Precocious Pseudopuberty Medication

  • Author: Robert J Ferry Jr, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Mar 30, 2012
 

Medication Summary

The underlying pathophysiology of gonadotropin-independent precocious puberty is autonomous function of the gonadal axis; thus, the use of gonadotropin-releasing hormone (GnRH) analogs does not appear to be effective in the management of these disorders. No medications are routinely used in young children with a US Food and Drug Administration (FDA)-approved indication for the treatment of gonadotropin-independent precocious puberty. Therefore, a physician with expertise in the area should closely monitor the use of medications.

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Steroid synthesis inhibitors

Class Summary

Ketoconazole blocks enzymes in the steroid biosynthetic pathway. It primarily inhibits C-17,29-desmolase, the enzyme responsible for androstenedione biosynthesis.

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Ketoconazole (Nizoral)

 

More commonly used in treating fungal infections, but may be used in treating precocious pseudopuberty. It inhibits steroid synthesis at the level of 17 α -hydroxylase/17,20-lyase, a key enzyme in sex steroid production. It also inhibits testosterone binding to its binding globulin. In some cases, especially in those children with markedly advanced bone age, a rapid decrease in sex hormone levels may trigger true central puberty. In this event, add GnRH analogs to the treatment regimen.

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Antiandrogens

Class Summary

These drugs block the effect of testosterone and dihydrotestosterone at the androgen receptor.

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Spironolactone (Aldactone)

 

Mainly used as an antimineralocorticoid diuretic. It is also a weak competitive androgen antagonist. Other properties include inhibition of 17 α -hydroyxlase/17,20-lyase and interference with testosterone binding to sex hormone binding globulin. It is typically used to treat precocious pseudopuberty in conjunction with another drug (eg, an aromatase inhibitor). Specific nonsteroidal androgen antagonists (eg, flutamide) are more effective; however, they also carry greater toxicity. Therefore, the latter class of drug is used only in children in the context of clinical trials in the United States. As noted above, adjunctive use of GnRH analogs may be required if true central puberty occurs as a complication of treatment.

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Aromatase inhibitors

Class Summary

This category of drugs is usually used in conjunction with an antiandrogen. Aromatase inhibitors prevent the conversion of androstenedione to estrone and testosterone to estrogen. Because estrogens play a major role in epiphyseal maturation (besides their obvious role in generating female secondary sexual effects), inhibiting estrogen production has salutary effects on slowing the progress of precocious pseudopuberty.

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Testolactone (Teslac)

 

First-generation aromatase inhibitor used to prevent conversion of androstenedione to estrone and testosterone to estrogen in children. Newer preparations are now available, but no new agents have had published clinical trials. As noted above, adjunctive use of GnRH analogs may be required if true central puberty occurs as a complication of treatment.

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Antiestrogens

Class Summary

Estrogen receptor blockade (eg, with tamoxifen) may be an alternative to aromatase inhibitors and progestins in the treatment of MAS in girls. The predominant problem in childhood is precocious pseudopuberty associated with excess estrogen secretion from ovarian cysts.

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Tamoxifen (Nolvadex)

 

Competitively binds to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. This drug is currently being tested in clinical trials. A single case report suggested a dose of 10-30 mg PO daily is effective in controlling estrogenic affects in MAS.

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Contributor Information and Disclosures
Author

Robert J Ferry Jr, MD  Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Coauthor(s)

Cydney L Fenton, MD  Director, Center for Diabetes and Endocrinology, Akron Children's Hospital

Cydney L Fenton, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD  Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting fee Consulting

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

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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.
 
 
 
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