This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nunez, S. B. Articles by Feuillan, P. P. Search for Related Content PubMed PubMed Citation Articles by Nunez, S. B. Articles by Feuillan, P. P.

Lack of Efficacy of Fadrozole in Treating Precocious Puberty in Girls with the McCune-Albright Syndrome

Developmental Endocrinology Branch (P.P.F.), National Institutes of Child Health and Human Development, and Warren G. Maguson Clinical Center (K.C., J.J.), National Institutes of Health, Bethesda, Maryland 20892; Children’s National Medical Center (S.B.N.), Washington, D.C. 20010; and Lilly Research Laboratories (G.B.C.), Eli Lilly and Company, Indianapolis, Indiana 46285

Address all correspondence and requests for reprints to: Penelope P. Feuillan, M.D., Developmental Endocrinology Branch, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive, 9000 Rockville Pike, Bethesda, Maryland 20892. E-mail: pfeuill{at}helix.nih.gov.

We administered the aromatase inhibitor fadrozole to 16 girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome. The girls’ ages ranged from 3.2–9.7 yr, and their bone ages ranged from 5.75–14.25 yr. After baseline evaluations, fadrozole was started at a dose of 240 µg/kg·d (equivalent to the dose recommended for therapy of estrogen-dependent breast cancer) for 12–21 months and increased to 480 µg/kg·d for an additional 12 months in 10 girls. During treatment, seven girls had evidence of central precocious puberty; hence, the GnRH agonist deslorelin (4 µg/kg·d sc) was added to their regimen. One girl was on a long-acting GnRH agonist from the start of treatment. Patients were evaluated at 2–6-month intervals throughout treatment. After the first 6–12 months of treatment, fadrozole showed some benefits in 10 girls, including decrease in frequency of menses and/or rates of linear growth and bone maturation; however, fadrozole had no significant benefit in the group as a whole. The seven girls with evidence of central precocious puberty had no slowing in the progression of their puberty during the combined fadrozole and GnRH analog treatment. Adverse effects of fadrozole included inhibition of cortisol and aldosterone biosynthesis at the dose of 480 µg/kg·d, without clinical evidence of adrenal insufficiency. In addition, three patients complained of nonspecific abdominal pain during fadrozole treatment. In one patient, this resolved with a reduction in dose from 480 to 240 µg/kg·d; in two patients, it resolved spontaneously. One girl had muscle weakness and constipation on the 480 µg/kg·d. This resolved after discontinuation of the drug. We conclude that fadrozole is not sufficiently potent to block estrogen synthesis in most girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome and may impair the adrenocortical stress response.

Abbreviations: A, Androstenedione; BA, bone age; CA, chronological age; E1, estrone; E2, estradiol; MAS, McCune-Albright syndrome; MOV, mean ovarian volume; T, testosterone.

This article has been cited by other articles:

				J. Mieszczak, E. S. Lowe, P. Plourde, and E. A. Eugster The Aromatase Inhibitor Anastrozole Is Ineffective in the Treatment of Precocious Puberty in Girls with McCune-Albright Syndrome J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2751 - 2754. [Abstract] [Full Text] [PDF]

				D. I. Shulman, G. L. Francis, M. R. Palmert, E. A. Eugster, and for the Lawson Wilkins Pediatric Endocrine Society Use of Aromatase Inhibitors in Children and Adolescents With Disorders of Growth and Adolescent Development Pediatrics, April 1, 2008; 121(4): e975 - e983. [Abstract] [Full Text] [PDF]

				P. Feuillan, K. Calis, S. Hill, T. Shawker, P. G. Robey, and M. T. Collins Letrozole Treatment of Precocious Puberty in Girls with the McCune-Albright Syndrome: A Pilot Study J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2100 - 2106. [Abstract] [Full Text] [PDF]