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, 3^rd 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 mo for 12-36 mo while on treatment with letrozole 1.5 - 2.0 mg /M²/d.

Setting: An open-label therapeutic trial at a single clinical center.

Patients: Nine girls age 3 - 8 yr with MAS and/or gonadotropin-independent puberty.

Main outcome measures: Rates of linear growth, bone age (BA) advance (BA/CA), mean ovarian volume (MOV), E, episodes of vaginal bleeding, and levels of the indices of bone metabolism: serum osteocalcin (OC) and alkaline phosphatase (AP), urinary hydroxyproline (OHP), pyridinoline (PYR), deoxypyridinoline (dPYR) and N telopeptides (NTP).

Results: Girls had decreased rates of growth (P 0.01) and bone age advance (BA/CA, P 0.004), and cessation or slowing in their rates of bleeding over 12 - 36 mo of therapy. MOV, E and indices of bone metabolism fell after 6 mo (P 0.05), but tended to rise by 24 - 36 mo. 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. (Clinicaltrials.gov number, NCT00006174)