What is the recommended diagnostic and treatment approach for a patient with a suspected Polycystic Ovary Syndrome (PCOS) panel?

Diagnostic and Treatment Approach for Polycystic Ovary Syndrome (PCOS)

The recommended diagnostic approach for PCOS requires laboratory confirmation of biochemical hyperandrogenism as part of the Rotterdam criteria, where at least two of three criteria must be present: chronic anovulation, hyperandrogenism (clinical or biochemical), and polycystic ovaries, with exclusion of other relevant disorders. 1

Diagnostic Approach

Step 1: Diagnostic Criteria Assessment (Rotterdam Criteria)

• Confirm presence of at least two of the following three criteria:
  1. Chronic anovulation (oligomenorrhea or amenorrhea)
  2. Hyperandrogenism (clinical or biochemical)
  3. Polycystic ovaries on ultrasound

Step 2: First-Line Laboratory Tests

• Total testosterone (TT) and free testosterone (FT) using mass spectrometry
  • TT: sensitivity 74%, specificity 86%
  • FT: sensitivity 89%, specificity 83% 1
• Free Androgen Index (FAI) as alternative to FT when mass spectrometry unavailable
  • Sensitivity 78%, specificity 85% 1
• Additional androgen tests:
  • Androstenedione (A4): sensitivity 75%, specificity 71%
  • Dehydroepiandrosterone sulfate (DHEAS): sensitivity 75%, specificity 67% 1

Step 3: Ultrasound Assessment

• Diagnostic threshold: ≥20 follicles (2-9mm) per ovary or ovarian volume ≥10ml
• Note: Ultrasound findings alone are insufficient and must correlate with clinical and biochemical findings 1, 2

Step 4: Exclusion of Other Disorders

• Thyroid disorders: Thyroid-Stimulating Hormone (TSH)
• Hyperprolactinemia: Prolactin
• Late-onset congenital adrenal hyperplasia: 17-hydroxyprogesterone
• Cushing's syndrome: overnight dexamethasone suppression test or 24-hour urinary free cortisol 1

Step 5: Metabolic Assessment

• Fasting lipid profile
• Fasting glucose/insulin ratio
• 2-hour 75g oral glucose tolerance test (OGTT) for patients with BMI >25 kg/m² 1

Treatment Approach

First-Line Interventions

1. Lifestyle modifications (for all patients)
   • Low glycemic index diet
   • Regular physical activity
   • Weight loss if overweight/obese 1, 3

For Patients Not Seeking Pregnancy

1. Oral contraceptives

   • Regulates menstrual cycles
   • Prevents endometrial hyperplasia
   • Lowers androgens
   • Increases sex hormone-binding globulin 1, 3

2. Anti-androgens (second-line, add to oral contraceptives)

   • Spironolactone for hirsutism and acne 3

For Patients Seeking Pregnancy

1. Letrozole (first-line for ovulation induction) 3

For Metabolic Complications

1. Metformin
   • Improves insulin sensitivity
   • Reduces androgen levels
   • Associated with minor but significant weight loss regardless of BMI 1, 4

Important Considerations and Pitfalls

• Phenotype identification: Clearly document which PCOS phenotype the patient has, as this affects long-term health implications 5

• Timing of hormone measurements: Ideally taken during early follicular phase of menstrual cycle in menstruating women 1

• Combined therapy: Consider combined treatment with metformin and oral contraceptives even in normal-weight PCOS patients 4

• Regular screening: PCOS patients require ongoing surveillance for:

  • Impaired glucose tolerance (particularly rapid progression in obese women)
  • Hyperlipidemia
  • Endometrial hyperplasia
  • Depression and obstructive sleep apnea 1, 3

• Common diagnostic pitfall: Polycystic ovaries are frequently seen incidentally on ultrasound and are not necessarily indicative of PCOS without other criteria being met 2