86% for PCOS diagnosis 2
• LC-MS/MS is the preferred assay method for testosterone measurement, showing superior specificity (92%) compared to direct immunoassays (78%), though sensitivity remains similar across methods (71-74%) 2
• If total testosterone is normal but clinical suspicion remains high, measure androstenedione, particularly if levels exceed 10.0 nmol/L which may indicate adrenal or ovarian tumor 1
• Consider measuring DHEAS to exclude non-classical congenital adrenal hyperplasia, especially when elevated 1

Exclusion of Other Endocrine Disorders

• Measure TSH to rule out thyroid dysfunction as an alternative cause of menstrual irregularity 1
• Obtain morning resting serum prolactin to exclude hyperprolactinemia as a competing diagnosis 1
• Measure LH and FSH between cycle days 3-6, with an LH/FSH ratio >2 supporting (but not diagnostic of) PCOS 1
• Check mid-luteal progesterone levels to confirm anovulation, with levels <6 nmol/L indicating anovulation 1

Metabolic Screening

• Perform a 2-hour 75g oral glucose tolerance test (OGTT) to screen for glucose intolerance and type 2 diabetes, as this is the best simple office-based method to assess both insulin resistance and glucose intolerance simultaneously 1, 3
• The OGTT provides superior prognostic and treatment implications compared to fasting glucose alone 3
• Obtain a fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides, as 22-27% of PCOS patients meet criteria for metabolic syndrome regardless of diagnostic criteria used 1, 4

Additional Insulin Resistance Assessment

Practical Office-Based Measures

• Calculate the fasting glucose-to-insulin ratio (G:I ratio), which shows strong correlation with gold-standard insulin sensitivity measures (r=0.73) 5
• A fasting G:I ratio <4.5 has 95% sensitivity and 84% specificity for detecting insulin resistance in PCOS, making it an excellent screening tool 5
• This ratio outperforms fasting insulin alone (r=0.50) or fasting glucose alone (r=0.24, non-significant) for predicting insulin resistance 5
• Calculate HOMA-IR as an alternative measure of insulin resistance, though the G:I ratio demonstrates superior predictive value 4, 5

Anthropometric Measurements

• Calculate BMI and measure waist-hip ratio (WHR) to assess obesity patterns, as WHR is a significant independent predictor of insulin resistance (β=0.361, p=0.048) 1, 6
• A WHR >0.9 indicates truncal obesity and predicts development of insulin resistance and cardiovascular complications 1, 6

Red Flag Screening

When to Suspect Alternative Diagnoses

• Screen for Cushing's syndrome if the patient presents with buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies 1
• Consider androgen-secreting tumors with rapid symptom onset, severe hirsutism, or markedly elevated testosterone levels 1
• Elevated DHEAS warrants evaluation for congenital adrenal hyperplasia 1

Important Clinical Caveats

Assay Method Considerations

• Direct immunoassays for testosterone have lower specificity (78%) compared to LC-MS/MS (92%), which may lead to false positives 2
• The diagnostic accuracy of testosterone varies by PCOS diagnostic criteria used—Rotterdam criteria show higher sensitivity (77%) but lower specificity (83%) compared to NIH criteria (sensitivity 51%, specificity 94%) 2

Metabolic Risk Assessment

• All women with PCOS require metabolic screening regardless of which diagnostic criteria are applied (NIH, Rotterdam, or AES), as insulin resistance and metabolic syndrome prevalence remains substantial (22-27%) across all definitions 4
• Approximately 50-70% of PCOS women have some degree of insulin resistance, making metabolic assessment essential even in lean patients 3
• The combination of hyperandrogenemia and central obesity represents the strongest predictor of insulin resistance and future cardiovascular risk 6

Timing and Interpretation

• Perform androgen testing in the follicular phase (days 3-6) when possible for consistency 1
• Insulin resistance assessment is particularly important in obese PCOS patients, as obesity compounds the inherent insulin resistance of the syndrome 3
• The OGTT provides both diagnostic information (glucose intolerance) and prognostic value (cardiovascular risk stratification) that fasting measures alone cannot capture 3