What hormones should be checked in a 17-year-old female with suspected Polycystic Ovary Syndrome (PCOS)?

Hormonal Testing for a 17-Year-Old with Suspected PCOS

For a 17-year-old with suspected PCOS, measure total testosterone (preferably by LC-MS/MS) and free testosterone as first-line tests, along with TSH and prolactin to exclude other conditions, while avoiding ultrasound and AMH testing due to poor specificity in adolescents. 1

Essential First-Line Hormone Tests

Androgen Assessment

• Total testosterone is the single best initial biochemical marker, with 74% sensitivity and 86% specificity for PCOS diagnosis 1
• Free testosterone (calculated or measured) demonstrates superior sensitivity of 89% with 83% specificity and should be assessed alongside total testosterone 1
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the mandatory preferred assay method, showing superior specificity (92%) compared to direct immunoassays (78%) 1
• If total or free testosterone are not elevated but clinical suspicion remains high, measure androstenedione (sensitivity 75%, specificity 71%) and DHEAS (sensitivity 75%, specificity 67%) as second-line tests 1

Exclusion of Other Conditions

• TSH must be measured to rule out thyroid disease as a cause of menstrual irregularity 1
• Prolactin level should be measured using morning resting serum levels to exclude hyperprolactinemia 1
• If prolactin is elevated, confirm with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation 1

Additional Hormonal Tests to Consider

Gonadotropins

• LH and FSH should be measured between days 3-6 of menstrual cycle (if cycles occur) 1
• An LH/FSH ratio >2 suggests PCOS, though this is abnormal in only 35-44% of women with PCOS, making it a poor standalone diagnostic marker 1, 2
• Do not rely on LH/FSH ratio alone for diagnosis due to its low sensitivity 2

Progesterone

• Mid-luteal phase progesterone levels should be measured to confirm anovulation, with levels <6 nmol/L indicating anovulation 1

Metabolic Screening (Essential in All PCOS Cases)

• Two-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes 1
• Fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides 1
• Calculate BMI and measure waist-hip ratio (WHR >0.9 indicates truncal obesity) 1
• Fasting glucose and insulin levels, with glucose/insulin ratio >4 suggesting reduced insulin sensitivity 1

Critical Considerations for Adolescents

What NOT to Do

• Do not use ultrasound for PCOS diagnosis in adolescents with gynecological age <8 years post-menarche due to high false-positive rates from normal multifollicular ovaries 1
• Do not use AMH levels as a diagnostic test due to lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS, particularly in younger women 3, 1
• Avoid relying on LH/FSH ratio as the primary diagnostic criterion given its poor sensitivity 2

Diagnostic Approach in Adolescents

• In adolescent females, PCOS diagnosis requires hyperandrogenism (clinical or biochemical) in the presence of persistent oligomenorrhea lasting 2-3 years beyond menarche 3
• Clinical assessment including menstrual pattern and physical signs of hyperandrogenism remains paramount 1
• Ultrasound should not be used as a first-line diagnostic tool until at least 8 years post-menarche 3, 1

Important Caveats

Hormonal Contraception Interference

• If the patient is on hormonal contraception (including progestin-only implants like Implanon), hormone testing is unreliable and should be deferred until after removal or expiration of the contraceptive 1
• Progestin-only implants suppress the hypothalamic-pituitary-ovarian axis, making LH/FSH ratios and testosterone levels unreliable 1

Interpretation Pitfalls

• Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition 1
• The presence of clinical hyperandrogenism (hirsutism, acne, or alopecia) plus irregular menstrual cycles can establish PCOS diagnosis even with normal laboratory values 1
• Testosterone levels >4.8 nmol/L warrant exclusion of other causes of hyperandrogenism such as androgen-secreting tumors 4

Differential Diagnosis Testing

• If DHEAS is elevated, consider non-classical congenital adrenal hyperplasia 3, 1
• Screen for Cushing's syndrome if patient has buffalo hump, moon facies, hypertension, abdominal striae, or central fat distribution 1
• Consider androgen-secreting tumors if rapid onset of symptoms, severe hirsutism, or very high testosterone levels 1