What is the recommended workup and treatment for a female patient suspected of having Polycystic Ovary Syndrome (PCOS) with symptoms of hyperandrogenism, irregular menstrual cycles, and potential infertility?

Workup for Polycystic Ovary Syndrome (PCOS)

The workup for PCOS requires meeting two of three Rotterdam criteria: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, and polycystic ovarian morphology on ultrasound, while excluding other causes of hyperandrogenism. 1, 2

Clinical History and Physical Examination

Document these specific elements:

• Menstrual history: Cycle length >35 days suggests chronic anovulation 1
• Onset and duration of androgen excess signs: Rapid onset or severe virilization requires immediate evaluation for androgen-secreting tumors 1, 2
• Medication review: Specifically ask about exogenous androgens, valproate, and hormonal contraceptives 3, 1
• Lifestyle factors: Diet, exercise patterns (excessive exercise can cause hypothalamic amenorrhea), alcohol, smoking 1
• Family history: Cardiovascular disease and diabetes 1
• Physical signs of hyperandrogenism: Acne, male-pattern balding, hirsutism, clitoromegaly 1
• Anthropometric measurements: Calculate BMI and waist-hip ratio 1

Laboratory Testing

First-Line Hormonal Assessment

Total testosterone via liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the single best initial biochemical marker with 74% sensitivity and 86% specificity. 1 This method is superior to immunoassays with 92% specificity versus 78%. 1

Calculated free testosterone using the Vermeulen equation has the highest sensitivity at 89% with 83% specificity and should be calculated from high-quality total testosterone and SHBG measurements. 1

Additional androgen testing:

• Free androgen index (FAI): 78% sensitivity, 85% specificity, but use cautiously when SHBG <30 nmol/L 1
• Androstenedione: 75% sensitivity, 71% specificity, particularly useful when SHBG is low 1
• DHEAS: 75% sensitivity, 67% specificity, most reliable for adrenal androgen production, especially valuable in women <30 years 1

Exclude Other Diagnoses

Measure these to rule out mimicking conditions:

• 17-hydroxyprogesterone: >2.5 nmol/L suggests non-classical congenital adrenal hyperplasia 3
• TSH and prolactin: Rule out thyroid disease and hyperprolactinemia 3, 1
• 24-hour urinary free cortisol or overnight dexamethasone suppression test: If Cushing's syndrome suspected (buffalo hump, moon facies, hypertension, abdominal striae) 1

Metabolic Screening (Essential for All PCOS Patients)

All women with PCOS require metabolic screening regardless of BMI, as insulin resistance occurs independently of body weight. 1

• Fasting glucose and 2-hour oral glucose tolerance test: Screen for type 2 diabetes and impaired glucose tolerance 3, 1, 2
• Fasting lipid profile: Screen for dyslipidemia 1, 2
• Glucose/insulin ratio: Ratio >4 suggests reduced insulin sensitivity 3

Imaging

Transvaginal Ultrasound (First-Line in Adults)

Use transvaginal ultrasound with ≥8 MHz transducer frequency for optimal resolution in adults ≥18 years. 3, 1

Polycystic ovarian morphology is defined by ≥20 follicles (2-9mm diameter) per ovary, which has 87.64% sensitivity and 93.74% specificity. 3, 1 This is the gold standard ultrasonographic marker.

Alternative threshold when accurate follicle counting is difficult:

• Ovarian volume >10 mL in at least one ovary 3, 1

Report must include:

• Ovarian volumes for both ovaries 4
• Antral follicle counts 4
• Presence of dominant follicle or corpus luteum 4
• Increased echogenicity of ovarian stroma (most sensitive and specific sign, though subjective) 3

Age-Specific Ultrasound Considerations

Do not use ultrasound as a first-line diagnostic tool in adolescents (<20 years, at least 1 year post-menarche) due to poor specificity and high false-positive rates. 1 In this age group, require all three Rotterdam criteria (clinical/biochemical hyperandrogenism, ovulatory dysfunction persisting 2-3 years beyond menarche, and polycystic ovarian morphology) before diagnosis. 1, 2

Important Imaging Pitfall

Up to one-third of reproductive-aged women without PCOS have polycystic ovarian morphology on ultrasound. 1 The presence of multiple small follicles alone is insufficient for diagnosis—you must meet the full Rotterdam criteria. 1

Critical Diagnostic Considerations

Hormonal Contraception Interference

Remove or allow expiration of progestin-only implants (Implanon) before hormonal testing, as they suppress the hypothalamic-pituitary-ovarian axis and make hormone levels unreliable for PCOS diagnosis. 1 This includes making LH/FSH ratios and testosterone measurements uninterpretable. 1

Anti-Müllerian Hormone (AMH)

Do not use AMH for clinical diagnosis of PCOS. 1 Despite elevated levels in PCOS, there is lack of standardization across assays, no validated cut-offs, significant overlap with normal women, and age-dependent variability. 1

Timing of Evaluation in Adolescents

It is reasonable to delay evaluation for PCOS in adolescents until two years after menarche to avoid false-positive diagnoses during normal pubertal development. 2

Additional Screening for Comorbidities

• Liver function tests (AST, ALT): Screen for nonalcoholic fatty liver disease at diagnosis and annually 3
• Blood pressure monitoring: Assess cardiovascular risk 1
• Depression and eating disorder screening: Use validated tools 3

Common Pitfalls to Avoid

1. Do not diagnose PCOS based solely on ultrasound findings—polycystic ovaries are common in normal women 1
2. Do not miss androgen-secreting tumors—rapid onset and severe hyperandrogenism require immediate evaluation 1, 2
3. Do not test hormones while patient is on hormonal contraception—results will be unreliable 1
4. Do not skip metabolic screening in lean women—insulin resistance occurs at any BMI 1
5. Do not use transabdominal ultrasound alone for follicle counting—it lacks the resolution needed for accurate assessment 3