What is the appropriate workup and management for a female patient of reproductive age presenting with symptoms suggestive of Polycystic Ovary Syndrome (PCOS), including irregular menstrual cycles, hirsutism, acne, and obesity?

Workup of PCOS

The workup for PCOS requires measuring total and free testosterone (preferably by LC-MS/MS), TSH, prolactin, a 2-hour oral glucose tolerance test, and fasting lipids, while ultrasound is only needed if both clinical/biochemical hyperandrogenism AND menstrual irregularity are not already present. 1

Diagnostic Criteria

PCOS diagnosis requires at least 2 of 3 Rotterdam criteria: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. 1, 2, 3

• Clinical hyperandrogenism includes hirsutism, acne, or androgenic alopecia 4, 2
• Biochemical hyperandrogenism is confirmed by elevated androgens on laboratory testing 1
• Importantly, you can diagnose PCOS with just clinical hyperandrogenism plus irregular cycles—normal lab values do NOT exclude PCOS 1

Essential Laboratory Tests

First-Line Androgen Assessment

Measure total testosterone AND free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as your primary androgen tests. 1

• Total testosterone has 74% sensitivity and 86% specificity 1
• Free testosterone performs even better with 89% sensitivity and 83% specificity 1
• LC-MS/MS is mandatory—it has 92% specificity compared to only 78% for direct immunoassays, which produce false positives 1
• If LC-MS/MS unavailable, calculate Free Androgen Index (FAI) as an alternative 1

Second-Line Androgen Tests (Only if First-Line Normal)

If testosterone levels are normal but clinical suspicion remains high:

• Measure androstenedione (75% sensitivity, 71% specificity) 1
• Measure DHEAS (75% sensitivity, 67% specificity) 1
• These have poorer specificity than testosterone and should only be adjunctive tests 1

Mandatory Exclusion Tests

Measure TSH to exclude thyroid disease causing menstrual irregularity. 5, 1

Measure prolactin using morning resting samples to exclude hyperprolactinemia. 5, 1

• The American College of Endocrinology recommends confirming prolactin elevation with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation 5
• Hyperprolactinemia mimics PCOS by suppressing GnRH pulsatility, causing anovulation and menstrual irregularity 5
• If hypothyroidism is found, treat it first—this alone may normalize prolactin and restore menses 5

Metabolic Screening (Mandatory for All PCOS Patients)

Perform a 2-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes. 1

Obtain fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides. 1

• Target LDL <100 mg/dL, HDL >35 mg/dL, triglycerides <150 mg/dL 1
• Monitor cardiovascular risk factors every 6-12 months 1

Calculate BMI and measure waist-hip ratio to assess central obesity. 1

• WHR >0.9 indicates truncal obesity 1
• Central obesity exacerbates metabolic, reproductive, and psychological features of PCOS 6

Additional Hormonal Tests to Consider

Measure LH and FSH between cycle days 3-6 to assess hormonal imbalance. 1

• LH/FSH ratio >2 suggests PCOS, but this is only abnormal in 35-44% of women with PCOS, making it a poor standalone marker 1

Measure mid-luteal progesterone to confirm anovulation. 5, 1

• Levels <6 nmol/L indicate anovulation 1

Ultrasound Criteria

Use transvaginal ultrasound with ≥8 MHz transducer for optimal resolution in adults. 1

Polycystic ovarian morphology is defined as:

• ≥20 follicles (2-9mm) per ovary (87.64% sensitivity, 93.74% specificity) 1, 2
• OR ovarian volume ≥10 mL (81.48% sensitivity, 81.04% specificity) 1, 2

Critical Ultrasound Caveats

If the patient has both irregular cycles AND clinical/biochemical hyperandrogenism, ultrasound is NOT necessary for diagnosis. 1

Do NOT use ultrasound in adolescents with gynecological age <8 years (<8 years post-menarche) due to high false-positive rates from normal multifollicular ovaries. 1, 2

Anti-Müllerian Hormone (AMH)

Do NOT use AMH as an alternative for detecting polycystic ovarian morphology or as a single diagnostic test. 1

• While AMH ≥35 pmol/L shows 92% sensitivity and 97% specificity, it lacks assay standardization and validated cut-offs 1
• AMH has significant overlap between women with and without PCOS 1

When to Screen for Other Conditions

Screen for Cushing's syndrome if patient has buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies. 1

Consider androgen-secreting tumors if rapid onset of symptoms, severe hirsutism, or very high testosterone levels. 1

• Androstenedione >10.0 nmol/L suggests adrenal/ovarian tumor 1

Consider non-classical congenital adrenal hyperplasia if DHEAS is elevated. 1

Common Pitfalls to Avoid

• Do not rely solely on LH/FSH ratio—it's abnormal in only 35-44% of PCOS cases 1
• Do not use direct immunoassays for testosterone—they have 14% lower specificity than LC-MS/MS 1
• Do not exclude PCOS based on normal testosterone—30% of confirmed PCOS patients have normal levels 1
• Do not order ultrasound if both hyperandrogenism and menstrual irregularity are already documented 1
• Do not use ultrasound as first-line diagnostic in adolescents 1, 2

Weight Assessment and Lifestyle Intervention

Monitor weight and waist circumference at every visit, as weight gain is accelerated in PCOS compared to unaffected women. 6

• Obesity prevalence in PCOS has increased from 51% in the 1990s to 74% in recent decades 6
• Weight gain escalates from adolescence, requiring early vigilance 6
• Central obesity exacerbates metabolic, reproductive, and psychological features of PCOS 6