Growth hormone in combination with leuprorelin in pubertal children with idiopathic short stature

Area of Science:

• Pediatric Endocrinology
• Growth Hormone Therapy
• Puberty Induction

Background:

• Idiopathic short stature (ISS) is a condition characterized by short height without a clear identifiable cause.
• Growth hormone (GH) therapy is a common treatment for ISS.
• The combined use of GH with gonadotrophin-releasing hormone (GnRH) agonists to delay puberty and potentially increase final height is an off-label practice with limited randomized controlled trial (RCT) data.

Purpose of the Study:

• To evaluate the efficacy of combining GH with GnRH agonists in increasing near-adult height (NAH) in patients with ISS.
• To assess the safety profile of this combination therapy.

Main Methods:

• A randomized controlled trial involving patients with ISS at puberty onset.
• Participants were randomized to receive either GH with leuprorelin (combination group) or GH alone (control group).
• The primary outcome measure was the NAH standard deviation score (SDS). Study treatments were prematurely discontinued due to regulatory requests.

Main Results:

• Baseline height SDS was similar in both groups (-2.5).
• After 2 years, height SDS increased to -2.3 in the combination group and -1.8 in the GH alone group.
• Mean NAH SDS was similar between the groups (-1.8 for combination, -1.9 for GH alone).
• Treatment-emergent adverse events and bone fractures were more frequent in the combination group.

Conclusions:

• Premature study discontinuation prevented statistical comparison of NAH SDS between groups.
• Combined GH and GnRH agonist treatment resulted in slower growth in the initial 2-3 years compared to GH alone.
• Mean NAH SDS was comparable between the groups.
• No new GH-related safety concerns were identified, but a potential increase in bone fracture incidence with combination therapy was observed.