PCOS Workup for Reproductive-Age Women
Diagnostic Criteria
The diagnosis of PCOS requires at least two of three Rotterdam criteria: (1) hyperandrogenism (clinical or biochemical), (2) ovulatory dysfunction (oligo- or anovulation), and (3) polycystic ovarian morphology on ultrasound—after excluding other causes of androgen excess. 1, 2
Clinical History and Physical Examination
Essential History Elements
- Menstrual history: Cycle length >35 days suggests chronic anovulation; persistent oligomenorrhea 2-3 years beyond menarche predicts ongoing dysfunction 2, 3
- Onset and duration of hyperandrogenic signs: Rapid onset with severe symptoms suggests androgen-secreting tumor rather than PCOS 2, 4
- Medication review: Document use of exogenous androgens or hormonal contraceptives (which suppress the hypothalamic-pituitary-ovarian axis and make hormone testing unreliable) 2
- Family history: Cardiovascular disease and diabetes 2
- Lifestyle factors: Diet, exercise patterns, alcohol, smoking 2
Physical Examination Findings
- Signs of hyperandrogenism: Hirsutism, acne (especially severe or treatment-resistant), androgenic alopecia (vertex/crown pattern or bitemporal recession), clitoromegaly 2, 3
- Anthropometric measurements: Calculate BMI and waist-to-hip ratio to assess central obesity 1, 2
- Acanthosis nigricans: Check neck, axillae, under breasts, and vulva—indicates insulin resistance 1
- Exclude Cushing's syndrome: Look for buffalo hump, moon facies, hypertension, abdominal striae 2
Laboratory Testing
First-Line Hormonal Assessment
Measure total testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which is the single best initial biochemical marker with 74% sensitivity and 86% specificity—superior to direct immunoassays (92% vs 78% specificity). 1, 2
- Calculated free testosterone (using Vermeulen equation from high-quality total testosterone and SHBG) has the highest sensitivity at 89% with 83% specificity 2
- Free androgen index (FAI): 78% sensitivity and 85% specificity, but use cautiously when SHBG <30 nmol/L 2
- Androstenedione: 75% sensitivity and 71% specificity; useful when SHBG is low 2
- DHEAS: 75% sensitivity and 67% specificity; most reliable for adrenal androgen production, particularly valuable in women <30 years 2
Exclusion of Other Diagnoses
- TSH: Exclude thyroid disease as cause of menstrual irregularity 1
- Prolactin: Exclude hyperprolactinemia 1, 2
- 17-hydroxyprogesterone: Exclude non-classic congenital adrenal hyperplasia 1, 2
- Dexamethasone suppression test: Consider if clinical features suggest Cushing's syndrome 1, 2
Critical caveat: All hormonal testing must be performed in the absence of hormonal contraception, as progestin-containing methods (including Implanon) suppress the hypothalamic-pituitary-ovarian axis and render results unreliable. 2
Ultrasound Assessment
Optimal Imaging Technique
Use transvaginal ultrasound with ≥8 MHz transducer frequency for optimal resolution in adults. 1, 2
Diagnostic Thresholds
- Gold standard: ≥20 follicles per ovary (2-9mm diameter) with 87.64% sensitivity and 93.74% specificity 1, 2
- Alternative marker: Ovarian volume >10 mL when accurate follicle counting is difficult 1, 2
- Ensure no corpus luteum, cyst, or dominant follicle is present 1
Age-Specific Considerations
Do not use ultrasound for diagnosis in adolescents <8 years post-menarche or <20 years of age due to poor specificity and high false-positive rates from physiologically normal multifollicular ovaries. 1, 2 In this population, rely on clinical and biochemical hyperandrogenism plus menstrual irregularity persisting 2-3 years beyond menarche. 2, 3
Important Pitfall
Up to one-third of reproductive-aged women without PCOS have polycystic ovarian morphology on ultrasound, so ultrasound findings alone are insufficient for diagnosis. 2 The presence of multiple small follicles without meeting other Rotterdam criteria does not establish PCOS. 2
Metabolic Screening
All women with PCOS should be screened for metabolic dysfunction regardless of BMI, as insulin resistance occurs independently of body weight. 1
Required Metabolic Tests
- 2-hour oral glucose tolerance test (75g): Detect type 2 diabetes and glucose intolerance, regardless of BMI 1, 2, 4
- Fasting lipid profile: Screen for dyslipidemia 2, 5
- Blood pressure: Screen for hypertension 1
Rationale: Women with PCOS are four times more likely to develop type 2 diabetes and have twice the prevalence of metabolic syndrome compared to the general population. 4 Metabolic complications including hepatic steatosis, vascular thrombosis, stroke, and cardiovascular events are increased. 1
Anti-Müllerian Hormone (AMH) Considerations
Do not use AMH levels for PCOS diagnosis, as there is lack of standardization across assays, no validated cut-offs, significant overlap between women with and without PCOS, and age-dependent variability. 1, 2 While AMH is elevated in PCOS and shows promise as a research tool, it is not yet recommended for clinical diagnosis. 2
Summary Algorithm
- Clinical assessment: Document menstrual irregularity (cycle >35 days), signs of hyperandrogenism (hirsutism, acne, alopecia), BMI, waist-to-hip ratio, acanthosis nigricans
- Hormonal testing (off contraception): Total testosterone via LC-MS/MS, calculated free testosterone, TSH, prolactin, 17-hydroxyprogesterone
- Ultrasound (if ≥8 years post-menarche): Transvaginal with ≥8 MHz transducer; count follicles per ovary (≥20 = positive) or measure ovarian volume (>10 mL = positive)
- Metabolic screening: 2-hour 75g OGTT, fasting lipid profile, blood pressure
- Diagnosis: Confirm ≥2 of 3 Rotterdam criteria after excluding other causes
Weight assessment is critical: Obesity affects the majority of women with PCOS, exacerbates metabolic and reproductive features, and weight gain rates are higher in PCOS (BMI increases of one unit associated with 9% higher PCOS prevalence). 6 Early vigilance and lifestyle intervention are essential, as weight gain escalates from adolescence. 6