What is the evaluation and management approach for a 15-year-old female patient with secondary amenorrhea (absence of menstruation) for 3 months?

Evaluation and Management of Secondary Amenorrhea in a 15-Year-Old

For a 15-year-old with 3 months of absent periods, immediate evaluation is warranted because this meets the diagnostic threshold for secondary amenorrhea in adolescents with previously regular cycles. 1

Diagnostic Criteria in Adolescents

The absence of menstruation for 3 months in a patient who previously had regular cycles meets the definition of secondary amenorrhea and requires evaluation. 1 This is a more conservative threshold than the traditional 6-month criterion used in adults with irregular cycles. 1, 2

Immediate Red Flag Assessment

Before proceeding with routine workup, assess for symptoms requiring urgent evaluation:

• Galactorrhea (suggests hyperprolactinemia and possible pituitary pathology) 1, 3
• Headaches or visual changes (suggests pituitary adenoma) 1, 3
• Signs of eating disorder or significant weight loss (suggests functional hypothalamic amenorrhea with bone health risks) 1, 3
• Symptoms of hyperandrogenism (hirsutism, severe acne suggesting PCOS) 1

Any of these findings warrant immediate specialist referral and expedited workup. 2

Initial Laboratory Evaluation

Order the following tests simultaneously as first-line evaluation:

• Pregnancy test (mandatory first step to exclude pregnancy) 3, 2, 4
• FSH and LH levels (to identify primary ovarian insufficiency and PCOS; LH/FSH ratio >2 suggests PCOS) 3, 2
• Prolactin level (elevated >20 μg/L suggests hyperprolactinemia) 3, 2
• TSH level (to identify thyroid dysfunction as a reversible cause) 3, 2
• Estradiol level (low levels suggest hypoestrogenism from functional hypothalamic amenorrhea) 3, 2

Draw FSH, LH, and testosterone at any time since the patient is amenorrheic. 2

Physical Examination Focus

• Calculate BMI (obesity associated with PCOS; low BMI with functional hypothalamic amenorrhea) 2
• Assess for signs of hyperandrogenism (hirsutism, acne) 2
• Evaluate breast development (Tanner staging to confirm adequate pubertal progression) 3, 2
• Check for galactorrhea (suggests hyperprolactinemia) 2
• Thyroid examination (enlargement or nodules) 2

Detailed History Components

• Menstrual history: Age of menarche, previous cycle regularity, duration of current amenorrhea 2, 5
• Weight changes and eating patterns: Screen for disordered eating, which is common in adolescent functional hypothalamic amenorrhea 3, 2
• Exercise habits: Excessive exercise can cause hypothalamic amenorrhea and Female Athlete Triad 3, 2
• Psychosocial stressors: Stress is a trigger for functional hypothalamic amenorrhea 3, 5
• Medication use: Antipsychotics, antiepileptics, and hormonal contraceptives can cause amenorrhea 2

Imaging Studies

Pelvic ultrasound is indicated to:

• Assess ovarian morphology (polycystic ovaries in PCOS) 3, 2
• Measure endometrial thickness (thin <5 mm suggests estrogen deficiency; thick >8 mm suggests chronic anovulation) 2
• Evaluate for structural abnormalities 3

Transvaginal ultrasound is more sensitive than transabdominal, though transabdominal may be more appropriate in adolescents. 2

Interpretation of Results and Diagnosis

Based on FSH levels:

• Elevated FSH (>40 mIU/mL): Primary ovarian insufficiency—confirm with repeat FSH in 4 weeks (two elevated values required); order karyotype if confirmed 2, 4
• Low FSH with low estradiol: Functional hypothalamic amenorrhea—evaluate for eating disorders, excessive exercise, stress 3, 2
• Normal FSH with LH/FSH ratio >2: PCOS—check androgen profile and assess for metabolic syndrome 3, 2
• Elevated prolactin: Hyperprolactinemia—obtain brain MRI to evaluate for pituitary adenoma 3

Additional diagnostic clues:

• LH/FSH ratio <1 with low estradiol and thin endometrium (<5 mm) strongly suggests functional hypothalamic amenorrhea, even if polycystic ovaries are present on ultrasound 2
• Normal/elevated estradiol with LH/FSH ratio >2 suggests PCOS 2

Management Based on Etiology

Functional Hypothalamic Amenorrhea:

• Address underlying stressors through counseling about stress management, adequate nutrition, and appropriate activity levels 3
• Screen thoroughly for eating disorders (adolescents often minimize or deny disordered eating) 3
• Order DXA scan for bone mineral density if amenorrhea extends beyond 6 months, as these patients are at high risk for decreased bone density and stress fractures 3
• Consider estrogen replacement therapy if low estrogen persists despite addressing stressors, to prevent long-term bone loss 3

PCOS:

• Screen for glucose intolerance, dyslipidemia, and metabolic syndrome 3, 4
• Induce menstrual bleeding with cyclic progestogen to prevent endometrial hyperplasia 6
• Consider combined oral contraceptives for cycle regulation, contraception, and treatment of hyperandrogenism 6

Primary Ovarian Insufficiency:

• Refer to specialist for karyotype analysis and further evaluation 2
• Initiate hormone replacement therapy to reduce risk of osteoporosis, cardiovascular disease, and urogenital atrophy 3
• Counsel that patients can maintain unpredictable ovarian function and should not be presumed infertile 2, 4

Hyperprolactinemia:

• Obtain brain MRI to evaluate for pituitary adenoma 3
• Refer to endocrinology for prolactin-lowering medication (dopamine agonists) 6
• Treatment should be performed in specialist centers with pituitary-specific multidisciplinary teams 3

Critical Pitfalls to Avoid

• Do not assume all amenorrhea in stressed or athletic adolescents is benign—other pathology must be excluded through proper workup 3
• Do not overlook eating disorders—adolescents frequently minimize or deny disordered eating behaviors 3
• Do not delay bone density assessment—if amenorrhea persists beyond 6 months, order DXA scan regardless of etiology 3
• Do not assume patients with primary ovarian insufficiency are infertile—they can maintain unpredictable ovarian function 2, 4
• Do not fail to perform pregnancy test first—failing to exclude pregnancy leads to misinterpretation of all other hormonal results 2