Aim: The objective of this study was to determine estradiol levels and assess their relationship to pubertal growth in girls. Methods: Thirty-seven 24-hour profiles of serum 17β-estradiol were retrospectively analyzed in relation to growth in 27 healthy girls admitted for short/tall stature (n = 20) or recruited as healthy volunteers at Göteborg Pediatric Growth Research Center (GP-GRC). Inclusion Criteria: Birth weight and length above –2 SDS, gestational age 37–42 weeks, prepubertal height and weight within ±3 SDS and normal growth hormone secretion. Serum estradiol was determined by a validated ultrasensitive extraction radioimmunoassay (detection limit 4 pmol/l). A sixth-grade polynomial was fitted to each girl’s growth data. Growth velocity and age at peak height velocity (PHV) was calculated. Results: A dose-response model was used to find the morning 17β-estradiol level at which half of the maximal pubertal growth up to PHV had occurred, EC50, which was 20 pmol/l with a 95% confidence interval of 13–31. When 17β-estradiol exceeds early pubertal levels (Tanner breast stage 2, 10–51 pmol/l), less than 25% of the potential pubertal growth velocity up to PHV remains. Conclusions: Morning 17β-estradiol in the low early pubertal range (13–31 pmol/l) is associated with increasing growth velocity.

1.
Perry RJ, Farquharson C, Ahmed SF: The role of sex steroids in controlling pubertal growth. Clin Endocrinol (Oxf) 2008;68:4–15.
2.
Emons J, Chagin AS, Savendahl L, Karperien M, Wit JM: Mechanisms of growth plate maturation and epiphyseal fusion. Horm Res Paediatr 2011;75:383–391.
3.
Herrmann BL, Saller B, Janssen OE, Gocke P, Bockisch A, Sperling H, Mann K, Broecker M: Impact of estrogen replacement therapy in a male with congenital aromatase deficiency caused by a novel mutation in the cyp19 gene. J Clin Endocrinol Metab 2002;87:5476–5484.
4.
Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER: Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med 1997;337:91–95.
5.
Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS: Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994;331:1056–1061.
6.
Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K: Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995;80:3689–3698.
7.
Ankarberg-Lindgren C, Norjavaara E: A purification step prior to commercial sensitive immunoassay is necessary to achieve clinical usefulness when quantifying serum 17β-estradiol in prepubertal children. Eur J Endocrinol 2008;158:117–124.
8.
Ankarberg-Lindgren C, Norjavaara E: Estradiol in pediatric endocrinology. Am J Clin Pathol 2009;132:978–980.
9.
Ankarberg-Lindgren C, Norjavaara E: Twenty-four hours secretion pattern of serum estradiol in healthy prepubertal and pubertal boys as determined by a validated ultra-sensitive extraction RIA. BMC Endocr Disord 2008;8:10.
10.
Norjavaara E, Ankarberg C, Albertsson-Wikland K: Diurnal rhythm of 17β-estradiol secretion throughout pubertal development in healthy girls: evaluation by a sensitive radioimmunoassay. J Clin Endocrinol Metab 1996;81:4095–4102.
11.
Marshall WA, Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.
12.
Tanner JM: Growth at Adolescence. Oxford, Blackwell Scientific, 1962.
13.
Wikland KA, Luo ZC, Niklasson A, Karlberg J: Swedish population-based longitudinal reference values from birth to 18 years of age for height, weight and head circumference. Acta Paediatr 2002;91:739–754.
14.
Tanner J, Whitehouse R, Cameron N, Marshall W, Healy M, Goldstein H: Assessment of skeletal Maturity and Prediction of Adult Height (TW2 Method). New York, Academic Press, 1983.
15.
Ankarberg-Lindgren C, Elfving M, Wikland KA, Norjavaara E: Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls. J Clin Endocrinol Metab 2001;86:3039–3044.
16.
Paris F, Servant N, Terouanne B, Balaguer P, Nicolas JC, Sultan C: A new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity in children. J Clin Endocrinol Metab 2002;87:791–797.
17.
Janfaza M, Sherman TI, Larmore KA, Brown-Dawson J, Klein KO: Estradiol levels and secretory dynamics in normal girls and boys as determined by an ultrasensitive bioassay: a 10-year experience. J Pediatr Endocrinol Metab 2006;19:901–909.
18.
Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–310.
19.
Voss LD, Bailey BJ, Cumming K, Wilkin TJ, Betts PR: The reliability of height measurement (the Wessex Growth Study). Arch Dis Child 1990;65:1340–1344.
20.
Werther G: Measuring height: to stretch or not to stretch? Lancet 1998;351:309–310.
21.
Gelander L: Growth in prepubertal children: short-term changes and endocrine regulation. The one-year growth study; PhD thesis Göteborg, 1998.
22.
Klein KO, Martha PM Jr, Blizzard RM, Herbst T, Rogol AD: A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. II. Estrogen levels as determined by an ultrasensitive bioassay. J Clin Endocrinol Metab 1996;81:3203–3207.
23.
Albertsson-Wikland K, Rosberg S, Lannering B, Dunkel L, Selstam G, Norjavaara E: Twenty-four-hour profiles of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels: a semilongitudinal study throughout puberty in healthy boys. J Clin Endocrinol Metab 1997;82:541–549.
24.
Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J: Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci USA 2001;98:6871–6876.
25.
Carel JC, Lahlou N, Roger M, Chaussain JL: Precocious puberty and statural growth. Hum Reprod Update 2004;10:135–147.
26.
Bord S, Horner A, Beavan S, Compston J: Estrogen receptors α and β are differentially expressed in developing human bone. J Clin Endocrinol Metab 2001;86:2309–2314.
27.
Nilsson O, Chrysis D, Pajulo O, Boman A, Holst M, Rubinstein J, Martin Ritzen E, Savendahl L: Localization of estrogen receptors-α and -β and androgen receptor in the human growth plate at different pubertal stages. J Endocrinol 2003;177:319–326.
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