What bloodwork is recommended for a female patient of childbearing age suspected of having Polycystic Ovary Syndrome (PCOS)?

Bloodwork for PCOS

For a female patient of childbearing age suspected of having PCOS, order total or free testosterone (using mass spectrometry), TSH, prolactin, a 2-hour 75-gram oral glucose tolerance test, and a fasting lipid panel as your core diagnostic and metabolic screening tests. 1, 2

Core Diagnostic Laboratory Tests

Androgen Assessment:

• Measure total testosterone or free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as your first-line test, which shows pooled sensitivity of 74% and specificity of 86% for total testosterone, and superior sensitivity of 89% with specificity of 83% for free testosterone 1
• LC-MS/MS is mandatory over direct immunoassays because it demonstrates superior specificity (92% vs 78%) and avoids false positives 1
• If total or free testosterone are normal but clinical suspicion remains high, add androstenedione (sensitivity 75%, specificity 71%) and DHEAS (sensitivity 75%, specificity 67%) as second-line tests 1
• Calculate Free Androgen Index (FAI) as an alternative if LC-MS/MS is unavailable 1

Exclusion of Other Endocrine Disorders:

• Measure TSH to rule out thyroid disease as a cause of menstrual irregularity, which is essential before confirming PCOS 1, 2
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia, with levels >20 μg/L considered abnormal 1
• Measure 17-hydroxyprogesterone to exclude nonclassic congenital adrenal hyperplasia, particularly if DHEAS is elevated 2

Mandatory Metabolic Screening

Glucose Metabolism:

• Order a 2-hour oral glucose tolerance test with 75-gram glucose load for all PCOS patients regardless of BMI, as this is superior to hemoglobin A1C or fasting glucose alone for detecting impaired glucose tolerance 2, 3
• The American College of Obstetricians and Gynecologists and Endocrine Society preferentially recommend the 2-hour OGTT over A1C or fasting glucose because it is a superior indicator of impaired glucose tolerance/diabetes in PCOS 3

Lipid Assessment:

• Order a fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides to assess dyslipidemia driven by insulin resistance 2
• Target LDL <100 mg/dL, HDL >35 mg/dL, and triglycerides <150 mg/dL 4

Insulin Resistance Markers:

• Measure fasting glucose and insulin levels, with a glucose/insulin ratio >4 suggesting reduced insulin sensitivity 1
• Calculate BMI and measure waist-hip ratio, with WHR >0.9 indicating truncal obesity and increased metabolic risk 1, 2

Additional Tests for Specific Clinical Scenarios

For Fertility Evaluation:

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

Anti-Müllerian Hormone (AMH):

• Do not use AMH as an alternative for detecting polycystic ovarian morphology or as a single diagnostic test due to lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS 2
• AMH ≥35 pmol/L (5 ng/mL) shows high sensitivity (92%) and specificity (97%), but requires further validation and should not replace standard diagnostic criteria 1

Critical Diagnostic Considerations

Important Caveats:

• 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, as the Rotterdam criteria require only two of three features 1
• If the patient has both irregular menstrual cycles AND clinical/biochemical hyperandrogenism, ultrasound is not necessary for PCOS diagnosis 2

Common Pitfall:

• Many obstetrician-gynecologists underutilize metabolic screening, with only 7% ordering the recommended 2-hour OGTT and 22.3% not ordering any screening test at initial visit 3
• The most commonly used but less optimal tests are hemoglobin A1C (51.0%) and fasting glucose (42.7%), which miss impaired glucose tolerance that the OGTT would detect 3

Surveillance and Follow-up

• Repeat OGTT every 2-5 years and lipid profile every 2 years in all women with PCOS 3
• Screen for depression and obstructive sleep apnea, as patients with PCOS are at increased risk 5
• Monitor cardiovascular risk factors every 6-12 months, including weight changes and blood pressure 4