Management Guidelines for Amenorrhea in Adolescents
Initial Diagnostic Evaluation
Rule out pregnancy first with urine or serum hCG test in any adolescent presenting with amenorrhea, regardless of reported sexual history. 1
Primary Amenorrhea Assessment
- Perform Tanner staging to determine pubertal development status 2
- If no breast development by age 13 years, this represents delayed puberty requiring earlier intervention 2
- If breast development has occurred but no menarche by age 16, or failure to progress through puberty for ≥12 months, proceed with full evaluation 2
Core Laboratory Testing
Obtain the following hormonal tests for both primary and secondary amenorrhea 2, 1:
- FSH and LH (to differentiate hypogonadotropic hypogonadism from primary ovarian insufficiency)
- Prolactin (to screen for hyperprolactinemia, which accounts for ~20% of secondary amenorrhea) 2
- TSH and free T4 (thyroid dysfunction is a common cause) 2, 1
- Estradiol level (for primary amenorrhea evaluation) 2
Clinical Assessment Parameters
Document the following specific details 2, 1:
- Height and BMI (to identify relative energy deficiency)
- Dietary intake patterns and weekly physical activity hours
- Presence of hirsutism or galactorrhea
- History of pelvic pain
- Sexual activity history
Imaging Studies
- Pelvic ultrasound is recommended to assess uterine and ovarian anatomy in primary amenorrhea and to evaluate for polycystic ovarian morphology in secondary amenorrhea 2
Management by Etiology
Functional Hypothalamic Amenorrhea (FHA)
FHA accounts for 20-35% of secondary amenorrhea cases and requires non-pharmacological interventions as the priority. 2, 1
Primary Management Approach
- Increase energy availability to >30 kcal/kg fat-free mass/day 1
- Address underlying stressors through counseling about stress management, adequate nutrition, and appropriate activity levels 1
- Screen for eating disorders and excessive exercise (common causes in adolescents) 1
Critical Pitfall to Avoid
Do not prescribe combined oral contraceptives to "regulate cycles" in hypothalamic amenorrhea without first addressing underlying energy deficiency—this masks the problem and may worsen bone health. 1
When to Refer
- Intensive interdisciplinary treatment is required for clinical eating disorders, including counseling with a mental health practitioner and nutritional education 1
- Patients with FHA are at risk for decreased bone density and should be evaluated for eating disorders 2, 3
Polycystic Ovary Syndrome (PCOS)
PCOS is one of the most common causes of secondary amenorrhea in adolescents. 2
Hormonal Management
- Combined oral contraceptives containing 30-35 μg ethinyl estradiol with levonorgestrel or norgestimate are recommended for cycle control and reduction of androgen effects 1
- Use monophasic formulations when prescribing for contraception needs combined with cycle regulation, treatment of dysmenorrhea, heavy bleeding, or acne 1
- When contraception is not necessary, sequential progestins can be prescribed 4
Long-term Monitoring
- Patients with PCOS are at risk for glucose intolerance, dyslipidemia, and other aspects of metabolic syndrome 3
Hyperprolactinemia
Measure serum prolactin in adolescents presenting with delayed puberty, galactorrhea, visual field loss, growth or pubertal arrest, or menstrual disturbance. 5
Diagnostic Considerations
- A single prolactin measurement taken at any time of day is sufficient to assess hyperprolactinemia 5
- For modestly elevated prolactin (up to 5 times upper limit of normal), repeat sampling on a different day with 2-3 samples at 20-60 minute intervals using an indwelling cannula to differentiate stress-related hyperprolactinemia from organic disease 5
- Use age-specific and sex-specific prolactin reference ranges 5
- Exclude confounding conditions: hypothyroidism, renal/hepatic impairment, and medications causing hyperprolactinemia 5
Red Flags Requiring Immediate Evaluation
- Galactorrhea suggesting hyperprolactinemia 1
- Headaches or visual changes suggesting pituitary pathology 1
Primary Ovarian Insufficiency (POI)
POI is defined by elevated FSH levels within the menopausal range (recorded at least twice four weeks apart) in patients younger than 40 years with oligo/amenorrhea. 5
Hormonal Replacement Therapy
- Initiate estrogen replacement therapy with cyclic progestogen to induce menstrual cycles and prevent bone loss in patients with hypogonadotropic hypogonadism 2
- HRT is indicated to reduce risk of osteoporosis, cardiovascular diseases, urogenital atrophy, and to improve quality of life 5
- For prepubertal patients with early-onset POI, HRT is indicated to induce progression of secondary sexual characteristics 5
Important Counseling Point
- Patients with POI can maintain unpredictable ovarian function and should not be presumed infertile 3
Iatrogenic POI (Chemo- or Radio-Induced)
Approximately 8-10% of female survivors of pediatric cancer develop POI. 5
- Manage with a multidisciplinary team including gynecologists, pediatricians, endocrinologists, dietitians, and psychologists 5
- Tailor HRT formulation to patient's demographic, clinical, and psychological profile to improve compliance 5
Specific Treatment Protocols
Secondary Amenorrhea Treatment
For secondary amenorrhea due to progesterone deficiency, progesterone capsules may be given as a single daily dose of 400 mg at bedtime for 10 days. 6
- Administration of 10 days of progesterone therapy (300-400 mg/day) results in 73.8-76.8% of women experiencing withdrawal bleeding 6
- Take progesterone capsules at bedtime as some women become very drowsy and/or dizzy 6
- In rare cases, symptoms may include blurred vision, difficulty speaking, difficulty with walking, and feeling abnormal—discuss these with healthcare provider immediately 6
Contraindications
Do not use progesterone capsules if patient 6:
- Is allergic to peanuts (product contains peanut oil)
- Has unusual vaginal bleeding
- Currently has or has had certain cancers
- Had a stroke or heart attack
- Currently has or has had blood clots
- Currently has or has had liver problems
- Thinks she may be pregnant
Endometrial Protection in Estrogen Users
A postmenopausal woman with a uterus taking estrogens should take a single daily dose of 200 mg progesterone capsules at bedtime for 12 continuous days per 28-day cycle. 6
- This regimen significantly reduces the rate of endometrial hyperplasia (6% combination versus 64% estrogen alone) 6
Bone Health Considerations
DXA scan for bone mineral density assessment is recommended for patients with amenorrhea lasting >6 months. 2, 1
- Low estrogen levels in secondary amenorrhea increase risk for decreased bone mineral density and stress fractures 2
- Athletes with amenorrhea require evaluation for Relative Energy Deficiency in Sport (RED-S) 2
- Preservation of bone density should be discussed with amenorrheic patients since many causes can result in decreased bone density that may be irreversible 7
Follow-Up and Monitoring
Schedule follow-up within 3-6 months to assess response to non-pharmacological interventions, return of spontaneous menses, and bone density if amenorrhea is prolonged. 1
Goal of Treatment
- The goal is restoration of spontaneous, regular menstrual cycles rather than artificially induced withdrawal bleeding, indicating restoration of normal hypothalamic-pituitary-ovarian axis function and optimal bone health 1
When to Refer to Specialist
Refer to endocrinology or gynecology when 1:
- Amenorrhea persists >6 months despite initial management
- Abnormal hormone levels suggest specific pathology (elevated FSH, prolactin abnormalities)
- Clinical eating disorder is suspected or confirmed
- Significant psychological stress contributes to hypothalamic amenorrhea
Special Populations
Turner Syndrome and Chromosomal Abnormalities
- If FSH is elevated in primary amenorrhea, this indicates primary ovarian failure, mainly related to Turner syndrome 4
- Patients with Turner syndrome (or variant) should be treated by a physician familiar with appropriate screening and treatment measures 3
Anatomic Abnormalities
- If pubertal development is normal in primary amenorrhea, pelvic ultrasound may visualize hindering of menses output or absence of uterus (Rokitansky syndrome or androgen insensitivity syndrome) 4