Letrozole Treatment of Precocious Puberty in Girls with the McCune-Albright Syndrome: A Pilot Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 6; pp. 2100 - 2106
• Main Authors: Feuillan, Penelope, Calis, Karim, Hill, Suvimol, Shawker, Thomas, Robey, Pamela Gehron, Collins, Michael T.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.06.2007; Endocrine Society
• Subjects: 17β-Estradiol; Alkaline phosphatase; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - blood; Aromatase; Biological and medical sciences; Biomarkers - blood; Biomarkers - urine; Bleeding; Bone and Bones - metabolism; Bone dysplasia; Bone growth; Bone turnover; Child; Child, Preschool; Cysts; Deoxypyridinoline; Estrogens; Feeding. Feeding behavior; Female; Fibrous dysplasia; Fibrous Dysplasia, Polyostotic - complications; Fibrous Dysplasia, Polyostotic - metabolism; Fundamental and applied biological sciences. Psychology; Girls; Gonadotropin-releasing hormone; Gonadotropins; Growth - drug effects; Humans; Hydroxyproline; Male; McCune-Albright syndrome; Menstruation - drug effects; Metabolism; Nitriles - administration & dosage; Nitriles - adverse effects; Nitriles - blood; Osteocalcin; Ovarian Cysts - drug therapy; Ovarian Cysts - etiology; Ovaries; Patients; Pilot Projects; Pituitary (anterior); Puberty; Puberty - drug effects; Puberty, Precocious - drug therapy; Puberty, Precocious - etiology; Puberty, Precocious - metabolism; Pyridinoline; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Human; Antineoplastic agent; Nutrition; Enzyme; Antiestrogen; Diseases of the osteoarticular system; Enzyme inhibitor; Metabolic diseases; Antihormone; Estrogen synthase; Genetic disease; Precocious puberty; Treatment; Pseudohypoparathyroidism; Triazole derivatives; Albright disease; Female; Non steroid compound; Osteochondrodysplasia; Child; Endocrinology; Letrozole
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-2350

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/m2·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 ≤ 0.01) and bone age advance (P ≤ 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 ≤ 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.