Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity.

OBJECTIVE The objective of the study was to determine whether height gain after discontinuation of gonadotropin-suppressive (GnRHa) therapy differs in girls with sexual precocity diagnosed at various ages and assess its influence on final height (FHt) outcome. DESIGN We compared data on post-GnRHa treatment course and FHt of 115 girls [22 diagnosed before chronological age of 6 yr; 38 between ages 6 and 8 yr; and 55 early fast puberty (EFP) between ages 8 and 9 yr] treated with GnRHa from Tanner stage 2-3 to chronological age 11-12 yr and bone age 12-12.5 yr. RESULTS Despite comparable bone age at cessation of treatment, similar time to resumption of puberty (0.6 +/- 0.7, 0.5 +/- 0.7, and 0.5 +/- 0.7 yr), and age at menarche (12.6 +/- 0.5, 12.6 +/- 0.6, and 12.7 +/- 0.9 yr), height gain from cessation of therapy to FHt was greater and time to epiphyseal fusion was longer in the younger central precocious puberty (CPP) than in the older CPP (P < 0.05) and EFP (P < 0.001) groups. The percentage of residual growth predicted at discontinuation of treatment was achieved only by the younger CPP (6.6 +/- 1.6% vs. 6.7 +/- 1.6%), whereas in older CPP and EFP, it was significantly lower (6.2 +/- 1.6% vs. 4.6 +/- 2.7% and 6.3 +/- 1.5% vs. 3.6 +/- 1.5%, respectively). FHt of these two groups was compromised, compared with FHt predicted at discontinuation of treatment (P < 0.01 and P < 0.001, respectively). CONCLUSIONS Girls with sexual precocity diagnosed after the age of 6 yr exhibit earlier epiphyseal fusion with diminished posttreatment height gain and compromised FHt. Because recovery of gonadal axis was similar in all girls, differences were probably due to pretreatment intrinsic changes in the growth plate. Prediction of residual growth at discontinuation of treatment is unreliable in these girls.

[1]  L. Sävendahl.  Hormonal Regulation of Growth Plate Cartilage , 2005, Hormone Research in Paediatrics.

[2]  D. Chrysis,et al.  Localization of estrogen receptors-alpha and -beta and androgen receptor in the human growth plate at different pubertal stages. , 2003, The Journal of endocrinology.

[3]  M. Phillip,et al.  Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height. , 2002, The Journal of clinical endocrinology and metabolism.

[4]  J. Yanovski,et al.  The relation between skeletal maturation and adiposity in African American and Caucasian children. , 2001, The Journal of pediatrics.

[5]  K. Klein,et al.  Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. , 2001, The Journal of clinical endocrinology and metabolism.

[6]  W. Crowley,et al.  The longitudinal study of adrenal maturation during gonadal suppression: evidence that adrenarche is a gradual process. , 2001, The Journal of clinical endocrinology and metabolism.

[7]  J. Baron,et al.  Effects of estrogen on growth plate senescence and epiphyseal fusion , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A F Roche,et al.  CDC growth charts: United States. , 2000, Advance data.

[9]  J. Bertherat,et al.  Pathogenesis of adrenocortical incidentalomas and genetic syndromes associated with adrenocortical neoplasms. , 2000, Endocrinology and metabolism clinics of North America.

[10]  W. Crowley,et al.  Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[11]  D. McDonnell,et al.  The Estrogen Receptor ␤-isoform (er␤) of the Human Estrogen Receptor Modulates Er␣ Transcriptional Activity and Is a Key Regulator of the Cellular Response to Estrogens and Antiestrogens* , 2022 .

[12]  P. Kaplowitz,et al.  Reexamination of the Age Limit for Defining When Puberty Is Precocious in Girls in the United States: Implications for Evaluation and Treatment , 1999, Pediatrics.

[13]  A. Balsamo,et al.  Randomised trial of LHRH analogue treatment on final height in girls with onset of puberty aged 7.5–8.5 years , 1999, Archives of disease in childhood.

[14]  J. Coste,et al.  Lack of effect of GnRH agonists on final height in girls with advanced puberty: a randomized long-term pilot study. , 1999, The Journal of clinical endocrinology and metabolism.

[15]  J. Carel,et al.  Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[16]  W. Greulich,et al.  Radiographic Atlas of Skeletal Development of the Hand and Wrist , 1999 .

[17]  R. Considine,et al.  Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children. , 1998, The Journal of clinical endocrinology and metabolism.

[18]  G. Cutler.  The role of estrogen in bone growth and maturation during childhood and adolescence , 1997, The Journal of Steroid Biochemistry and Molecular Biology.

[19]  R. Odink,et al.  Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. , 1996, Archives of disease in childhood.

[20]  F. Conte,et al.  Long-term effect of gonadotropin-releasing hormone agonist therapy on final and near-final height in 26 children with true precocious puberty treated at a median age of less than 5 years. , 1995, The Journal of clinical endocrinology and metabolism.

[21]  G. Kletter,et al.  Clinical review 60: Effects of gonadotropin-releasing hormone analog therapy on adult stature in precocious puberty. , 1994, The Journal of clinical endocrinology and metabolism.

[22]  P. Hindmarsh,et al.  Standards for ovarian volume in childhood and puberty. , 1993, Fertility and sterility.

[23]  M. Wheeler,et al.  Physical changes of puberty. , 1991, Endocrinology and metabolism clinics of North America.

[24]  H. Meyer-Bahlburg,et al.  Idiopathic precocious puberty in girls: long-term effects on adolescent behavior. , 1986, Acta endocrinologica. Supplementum.

[25]  J M Tanner,et al.  Standards for Children's Height at Ages 2-9 Years Allowing for Height of Parents , 1970, Archives of disease in childhood.

[26]  J M Tanner,et al.  Variations in pattern of pubertal changes in girls. , 1969, Archives of disease in childhood.

[27]  N. Bayley,et al.  Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. , 1952, The Journal of pediatrics.

[28]  J. Baron,et al.  Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty. , 2004, The Journal of clinical endocrinology and metabolism.

[29]  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.

[30]  Z. Laron,et al.  Final height of girls with central precocious puberty, untreated versus treated with cyproterone acetate or GnRH analogue. A comparative study with re-evaluation of predictions by the Bayley-Pinneau method. , 1997, Hormone research.

[31]  Z. Laron,et al.  Pubertal development, growth and final height in girls with sexual precocity after therapy with the GnRH analogue D-TRP-6-LHRH. A report on 15 girls, followed after cessation of gonadotrophin suppressive therapy. , 1990, Hormone research.

[32]  W. Crowley,et al.  Adrenarche and skeletal maturation during luteinizing hormone releasing hormone analogue suppression of gonadarche. , 1986, The Journal of clinical investigation.

[33]  W. Dixon,et al.  BMDP statistical software , 1983 .