What are the treatment guidelines for secondary amenorrhea in an adolescent?

Treatment Guidelines for Secondary Amenorrhea in Adolescents

The cornerstone of treatment for secondary amenorrhea in adolescents is identifying and correcting the underlying cause—particularly addressing low energy availability, eating disorders, and hypothalamic dysfunction—rather than simply prescribing hormonal contraceptives to induce withdrawal bleeding. 1

Initial Diagnostic Approach

Rule out pregnancy first with a urine or serum hCG test in any adolescent presenting with secondary amenorrhea, regardless of reported sexual history. 2, 3

Obtain core hormonal laboratory tests strategically:

• FSH, LH, prolactin, TSH, and free T4 to differentiate between hypogonadotropic hypogonadism and primary ovarian insufficiency 2, 3
• Estradiol and testosterone levels to assess ovarian function and hyperandrogenism 3
• Measure LH and FSH between cycle days 3-6 with three estimations 20 minutes apart if PCOS is suspected 2
• Prolactin levels >20 μg/L are abnormal and indicate hyperprolactinemia as a potential cause 2

Assess for specific clinical features:

• Height, BMI, dietary intake, and weekly physical activity hours to identify relative energy deficiency 1, 3
• Signs of hyperandrogenism (acne, hirsutism) suggesting PCOS 2, 3
• Galactorrhea indicating hyperprolactinemia 2, 3
• Weight loss, excessive exercise, or psychological stress suggesting functional hypothalamic amenorrhea 1, 2

Common Etiologies and Specific Management

Functional Hypothalamic Amenorrhea (FHA) / Relative Energy Deficiency in Sport (RED-S)

Non-pharmacological interventions are the priority and should be implemented before any hormonal therapy is considered. 1

Increase energy availability to >30 kcal/kg fat-free mass/day through:

• Nutritional counseling with a sports dietitian to eliminate energy deficit 1
• Reduce excessive exercise intensity or volume to restore energy balance 1, 2
• Address psychological stressors contributing to low energy availability 1

Multidisciplinary team approach is essential including:

• Physician for medical monitoring 1
• Mental health provider for psychological evaluation and treatment 1
• Sports dietitian for nutritional rehabilitation 1

Combined oral contraceptives (COCs) do NOT restore spontaneous menses and may actually compromise bone health by reducing hepatic IGF-1 production, providing false reassurance when withdrawal bleeding occurs. 1

Pharmacological treatment should only be considered if:

• Symptoms of estrogen deficiency (vaginal dryness, dyspareunia) are present 1
• Impaired bone health persists despite non-pharmacological therapy 1
• Infertility treatment is needed 1

Eating Disorders

Distinguish between unintentional low energy availability, disordered eating, and clinical eating disorders as treatment intensity differs significantly. 1

For mild disordered eating:

• Nutritional education alone may be sufficient to eliminate low energy availability 1

For significant disordered eating:

• Counseling with a mental health practitioner plus nutritional education 1

For clinical eating disorders (anorexia nervosa, bulimia nervosa):

• Intensive interdisciplinary treatment is required per American Psychiatric Association Practice Guidelines 1
• Selective serotonin reuptake inhibitors can be helpful for bulimia nervosa 1
• Limited evidence supports medications for weight restoration or relapse prevention in anorexia nervosa 1
• Psychotropic medications may benefit comorbid anxiety, depression, or obsessive-compulsive behaviors 1

Polycystic Ovary Syndrome (PCOS)

PCOS is the most common cause of secondary amenorrhea in adolescents, affecting 4-6% of the general female population. 2

When contraception is not needed:

• Sequential progestins (e.g., medroxyprogesterone acetate 10 mg for 10-14 days monthly) to induce withdrawal bleeding and provide endometrial protection 3

When contraception is needed or hyperandrogenism requires treatment:

• Combined oral contraceptives containing 30-35 μg ethinyl estradiol with levonorgestrel or norgestimate provide cycle control and reduce androgen effects 2, 4

Screen for metabolic complications including glucose intolerance, dyslipidemia, and other features of metabolic syndrome. 5

Hyperprolactinemia

Obtain pituitary MRI if prolactin is elevated to evaluate for prolactinoma or other hypothalamic-pituitary abnormalities. 2

Treatment depends on underlying cause and may include dopamine agonists for prolactinomas.

Primary Ovarian Insufficiency

Elevated FSH indicates primary ovarian failure, most commonly related to Turner syndrome in adolescents. 3

Hormone replacement therapy with estrogen and progestins is essential to avoid hypoestrogenism and optimize bone health. 3

Patients can maintain unpredictable ovarian function and should not be presumed infertile. 5

Hormonal Management Considerations

When Hormonal Therapy is Appropriate

For adolescents requiring menstrual suppression or contraception with medical indications:

Levonorgestrel IUD is the preferred first-line option for:

• Heavy menstrual bleeding requiring suppression 4, 6
• Medical conditions where estrogen is contraindicated 4, 6
• Desire for long-term, highly effective contraception without daily adherence 6
• Provides ≥75% continuation rates at 1 year with high satisfaction 4
• No negative effect on long-term fertility with rapid return to fertility after removal 6

Combined oral contraceptives are appropriate for:

• Contraception needs combined with cycle regulation 2, 4
• Treatment of dysmenorrhea, heavy bleeding, or acne 2
• Use monophasic formulations with 30-35 μg ethinyl estradiol and levonorgestrel or norgestimate 4

Depot medroxyprogesterone acetate (DMPA) considerations:

• Provides dysmenorrhea improvement and iron-deficiency anemia protection 4
• Causes menstrual irregularities in nearly all patients initially requiring counseling 2, 4
• May reduce bone mineral density though substantial recovery occurs after discontinuation 4
• Recommend calcium 1300 mg and vitamin D 600 IU daily for teens using DMPA 4

Critical Pitfalls to Avoid

Do not prescribe COCs to "regulate cycles" in hypothalamic amenorrhea without first addressing underlying energy deficiency—this masks the problem and may worsen bone health. 1

Do not assume infertility in primary ovarian insufficiency—ovarian function can be unpredictable. 5

Do not overlook bone density concerns—many causes of amenorrhea result in decreased bone density that may be irreversible. 7

Do not miss eating disorders—denial and minimization are common, requiring careful assessment beyond patient self-report. 1

Referral Indications

Refer to endocrinology or gynecology when: 2

• Amenorrhea persists >6 months despite initial management
• Abnormal hormone levels suggest specific pathology (elevated FSH, prolactin abnormalities)
• Signs of hyperandrogenism with menstrual irregularity are present
• Infertility concerns arise
• Suspected structural abnormalities on imaging

Refer to mental health specialist when: 1

• Clinical eating disorder is suspected or confirmed
• Significant psychological stress contributes to hypothalamic amenorrhea
• Comorbid anxiety, depression, or obsessive-compulsive behaviors are present

Follow-Up and Monitoring

Schedule follow-up within 3-6 months to assess:

• Response to non-pharmacological interventions (weight gain, energy availability improvement) 1
• Return of spontaneous menses 1
• Bone density if amenorrhea is prolonged 7
• Metabolic parameters in PCOS 5

The goal is restoration of spontaneous, regular menstrual cycles rather than artificially induced withdrawal bleeding, as this indicates restoration of normal hypothalamic-pituitary-ovarian axis function and optimal bone health. 1