Gonadotropin-releasing hormone (
GnRH) analog
therapy relies primarily on the ability of these compounds to bind to and modulate
GnRH-receptor activity.
GnRH analogs have been used in pediatric patients where endogenous
gonadotropin release is undesirable or potentially harmful, such as in: (i) patients with
central precocious puberty (
CPP); (ii) healthy short children where pubertal delay would provide an opportunity to supplement pre-pubertal linear growth; and (iii) children with
malignancies and other disorders where treatment requires the use of gonadotoxic compounds. In the first two groups of patients,
GnRH agonists may be used alone or in conjunction with
somatropin (
growth hormone [GH]) to prevent early skeletal maturation and increase the subsequent adult height, while in the latter case,
GnRH agonists are used alone or in conjunction with
GnRH antagonists in an attempt to preserve gonadal function.In children and adolescents with
CPP, timely use of
GnRH agonists alone can result in an adult height within the genetic potential of the individual (target height); however, minimal height is gained when
GnRH agonist
therapy is commenced after a marked advancement of skeletal age. This provides the rationale for combined
therapy with
GnRH agonists and
somatropin in such patients, and studies have shown improved growth with this approach compared with
GnRH agonists alone. Combination
therapy with
GnRH agonists and
somatropin has also been shown to increase adult heights to a greater extent than
GnRH agonists alone in pediatric patients with concomitant
CPP and GH deficiency, those with idiopathic short stature, and those born small for gestational age; however, such combination
therapy has shown no increased benefit over
somatropin alone in pediatric patients with GH deficiency. Limited results in children and adolescents with
congenital adrenal hyperplasia and chronic
primary hypothyroidism have also shown increased growth rates, while no growth benefit was seen in pediatric renal transplant recipients.
GnRH analogs also have potential as gonadoprotective agents; studies of
GnRH agonists used alone and in combination with
GnRH antagonists in women undergoing cytotoxic
therapy have shown increased preservation of reproductive potential in patients who were receiving
GnRH analog
therapy versus those who were not.The adverse effects of
GnRH analogs mainly consist of menopausal-like complaints. Increases in bodyweight and body mass index in children receiving
GnRH agonist
therapy have been shown; however, these increases do not persist after discontinuation of
therapy. Adult bone mineral density and fertility are also not adversely affected by childhood
GnRH agonist
therapy.
GnRH analog
therapy appears to be both well tolerated and effective in pediatric patients, as it allows the preservation or improvement of adult height, and shows no longstanding negative effects on body composition, bone density, reproductive function, or endocrine physiology. These agents may also be useful for preservation of gonadal function in children and adolescents undergoing cytotoxic
therapy.