What is the workup to evaluate for Polycystic Ovary Syndrome (PCOS)?

Diagnostic Workup for Polycystic Ovary Syndrome (PCOS)

The diagnostic workup for PCOS should include assessment of hyperandrogenism (clinical and biochemical), ovulatory dysfunction, and polycystic ovary morphology, with total testosterone (TT) and free testosterone (FT) as first-line laboratory tests for biochemical hyperandrogenism. 1

Diagnostic Criteria

PCOS is diagnosed according to the Rotterdam criteria, requiring at least two of the following three findings:

• Hyperandrogenism (clinical or biochemical) 1, 2
• Ovulatory dysfunction (oligomenorrhea or amenorrhea) 2
• Polycystic ovary morphology on ultrasound 1, 2

Clinical Assessment

History

• Menstrual history: Cycle length >35 days suggests chronic anovulation 3
• Hyperandrogenism symptoms: Gradual onset of hirsutism, acne, or alopecia 3
• Metabolic symptoms: Weight changes, signs of insulin resistance 2
• Family history: PCOS has a strong genetic component 2

Physical Examination

• Clinical signs of hyperandrogenism:
  • Hirsutism: Assess using Ferriman-Gallwey scoring system 3
  • Acne: Particularly severe or treatment-resistant acne 3
  • Androgenic alopecia: Vertex, crown, or diffuse pattern 3
• Body mass index (BMI): Obesity is common but not required for diagnosis 2
• Signs of insulin resistance: Acanthosis nigricans 4

Laboratory Testing

First-Line Tests

• Total testosterone (TT): Sensitivity 74%, specificity 86% 1
• Free testosterone (FT): Should be assessed by equilibrium dialysis or calculated using FAI 1
• Calculated free testosterone (cFT): Sensitivity 89%, specificity 83% 1
• Free androgen index (FAI): Sensitivity 78%, specificity 85% 1

Second-Line Tests (if TT or FT not elevated)

• Androstenedione (A4): Sensitivity 75%, specificity 71% 1
• Dehydroepiandrosterone sulfate (DHEAS): Sensitivity 75%, specificity 67% 1

Testing Method Considerations

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the preferred method for androgen measurement due to superior accuracy 1
• Direct immunoassays have lower sensitivity and specificity compared to LC-MS/MS 1

Additional Tests to Exclude Other Conditions

• 17-hydroxyprogesterone: To rule out congenital adrenal hyperplasia 3
• Thyroid function tests: To exclude thyroid dysfunction 5
• Prolactin: To rule out hyperprolactinemia 5
• Fasting glucose and insulin: To assess for insulin resistance 2, 4
• Lipid profile: To evaluate metabolic risks 2

Imaging

• Transvaginal ultrasound: To assess for polycystic ovary morphology 1
  • Diagnostic criteria: ≥25 small follicles (2-9 mm) in the whole ovary 3
  • Ovarian volume ≥10 mL indicates increased ovary size 3
  • Note: Not recommended as first-line in adolescents <17 years 3

Special Considerations

Adolescents

• Diagnosis requires more stringent criteria: All three Rotterdam criteria should be met 4
• Evaluation should be delayed until 2 years post-menarche 4
• Persistent oligomenorrhea 2-3 years beyond menarche suggests underlying ovarian dysfunction 3

Rapid Onset or Severe Virilization

• Requires immediate evaluation for androgen-secreting tumors 4
• Additional testing may include adrenal imaging 5

Pitfalls to Avoid

• Relying solely on direct immunoassay methods for testosterone measurement, which have lower accuracy 1
• Diagnosing PCOS in adolescents too early (within 2 years of menarche) 4
• Failing to exclude other causes of hyperandrogenism and irregular menses 5
• Using ultrasound as first-line investigation in women <17 years 3
• Overlooking metabolic complications: Patients with PCOS have twice the risk of metabolic syndrome 4

By following this comprehensive diagnostic approach, clinicians can accurately diagnose PCOS and identify associated metabolic risks, allowing for appropriate interventions based on the patient's specific phenotype and health concerns.