What is the approach to testosterone therapy in children (pediatric population) with hypogonadism?

Testosterone Therapy in Children with Hypogonadism

Testosterone replacement therapy (TRT) is indicated for children with confirmed hypogonadism, with treatment approaches varying based on age, pubertal status, underlying etiology, and fertility considerations.

Diagnostic Evaluation

Before initiating testosterone therapy in pediatric patients, a thorough diagnostic evaluation is essential:

• Confirm hypogonadism with two morning testosterone measurements between 8-10 AM 1
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary hypogonadism 1
• Check serum prolactin levels in patients with low testosterone and low/normal LH levels 1
• Consider pituitary MRI if testosterone is <150 ng/dL with low/normal LH, regardless of prolactin levels 1
• Assess baseline hemoglobin, hematocrit, and cardiovascular risk factors 1
• Evaluate for symptoms consistent with hypogonadism based on age and developmental stage 1

Treatment Approach by Age and Condition

Prepubertal Boys

• For constitutional delay of growth and puberty (CDGP):

  • Short-term testosterone therapy with testosterone enanthate (TE) is safe and effective for inducing puberty and increasing growth 2
  • Typical starting dose: 50-100 mg IM every 4 weeks for 3-6 months 3

• For permanent hypogonadism (e.g., Klinefelter syndrome, hypopituitarism):

  • Begin with low-dose testosterone to initiate puberty (50-100 mg IM monthly) 3
  • Gradually increase dose over 2-3 years to mimic normal pubertal progression 3, 4

Adolescent Boys

• For permanent hypogonadism:

  • Long-term testosterone therapy should be given for hypothalamic or pituitary gonadotropin deficiency, or for primary hypogonadism such as Klinefelter syndrome 3
  • Increase dose to adult replacement levels (typically 100-200 mg IM every 2 weeks) 3, 5
  • Target testosterone levels in the mid-tertile of normal range (450-600 ng/dL) 1

• For constitutional delay:

  • Short-term therapy (3-6 months) often sufficient to "jump-start" puberty 2
  • Reassess need for continued therapy after initial course 2

Formulation Options

1. Intramuscular testosterone (FDA-approved for adolescents):

   • Testosterone enanthate or cypionate
   • Advantages: Cost-effective, well-established safety profile in adolescents
   • Disadvantages: Fluctuating levels, pain at injection site 3, 2

2. Transdermal preparations (patches, gels):

   • Emerging evidence supports safety and efficacy for inducing puberty 2
   • Advantages: More stable day-to-day levels
   • Disadvantages: Adult dosing makes titration difficult for adolescents, risk of transfer to others 1, 2

3. Testosterone pellets (FDA-approved for adolescents):

   • Advantages: Long-acting (3-6 months), stable levels
   • Disadvantages: Requires surgical implantation, difficult to adjust dose 1, 2

4. Oral testosterone undecanoate:

   • Limited evidence supports short-term use in CDGP 2
   • Not widely used in US pediatric practice

Monitoring Protocol

• Testosterone levels: Check 2-3 months after treatment initiation or dose change 1

  • For IM injections: Measure midway between injections
  • For transdermal: Can measure at any time, but levels may vary

• Growth parameters: Height, weight, and growth velocity at each visit 6

• Bone age: Annual assessment to monitor skeletal maturation

• Hemoglobin/hematocrit: Monitor for erythrocytosis, a common side effect 1, 5

• Bone mineral density: Consider baseline and follow-up DEXA scans 5

• Psychosocial development: Assess impact on well-being and psychosocial maturation 4

Special Considerations

• Prader-Willi Syndrome: Consider trial of human chorionic gonadotropin (hCG) for undescended testes before surgery to avoid general anesthesia risks 6

• Fertility concerns: Assess fertility desires before initiating treatment 1

  • Consider alternatives like hCG therapy or selective estrogen receptor modulators if fertility preservation is important 1

• Iatrogenic premature ovarian insufficiency: For female patients with chemotherapy/radiation-induced POI, hormonal therapy is indicated to decrease morbidity risks and treat symptoms of hypoestrogenism 6

Dose Adjustment Guidelines

Pre-Dose Morning Testosterone	Dose Adjustment
>750 ng/dL	Decrease daily dose by 20-25%
350-750 ng/dL	No change
<350 ng/dL	Increase daily dose by 20-25%

Common Pitfalls and Challenges

• Underdosing: 24% of adolescents receive lower testosterone doses than recommended 5

• Inadequate monitoring: Many adolescents lack appropriate pre-treatment (12%) or on-treatment (17%) testosterone levels 5

• Failure to adjust doses: 28% of adolescents with low on-treatment testosterone levels have no dose adjustments 5

• Lack of bone density monitoring: 63% of adolescents on testosterone therapy do not receive DEXA scans 5

• Inadequate hematocrit monitoring: 31% of adolescents lack hematocrit monitoring 5

• Inappropriate formulations: Most testosterone preparations are designed for adults, making appropriate dosing challenging in pediatric patients 7, 2

Testosterone therapy in children and adolescents with hypogonadism requires careful consideration of the underlying etiology, pubertal status, and long-term goals. While evidence supports the use of testosterone for both constitutional delay and permanent hypogonadism, current practice is largely based on expert opinion rather than robust clinical trials specific to pediatric populations. Close monitoring and appropriate dose adjustments are essential to optimize outcomes and minimize potential adverse effects.