What is the initial evaluation and management for a 17-year-old female with secondary amenorrhea presenting at a pediatric office, including recommended laboratory tests and potential referral to a gynecologist (GYN)?

Initial Laboratory Workup and Referral for Secondary Amenorrhea in a 17-Year-Old

All adolescents presenting with secondary amenorrhea should undergo first-line laboratory testing including pregnancy test, FSH, LH, TSH, prolactin, and estradiol levels, and referral to gynecology or endocrinology is warranted when laboratory abnormalities are identified or when specific high-risk conditions are suspected. 1, 2

Mandatory Initial Laboratory Tests

The following tests must be ordered for every patient with secondary amenorrhea:

• Pregnancy test (uCG or serum β-hCG) - This is the absolute first test and must be performed before interpreting any other hormonal results 1, 3, 4
• FSH and LH levels - Draw between cycle days 3-6 if any bleeding occurs, or at any time in amenorrheic patients 1, 2
• TSH - Identifies thyroid dysfunction as a reversible cause 1, 2
• Prolactin - Elevated levels (>20 μg/L) suggest hyperprolactinemia from pituitary adenoma or medication effect 1
• Estradiol - Helps differentiate functional hypothalamic amenorrhea (low levels) from PCOS (normal/elevated levels) 1

Interpretation of Laboratory Results

LH/FSH ratio >2 strongly suggests PCOS, while a ratio <1 is seen in approximately 82% of functional hypothalamic amenorrhea cases 1

• Elevated FSH (>40 mIU/mL) indicates primary ovarian insufficiency and requires confirmation with repeat testing 4 weeks later (two elevated values required for diagnosis) 1, 2
• Low estradiol with low LH/FSH suggests functional hypothalamic amenorrhea 1
• Normal/elevated estradiol with elevated LH/FSH ratio suggests PCOS 1

Additional Testing Based on Clinical Context

Consider these tests when specific clinical features are present:

• Testosterone and androstenedione - When hirsutism, acne, or other signs of hyperandrogenism are present (testosterone >2.5 nmol/L suggests PCOS) 1, 2
• Pelvic ultrasound - Indicated when hormonal tests suggest ovarian pathology or to assess endometrial thickness 1, 2
  • Thin endometrium (<5 mm) suggests estrogen deficiency
  • Thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen 1

Critical History and Physical Examination Elements

Focus your clinical assessment on these specific areas:

• Weight changes, eating patterns, and exercise habits - Screen for Female Athlete Triad or disordered eating 1, 2
• Medication history - Document use of hormonal contraceptives, antipsychotics, and antiepileptics 1, 2
• BMI calculation - Obesity is associated with PCOS and menstrual irregularities 1, 2
• Galactorrhea, hirsutism, or acne - Suggests hyperandrogenism or hyperprolactinemia 1, 2
• Tanner staging - Assess breast and pubic hair development 1

Referral Criteria to Gynecology or Endocrinology

Refer when any of the following are present:

• Persistently abnormal hormone levels after initial testing 1, 2
• Elevated FSH suggesting primary ovarian insufficiency 1, 2
• Signs or symptoms of eating disorder or Female Athlete Triad 1, 2
• Severe menstrual irregularities not responding to initial management 2
• Failure of pubertal progression or delayed puberty 2
• Clinical concern for PCOS, hypothalamic amenorrhea, or hyperprolactinemia requiring specialized management 5, 2

Common Pitfalls to Avoid

• Never interpret hormonal results without first excluding pregnancy - This is the most common error and leads to misdiagnosis 1
• Do not assume chemotherapy-induced amenorrhea equals menopause in cancer survivors - Hormone levels can be unreliable 1
• Do not miss functional hypothalamic amenorrhea with polycystic ovarian morphology on ultrasound - These patients have low LH, low estradiol, thin endometrium (<5 mm), and LH/FSH ratio <1 despite ovarian appearance 1
• Patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile 1, 3, 4

Special Considerations for Adolescents

• Evaluate thin or athletic patients for disordered eating or excessive exercise 1
• Consider DXA scan for bone mineral density if amenorrhea has lasted >6 months, history of eating disorders, or BMI <18.5 kg/m² 6
• Screen for metabolic syndrome components in patients with suspected PCOS 4