What laboratory tests and treatments are recommended for the diagnosis and management of Polycystic Ovary Syndrome (PCOS)?

Laboratory Testing for PCOS

Measure total testosterone or free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS), thyroid-stimulating hormone, prolactin, a 2-hour oral glucose tolerance test with 75g glucose load, and a fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides as your core diagnostic workup. 1

First-Line Androgen Assessment

• Total testosterone (TT) and free testosterone (FT) are the mandatory first-line tests for biochemical hyperandrogenism, with TT showing 74% sensitivity and 86% specificity, while FT demonstrates superior sensitivity of 89% with 83% specificity. 1
• LC-MS/MS is the required assay method, showing superior specificity (92%) compared to direct immunoassays (78%), which produce false positives. 1
• If LC-MS/MS is unavailable, calculate Free Androgen Index (FAI) using total testosterone and sex hormone-binding globulin levels. 1

Second-Line Androgen Testing (If Clinical Suspicion Remains High)

• Measure androstenedione (A4) if TT/FT are normal but clinical features suggest PCOS, with sensitivity of 75% and specificity of 71%. 1
• Measure DHEAS as an adjunctive test, with sensitivity of 75% and specificity of 67%, though both have poorer specificity than TT/FT. 1
• Measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 2

Mandatory Metabolic Screening (All Patients Regardless of BMI)

• Perform a 2-hour oral glucose tolerance test with 75g glucose load in all women with PCOS to screen for type 2 diabetes and glucose intolerance, as they have demonstrated increased risk. 3, 1
• Obtain fasting lipid panel including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, as women with PCOS frequently have dyslipidemia with disproportionately elevated LDL and decreased HDL. 3, 1
• Calculate body mass index (BMI) and waist-hip ratio to assess central obesity, with WHR >0.9 indicating truncal obesity. 1, 2

Exclusion of Alternative Diagnoses

• Measure TSH to rule out thyroid disease as a cause of menstrual irregularity. 1, 2
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia. 1
• Consider dexamethasone suppression test if patient has buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies to exclude Cushing's syndrome. 3, 2

Optional Tests (Context-Dependent)

• Measure LH and FSH between days 3-6 of menstrual cycle, with LH/FSH ratio >2 suggesting PCOS, though this is abnormal in only 35-44% of women with PCOS, making it a poor standalone diagnostic marker. 1
• Measure mid-luteal phase progesterone to confirm anovulation, with levels <6 nmol/L indicating anovulation. 1
• Anti-Müllerian hormone (AMH) ≥35 pmol/L shows 92% sensitivity and 97% specificity, but should not replace ultrasound or serve as a standalone diagnostic test due to lack of assay standardization. 1, 2

Critical Diagnostic Caveat

• Remember that 30% of women with confirmed PCOS have normal testosterone levels, and clinical hyperandrogenism (hirsutism, acne, alopecia) plus irregular menstrual cycles alone can establish the diagnosis without any abnormal laboratory values using Rotterdam criteria. 1
• The Rotterdam criteria require only two of three features: oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. 1, 4

Ultrasound Considerations

• Transvaginal ultrasound with ≥8 MHz transducer showing ≥20 follicles per ovary and/or ovarian volume ≥10 mL confirms polycystic ovarian morphology. 1, 2
• Ultrasound should not be used for diagnosis in adolescents with gynecological age <8 years due to high incidence of multifollicular ovaries at this stage. 2
• When clinical features (irregular cycles and hyperandrogenism) are present, ultrasound is not necessary for diagnosis but will identify the complete PCOS phenotype. 2