Abstract
Background:
Reduction of adult height by sex steroid treatment was introduced decades ago in tall statured children, but controlled trials are lacking and treatment is controversial. In this study, we wanted to evaluate the phenotypic characteristics in girls referred due to tall stature and the effect of oral administration of 17β-estradiol on predicted adult height in girls.
Methods:
A single-centre retrospective observational study of 304 girls evaluated consecutively due to tall stature between 1993 and 2013. 207 patients diagnosed with constitutionally tall stature (CTS), 60 (29%) girls ended up being treated with 17β-estradiol with a duration of 1.7 y (1.2; 2.5) (median (25; 75 percentile)), and final height was available in 26 girls.
Results:
At baseline, 20% of girls with CTS had supranormal IGF-I, whereas reproductive hormones were within the normal range. Final adult height was reduced with 1.6 ± 2.1 cm in the girls treated with 17β-estradiol when compared to initial prediction. Chronological age, bone age, estradiol, and IGF-I at baseline or estrogen dose did not predict height reduction.
Conclusions:
Serum IGF-I was elevated tall statured children, but did not predict the effect of treatment with 17β-estradiol, which caused a modest reduction in final adult height.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Drop SL, De Waal WJ, De Muinck Keizer-Schrama SM. Sex steroid treatment of constitutionally tall stature. Endocr Rev 1998;19:540–58.
Binder G, Grauer ML, Wehner AV, Wehner F, Ranke MB. Outcome in tall stature. Final height and psychological aspects in 220 patients with and without treatment. Eur J Pediatr 1997;156:905–10.
Thodberg HH, Jenni OG, Caflisch J, Ranke MB, Martin DD. Prediction of adult height based on automated determination of bone age. J Clin Endocrinol Metab 2009;94:4868–74.
Rayner JA, Pyett P, Astbury J. The medicalisation of ‘tall’ girls: A discourse analysis of medical literature on the use of synthetic oestrogen to reduce female height. Soc Sci Med 2010;71:1076–83.
Coste J, Pouchot J, Carel JC. Height and health-related quality of life: a nationwide population study. J Clin Endocrinol Metab 2012;97:3231–9.
Grüters A, Heidemann P, Schlüter H, Stubbe P, Weber B, Helge H. Effect of different oestrogen doses on final height reduction in girls with constitutional tall stature. Eur J Pediatr 1989;149:11–3.
Bartsch O, Weschke B, Weber B. Oestrogen treatment of constitutionally tall girls with 0.1 mg/day ethinyl oestradiol. Eur J Pediatr 1988;147:59–63.
Joss EE, Zeuner J, Zurbrügg RP, Mullis PE. Impact of different doses of ethinyl oestradiol on reduction of final height in constitutionally tall girls. Eur J Pediatr 1994;153:797–801.
Werder EA, Waibel P, Sege D, Flury R. Severe thrombosis during oestrogen treatment for tall stature. Eur J Pediatr 1990;149:389–90.
Rask O, Nilsson KO, Berntorp E. Oestrogen treatment of constitutional tall stature in girls: is there a risk of thrombosis or bleeding? Acta Paediatr 2008;97:342–7.
Venn A, Bruinsma F, Werther G, et al. Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility. Lancet 2004;364:1513–8.
Hendriks AE, Drop SL, Laven JS, Boot AM. Fertility of tall girls treated with high-dose estrogen, a dose-response relationship. J Clin Endocrinol Metab 2012;97:3107–14.
Benyi E, Kieler H, Linder M, et al. Risks of malignant and non-malignant tumours in tall women treated with high-dose oestrogen during adolescence. Horm Res Paediatr 2014;82:89–96.
Benyi E, Berner M, Bjernekull I, et al. Efficacy and Safety of Percutaneous Epiphysiodesis Operation around the Knee to Reduce Adult Height in Extremely Tall Adolescent Girls and Boys. Int J Pediatr Endocrinol 2010;2010:740629.
Radivojevic U, Thibaud E, Samara-Boustani D, Duflos C, Polak M. Effects of growth reduction therapy using high-dose 17beta-estradiol in 26 constitutionally tall girls. Clin Endocrinol (Oxf) 2006;64:423–8.
de Waal WJ, Greyn-Fokker MH, Stijnen T, et al. Accuracy of final height prediction and effect of growth-reductive therapy in 362 constitutionally tall children. J Clin Endocrinol Metab 1996;81:1206–16.
Sorgo W, Scholler K, Heinze F, Heinze E, Teller WM. Critical analysis of height reduction in oestrogen-treated tall girls. Eur J Pediatr 1984;142:260–5.
Venn A, Hosmer T, Hosmer D, et al. Oestrogen treatment for tall stature in girls: estimating the effect on height and the error in height prediction. Clin Endocrinol (Oxf) 2008;68:926–9.
Joss EE, Temperli R, Mullis PE. Adult height in constitutionally tall stature: accuracy of five different height prediction methods. Arch Dis Child 1992;67:1357–62.
Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford California, Stanford Univ Press. 1959.
Thodberg HH, Kreiborg S, Juul A, Pedersen KD. The BoneXpert method for automated determination of skeletal maturity. IEEE Trans Med Imaging 2009;28:52–66.
Thodberg HH, Neuhof J, Ranke MB, Jenni OG, Martin DD. Validation of bone age methods by their ability to predict adult height. Horm Res Paediatr 2010;74:15–22.
Tanner, J.M, Healy, M, Goldstein, H, Cameron, N. Assessment of Skeletal Maturity and Prediction of Adult Height (TW3 Method). 3rd edn. London: Saunders/Harcourt; 2001.
Gourmelen M, Le Bouc Y, Girard F, Binoux M. Serum levels of insulin-like growth factor (IGF) and IGF binding protein in constitutionally tall children and adolescents. J Clin Endocrinol Metab 1984;59:1197–203.
Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB. Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab 1993;76:1610–6.
Juul A, Bang P, Hertel NT, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994;78:744–52.
Sørensen K, Aksglaede L, Petersen JH, Andersson AM, Juul A. Serum IGF1 and insulin levels in girls with normal and precocious puberty. Eur J Endocrinol 2012;166:903–10.
Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.
Tinggaard J, Aksglaede L, Sørensen K, et al. The 2014 Danish references from birth to 20 years for height, weight and body mass index. Acta Paediatr 2014;103:214–24.
Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR. A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 1990;70:1292–8.
Juul A, Dalgaard P, Blum WF, et al. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 1995;80:2534–42.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Figure S1 (download EPS )
(EPS 8038 kb)
Supplementary Figure S2 (download EPS )
(EPS 8307 kb)
Supplementary Figure S3 (download EPS )
(EPS 5000 kb)
Rights and permissions
About this article
Cite this article
Upners, E., Juul, A. Evaluation and phenotypic characteristics of 293 Danish girls with tall stature: effects of oral administration of natural 17β-estradiol. Pediatr Res 80, 693–701 (2016). https://doi.org/10.1038/pr.2016.128
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2016.128
This article is cited by
-
Tall stature: a difficult diagnosis?
Italian Journal of Pediatrics (2017)
