eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Precocious Puberty: Treatment & Medication
Updated: Jun 30, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Surgical Care
When central precocious puberty (CPP) is caused by a CNS tumor other than a hamartoma, a resection should be attempted to the extent possible without impinging on vital structures such as the optic nerves. Radiation therapy is often indicated if surgical resection is incomplete. Unfortunately, removal of the tumor rarely causes regression of precocious puberty.
Medication
Gonadotropin-releasing hormone analog
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 Resende et al has been published.14
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. Annual cost is approximately $10,000-15,000. 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. Recently, a study that examined the 3-mo formulation of Lupron-Depot 11.25 mg, which has not been approved for children, reported that the suppression of LH and FSH levels was nearly as good as Lupron-Depot 7.5 mg administered monthly and that the clinical effectiveness was equivalent (Badaru, 2006). This is obviously more convenient for the family, and further studies on this dosage form are needed.
Adult
Pediatric
Depot preparation initial dose: 300 mcg/kg/mo IM; standard kits available as 7.5 mg, 11.25 mg, or 15 mg vials; some children may require even higher doses to completely suppress gonadotropins and sex steroids
Subcutaneous preparation daily dose: 50 mcg/kg/d SC; dosage increases may be required; preparation available as 5 mg/mL (2.8 mL multidose vial)
None reported
Documented hypersensitivity; pernicious anemia; approximately 5% of individuals develop an immune response to the encapsulation material of depot preparation; discontinue depot preparation if sterile abscess forms at injection site and/or systemic symptoms develop, including fever and chills; daily SC preparation usually may be substituted without incident, or another daily preparation may be used
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor every 4-6 mo; linear growth rate should slow to reference range for age; initial stimulation of puberty may be seen in first several weeks of therapy, and estrogen withdrawal bleeding may be noted in girls with advanced puberty within 4-6 wk of treatment; demonstrating that the dose used fully suppresses rise in LH and FSH levels normally seen 20-40 min after injecting 100 mcg is suggested in treating girls; testing may not be needed for boys because decline in serum testosterone levels to <20 ng/dL and decrease in size of testes is adequate to assess effectiveness; monitor bone age at least yearly to document slowing of progression and to reassess adult height prediction, which is often subnormal at onset of treatment and improves with therapy
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).
Adult
Not indicated
Pediatric
Supprelin LA: 1 implant/12 mo; each implant contains 50 mg histrelin acetate (delivers about 65 mcg/d); SC insert implant at inner aspect of upper arm; provides continuous release of histrelin for 12 mo
Discontinue at appropriate time of puberty (approximately age 11 y for girls and age 12 y for boys)
None reported
Documented hypersensitivity to GnRH or GnRH agonist analogs; pregnancy
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor response by monitoring growth and breast development and measuring basal and GnRH-stimulated LH levels and estradiol by an ultrasensitive assay
Gonadotropin-releasing hormone (GnRH) agonist
These potent long-acting synthetic derivatives of native GnRH 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.
Nafarelin acetate (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.
Adult
Pediatric
1600 mcg/d intranasally divided as 2 sprays (400 mcg) in each nostril bid, may increase to 1800 mcg/d (3 sprays [600 mcg] into alternating nostrils tid [total of 9 sprays/d]) if necessary for suppression
None reported
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Do not administer within 2 h of a nasal decongestant; monitor every 4-9 mo; linear growth rate should slow to reference range for age; initial stimulation of puberty may be seen in first several weeks of therapy; estrogen withdrawal bleeding may be noted in girls with advanced puberty within the first 4-6 wk of treatment
Demonstrating that the dose used fully suppresses rise in LH and FSH levels normally seen 20-40 min after injecting GnRH is suggested in treating girls; testing may not be needed for boys because decline in serum testosterone level to <20 ng/dL and decrease in size of testes is adequate to assess effectiveness; monitor bone age at least yearly to document slowing of progression and to reassess adult height prediction, which is often subnormal at onset of treatment and improves with therapy
Progestin
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 acetate (Depo-Provera) 150 mg
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.
Adult
Pediatric
150 mg IM every 3 mo
Aminoglutethimide decreases bioavailability of medroxyprogesterone; may slightly decrease elimination of digitoxin or warfarin
Documented hypersensitivity; thrombophlebitis; cerebral apoplexy; liver dysfunction; undiagnosed vaginal bleeding
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
At higher doses, causes adverse cushingoid effects in some patients; experienced personnel should administer injections as sterile abscess formation has been reported with improper injection technique; other adverse effects are rare in children
More on Precocious Puberty |
| Overview: Precocious Puberty |
| Differential Diagnoses & Workup: Precocious Puberty |
 Treatment & Medication: Precocious Puberty |
| Follow-up: Precocious Puberty |
| Multimedia: Precocious Puberty |
| References |
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References
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Further Reading
Keywords
precocious puberty, early puberty, central precocious puberty, CPP, premature thelarche, premature pubarche, precocious pseudopuberty, hyperovarianism, early onset of puberty, sexual precocity, precocious puberty, idiopathic CPP, inappropriate sexual behaviors, increased masturbation, short stature, breast enlargement, clitoral enlargement, enlarged testes, congenital adrenal hyperplasia, familial male precocious puberty, Leydig-cell tumors, HCG-secreting tumors, premature adrenarche, increased body fat, astrocytomas, gliomas, germ cell tumors secreting human chorionic gonadotropin, germ cell tumors secreting HCG, hypothalamic hamartomas, hydrocephalus, arachnoid cysts, suprasellar cysts, treatment, diagnosis
