What are the diagnostic criteria and management options for Polycystic Ovary Syndrome (PCOS) according to the Rotterdam criteria?

Rotterdam Criteria for PCOS Diagnosis

PCOS is diagnosed when at least 2 of 3 Rotterdam criteria are present: (1) oligo- or anovulation, (2) clinical and/or biochemical hyperandrogenism, and (3) polycystic ovarian morphology on ultrasound—after excluding other disorders such as thyroid disease, hyperprolactinemia, and congenital adrenal hyperplasia. 1, 2

Diagnostic Criteria Breakdown

Criterion 1: Oligo- or Anovulation

• Menstrual cycle length >35 days indicates chronic anovulation 1
• Document menstrual history carefully, noting onset and duration of irregularities 1
• Mid-luteal progesterone <6 nmol/L confirms anovulation if measurement is needed 3

Criterion 2: Clinical and/or Biochemical Hyperandrogenism

Clinical hyperandrogenism includes:

• Hirsutism (excess terminal hair in male-pattern distribution) 1, 2
• Acne, particularly persistent or treatment-resistant 2
• Androgenic alopecia (male-pattern baldness) 1
• Clitoromegaly in severe cases 1

Biochemical hyperandrogenism testing:

• Total testosterone (TT) is the single best initial marker with 74% sensitivity and 86% specificity 1
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is mandatory for accurate measurement, showing 92% specificity versus 78% for direct immunoassays 1
• Calculated free testosterone (cFT) has the highest sensitivity at 89% with 83% specificity 1
• Free androgen index (FAI) shows 78% sensitivity and 85% specificity, but use cautiously when SHBG <30 nmol/L 1
• If TT/FT are normal but clinical suspicion remains high, measure androstenedione (75% sensitivity, 71% specificity) and DHEAS (75% sensitivity, 67% specificity) 1

Critical caveat: Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition 3. Clinical hyperandrogenism alone (hirsutism, acne, or alopecia) plus irregular cycles is sufficient for diagnosis without abnormal laboratory values. 3

Criterion 3: Polycystic Ovarian Morphology (PCOM)

Ultrasound diagnostic thresholds:

• ≥20 follicles per ovary (2-9mm diameter) is the gold standard with 87.64% sensitivity and 93.74% specificity 4, 1
• Ovarian volume >10 mL serves as alternative when accurate follicle counting is difficult 4, 1
• Follicle number per single cross-section (FNPS) can be used as secondary alternative 4, 1

Technical specifications:

• Transvaginal ultrasound with ≥8 MHz transducer frequency is required for optimal resolution in adults 4, 1
• Document three dimensions and volume of each ovary 5
• Ensure no corpora lutea, cysts, or dominant follicles ≥10mm are present 5

Age-specific restrictions:

• Do NOT use ultrasound as first-line diagnostic tool in adolescents (<8 years post-menarche or <20 years) due to poor specificity and high false-positive rates 4, 1
• In adolescents, rely on clinical/biochemical hyperandrogenism plus menstrual irregularity persisting 2-3 years beyond menarche 1

Mandatory Exclusion of Other Disorders

Before confirming PCOS diagnosis, exclude:

• Thyroid disease: Measure TSH 1, 3
• Hyperprolactinemia: Morning resting serum prolactin 3
• Cushing's syndrome: Screen if buffalo hump, moon facies, hypertension, abdominal striae present 1, 3
• Androgen-secreting tumors: Consider if rapid onset, severe hirsutism, or very high testosterone (>10.0 nmol/L androstenedione suggests tumor) 1, 3
• Non-classic congenital adrenal hyperplasia: Measure DHEAS if elevated 1, 3
• Primary ovarian failure: Check FSH levels 1

Management Algorithm

Step 1: Lifestyle Modification (Foundation for All Patients)

• Weight loss of as little as 5% of initial weight improves metabolic and reproductive abnormalities 1
• Implement regular exercise and caloric restriction before drug therapy 1
• This is first-line therapy regardless of other interventions 1, 2

Step 2: Management Based on Primary Concern

For patients NOT desiring pregnancy:

• Combined oral contraceptive pills (OCPs) are first-line therapy for menstrual irregularities, hirsutism, and acne 1, 2
• Add spironolactone (antiandrogen) as second-line for persistent hirsutism 1, 2
• Medroxyprogesterone acetate (depot or intermittent oral) can suppress circulating androgens 1
• Mechanical hair removal, electrolysis, and laser vaporization for cosmetic management 1

For patients desiring pregnancy:

• Letrozole is first-line therapy for ovulation induction 2
• Clomiphene citrate remains an alternative first-line option with 80% ovulation rate and 50% conception rate 1
• Low-dose gonadotropin therapy for those who fail clomiphene, with lower risk of ovarian hyperstimulation 1
• In patients with BMI >30 kg/m², ovulation induction should be preceded by metabolic improvement through lifestyle modifications 6

For metabolic complications:

• Metformin improves insulin sensitivity, glucose tolerance, and ovulation frequency 1, 2
• Metformin added to lifestyle management is first-line for insulin resistance 1

Step 3: Mandatory Metabolic Screening

All women with PCOS require:

• Screen for type 2 diabetes and glucose intolerance with 2-hour oral glucose tolerance test (75g glucose load) 1, 3
• Fasting lipid panel: total cholesterol, LDL, HDL, triglycerides 1, 3
• Calculate BMI and waist-hip ratio (WHR >0.9 indicates truncal obesity) 1, 3
• Blood pressure measurement 6
• If BMI >30 kg/m² and fasting glucose is normal, OGTT is still recommended 6

Step 4: Long-term Monitoring

• Screen for depression and obstructive sleep apnea 2
• Regular cardiovascular risk factor screening 1
• Awareness of at least twofold increased risk of endometrial cancer 2
• Monitor for development of type 2 diabetes, dyslipidemia, and cardiovascular disease 3

Common Pitfalls to Avoid

• Do not rely solely on LH/FSH ratio >2, as it is abnormal in only 35-44% of women with PCOS 3
• Do not use Anti-Müllerian Hormone (AMH) as sole diagnostic test—it requires further validation despite 92% sensitivity and 97% specificity at ≥35 pmol/L 3
• Do not exclude PCOS diagnosis based on normal testosterone alone—30% of confirmed PCOS cases have normal levels 3
• Do not use ultrasound in adolescents <8 years post-menarche as primary diagnostic tool 5, 1
• Do not use direct immunoassays for testosterone—insist on LC-MS/MS for accuracy 1
• Presence of IUD does not interfere with ovarian imaging, as IUD sits in endometrial cavity while ovaries are separate lateral structures 5