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


METHODS
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.


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


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


METHODS
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.
Feuillan
Penelope
P
National Institutes of Health, Bethesda, MD 20892, USA. feuillap@mail.nih.gov
Calis
Karim
K
Hill
Suvimol
S
Shawker
Thomas
T
Robey
Pamela Gehron
PG
Collins
Michael T
MT
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications* / Q000378:metabolism; D006128:Growth / Q000187:drug effects; D006801:Humans; D000077289:Letrozole; D008297:Male; D008598:Menstruation / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D010048:Ovarian Cysts / Q000188:drug therapy / Q000209:etiology; D010865:Pilot Projects; D011627:Puberty / Q000187:drug effects; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
D000970:Antineoplastic Agents; D015415:Biomarkers; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole