How do you diagnose or rule out Polycystic Ovary Syndrome (PCOS)?

Diagnosing and Ruling Out Polycystic Ovary Syndrome (PCOS)

To rule out PCOS, clinicians must perform a comprehensive evaluation including assessment of hyperandrogenism, menstrual patterns, and ovarian morphology, while systematically excluding other conditions that can mimic PCOS. 1

Diagnostic Criteria

According to the Rotterdam criteria, PCOS is diagnosed when at least two of the following three criteria are present:

1. Clinical or biochemical hyperandrogenism
2. Oligo-anovulation
3. Polycystic ovarian morphology on ultrasound

Clinical Assessment

• History evaluation:

  • Onset and duration of hyperandrogenic symptoms 2
  • Menstrual history (cycle length >35 days suggests chronic anovulation) 1
  • Medication use, especially exogenous androgens 2
  • Lifestyle factors (diet, exercise, alcohol use, smoking) 2
  • Family history of cardiovascular disease and diabetes 1

• Physical examination:

  • Signs of hyperandrogenism: hirsutism, acne, androgenic alopecia 1
  • Distribution of body hair 2
  • Presence of clitoromegaly 2
  • Ovarian enlargement on pelvic examination 1
  • Signs of insulin resistance: obesity, acanthosis nigricans 2, 1
  • Evaluate for signs of other conditions (Cushing's syndrome, etc.) 2

Laboratory Testing

• First-line tests:

  • Total testosterone and free/bioavailable testosterone (preferably using LC-MS/MS method) 1
  • Thyroid-stimulating hormone (TSH) 2, 1
  • Prolactin 2, 1
  • Two-hour oral glucose tolerance test with 75g glucose load 2, 1
  • Fasting lipid profile 2, 1

• Additional tests to rule out other conditions:

  • 17-hydroxyprogesterone (to rule out non-classic congenital adrenal hyperplasia) 3
  • Overnight dexamethasone suppression test or 24-hour urinary free cortisol (if Cushing's syndrome is suspected) 3
  • DHEA-S (if adrenal hyperandrogenism or tumors are suspected) 3

Imaging

• Transvaginal ultrasound to assess ovarian morphology:
  • Diagnostic criteria: ≥20 follicles per ovary (2-9mm) and/or ovarian volume ≥10ml 1
  • MRI of pelvis without contrast as an alternative for patients who cannot tolerate transvaginal ultrasound 1

Differential Diagnosis

It's crucial to rule out other causes of hyperandrogenism and menstrual irregularities:

1. Androgen-secreting tumors (ovarian or adrenal): Consider in cases of rapid onset, severe hyperandrogenism, or virilization 3

2. Non-classic congenital adrenal hyperplasia (NCCAH): Diagnosed with elevated basal or ACTH-stimulated 17-hydroxyprogesterone 3

3. Cushing's syndrome: Consider in patients with accompanying signs of hypercortisolism (buffalo hump, moon facies, abdominal striae, easy bruising) 2, 3

4. Hyperprolactinemia: Rule out in women with recent oligomenorrhea and mild hyperandrogenism 3

5. Other conditions to exclude:

   • Thyroid disorders
   • Acromegaly
   • Primary ovarian failure
   • Exogenous androgen use
   • Genetic defects in insulin action 2, 1

Common Pitfalls and Caveats

• Adolescent diagnosis challenges: Hyperandrogenism is central to presentation in adolescents, but normal pubertal changes can mimic PCOS symptoms 4

• Postmenopausal diagnosis challenges: No consistent phenotype exists in postmenopausal women 4

• Obesity and insulin resistance: Present in many PCOS patients but not diagnostic criteria on their own 5

• Ultrasound limitations: Follicle number per ovary (FNPO) has higher diagnostic accuracy (sensitivity 84%, specificity 91%) than ovarian volume alone 1

• Ethnicity variations: Different ethnic groups may present with varying phenotypes of PCOS 6

• Long-term health implications: Women with PCOS have increased risk of type 2 diabetes, cardiovascular disease, endometrial cancer, and psychological disorders 1, 5

By systematically evaluating these criteria and ruling out other conditions, clinicians can accurately diagnose or rule out PCOS and develop appropriate management strategies for affected patients.