What laboratory tests and treatment options are recommended for a patient with suspected Polycystic Ovary Syndrome (PCOS)?

Laboratory Testing for Suspected PCOS

Core Diagnostic Laboratory Tests

Measure total testosterone or free testosterone as first-line androgen testing using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which demonstrates superior specificity (92%) compared to direct immunoassays (78%). 1

Essential Hormone Panel

• Total testosterone (TT) shows pooled sensitivity of 74% and specificity of 86% for PCOS diagnosis 1
• Free testosterone (FT) demonstrates superior sensitivity of 89% with specificity of 83% 1
• Calculated Free Androgen Index (FAI) can be used as an alternative if LC-MS/MS is unavailable 1
• TSH must be measured to exclude thyroid disease as a cause of menstrual irregularity 1, 2
• Prolactin should be measured using morning resting serum levels to exclude hyperprolactinemia, with levels >20 μg/L considered abnormal 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 Therefore, normal testosterone does not exclude PCOS if clinical features (hirsutism, acne, irregular cycles) are present.

Second-Line Androgen Testing (If TT/FT Normal but Clinical Suspicion High)

• Androstenedione (A4) with sensitivity of 75% and specificity of 71% 1
• DHEAS with sensitivity of 75% and specificity of 67% 1
• 17-hydroxyprogesterone to exclude non-classical congenital adrenal hyperplasia 2, 3

Important note: A4 and DHEAS have poorer specificity than TT/FT and should only be used as adjunctive tests when first-line testing is normal but clinical suspicion remains high. 1

Mandatory Metabolic Screening

All women with PCOS should be screened for metabolic abnormalities regardless of body weight, as insulin resistance occurs independently of BMI. 2

Glucose Metabolism Assessment

• Two-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes, regardless of BMI 1, 2
• Fasting glucose and insulin levels with glucose/insulin ratio >4 suggesting reduced insulin sensitivity 1

Lipid and Cardiovascular Risk Assessment

• Fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides (target LDL <100 mg/dL, HDL >35 mg/dL, triglycerides <150 mg/dL) 1
• BMI calculation with BMI >25 considered obese 1, 2
• Waist-hip ratio with WHR >0.9 indicating truncal obesity and increased metabolic risk 1
• Look for acanthosis nigricans on physical examination (neck, axillae, under breasts, vulva), which indicates underlying insulin resistance 2

Optional Tests for Specific Clinical Scenarios

Ovulation Assessment (If Fertility Desired)

• Progesterone measured in mid-luteal phase, with levels <6 nmol/L indicating anovulation 1
• LH and FSH measured between days 3-6 of menstrual cycle, with LH/FSH ratio >2 suggesting PCOS (though abnormal in only 35-44% of PCOS cases, making it a poor standalone marker) 1

Exclusion of Other Causes of Hyperandrogenism

• Dexamethasone suppression test if Cushing's syndrome suspected (buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, proximal myopathies) 2, 3
• 24-hour urinary free cortisol as alternative screening for Cushing's syndrome 3
• Consider androgen-secreting tumors if rapid onset of symptoms, severe hirsutism, virilization, or very high testosterone levels 1, 2

Critical pitfall: If prolactin is elevated, confirm with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation. 1

Tests NOT Recommended

• Anti-Müllerian hormone (AMH) should NOT be used as an alternative for detecting polycystic ovarian morphology or as a single test for PCOS diagnosis due to lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS 1, 2
• Ultrasound should NOT be used for PCOS diagnosis in those with gynecological age <8 years (<8 years after menarche) due to high incidence of multifollicular ovaries being physiologically normal at this life stage 1, 2

Diagnostic Algorithm Summary

If irregular menstrual cycles AND clinical/biochemical hyperandrogenism are both present, ultrasound is not necessary for PCOS diagnosis (though it will identify the complete PCOS phenotype). 1 The Rotterdam criteria require only two of three features: oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. 1, 2