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

Laboratory Workup for Suspected PCOS

Order total testosterone or free testosterone (preferably by LC-MS/MS), TSH, prolactin, 2-hour oral glucose tolerance test with 75g glucose load, and fasting lipid panel as your core diagnostic laboratory tests. 1, 2

First-Line Hormonal Tests

Androgen Assessment

• Measure total testosterone (TT) and free testosterone (FT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as your primary androgen markers, with TT showing 74% sensitivity and 86% specificity, while FT demonstrates superior sensitivity of 89% with 83% specificity 1
• LC-MS/MS is mandatory over direct immunoassays because it provides superior specificity (92% vs 78%), reducing false positives 1
• If TT or FT are normal but clinical suspicion remains high, add androstenedione (A4) and DHEAS as second-line tests, though these have poorer specificity (71% and 67% respectively) 1

Exclusion of Other Endocrine Disorders

• 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, 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 (Mandatory for All Patients)

Glucose Metabolism

• Order a 2-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes, regardless of BMI 1, 2
• This is essential because women with PCOS are four times more likely to develop type 2 diabetes than the general population 3
• Consider measuring fasting glucose/insulin ratio, with a ratio >4 suggesting reduced insulin sensitivity 1

Lipid Assessment

• Order fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides to assess dyslipidemia driven by insulin resistance 1, 2
• Target values: LDL <100 mg/dL, HDL >35 mg/dL, triglycerides <150 mg/dL 1

Anthropometric Measurements

• Calculate BMI to assess obesity (BMI >25 considered obese in this context) 1, 2
• Measure waist-hip ratio to identify central obesity, with WHR >0.9 indicating truncal obesity that exacerbates metabolic, reproductive, and psychological features 1

Additional Tests When Clinically Indicated

For Fertility Evaluation

• Measure LH and FSH between days 3-6 of menstrual cycle (average of three estimations taken 20 minutes apart), though an LH/FSH ratio >2 is abnormal in only 35-44% of PCOS cases, making it a poor standalone marker 1
• Measure progesterone during mid-luteal phase to confirm anovulation, with levels <6 nmol/L indicating anovulation 1

To Exclude Specific Conditions

• Measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia, especially if DHEAS is elevated 1, 2
• 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 1, 2
• If rapid onset of symptoms, severe hirsutism, or very high testosterone levels (suggesting androgen-secreting tumor), immediate evaluation is required 1, 3

Critical Diagnostic Considerations

Important: Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition 1. A woman can be diagnosed with PCOS based solely on clinical hyperandrogenism (hirsutism, acne, or alopecia) plus irregular menstrual cycles, without any abnormal laboratory values, per Rotterdam criteria 1.

What NOT to Order

• Do not use AMH levels as an alternative for detecting polycystic ovarian morphology or as a single diagnostic test due to lack of assay standardization, no validated cut-offs, and significant overlap between women with and without PCOS 1, 2
• Do not rely on LH/FSH ratio alone as it is abnormal in only 35-44% of PCOS cases 1

Common Pitfalls to Avoid

• Screen all women with PCOS for metabolic dysfunction regardless of body weight, as insulin resistance occurs independently of BMI and affects both lean and overweight women 2
• Remember that the presence of clinical features (irregular cycles + hyperandrogenism) can establish diagnosis even when laboratory tests return normal 1
• Monitor cardiovascular risk factors every 6-12 months, including weight changes and blood pressure 1