What screening tests should be ordered for a 21‑year‑old female with obesity, irregular menses, and excess axillary hair suspected of having polycystic ovary syndrome?

Screening Tests for Suspected PCOS in a 21-Year-Old Female

Order total testosterone (or free testosterone) by LC-MS/MS, TSH, prolactin, a 2-hour 75-gram oral glucose tolerance test, and a fasting lipid panel as your core screening battery. 1

First-Line Hormonal Assessment

Androgen Testing

• Measure total testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which demonstrates 74% sensitivity and 86% specificity for detecting hyperandrogenism; this is your single best initial biochemical marker. 1
• Alternatively, calculated free testosterone shows superior sensitivity at 89% with 83% specificity and should be calculated using the Vermeulen equation from high-quality total testosterone and SHBG measurements. 1
• Avoid direct immunoassays for testosterone, as they have significantly lower specificity (78%) compared to LC-MS/MS (92%), leading to false-positive results. 1

Exclusion of Other Endocrine Disorders

• Measure serum TSH to rule out thyroid disease as a cause of menstrual irregularity; thyroid dysfunction can mimic PCOS presentation. 1, 2
• Obtain a morning resting prolactin level to exclude hyperprolactinemia; women with PCOS have a 3.15-fold increased risk of elevated prolactin, but hyperprolactinemia itself causes anovulation and must be excluded before confirming PCOS. 1, 3

Mandatory Metabolic Screening

Glucose Metabolism Assessment

• Perform a 2-hour oral glucose tolerance test with a 75-gram glucose load rather than hemoglobin A1C or fasting glucose alone; the OGTT is superior for detecting impaired glucose tolerance in PCOS patients, who have substantially higher rates of insulin resistance and type 2 diabetes. 1, 2, 4
• Women with PCOS are four times more likely to develop type 2 diabetes compared to the general population, making this screening essential regardless of age or BMI. 2

Cardiovascular Risk Assessment

• Order a fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides; metabolic syndrome is twice as common in PCOS patients, and dyslipidemia prevalence is markedly elevated. 1, 3, 2
• Calculate BMI and measure waist-hip ratio; a WHR >0.9 indicates truncal obesity and heightened metabolic risk. 1, 3

Second-Line Androgen Tests (If Primary Results Are Normal)

• If total testosterone and free testosterone are normal but clinical suspicion remains high, measure androstenedione (sensitivity 75%, specificity 71%) and DHEAS (sensitivity 75%, specificity 67%). 1
• Androstenedione >10 nmol/L raises suspicion for an adrenal or ovarian androgen-secreting tumor, particularly if symptoms have rapid onset or severe virilization. 1, 2
• Elevated DHEAS (age-adjusted thresholds: ≥3800 ng/mL for ages 20-29) should prompt evaluation for non-classical congenital adrenal hyperplasia. 1

Ovulatory Function Assessment

• Measure LH and FSH on cycle days 3-6 (if cycles occur), averaging three samples taken 20 minutes apart; an LH/FSH ratio >2 supports PCOS but is present in only 35-44% of affected women, limiting its diagnostic utility. 1
• Obtain mid-luteal phase progesterone (approximately day 21 of a 28-day cycle); levels <6 nmol/L confirm anovulation. 1

Ultrasound Considerations

• Transvaginal ultrasound is NOT mandatory if both irregular menses AND clinical/biochemical hyperandrogenism are present, as two Rotterdam criteria are sufficient for diagnosis. 3
• If ultrasound is performed, ≥20 follicles per ovary (2-9mm diameter) has 87.64% sensitivity and 93.74% specificity, or ovarian volume >10 mL can serve as an alternative threshold. 1, 3
• Use transvaginal ultrasound with ≥8 MHz transducer frequency for optimal resolution in adults. 1, 3

Critical Diagnostic Pitfalls to Avoid

Do NOT Use AMH for Diagnosis

• Anti-Müllerian hormone should NOT be used as a stand-alone test or alternative for polycystic ovarian morphology due to lack of assay standardization, absent validated cut-offs, and considerable overlap between women with and without PCOS. 1, 3
• Although AMH ≥35 pmol/L shows 92% sensitivity and 97% specificity in research, this threshold requires validation across diverse populations before clinical adoption. 1

Recognize That Normal Labs Don't Exclude PCOS

• Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition. 1
• Clinical assessment remains paramount; a woman can be diagnosed with PCOS based solely on clinical hyperandrogenism (hirsutism, acne) plus irregular menstrual cycles without any abnormal laboratory values, per Rotterdam criteria. 1

Screen for Serious Mimics

• If rapid onset of symptoms, severe hirsutism, or very high testosterone levels, immediately evaluate for androgen-secreting tumors. 1, 2
• If buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies, screen for Cushing's syndrome. 1, 3

Additional Screening Recommended at Diagnosis

• Screen for depression and anxiety, as these conditions are highly prevalent in PCOS and significantly impact quality of life. 3, 5
• Measure serum 25-hydroxy-vitamin D, as deficiency is present in 67-85% of women with PCOS. 3
• Assess blood pressure to screen for hypertension, which is more common in PCOS patients. 3