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 your first-line androgen test using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which demonstrates 74% sensitivity and 86% specificity for PCOS diagnosis. 1

Essential Hormone Panel

• Total testosterone (TT) or free testosterone (FT) should be measured using LC-MS/MS, which shows superior specificity (92%) compared to direct immunoassays (78%) that may produce false positives 1
• Free testosterone demonstrates even better sensitivity (89%) with 83% specificity, making it an excellent first-line option 1
• Calculate Free Androgen Index (FAI) if LC-MS/MS is unavailable as an alternative method 1

Mandatory Exclusion Tests

• Thyroid-stimulating hormone (TSH) must be measured to rule out thyroid disease as a cause of menstrual irregularity 1, 2
• Prolactin levels should be obtained using morning resting serum samples to exclude hyperprolactinemia, with levels >20 μg/L considered abnormal 1
• Confirm prolactin elevation with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation 1

Metabolic Screening (Required for All Patients)

• Two-hour oral glucose tolerance test with 75g glucose load is mandatory regardless of BMI, as insulin resistance occurs independently of body weight 1, 2
• Fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides (target LDL <100 mg/dL, HDL >35 mg/dL, triglycerides <150 mg/dL) 1
• Calculate body mass index (BMI) and waist-hip ratio to assess central obesity, with WHR >0.9 indicating truncal obesity that exacerbates metabolic complications 1, 2

Second-Line Tests (Only If Clinical Suspicion Remains High)

• Androstenedione (A4) can be measured if testosterone is normal but suspicion persists, showing 75% sensitivity and 71% specificity 1
• DHEAS may be added, with 75% sensitivity and 67% specificity, but both have poorer specificity than TT/FT and should only serve as adjunctive tests 1
• 17-hydroxyprogesterone should be measured to exclude non-classical congenital adrenal hyperplasia, particularly if DHEAS is elevated 1, 2, 3

Additional Hormonal Assessment

• LH and FSH measured between cycle days 3-6, with LH/FSH ratio >2 suggesting PCOS, though this is abnormal in only 35-44% of cases, making it a poor standalone marker 1
• Mid-luteal progesterone (levels <6 nmol/L indicate anovulation) confirms ovulatory dysfunction 1

Critical Diagnostic Considerations

When Laboratory Tests May Be Normal

PCOS can be diagnosed based solely on clinical hyperandrogenism (hirsutism, acne, alopecia) plus irregular menstrual cycles without any abnormal laboratory values. 1

• Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal levels despite having the disease 1
• If the patient has both irregular cycles AND clinical/biochemical hyperandrogenism, ultrasound is not necessary for diagnosis 1, 2

Red Flags Requiring Immediate Evaluation

• Rapid onset of symptoms, severe hirsutism, or very high testosterone levels warrant evaluation for androgen-secreting tumors 1, 2
• Screen for Cushing's syndrome if buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies are present using dexamethasone suppression test or 24-hour urinary free cortisol 1, 2, 3
• Androstenedione levels >10.0 nmol/L suggest adrenal/ovarian tumor 1

Tests NOT Recommended

• Anti-Müllerian hormone (AMH) should NOT be used as an alternative for detecting polycystic ovarian morphology or as a single diagnostic test due to lack of standardization and no validated cut-offs, despite showing 92% sensitivity and 97% specificity 1, 2
• Ultrasound should NOT be used for diagnosis in adolescents with gynecological age <8 years post-menarche due to physiologically normal multifollicular ovaries at this stage 1, 2

Physical Examination Findings to Document

• Look for acanthosis nigricans on neck, axillae, under breasts, and vulva, which indicates underlying insulin resistance 2
• Document signs of hyperandrogenism including hirsutism pattern, acne distribution, and androgenic alopecia 1, 4

Monitoring After Diagnosis

• Repeat metabolic screening (lipids, glucose tolerance) every 6-12 months along with weight and blood pressure monitoring 1
• Screen for depression and obstructive sleep apnea, as patients with PCOS are at increased risk 5