What is the evaluation and treatment approach for a teenage girl with primary or secondary amenorrhea (absence of menstruation) and normal hormone levels?

Amenorrhea in a Teenager with Normal Hormones

In a teenager with amenorrhea and normal hormone levels (normal FSH, LH, estradiol, prolactin, TSH), the most likely diagnosis is functional hypothalamic amenorrhea (FHA), and the primary treatment is addressing underlying energy deficits through increased caloric intake, reduced exercise intensity, and stress management rather than hormonal therapy. 1, 2

Diagnostic Approach

Initial Evaluation Focus

When hormones are normal, your evaluation should specifically target:

• Energy availability calculation: Determine if the patient is consuming >30 kcal/kg fat-free mass/day 1, 2
• Exercise patterns: Document hours per week and intensity of physical activity 1, 2
• Nutritional assessment: Evaluate for restrictive eating, weight loss history, and body mass index 1, 2
• Psychological stressors: Screen for academic pressure, family issues, and mental health concerns 2
• Eating disorder screening: Use validated tools as adolescents often minimize or deny disordered eating 1, 2

Anatomic Considerations

If this is primary amenorrhea with normal hormones and normal breast development:

• Pelvic ultrasound is mandatory to exclude outflow tract obstruction (imperforate hymen, transverse vaginal septum) or Müllerian agenesis 1, 2
• These anatomic causes can present with normal hormone levels because the hypothalamic-pituitary-ovarian axis is intact 3

Understanding Functional Hypothalamic Amenorrhea

FHA accounts for 20-35% of secondary amenorrhea cases and is the most common cause in adolescents with normal hormone levels 2, 4. The pathophysiology involves:

• Energy deficit suppresses GnRH secretion, mediated partly by leptin, leading to disrupted LH pulsatility 4
• Inadequate energy availability below 30 kcal/kg fat-free mass/day in women causes suppressed bone formation 1
• The hormonal profile may appear "normal" because FSH/LH are not elevated (distinguishing it from primary ovarian insufficiency) and estradiol may be low-normal rather than frankly low 2, 4

Treatment Algorithm

First-Line Management (Non-Hormonal)

Address the underlying energy deficit as primary therapy:

• Increase caloric intake to achieve >30 kcal/kg fat-free mass/day 1, 2
• Reduce exercise volume and intensity if excessive (>10 hours/week of intense training warrants evaluation) 1
• Stress management counseling addressing academic, social, and psychological pressures 2
• Nutritional counseling by a sports dietitian experienced with energy availability assessment 1

Important caveat: Recovery of menstrual function may take >6 months despite addressing energy deficits, so patience is required 1

When to Consider Hormonal Therapy

Hormonal replacement should be considered if:

• Amenorrhea persists >6 months despite addressing stressors and energy availability 1, 2
• DXA scan shows low bone mineral density (Z-score <-1.0) 1, 2
• This is critical because 90% of peak bone mass is attained by age 18, making adolescence a crucial window 1

Hormonal Replacement Specifics

If hormonal therapy is indicated for bone protection:

• Transdermal estradiol (100 μg patch twice weekly) with cyclic micronized progesterone (200 mg for 12 days/month) is preferred over oral contraceptives for bone health 1
• Oral contraceptives do not correct the underlying cause and do not protect bone mineral density as effectively as physiologic estrogen replacement 1
• For secondary amenorrhea treatment specifically, progesterone 400 mg daily for 10 days can induce withdrawal bleeding 5

Critical Red Flags Requiring Immediate Evaluation

Even with "normal" hormones, evaluate urgently if:

• Galactorrhea (suggests hyperprolactinemia that may be intermittent) 2, 6
• Headaches or visual changes (suggests pituitary pathology) 2
• Significant weight loss or signs of eating disorder (requires multidisciplinary eating disorder team) 1, 2
• Hirsutism or acne (may indicate PCOS with normal initial labs or late-onset congenital adrenal hyperplasia) 1, 7

Common Pitfalls to Avoid

• Do not assume amenorrhea in athletes is benign – other pathology must be excluded even when the clinical picture suggests FHA 1, 2
• Do not prescribe oral contraceptives as first-line therapy – this masks the problem without addressing the underlying energy deficit and provides false reassurance 1
• Do not overlook eating disorders – adolescents frequently minimize symptoms, and direct questioning about specific behaviors is necessary 1, 2
• Do not delay bone density assessment – if amenorrhea extends beyond 6 months, DXA scanning is indicated regardless of age 1, 2

Monitoring and Follow-Up

• Reassess every 3 months for return of menses, weight trends, and compliance with nutritional/exercise modifications 2
• Repeat DXA scan annually if bone density is low and amenorrhea persists 1
• Consider endocrinology referral if primary care provider lacks experience managing FHA or if amenorrhea persists despite 6 months of appropriate intervention 2
• Mid-luteal progesterone testing (day 21 of cycle) can confirm ovulation if cycles resume 2

Special Consideration: Polycystic Ovary Syndrome

While PCOS typically presents with elevated androgens, some patients may have normal initial hormone levels but still have PCOS:

• Pelvic ultrasound showing polycystic ovarian morphology with menstrual irregularity suggests PCOS even without hyperandrogenism 1, 2
• If PCOS is diagnosed, cyclic progestins (not estrogen-progestin contraceptives) should be used to prevent endometrial hyperplasia: progesterone 200 mg daily for 12 days per 28-day cycle 5, 7
• Screen for metabolic syndrome components (glucose intolerance, dyslipidemia) in PCOS patients 8