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Long-acting gonadotropin-releasing hormone agonists for treatment of central (gonadotropin-dependent) precocious puberty

Long-acting gonadotropin-releasing hormone agonists for treatment of central (gonadotropin-dependent) precocious puberty
GnRH agonist Trade names and availability Dose, frequency, and method of administration
Histrelin acetate subcutaneous implant Supprelin LA (US) Subcutaneous implant. Children ≥2 years – 50 mg implant surgically inserted every 12 months. Releases approximately 65 mcg per day over 12 months.
Leuprolide acetate (leuprorelin) 1-month formulations:
  • Lupron Depot-Ped (1 month) (US)
  • Lupron Depot (1 month SR) (CAN)
  • Lucrin, Lutrate, Lorelin Depot, others (EU, UK, elsewhere)

Intramuscular depot injection, given every 28 days.

Available strengths:
  • 3.75*, 7.5, 11.25, or 15 mg

Typical starting dose is 7.5 mg but may vary among countries.
3-month formulations:
  • Lupron Depot-Ped (3 month)
  • Lucrin Depot Paediatric (3 month) (AU)

Intramuscular depot injection, given every 3 months.

Available strengths:
  • 11.25 or 30 mg

Criteria for selection of the 11.25 mg versus 30 mg dose have not been established.
6-month formulations:
  • Fensolvi (US)
  • Lupron Depot-Ped (6 month) (US)

Subcutaneous injection (Fensolvi) or intramuscular depot injection (Lupron Depot-Ped).

Available strength:
  • 45 mg
Triptorelin pamoate

Gonapeptyl (UK, EU, SA, elsewhere)

Decapeptyl (UK, elsewhere)

Triptodur (US)

Intramuscular depot injections

Available strengths:
  • 3.75 mg every 28 days
  • 11.25 mg every 3 months
  • 22.5 mg every 6 months
Approval of these GnRH agonists for use in central precocious puberty, dosing, and schedules of administration vary between products in different countries. Consult local product information. Short-acting GnRH preparations requiring daily subcutaneous injections or multiple daily dosing nasal spray (such as nafarelin) are not recommended, due to compliance difficulty; use of these products usually is limited to patients with sterile abscesses from depot injections. Note that the doses used to treat central precocious puberty in children are substantially higher than those used in adults for other indications, such as prostate cancer and endometriosis.

GnRH: gonadotropin-releasing hormone; US: United States; SR: sustained-release; CAN: Canada; EU: European Union; UK: United Kingdom; AU: Australia; SA: South America.

* Strength not approved for treatment of central precocious puberty in the United States but may be approved elsewhere.

¶ In the United States, Canada, and some other countries, prescribing information includes higher starting doses for children weighing >25 kg, but some experts recommend against weight-based dosing[1].
Reference:
  1. Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr 2019; 91:357.
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