What is the best course of action for a 17-year-old female patient with secondary amenorrhea, previously regular menstrual cycles, normal Complete Blood Count (CBC) and Comprehensive Metabolic Panel (CMP), normal Thyroid-Stimulating Hormone (TSH) and prolactin levels, and slightly low Follicular-Stimulating Hormone (FSH) levels, who has been experiencing increased stress due to college applications?

Secondary Amenorrhea in a 17-Year-Old with Stress and Low FSH

This patient most likely has functional hypothalamic amenorrhea (FHA) triggered by psychological stress, and the initial management should focus on addressing the stressor through counseling about stress management, adequate nutrition, and monitoring for 3-6 months before pursuing additional hormonal interventions. 1, 2

Understanding the Clinical Picture

Your patient's presentation is classic for stress-induced FHA:

• Previously regular cycles with abrupt cessation suggests a functional rather than structural cause 3
• Low-normal FSH (1.6 IU/L) with normal LH (6.7 IU/L) indicates suppressed gonadotropin secretion, not ovarian failure 1, 3
• Normal prolactin and TSH effectively rules out hyperprolactinemia and thyroid dysfunction 1, 2
• Identified stressor (college applications) with no eating disorder or excessive exercise history points directly to stress-mediated hypothalamic suppression 1, 2

Why This is FHA and Not Other Causes

FHA accounts for 20-35% of secondary amenorrhea cases and is caused by chronic stress suppressing pulsatile GnRH secretion from the hypothalamus, which subsequently decreases LH and FSH pulses, preventing ovulation. 1, 3 The mechanism involves kisspeptin neurons serving as the critical bridge between the stress response system and the reproductive axis, with cortisol and catecholamines directly suppressing the GnRH pulse generator. 1

Critical distinction from PCOS: While PCOS is the most common cause of secondary amenorrhea overall, your patient lacks the typical LH:FSH ratio >2 that strongly suggests PCOS. 1 Her LH:FSH ratio is approximately 4.2:1, but more importantly, she has low FSH rather than elevated LH, which is inconsistent with PCOS. 1, 3

Immediate Management Steps

1. Address the Stress Factor First 2

• Provide counseling about stress management techniques
• Discuss adequate nutrition and sleep hygiene
• Reassure that stress-induced amenorrhea is reversible with lifestyle modification 1, 2

2. Screen for Hidden Red Flags 2

Even though she denies dietary changes or excessive exercise, you must specifically assess:

• Eating disorder screening: Adolescents often minimize or deny disordered eating behaviors 2
• Energy availability: Calculate if she's consuming >30 kcal/kg fat-free mass/day 4
• Exercise patterns: Even "normal" exercise can be excessive relative to caloric intake 4, 2
• Weight trajectory: Any recent weight loss, even if BMI appears normal 4, 2

3. Additional Laboratory Testing to Consider

While not immediately necessary, if amenorrhea persists beyond 3 months:

• Mid-luteal progesterone (if cycles resume) to confirm ovulation 4
• Estradiol level to assess degree of hypoestrogenism 2

When to Escalate Evaluation

Obtain DXA scan for bone mineral density if amenorrhea extends beyond 6 months despite addressing stressors, as prolonged hypoestrogenic states significantly increase osteoporosis risk. 4, 2 This is particularly critical in adolescents, as 90% of peak bone mass is attained by age 18. 4

Critical Red Flags Requiring Immediate Further Workup

Do not wait 3-6 months if any of these develop: 2

• Galactorrhea (suggests hyperprolactinemia despite normal initial prolactin)
• Headaches or visual changes (suggests pituitary pathology)
• Signs of eating disorder or significant weight loss
• Hirsutism or acne (suggests hyperandrogenism/PCOS was missed)

Common Diagnostic Pitfall to Avoid

Approximately 40-47% of women with FHA have polycystic ovarian morphology (FHA-PCOM) on ultrasound, which can lead to misdiagnosis as PCOS. 1, 3 This distinction is critical because FHA-PCOM requires correction of energy deficit as primary treatment, not PCOS-directed therapy. 1 Your patient's hormonal profile (low FSH, normal LH:FSH ratio) argues against PCOS even if ultrasound later shows polycystic ovaries.

Expected Timeline and Follow-Up

• Reassess in 3 months: If menses have not resumed, consider more intensive evaluation for energy deficit and psychological stressors 2
• At 6 months of persistent amenorrhea: Strongly consider DXA scan and potentially estrogen replacement therapy to prevent bone loss 4, 2
• Pelvic ultrasound: Can be deferred unless other concerning features develop, as it's unlikely to change initial management in this clinical scenario 2, 3

Treatment Considerations if Amenorrhea Persists

If stress management alone doesn't restore cycles within 3-6 months:

• Estrogen replacement with cyclic progestogen may be necessary to prevent long-term complications including decreased bone mineral density 2, 5
• Combined oral contraceptives can provide both cycle regulation and bone protection, though they mask rather than treat the underlying problem 5
• Referral to endocrinology if you're not experienced with FHA treatment 4