What laboratory tests and evaluations are necessary for the confirmation of Polycystic Ovary Syndrome (PCOS)?

Laboratory Confirmation of PCOS

For PCOS diagnosis, measure total testosterone (preferably by LC-MS/MS), TSH, and prolactin as essential laboratory tests, with testosterone being the single most valuable biochemical marker showing 70% sensitivity for PCOS. 1, 2

Essential Hormonal Tests

Androgen Assessment

• Total testosterone is the primary and most sensitive biochemical marker for PCOS, demonstrating 70% abnormality rate in PCOS patients and pooled sensitivity of 74% with specificity of 86%. 1, 2
• Use LC-MS/MS (mass spectrometry) for testosterone measurement when available, as it shows superior specificity (92%) compared to direct immunoassays (78%), reducing false positives. 1
• Free or bioavailable testosterone can be measured as alternatives, though total testosterone remains the gold standard. 1, 3
• Androstenedione should be measured if testosterone is normal but clinical suspicion remains high, showing 53% abnormality rate in PCOS. 1, 2

Exclusion of Other Endocrine Disorders

• TSH must be measured to exclude thyroid disease as a cause of menstrual irregularity. 1, 4
• Prolactin level should be obtained using morning resting serum samples to exclude hyperprolactinemia. 1, 4
• DHEAS (dehydroepiandrosterone sulfate) should be measured to rule out non-classical congenital adrenal hyperplasia, particularly if levels are elevated (>10.0 nmol/L suggests adrenal/ovarian tumor). 1

Gonadotropin Measurements (Optional but Informative)

• LH and FSH should be measured between cycle days 3-6, with an LH/FSH ratio >2 suggesting PCOS, though this has low sensitivity (35-44%) and should not be used as a sole diagnostic criterion. 1, 2
• LH elevation >10 IU/L is associated with increased infertility and cycle disturbance in PCOS patients. 5
• The LH/FSH ratio should be abandoned as a primary biochemical criterion due to its poor sensitivity despite being historically emphasized. 2

Metabolic Screening (Essential for Risk Assessment)

Glucose Metabolism

• Perform a 2-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes, as all PCOS patients have increased metabolic risk. 1, 4
• Fasting glucose/insulin ratio can be measured, with a ratio >4 suggesting reduced insulin sensitivity. 1

Lipid Assessment

• Obtain fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides to assess cardiovascular risk. 1, 4

Anthropometric Measurements

• Calculate BMI to assess obesity, which correlates with hirsutism, elevated testosterone, and increased infertility rates. 1, 5
• Measure waist-hip ratio to identify central obesity (WHR >0.9 indicates truncal obesity). 1

Ovulatory Function Assessment

• Mid-luteal phase progesterone (cycle day 21-23) should be measured to confirm anovulation, with levels <6 nmol/L indicating anovulation. 1

Emerging Biomarkers (Not Yet Recommended for Routine Diagnosis)

• AMH levels should NOT be used as a single test or alternative for PCOS diagnosis, despite showing high sensitivity (92%) and specificity (97%) at threshold ≥35 pmol/L (5 ng/mL). 6, 1, 4
• The 2018 International Evidence-based Guideline explicitly states that serum AMH should not yet replace ultrasound for detecting polycystic ovarian morphology due to lack of standardization across assays and populations. 6

Diagnostic Algorithm Priority

The combination of testosterone, androstenedione, or LH (either alone or in combination) identifies 86% of PCOS cases, making these the definitive hormonal tests when combined with clinical features and ultrasound findings. 2

Key Clinical Pitfalls to Avoid

• Do not rely on LH/FSH ratio alone - it has only 35-44% sensitivity despite being historically popular. 2
• Ensure testosterone assays are validated for women - many commercial assays lack accuracy at female testosterone ranges. 1
• Screen for Cushing's syndrome if rapid symptom onset, buffalo hump, moon facies, hypertension, or abdominal striae are present before confirming PCOS. 1, 4
• Consider androgen-secreting tumors if testosterone >4.8 nmol/L, rapid onset, or severe hirsutism - these require exclusion before PCOS diagnosis. 1, 5
• Remember that Rotterdam criteria (requiring 2 of 3: hyperandrogenism, ovulatory dysfunction, polycystic ovaries) show higher sensitivity (77%) but lower specificity (83%) compared to NIH criteria. 1, 3