Precocious Puberty Medication

Updated: Jul 06, 2017
  • Author: Paul B Kaplowitz, MD, PhD; Chief Editor: Robert P Hoffman, MD  more...
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Medication

Gonadotropin-Releasing Hormone Agonists

Class Summary

Continuous administration of LHRH and GnRH agonists provides negative feedback and results in decreased levels of LH and FSH 2-4 wk after initiating treatment. An excellent review and consensus statement on the use of GnRH analogues in children by Carel J-C et al has been published. [27] 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, [32] which has the advantage of being more convenient for the family.

Potent, long-acting synthetic derivatives of native GnRH, such as natrelin, suppress 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.

Leuprolide acetate (Lupron, Lupron Depot-Ped, Lupron Depot 3 month)

Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels. Available in a monthly depot formulation in 7.5-, 11.25-, and 15-mg dose. Annual cost is approximately $10,000-20,000. Individualize duration of therapy according to age and maturity of child and predicted adult height; in most cases, continuing treatment after age 10-11 y is unnecessary.

Triptorelin (Triptodur, Trelstar, Trelstar Depot)

Indicated for central precocious puberty in pediatric patients aged 2 years or older. Triptorelin suppresses gonadotropin secretion via GnRH receptor desensitization and down-regulation. This reduces gonadal steroids to prepubertal levels.

Nafarelin (Synarel)

Analogue of GnRH that is approximately 200 times more potent than natural endogenous GnRH. Upon long-term administration, suppresses gonadotrope responsiveness to endogenous GnRH, thereby reducing secretion of LH and FSH, which in turn reduces ovarian and testicular steroid production. Administered intranasally to induce gonadotropin suppression. Consider as second-line agent if leuprolide proves difficult to administer. Adherence to a bid intranasal drug regimen may be difficult to achieve. Available as nasal spray; 200 mcg/spray. One 10 mL bottle contains 7-day supply for daily dose of 1600 mcg.

Histrelin (Supprelin LA)

LHRH agonist that is a potent inhibitor of gonadotropin secretion when administered long term. Desensitizes responsiveness of pituitary gonadotropin. Circulating LH and FSH levels initially increase following administration, leading to transient increase in concentration of gonadal steroids (testosterone and dihydrotestosterone in males and estrone and estradiol in premenopausal females). However, long-term administration decreases LH and FSH levels. Implant can provide continuous SC release of histrelin at nominal rate of 50-65 mcg/d over 12 mo. Indicated for CPP (neurogenic or idiopathic).

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Progestin

Class Summary

Before 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)

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.

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