Gonadotropin-Releasing Hormone Agonists

Class Summary

Continuous administration of GnRH agonists suppresses pituitary production of gonadotropins because they provide constant stimulus, whereas the pituitary responds only to pulsatile GnRH stimulation. In use since the late 1970s, GnRH agonists are safe and effective, resulting in decreased levels of LH, FSH, and sex steroids within 4 weeks after initiation of treatment. An excellent review and consensus statement on the use of GnRH analogues in children by Carel et al was been published in 2009,^[23] and an update to the consensus statement was published in 2019.^[49]In the past, the 1-month formulation of leuprolide, called Lupron Depot, was the mainstay of therapy. In 2011, 3-month formulations of Lupron Depot, 11.25 mg and 30 mg, were approved for children with precocious puberty. A study comparing the 1-month 7.5-mg leuprolide with the 11.25-mg 3-month leuprolide found that both preparations resulted in prompt and effective suppression of puberty, but LH and FSH levels were slightly higher with the 3-month dosing, which has the advantage of being more convenient for the family.^[50]

Triptorelin (Triptodur, Trelstar, Trelstar Depot)

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Indicated for central precocious puberty (CPP) in pediatric patients aged 2 years or older; works by the same mechanism as leuprolide. In 2017, the US Food and Drug Administration (FDA) approved a formulation of Triptodur 22.5 mg for CPP that needs to be administered only every 6 months.

Histrelin (Supprelin LA, Vantas)

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Histrelin is a potent inhibitor of gonadotropin secretion when administered long-term. The implant provides continuous SC release of histrelin at a nominal rate of 50-65 mcg/d over 12 months and is safe and effective for CPP. One study found that the implant remains effective in suppressing puberty for at least 2 years. The main disadvantage is the need to have visits with a surgeon to place and remove the implant, usually with light sedation, which increases the already high cost of about $40,000 per implant.

Leuprolide (Lupron Depot 3 Month, Eligard, Fensolvi)

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Available in a monthly depot formulation in 7.5-, 11.25-, and 15-mg doses and for the every 3-month formulation, in 11.25- and 30-mg doses. Annual cost is approximately $20,000-40,000. Individualize duration of therapy according to age and maturity of child and predicted adult height; in most cases, continuing treatment after age 10 years is unnecessary.

Class Summary

Before the availability of GnRH agonists, these agents were the mainstay of therapy. Progestins work by providing feedback suppression of pituitary gonadotropin secretion. They lack significant androgenic or estrogenic activity.

Medroxyprogesterone (Depo-Provera)

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Inhibits secretion of pituitary gonadotropin. Inhibits effect of LH. Effective at slowing breast growth and preventing or stopping menses when administered q3mo, although breakthrough bleeding may occur. Less used now due to relative ineffectiveness in reversing rapid advancement of skeletal maturation seen in CPP. Relatively inexpensive; consider when leuprolide cost is a factor and when adult height prediction is close to reference range or is not a major concern.

Questions

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Media Gallery

Graph represents the prevalence of breast development at Tanner stage 2 or greater by age and race.
Graph represents the prevalence of pubic hair at Tanner stage 2 or greater by age and race.