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

Diagnostic Workup for Polycystic Ovary Syndrome (PCOS)

The diagnostic workup for PCOS requires assessment of menstrual history, clinical hyperandrogenism, biochemical hyperandrogenism, and exclusion of other conditions that mimic PCOS. According to the Rotterdam criteria and international guidelines, diagnosis requires at least two of three features: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovary morphology 1.

Clinical Assessment

History

• Menstrual history: Onset and duration of menstrual irregularities (cycle length >35 days suggests chronic anovulation) 2
• Hyperandrogenism symptoms: Hirsutism, acne, alopecia 2
• Medication use: Including exogenous androgens 2
• Lifestyle factors: Diet, exercise, alcohol use, smoking 2
• Family history: Cardiovascular disease and diabetes 2

Physical Examination

• Hyperandrogenism signs:
  • Hirsutism (distribution of body hair)
  • Acne (severe or treatment-resistant acne may indicate PCOS) 2
  • Alopecia (typically vertex, crown or diffuse pattern) 3
  • Clitoromegaly (suggests more severe hyperandrogenism) 2
• Metabolic assessment:
  • BMI and waist-hip ratio calculation 2
  • Blood pressure measurement 1
  • Acanthosis nigricans (sign of insulin resistance) 2
• Pelvic examination: To assess for enlarged ovaries 2

Laboratory Testing

First-Line Tests

• Androgen assessment:
  • Total testosterone (TT) and free testosterone (FT) are recommended as first-line tests 2
  • Free testosterone should be assessed by equilibrium dialysis or calculated using free androgen index (FAI) 2
  • Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred method due to superior accuracy 2

Additional Hormone Tests

• If initial tests are negative:
  • Androstenedione (A4) and DHEAS may be considered, though they have poorer specificity 2
• Other hormonal tests:
  • Thyroid-stimulating hormone (to exclude thyroid disease) 2
  • Prolactin (to exclude hyperprolactinemia) 2
  • 17-hydroxyprogesterone (to exclude non-classic congenital adrenal hyperplasia) 1
  • Anti-Müllerian hormone (can be useful for diagnosis, especially when ultrasound is unavailable) 1

Metabolic Screening

• Glucose metabolism:
  • Two-hour oral glucose tolerance test with 75g glucose load (recommended for all women with PCOS) 2
  • Fasting glucose level 2
• Lipid profile:
  • Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides 2

Imaging

• Transvaginal ultrasound (using ≥8MHz transducer) to assess:
  • Follicle number per ovary (≥20 follicles measuring 2-9mm) 1
  • Ovarian volume (≥10ml indicates polycystic morphology) 1
  • Note: Ultrasound is not recommended as first-line in women <17 years of age 3

Differential Diagnosis

The following conditions should be excluded:

• Cushing's syndrome (buffalo hump, moon facies, hypertension, abdominal striae) 2
• Androgen-secreting tumors (rapid onset hirsutism, virilization) 2, 3
• Non-classic congenital adrenal hyperplasia 2
• Hyperprolactinemia 2
• Thyroid disorders 2
• Primary ovarian failure 2
• Acromegaly 2

Special Considerations

Adolescents

• Diagnosis is particularly challenging in adolescents 3
• Persistent oligomenorrhea 2-3 years post-menarche suggests PCOS 3
• Ultrasound is not recommended for diagnosis in girls <17 years 3
• Focus on menstrual irregularity and clinical/biochemical hyperandrogenism 4

Risk Assessment

• All women diagnosed with PCOS should be evaluated for:
  • Endometrial cancer risk 1
  • Cardiovascular disease risk factors 1
  • Type 2 diabetes risk 2
  • Mood disorders 1
  • Obstructive sleep apnea 1

Diagnostic Algorithm

1. Initial evaluation: Assess menstrual history and clinical signs of hyperandrogenism
2. Laboratory testing: Measure total and free testosterone levels using LC-MS/MS
3. Additional testing: If needed, assess androstenedione, DHEAS, TSH, prolactin
4. Metabolic screening: Perform OGTT and lipid profile
5. Imaging: Transvaginal ultrasound (if age ≥17 years)
6. Exclusion of other disorders: Rule out mimicking conditions
7. Diagnosis confirmation: Apply Rotterdam criteria (two of three: oligo/anovulation, hyperandrogenism, polycystic ovaries)

Following diagnosis, management should address reproductive function, hyperandrogenism, and metabolic abnormalities with lifestyle modifications as the foundation of treatment 1, 5.