What are the diagnostic criteria for Polycystic Ovary Syndrome (PCOS)?

Diagnostic Criteria for Polycystic Ovary Syndrome (PCOS)

PCOS is diagnosed using the Rotterdam criteria, which requires at least 2 of the following 3 features after excluding other causes: (1) oligo- or anovulation, (2) clinical and/or biochemical hyperandrogenism, and (3) polycystic ovarian morphology on ultrasound. 1, 2

Core Diagnostic Framework

The Rotterdam criteria create multiple phenotypes of PCOS, all of which are valid diagnoses 1, 3, 4:

• Phenotype A: Hyperandrogenism + oligo/anovulation + polycystic ovaries 3
• Phenotype B: Hyperandrogenism + oligo/anovulation (without polycystic ovaries) 3
• Phenotype C: Hyperandrogenism + polycystic ovaries (with regular ovulation) 3, 5
• Phenotype D: Oligo/anovulation + polycystic ovaries (without hyperandrogenism) 3, 5

Clinical Assessment

Document the following specific clinical features 1, 2:

• Menstrual history: Cycle length >35 days indicates chronic anovulation 1, 2
• Signs of hyperandrogenism: Hirsutism, acne, androgenic alopecia (male-pattern balding), clitoromegaly 1, 2
• Onset and duration: Gradual onset with worsening during weight gain is typical 2
• BMI and waist-hip ratio: Central obesity is a common metabolic feature 1, 2
• Medication review: Exclude exogenous androgen use 1
• Family history: Cardiovascular disease and diabetes 1

Biochemical Hyperandrogenism Testing

Total testosterone measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the single best initial biochemical marker, with 74% sensitivity and 86% specificity. 6, 2

Hierarchy of androgen testing 1, 6, 2:

• First-line: Total testosterone via LC-MS/MS (sensitivity 74%, specificity 86%) 6, 2
• Most sensitive: Calculated free testosterone using Vermeulen equation (sensitivity 89%, specificity 83%) 1, 2
• Alternative markers:
  • Free androgen index (FAI): sensitivity 78%, specificity 85% 1, 6
  • Androstenedione: sensitivity 75%, specificity 71% 1, 2
  • DHEAS: sensitivity 75%, specificity 67% 1, 2

Critical pitfall: Direct immunoassays for testosterone have inferior accuracy compared to LC-MS/MS (specificity 78% vs 92%) and should be avoided 1, 6

Important caveat: All androgen testing must be performed in the absence of hormonal contraception, as progestin-containing contraceptives suppress the hypothalamic-pituitary-ovarian axis and make results unreliable 1

Ultrasound Criteria for Polycystic Ovarian Morphology

Follicle number per ovary (FNPO) ≥20 follicles (2-9mm diameter) is the gold standard ultrasonographic marker, with 87.64% sensitivity and 93.74% specificity in adult women. 7, 1, 2

Technical specifications for optimal imaging 7, 1, 2:

• Preferred method: Transvaginal ultrasound with ≥8 MHz transducer frequency 7, 1, 2
• Primary marker: FNPO ≥20 follicles per ovary 7, 1, 2
• Alternative markers when accurate follicle counting is impossible:
  • Ovarian volume >10 mL 7, 1, 2
  • Follicle number per single cross-section (FNPS) 7, 1

Critical age-specific consideration: Ultrasound should NOT be used as a first-line diagnostic tool in adolescents (<20 years or <8 years post-menarche) due to poor specificity and high false-positive rates from normal multifollicular ovaries 1, 6, 2. In adolescents, rely on clinical and biochemical hyperandrogenism plus menstrual irregularity persisting 2-3 years beyond menarche 1

Differential Diagnosis - Mandatory Exclusions

Before confirming PCOS, exclude the following conditions 1:

• Cushing's syndrome: Buffalo hump, moon facies, hypertension, abdominal striae 1
• Androgen-secreting tumors: Rapid onset, severe hyperandrogenism 1
• Non-classic congenital adrenal hyperplasia 1
• Thyroid disease and prolactin disorders 1
• Primary hypothalamic amenorrhea and primary ovarian failure 1

Metabolic Screening - Required for All PCOS Patients

All women diagnosed with PCOS must be screened for type 2 diabetes, glucose intolerance, and dyslipidemia. 1, 2

Specific screening tests 1, 2:

• Glucose assessment: Fasting glucose and 2-hour glucose after 75-gram oral glucose load 2
• Lipid panel: Fasting lipoprotein profile to assess for elevated LDL and triglycerides 1, 2

Anti-Müllerian Hormone (AMH) - Not Recommended for Diagnosis

AMH is NOT recommended for clinical diagnosis of PCOS due to lack of standardization across assays, absence of established cut-offs, and significant overlap between women with and without PCOS. 1, 8

While AMH levels are significantly higher in women with PCOS and may emerge as a future marker for polycystic ovarian morphology, current limitations include age-dependent variability and lack of validated thresholds 1, 8

Common Diagnostic Pitfalls

• Polycystic ovaries alone are insufficient: Up to 22-33% of reproductive-aged women without PCOS have polycystic ovarian morphology on ultrasound 1, 4
• Post-contraception multifollicular appearance: Transient multifollicular ovaries can occur after discontinuing birth control and do not represent true PCOS 1
• Excessive exercise: Hypothalamic suppression from overtraining can mimic PCOS with amenorrhea 1
• Hormonal contraception interference: Remove or allow contraceptive implants/pills to clear before hormone testing 1