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

Abstract

ObjectiveThere is a scarcity of data from randomised controlled trials on the association of growth hormone (GH) with gonadotrophin-releasing hormone agonists in idiopathic short stature (ISS), although this off-label use is common. We aimed to test whether delaying pubertal progression could increase near-adult height (NAH) in GH-treated patients with ISS.MethodsPatients with ISS at puberty onset were randomised to GH with leuprorelin (combination, n = 46) or GH alone (n = 45). NAH standard deviation score (SDS) was the primary outcome measure. The French regulatory authority requested premature discontinuation of study treatments after approximately 2.4 years; patients from France were followed for safety.ResultsMean (s.d.) baseline height SDS was −2.5 (0.5) in both groups, increasing at 2 years to −2.3 (0.6) with combination and −1.8 (0.7) with GH alone. NAH SDS was −1.8 (0.5) with combination (n = 19) and −1.9 (0.8) with GH alone (n = 16). Treatment-emergent adverse events and bone fractures occurred more frequently with combination than GH alone.ConclusionDue to premature discontinuation of treatments, statistical comparison of NAH SDS between the two cohorts was not possible. During the first 2–3 years of treatment, patients treated with the combination grew more slowly than those receiving GH alone. However, mean NAH SDS was similar in the two groups. No new GH-related safety concerns were revealed. A potentially deleterious effect of combined treatment on bone fracture incidence was identified.

The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus

“…The fallopian tubes were thicker in the model group than the control group and returned to normal thickness after administration of the Fy formula. However, the fallopian tubes were significantly thinner in the leuprorelin group than the model group ( Supplementary Figure S2 ), suggesting that leuprorelin affects the normal development of sex organs and should be combined with growth hormone ( Benabbad et al, 2018 ). The Fy formula and leuprorelin decreased the serum levels of the hormones E2, LH and FSH compared with those in the model group, suggesting that the Fy formula can significantly delay puberty onset in female rats.…”

Should Skeletal Maturation Be Manipulated for Extra Height Gain?

“…The third set comprises two controlled studies on a short course of rhGH plus GnRHa ( 58 , 70 ). Set 4 contains two studies comparing the effect of the combination treatment with that of rhGH alone ( 71 , 72 ). Set 5 is the retrospective Israeli study in prepubertal and pubertal children on the effect of a GnRHa in addition to long-term rhGH treatment ( 73 ).…”

“…The result was impressive (AH 156.3 ± 5.9 vs. 146.3 ± 5.0 cm, so 10 cm difference). The large RCT comparing the combination treatment with rhGH alone ( 72 ) was unfortunately aborted at the request of the French regulatory authorities (LoE 2). NAH was only reported on 35 of the included 91 children, which did not show a difference between treatment regimens.…”

Achieving Optimal Short- and Long-term Responses to Paediatric Growth Hormone Therapy

“…The combination of a GnRHa with GH was reported to result in a significant increase in adult height in patients with GH deficiency (91,92) and also in those with idiopathic short stature (86,93) and born SGA (94). However, the GnRHa treatment has negative effects on body composition and, while these effects are reversible after GnRHa cessation, the effects on bone mineral density are of concern and could increase fracture risk (93,95,96).…”