What is the diagnostic approach for Polycystic Ovary Syndrome (PCOS)?

Diagnostic Approach for Polycystic Ovary Syndrome (PCOS)

The diagnosis of PCOS requires at least two of the following three criteria: chronic anovulation/oligo-amenorrhea, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. 1, 2

Initial Evaluation

History and Physical Assessment

• Menstrual patterns: Cycle length >35 days suggests chronic anovulation; even slightly irregular cycles (32-36 days) warrant assessment 1
• Hyperandrogenism symptoms:
  • Hirsutism (gradual onset, worsens with weight gain)
  • Acne (severe or resistant to conventional treatments)
  • Hair loss (vertex, crown, diffuse pattern) 1, 3
• Metabolic symptoms: Weight gain, skin tags, acanthosis nigricans (insulin resistance) 1

Laboratory Testing

1. First-line tests:

   • Total testosterone and free testosterone (preferably by liquid chromatography-mass spectrometry) 1
   • TSH and prolactin (to exclude thyroid disorders and hyperprolactinemia) 1, 4
   • Two-hour oral glucose tolerance test with 75g glucose load 1
   • Fasting lipid profile 1

2. Additional testing to exclude differential diagnoses:

   • 17-hydroxyprogesterone (to rule out non-classic congenital adrenal hyperplasia) 1, 4
   • Overnight dexamethasone suppression test or 24-hour urinary free cortisol (if Cushing's syndrome suspected) 4
   • Mid-luteal phase progesterone (<6 nmol/L indicates anovulation) 1
   • Fasting glucose/insulin ratio (>4 suggests normal insulin sensitivity) 1

Ultrasound Evaluation

• Preferred approach: Transvaginal ultrasound (if sexually active and acceptable to patient) 5
• Diagnostic criteria for polycystic ovarian morphology:
  • Using endovaginal ultrasound with ≥8MHz frequency: ≥20 follicles (2-9mm) per ovary and/or ovarian volume ≥10mL 5
  • Using older technology or transabdominal approach: ovarian volume ≥10mL 5
  • Ensure no corpus luteum, cysts, or dominant follicles are present 5

Important: Ultrasound should NOT be used for PCOS diagnosis within 8 years of menarche due to high incidence of multi-follicular ovaries in this life stage 5, 1

Diagnostic Criteria and Phenotypes

According to the Rotterdam criteria, PCOS diagnosis requires at least two of three features 2, 6:

1. Oligo/anovulation
2. Clinical and/or biochemical hyperandrogenism
3. Polycystic ovaries on ultrasound

This results in four phenotypes:

• Phenotype A: Anovulation + hyperandrogenism + PCO (complete phenotype)
• Phenotype B: Anovulation + hyperandrogenism (without PCO)
• Phenotype C: Hyperandrogenism + PCO (ovulatory PCOS)
• Phenotype D: Anovulation + PCO (without hyperandrogenism) 5

Important Considerations

Anti-Müllerian Hormone (AMH)

• Current recommendation: Serum AMH levels should NOT be used as an alternative for detecting PCOM or as a single test for PCOS diagnosis 5, 1
• Despite promising research showing high sensitivity and specificity in various studies (AUC values ranging from 0.67-0.956), standardization of assays and established cut-off levels are still needed 5

Differential Diagnosis

Always exclude other causes of hyperandrogenism and menstrual irregularity:

• Thyroid disorders
• Hyperprolactinemia
• Non-classic congenital adrenal hyperplasia
• Cushing's syndrome
• Androgen-secreting tumors (consider if rapid onset, severe symptoms, virilization)
• Exogenous androgens
• Acromegaly
• Primary ovarian failure 1, 4

Special Populations

Adolescents:

• Diagnosis is challenging as many PCOS features overlap with normal puberty
• Persistent oligomenorrhea 2-3 years post-menarche suggests underlying dysfunction
• Hyperandrogenism is central to presentation in adolescents
• Ultrasound not recommended in girls <17 years due to common multicystic ovaries 1, 3

Postmenopausal women:

• No consistent phenotype
• Diagnosis more challenging 2

Pitfalls to Avoid

1. Relying solely on ultrasound: In patients with irregular menstrual cycles and hyperandrogenism, ultrasound is not necessary for diagnosis 5

2. Using AMH as a diagnostic test: Despite promising research, AMH is not yet validated as a diagnostic tool 5, 1

3. Misdiagnosing isolated polycystic ovaries as PCOS: PCO morphology alone is found in 17-22% of women without the full syndrome 1

4. Missing serious underlying conditions: Always consider androgen-secreting tumors in cases of rapid-onset, severe hyperandrogenism with virilization 3, 4

5. Premature diagnosis in adolescents: Menstrual irregularities and varied cycle length are common in the first 2-3 years post-menarche 3