GnRH Agonists

GnRH Agonists in Pediatric Medicine

Key Points

GnRH agonists suppress pubertal development by desensitizing pituitary GnRH receptors
Primary medications: Leuprolide, Triptorelin, Histrelin
Used in central precocious puberty (CPP) and gender-affirming care
Require careful monitoring of growth, bone health, and pubertal development

Overview

Gonadotropin-releasing hormone (GnRH) agonists are synthetic peptides that mimic the action of natural GnRH but with greater potency and longer duration. These medications are cornerstone treatments in pediatric endocrinology for managing disorders of pubertal development.

Mechanism of Action

Physiological Basis

Initial stimulation of pituitary GnRH receptors
Continuous exposure leads to receptor downregulation
Results in suppression of LH and FSH secretion
Consequently reduces sex steroid production

Pharmacological Effects

The continuous exposure to GnRH agonists leads to:

Suppression of gonadotropin secretion within 2-4 weeks
Reduction in sex steroid levels to prepubertal range
Arrest of pubertal development
Regression of secondary sexual characteristics in early stages

Clinical Indications

Primary Indications

Central Precocious Puberty (CPP)
- Girls with onset of puberty before age 8
- Boys with onset of puberty before age 9
- Rapid progression of pubertal development
- Advanced bone age
Gender-Affirming Care
- Pubertal suppression in gender-diverse youth
- Part of comprehensive gender-affirming care

Secondary Indications

Growth preservation in early puberty
Management of severe menstrual disorders
Treatment of aggressive behavior in autism with precocious puberty

Administration & Dosing

Available Formulations

Leuprolide Acetate
- Monthly: 7.5-15 mg IM
- 3-monthly: 11.25-30 mg IM
- Starting dose based on body weight
Triptorelin
- 3-monthly: 11.25 mg IM
- 6-monthly formulation available
Histrelin Implant
- 50 mg subcutaneous implant
- Duration: 12 months

Administration Guidelines

Initiate treatment after confirmation of diagnosis
Consider loading dose in rapidly progressing cases
Maintain regular administration schedule
Document administration site and rotation

Monitoring & Safety

Monitoring Parameters

Clinical Monitoring
- Height and weight every 3-6 months
- Pubertal staging every 3-6 months
- Bone age radiograph annually
- Quality of life assessment
Laboratory Monitoring
- LH/FSH levels at 3-6 months
- Estradiol/Testosterone levels
- Annual bone density scan

Side Effects and Management

Common Side Effects
- Injection site reactions
- Initial pubertal flare
- Headaches
- Mood changes
Long-term Considerations
- Bone mineral density
- Growth velocity
- Psychological support
- Fertility preservation discussions