Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study.

Abstract

CONTEXT:

Girls with McCune-Albright syndrome (MAS) and related disorders have gonadotropin-independent precocious puberty due to estrogen secretion from ovarian cysts. Their puberty does not respond to GnRH agonist therapy, and short-acting aromatase inhibitors have had limited effectiveness.

OBJECTIVE:

Our objective was to assess the effectiveness of the potent, third-generation aromatase inhibitor letrozole in decreasing pubertal progression in girls with MAS and to assess the response of indices of bone turnover associated with the patients' polyostotic fibrous dysplasia.

DESIGN:

Subjects were evaluated at baseline and every 6 months for 12-36 months while on treatment with letrozole 1.5-2.0 mg/m(2).d.

SETTING:

This was an open-label therapeutic trial at a single clinical center.

PATIENTS:

Patients included nine girls aged 3-8 yr with MAS and/or gonadotropin-independent puberty.

MAIN OUTCOME MEASURES:

Measures included rates of linear growth, bone age advance, mean ovarian volume, estradiol, episodes of vaginal bleeding, and levels of the indices of bone metabolism: serum osteocalcin, alkaline phosphatase, urinary hydroxyproline, pyridinoline, deoxypyridinoline, and N-telopeptides.

RESULTS:

Girls had decreased rates of growth (P < or = 0.01) and bone age advance (P < or = 0.004) and cessation or slowing in their rates of bleeding over 12-36 months of therapy. Mean ovarian volume, estradiol, and indices of bone metabolism fell after 6 months (P < or = 0.05) but tended to rise by 24-36 months. Uterine volumes did not change. One girl had a ruptured ovarian cyst after 2 yr of treatment.

CONCLUSIONS:

This preliminary study suggests that letrozole may be effective therapy in some girls with MAS and/or gonadotropin-independent precocious puberty. Possible adverse effects include ovarian enlargement and cyst formation.

• Authors: Penelope Feuillan, Karim Calis, Suvimol Hill, Thomas Shawker, Pamela Gehron Robey, Michael T Collins
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 6 Pg. 2100-6 (Jun 2007) ISSN: 0021-972X [Print] United States
• PMID: 17405850 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Nitriles
• Triazoles
• Letrozole

Topics

• Antineoplastic Agents (administration & dosage, adverse effects, blood)
• Biomarkers (blood, urine)
• Bone and Bones (metabolism)
• Child
• Child, Preschool
• Female
• Fibrous Dysplasia, Polyostotic (complications, metabolism)
• Growth (drug effects)
• Humans
• Letrozole
• Male
• Menstruation (drug effects)
• Nitriles (administration & dosage, adverse effects, blood)
• Ovarian Cysts (drug therapy, etiology)
• Pilot Projects
• Puberty (drug effects)
• Puberty, Precocious (drug therapy, etiology, metabolism)
• Triazoles (administration & dosage, adverse effects, blood)