What blood work is recommended for a patient suspected of having Polycystic Ovary Syndrome (PCOS)?

Laboratory Evaluation for Suspected PCOS

For a patient with suspected PCOS, order total or free testosterone (preferably by LC-MS/MS), TSH, prolactin, a 2-hour 75g oral glucose tolerance test, and a fasting lipid panel as your core initial workup. 1, 2, 3

First-Line Essential Tests

Androgen Assessment

• Measure total testosterone or free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as your primary androgen marker, which shows pooled sensitivity of 74% and specificity of 86% for PCOS diagnosis 1
• LC-MS/MS is mandatory over direct immunoassays because it demonstrates superior specificity (92% vs 78%), reducing false positives 1, 2
• Free testosterone shows even better sensitivity (89%) with specificity of 83%, making it an excellent first-line option 1
• Important caveat: Total testosterone is abnormal in only 70% of confirmed PCOS cases, meaning 30% will have normal levels despite having the condition 1

Exclusion of Other Endocrine Disorders

• Measure TSH to rule out thyroid disease as an alternative cause of menstrual irregularity 1, 2, 3
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia, with levels >20 μg/L considered abnormal 1, 3
• If prolactin is elevated, confirm with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation 1
• Measure 17-hydroxyprogesterone to exclude nonclassic congenital adrenal hyperplasia 2, 3

Mandatory Metabolic Screening

• Order a 2-hour oral glucose tolerance test with 75g glucose load to screen for type 2 diabetes and glucose intolerance, regardless of BMI 1, 2, 3
• Order fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides to assess dyslipidemia driven by insulin resistance 1, 3
• Target values: LDL <100 mg/dL, HDL >35 mg/dL, triglycerides <150 mg/dL 1
• All women with PCOS require metabolic screening regardless of body weight, as insulin resistance occurs independently of BMI 2

Second-Line Tests (If Clinical Suspicion Remains High Despite Normal First-Line Tests)

Additional Androgen Markers

• Measure androstenedione (A4) if total testosterone and free testosterone are normal but clinical suspicion persists, with sensitivity of 75% and specificity of 71% 1
• Measure DHEAS as an adjunctive test, with sensitivity of 75% and specificity of 67% 1
• These have poorer specificity than testosterone and should only be used as supplementary tests, not primary markers 1

Gonadotropin Assessment

• Measure LH and FSH between days 3-6 of menstrual cycle, calculating based on an average of three estimations taken 20 minutes apart 1
• An LH/FSH ratio >2 suggests PCOS, but this is abnormal in only 35-44% of women with PCOS, making it a poor standalone diagnostic marker 1
• Critical pitfall: Do not rely on LH/FSH ratio as a primary diagnostic criterion due to its low sensitivity 4

Ovulation Assessment

• Measure progesterone during mid-luteal phase to confirm anovulation, with levels <6 nmol/L indicating anovulation 1

Physical Assessment Parameters

Anthropometric Measurements

• Calculate BMI to assess obesity, with BMI >25 considered obese 1, 2, 3
• Measure waist-hip ratio to identify central obesity, with WHR >0.9 indicating truncal obesity and increased metabolic risk 1, 3
• Central obesity exacerbates metabolic, reproductive, and psychological features of PCOS 1

Clinical Signs of Insulin Resistance

• Examine for acanthosis nigricans on neck, axillae, under breasts, and vulva, which indicates underlying insulin resistance 2, 3

Tests to Exclude Serious Pathology

When to Screen for Cushing's Syndrome

• Order dexamethasone suppression test if patient presents with buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies 1, 2

When to Consider Androgen-Secreting Tumors

• Suspect if rapid onset of symptoms, severe hirsutism, or very high testosterone levels (>4.8 nmol/L) 1, 5

Special Considerations

Anti-Müllerian Hormone (AMH)

• Do not use AMH levels as an alternative for detecting polycystic ovarian morphology or as a single test for PCOS diagnosis 1, 2
• While AMH ≥35 pmol/L shows 92% sensitivity and 97% specificity, it lacks assay standardization and validated cut-offs 1, 2

Ultrasound Considerations

• If the patient has both irregular menstrual cycles AND clinical/biochemical hyperandrogenism, ultrasound is not necessary for diagnosis 1, 2
• Ultrasound should not be used for PCOS diagnosis in adolescents with gynecological age <8 years post-menarche due to physiologically normal multifollicular ovaries 1, 2

Critical Diagnostic Algorithm

1. Start with testosterone (total or free by LC-MS/MS), TSH, prolactin, 2-hour OGTT, and fasting lipids 1, 2, 3
2. If testosterone normal but clinical suspicion high, add androstenedione and DHEAS 1
3. Measure 17-hydroxyprogesterone to exclude CAH 2, 3
4. Calculate BMI and waist-hip ratio, examine for acanthosis nigricans 2, 3
5. Remember: A woman can be diagnosed with PCOS based solely on clinical hyperandrogenism plus irregular menstrual cycles, without any abnormal laboratory values, per Rotterdam criteria 1