Use of Aromatase Inhibitors in Children and Adolescents With Disorders of Growth and Adolescent Development

Although treatment of children and adolescents who have disorders of growth and adolescent development with aromatase inhibitors is increasingly common, data for or against their use are extremely limited. Precocious puberty, short stature, and gynecomastia are conditions for which inhibition of the enzyme aromatase might prove beneficial to reduce clinical signs of estrogenization and/or estrogen-mediated skeletal maturation. In this report, we summarize the published data regarding the use of aromatase inhibitors in these conditions, and review known and potential benefits, safety concerns, and shortcomings of the available information.

[1]  T. Shawker,et al.  Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study. , 2007, The Journal of clinical endocrinology and metabolism.

[2]  W. Bonfig,et al.  Reduced final height outcome in congenital adrenal hyperplasia under prednisone treatment: deceleration of growth velocity during puberty. , 2007, The Journal of clinical endocrinology and metabolism.

[3]  M. Taskinen,et al.  Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition. , 2006, European Journal of Endocrinology.

[4]  Z. Hochberg,et al.  Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole. , 2006, The Journal of pediatrics.

[5]  P. Muti,et al.  Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. , 2006, Biochimica et biophysica acta.

[6]  L. Dunkel.  Use of aromatase inhibitors to increase final height , 2006, Molecular and Cellular Endocrinology.

[7]  L. Dunkel,et al.  Treatment with the aromatase inhibitor letrozole during adolescence increases near‐final height in boys with constitutional delay of puberty , 2006, Clinical endocrinology.

[8]  S. Lambard,et al.  Aromatase and estrogen receptors in male reproduction , 2006, Molecular and Cellular Endocrinology.

[9]  C. Adamsbaum,et al.  Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor. , 2006, European journal of endocrinology.

[10]  S. Yee,et al.  Potent CYP19 (aromatase) 1-[(benzofuran-2-yl)(phenylmethyl)pyridine, -imidazole, and -triazole inhibitors: synthesis and biological evaluation. , 2006, Journal of medicinal chemistry.

[11]  L. Dunkel,et al.  Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial. , 2005, The Journal of clinical endocrinology and metabolism.

[12]  E. Norjavaara,et al.  Testotoxicosis: current viewpoint. , 2005, Pediatric endocrinology reviews : PER.

[13]  C. Hasegawa,et al.  Structure–activity relationships of 2α-substituted androstenedione analogs as aromatase inhibitors and their aromatization reactions , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[14]  Silvia Gobbi,et al.  Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. , 2005, Journal of medicinal chemistry.

[15]  N. Mauras,et al.  Sperm analysis in growth hormone-deficient adolescents previously treated with an aromatase inhibitor: comparison with normal controls. , 2005, Fertility and sterility.

[16]  C. Kara,et al.  Sertoli Cell Tumor Causing Prepubertal Gynecomastia in a Boy with Peutz-Jeghers Syndrome: The Outcome of 1-Year Treatment with the Aromatase Inhibitor Testolactone , 2005, Hormone Research in Paediatrics.

[17]  P. Lønning,et al.  Endocrine effects of aromatase inhibitors and inactivators in vivo: Review of data and method limitations , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[18]  P. Lønning,et al.  Aromatase Inhibition: Translation into a Successful Therapeutic Approach , 2005, Clinical Cancer Research.

[19]  W. Moore,et al.  The Effect of Letrozole on Bone Age Progression, Predicted Adult Height, and Adrenal Gland Function , 2005, Journal of pediatric endocrinology & metabolism : JPEM.

[20]  M. Battaglia,et al.  Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  W. Sippell,et al.  Treatment of Pubertal Gynecomastia with the Specific Aromatase Inhibitor Anastrozole , 2004, Hormone Research in Paediatrics.

[22]  W. Moore,et al.  Use of aromatase inhibitors in children with short stature. , 2004, Pediatric endocrinology reviews : PER.

[23]  P. Backeljauw,et al.  Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial. , 2004, The Journal of clinical endocrinology and metabolism.

[24]  J. Wit,et al.  Benefit of postponing normal puberty for improving final height. , 2004, European journal of endocrinology.

[25]  Brenda J. Crowe,et al.  Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. , 2004, The Journal of clinical endocrinology and metabolism.

[26]  S. Bulun,et al.  Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. , 2004, The New England journal of medicine.

[27]  S. B. Nunez,et al.  Lack of efficacy of fadrozole in treating precocious puberty in girls with the McCune-Albright syndrome. , 2003, The Journal of clinical endocrinology and metabolism.

[28]  Yate-Ching Yuan,et al.  Structure–function studies of aromatase and its inhibitors: a progress report , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[29]  J. Yanovski,et al.  Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. , 2003, The New England journal of medicine.

[30]  W. Miller,et al.  The therapeutic potential of aromatase inhibitors , 2003, Expert opinion on investigational drugs.

[31]  L. Dunkel,et al.  A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled trial , 2001, The Lancet.

[32]  M. Arosio,et al.  Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up? , 2000, Journal of endocrinological investigation.

[33]  D. Merke,et al.  Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia. , 2000, The Journal of clinical endocrinology and metabolism.

[34]  M. Segni,et al.  Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone. , 2000, The Journal of clinical endocrinology and metabolism.

[35]  H. Sasano,et al.  Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. , 1999, Endocrine-Related Cancer.

[36]  E. Simpson.  Genetic mutations resulting in estrogen insufficiency in the male , 1998, Molecular and Cellular Endocrinology.

[37]  N. Mauras,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Testosterone Deficiency in Young Men: Marked Alterations in Whole Body Protein Kinetics, Strength, and Adiposity* , 2022 .

[38]  G. Chrousos,et al.  The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. , 1998, The Journal of clinical endocrinology and metabolism.

[39]  I. Silva,et al.  Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia , 1997, Archives of disease in childhood.

[40]  E. Simpson,et al.  Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. , 1995, The Journal of clinical endocrinology and metabolism.

[41]  J. Baron,et al.  Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. , 1994, The Journal of clinical investigation.

[42]  K. Korach,et al.  Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. , 1994, The New England journal of medicine.

[43]  G. Cutler,et al.  Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome. , 1993, The Journal of clinical endocrinology and metabolism.

[44]  M. Dowsett,et al.  Aromatase inhibitors and hormone-dependent cancers , 1990, The Journal of Steroid Biochemistry and Molecular Biology.

[45]  O. Pescovitz,et al.  Treatment of familial male precocious puberty with spironolactone and testolactone. , 1989, The New England journal of medicine.

[46]  P. Neumann,et al.  Behandlung der ausgeprägten Pubertätsgynäkomastie mit Tamoxifen , 1987 .

[47]  U. Eiholzer,et al.  Treatment of pubertal gynaecomastia with testolactone. , 1986, Acta endocrinologica. Supplementum.

[48]  J. Malley,et al.  Treatment of precocious puberty in the McCune-Albright syndrome with the aromatase inhibitor testolactone. , 1986, The New England journal of medicine.

[49]  J. Sparrow,et al.  Treatment of persistent pubertal gynecomastia with dihydrotestosterone heptanoate. , 1986, The Journal of pediatrics.

[50]  H. Kulin,et al.  Clomiphene in the treatment of adolescent gynecomastia. Clinical and endocrine studies. , 1983, American journal of diseases of children.

[51]  P. Stubbe,et al.  Endocrinological studies of the hypothalamo-pituitary gonadal axis during danazol treatment in pubertal boys with marked gynecomastia. , 1982, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[52]  A. Marks.  Management of the suicidal adolescent on a nonpsychiatric adolescent unit. , 1979, The Journal of pediatrics.

[53]  S. Hajdu,et al.  Gynecomastia: clinicopathologic study of 351 cases. , 1972, American journal of clinical pathology.

[54]  J. Gabrilove,et al.  A study of the histopathology of human gynecomastia. , 1971, The Journal of clinical endocrinology and metabolism.

[55]  P. Satoh,et al.  Aminoglutethimide (Elipten-Ciba) as an inhibitor of adrenal steroidogenesis: mechanism of action and therapeutic trial. , 1967, The Journal of clinical endocrinology and metabolism.

[56]  R. W. Rawson,et al.  Gynecomastia in adolescent boys. , 1961, JAMA.

[57]  N. Mauras,et al.  An Open Label 12-Month Pilot Trial on the Effects of the Aromatase Inhibitor Anastrozole in Growth Hormone (GH)-Treated GH Deficient Adolescent Boys , 2004, Journal of pediatric endocrinology & metabolism : JPEM.

[58]  Ole Eckhardt Poulsen,et al.  [Drug information]. , 2004, Ugeskrift for laeger.

[59]  N. Albers,et al.  McCune-Albright syndrome--the German experience. , 2002, Journal of pediatric endocrinology & metabolism : JPEM.

[60]  N. Albers,et al.  Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. , 2002, Journal of pediatric endocrinology & metabolism : JPEM.

[61]  L. Dimeglio,et al.  Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. , 2001, Jornal de Pediatria.

[62]  G. Cutler,et al.  Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset. , 1999, The Journal of clinical endocrinology and metabolism.

[63]  E. Krenning,et al.  Bone mineral density and body composition before and during treatment with gonadotropin-releasing hormone agonist in children with central precocious and early puberty. , 1998, The Journal of clinical endocrinology and metabolism.

[64]  G. Cutler,et al.  Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. , 1993, The Journal of clinical endocrinology and metabolism.

[65]  P. Leaverton,et al.  Secondary sex characteristics of boys 12 to 17 years of age: the U.S. Health Examination Survey. , 1979, The Journal of pediatrics.

[66]  E. A. Thompson,et al.  The involvement of human placental microsomal cytochrome P-450 in aromatization. , 1974, The Journal of biological chemistry.

[67]  M. Williams,et al.  Gynecomastia. Its incidence, recognition and host characterization in 447 autopsy cases. , 1963, The American journal of medicine.