How do I evaluate a reproductive‑age woman with oligo‑ or amenorrhea, clinical hyperandrogenism (hirsutism, acne, androgenic alopecia), possible weight gain or infertility for suspected polycystic ovary syndrome?

Evaluation of Suspected PCOS in Reproductive-Age Women

Begin with a morning fasting blood draw to simultaneously obtain hormonal and metabolic panels, then perform transvaginal ultrasound to confirm polycystic ovarian morphology—this single-visit approach maximizes diagnostic accuracy while efficiently ruling out alternative causes of hyperandrogenism. 1

Clinical Assessment: Key Features to Document

Menstrual History:

• Oligomenorrhea (cycles >35 days) or amenorrhea (absent bleeding >6 months) suggests chronic anovulation, the hallmark reproductive dysfunction in PCOS 1, 2
• Document cycle length, regularity since menarche, and any recent changes 3

Hyperandrogenic Signs:

• Hirsutism: Score terminal hair growth using the modified Ferriman-Gallwey method; scores ≥8 indicate clinical hyperandrogenism and are present in 70-80% of PCOS cases 2, 4, 5
• Acne: Persistent or severe acne, especially if resistant to standard dermatologic treatment, warrants endocrine evaluation 1
• Androgenic alopecia: Male-pattern hair loss (frontal-temporal thinning) is a slower-responding but significant marker 1, 5
• Rapid virilization (deepening voice, clitoromegaly, increased muscle mass) suggests androgen-secreting tumor rather than PCOS and requires urgent investigation 6

Metabolic Signs:

• Truncal obesity (waist-hip ratio >0.9) and acanthosis nigricans (dark, velvety skin in neck/axillae) indicate insulin resistance 1, 2
• Document BMI and waist circumference 7

First-Line Laboratory Testing (Morning Fasting Sample)

Androgen Panel (LC-MS/MS Preferred):

• Total testosterone (TT): Sensitivity 74%, specificity 86% for hyperandrogenism 1
• Free testosterone (FT) or calculated free androgen index (FAI): Sensitivity 89%, specificity 83%; FAI = (total testosterone/SHBG) × 100 1
• SHBG: Required for FAI calculation when LC-MS/MS unavailable 1
• Critical caveat: Direct immunoassay methods for free testosterone are highly inaccurate in women and must be avoided 1

Metabolic Screening (Mandatory for All PCOS Suspects):

• Fasting glucose followed by 2-hour 75-gram oral glucose tolerance test: PCOS patients have heightened diabetes risk 1
• Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides): Assess cardiovascular risk 3, 1
• Fasting insulin: Glucose/insulin ratio >4 suggests reduced insulin sensitivity 3

Exclusion Panel:

• TSH: Rule out thyroid disease mimicking PCOS 3, 1
• Prolactin: Exclude hyperprolactinemia, which causes similar menstrual irregularity 3, 1

Second-Line Laboratory Testing (If TT/FT Normal but Clinical Suspicion High)

• Androstenedione (A4): Sensitivity 75%, specificity 71% 1
• DHEAS: Sensitivity 75%, specificity 67%; only 8-33% of PCOS patients have elevated DHEAS, so it is not first-line 1
• 17-hydroxyprogesterone: Consider if non-classical congenital adrenal hyperplasia suspected 2
• LH/FSH ratio: Ratio >2 supports PCOS diagnosis 1

Imaging: Transvaginal Ultrasound (Day 3-9 of Cycle)

Polycystic Ovarian Morphology Criteria (2014 Updated Threshold):

• ≥25 follicles measuring 2-9 mm diameter in at least one ovary, OR
• Ovarian volume >10 mL in at least one ovary 3
• Increased echogenicity of ovarian stroma is the most sensitive/specific subjective finding 3
• Transabdominal ultrasound is acceptable only if transvaginal approach is not feasible; it reliably measures ovarian volume but is less accurate for follicle counts 3

Important distinction: Isolated polycystic ovaries (present in 17-33% of normal women) without clinical/biochemical hyperandrogenism or ovulatory dysfunction does NOT equal PCOS 3

Diagnostic Criteria: Rotterdam Consensus (Requires 2 of 3)

1. Clinical or biochemical hyperandrogenism (hirsutism, acne, alopecia, OR elevated androgens)
2. Oligo-ovulation or anovulation (irregular cycles, low mid-luteal progesterone)
3. Polycystic ovarian morphology on ultrasound (≥25 follicles or volume >10 mL) 3, 8

After excluding: thyroid disease, hyperprolactinemia, non-classical congenital adrenal hyperplasia, Cushing's syndrome, and androgen-secreting tumors 1, 2

Red Flags Requiring Urgent Investigation

• Total testosterone >200 ng/dL: Suggests androgen-secreting tumor 2
• DHEAS >600 μg/dL (age 20-29) or >2700 ng/mL (age 30-39): Raises concern for adrenocortical carcinoma 3, 1
• Rapid-onset virilization (weeks to months): Indicates tumor rather than PCOS 2, 6
• Palpable adnexal mass: Warrants imaging for ovarian tumor 2

Common Pitfalls to Avoid

Timing errors: Testosterone has diurnal variation; afternoon samples may miss 30% of cases with elevated morning levels. If afternoon testosterone is normal but clinical features are strong, repeat testing in the morning 1

Assay selection: Avoid direct immunoassays for free testosterone—they are inaccurate at low female concentrations. Use equilibrium dialysis, calculated FAI, or LC-MS/MS 1

Overlooking metabolic screening: PCOS is not just a reproductive disorder. Fasting glucose, OGTT, and lipid panels are mandatory to identify diabetes and cardiovascular risk, which affect long-term morbidity and mortality 1, 8

Confusing isolated polycystic ovaries with PCOS: One-third of reproductive-age women have polycystic ovaries on ultrasound without any clinical syndrome. Diagnosis requires clinical or biochemical hyperandrogenism PLUS ovulatory dysfunction 3

Missing alternative diagnoses: Always check TSH and prolactin before attributing symptoms to PCOS. Non-classical congenital adrenal hyperplasia and Cushing's syndrome present similarly but require different management 1, 2