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Published in: Journal of Endocrinological Investigation 8/2017

Open Access 01-08-2017 | Original Article

Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results

Authors: Anna Ruszala, Malgorzata Wojcik, Agata Zygmunt-Gorska, Dominika Janus, Joanna Wojtys, Jerzy B. Starzyk

Published in: Journal of Endocrinological Investigation | Issue 8/2017

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Abstract

Purpose

The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE).

Methods

In 14 TS (mean age 13.8), LE (17β-estradiol, 62.5 μg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17β-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed.

Results

There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17β-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 μIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group.

Conclusion

Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.
Literature
1.
go back to reference Klein KO, Baron J, ColliMJ, McDonnell DP, Cutler GB Jr (1994) Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. J Clin Invest 94(6):2475–2480CrossRefPubMedPubMedCentral Klein KO, Baron J, ColliMJ, McDonnell DP, Cutler GB Jr (1994) Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. J Clin Invest 94(6):2475–2480CrossRefPubMedPubMedCentral
2.
go back to reference Janfaza M, Sherman TI, Larmore KA, Brown-Dawson J, Klein KO (2006) Estradiol levels and secretory dynamics in normal girls and boys as determined by an ultrasensitive bioassay: a 10 year experience. J Pediatr Endocrinol Metab 19(7):901–909CrossRefPubMed Janfaza M, Sherman TI, Larmore KA, Brown-Dawson J, Klein KO (2006) Estradiol levels and secretory dynamics in normal girls and boys as determined by an ultrasensitive bioassay: a 10 year experience. J Pediatr Endocrinol Metab 19(7):901–909CrossRefPubMed
3.
go back to reference Courant F, Aksglaede L, Antignac JP et al (2010) Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography–tandem mass spectrometry method. J Clin Endocrinol Metab 95(1):82–92CrossRefPubMed Courant F, Aksglaede L, Antignac JP et al (2010) Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography–tandem mass spectrometry method. J Clin Endocrinol Metab 95(1):82–92CrossRefPubMed
4.
go back to reference Charmian A, Quigley CA, Wan X, Garg S, Kowal K, Cutler GB Jr, Ross JL (2014) Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 99(9):E1754–E1764CrossRef Charmian A, Quigley CA, Wan X, Garg S, Kowal K, Cutler GB Jr, Ross JL (2014) Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 99(9):E1754–E1764CrossRef
5.
go back to reference Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH (2006) Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 91(10):3897–3902CrossRefPubMed Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH (2006) Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 91(10):3897–3902CrossRefPubMed
6.
go back to reference Bondy CA (2007) Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab 92(1):10–25CrossRefPubMed Bondy CA (2007) Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab 92(1):10–25CrossRefPubMed
7.
go back to reference Wilson CA, Heinrichs C, Larmore KA et al (2003) Estradiol levels in girls with Turner’s syndrome compared to normal prepubertal girls as determined by an ultrasensitive assay. J Pediatr Endocrinol Metab 16(1):91–96CrossRefPubMed Wilson CA, Heinrichs C, Larmore KA et al (2003) Estradiol levels in girls with Turner’s syndrome compared to normal prepubertal girls as determined by an ultrasensitive assay. J Pediatr Endocrinol Metab 16(1):91–96CrossRefPubMed
8.
go back to reference Cappa M, Iughetti L, Loche S et al (2016) Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study. J Endocrinol Invest 39:667–677CrossRefPubMed Cappa M, Iughetti L, Loche S et al (2016) Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study. J Endocrinol Invest 39:667–677CrossRefPubMed
9.
go back to reference Dewhurst CJ, de Koos EB, Haines RM (1975) Replacement hormone therapy in gonadal dysgenesis. Br J Obstet Gynaecol 82(5):412–416CrossRefPubMed Dewhurst CJ, de Koos EB, Haines RM (1975) Replacement hormone therapy in gonadal dysgenesis. Br J Obstet Gynaecol 82(5):412–416CrossRefPubMed
10.
11.
go back to reference Kodama M, Komura H, Kodama T, Nishio Y, Kimura T (2012) Estrogen therapy initiated at an early age increases bone mineral density in Turner syndrome patients. Endocr J 59:153–159CrossRefPubMed Kodama M, Komura H, Kodama T, Nishio Y, Kimura T (2012) Estrogen therapy initiated at an early age increases bone mineral density in Turner syndrome patients. Endocr J 59:153–159CrossRefPubMed
12.
go back to reference Nakamura T, Tsuburai T, Tokinaga A, Nakajimab I, Kitayama R, Imai Y, Nagata T, Yoshida H, Hirahara F, Sakakibara H (2015) Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome. Endocrine J 62(11):965–970CrossRef Nakamura T, Tsuburai T, Tokinaga A, Nakajimab I, Kitayama R, Imai Y, Nagata T, Yoshida H, Hirahara F, Sakakibara H (2015) Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome. Endocrine J 62(11):965–970CrossRef
13.
go back to reference Carel JC, Elie C, Ecosse E et al (2006) Self-esteem and social adjustment in young women with Turner syndrome—influence of pubertal management and sexuality: population-based cohort study. J Clin Endocrinol Metab 91(8):2972–2979CrossRefPubMed Carel JC, Elie C, Ecosse E et al (2006) Self-esteem and social adjustment in young women with Turner syndrome—influence of pubertal management and sexuality: population-based cohort study. J Clin Endocrinol Metab 91(8):2972–2979CrossRefPubMed
14.
go back to reference Kwiterovich POJ (2008) Recognition and management of dyslipidemia in children and adolescents. J Clin Endocrinol Metab 93:4200–4209 Kwiterovich POJ (2008) Recognition and management of dyslipidemia in children and adolescents. J Clin Endocrinol Metab 93:4200–4209
15.
go back to reference Ross JL, McCauley E, Roeltgen D et al (1996) Self-concept and behavior in adolescent girls with Turner syndrome: potential estrogen effects. J Clin Endocrinol Metab 81(3):926–931PubMed Ross JL, McCauley E, Roeltgen D et al (1996) Self-concept and behavior in adolescent girls with Turner syndrome: potential estrogen effects. J Clin Endocrinol Metab 81(3):926–931PubMed
16.
go back to reference Brooks-Gunn J, Warren MP (1988) The psychological significance of secondary sexual characteristics in nine- to eleven-year-old girls. Child Dev 59(4):1061–1069CrossRefPubMed Brooks-Gunn J, Warren MP (1988) The psychological significance of secondary sexual characteristics in nine- to eleven-year-old girls. Child Dev 59(4):1061–1069CrossRefPubMed
17.
go back to reference Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB Jr (2000) Use of estrogen in young girls with Turner syndrome: effects on memory. Neurology 54(1):164–170CrossRefPubMed Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB Jr (2000) Use of estrogen in young girls with Turner syndrome: effects on memory. Neurology 54(1):164–170CrossRefPubMed
18.
go back to reference Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB Jr (1998) Effects of estrogen on nonverbal processing speed and motor function in girls with Turner’s syndrome. J Clin Endocrinol Metab 83(9):3198–3204PubMed Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB Jr (1998) Effects of estrogen on nonverbal processing speed and motor function in girls with Turner’s syndrome. J Clin Endocrinol Metab 83(9):3198–3204PubMed
19.
go back to reference Gravholt CH, Juul S, Naeraa RW, Hansen J (2009) Morbidity in Turner syndrome. J Clin Epidemiol 51:147–158CrossRef Gravholt CH, Juul S, Naeraa RW, Hansen J (2009) Morbidity in Turner syndrome. J Clin Epidemiol 51:147–158CrossRef
20.
go back to reference Lozano P, Henrikson NB, Dunn J, Morrison CC, Nguyen M, Whitlock EP (2016) Lipid screening in childhood for detection of multifactorial dyslipidemia: a systematic evidence review for the US Preventive Services Task Force. Evidence synthesis no. 140. AHRQ Publication No. 14-05204-EF-1. Agency for Healthcare Research and Quality, Rockville Lozano P, Henrikson NB, Dunn J, Morrison CC, Nguyen M, Whitlock EP (2016) Lipid screening in childhood for detection of multifactorial dyslipidemia: a systematic evidence review for the US Preventive Services Task Force. Evidence synthesis no. 140. AHRQ Publication No. 14-05204-EF-1. Agency for Healthcare Research and Quality, Rockville
21.
go back to reference Sagi L, Zuckerman-Levin N, Gawlik A, Ghizzoni L, Buyukgebiz A, Rakover Y, Bistritzer T, Admoni O, Vottero A, Baruch O, Fares F, Malecka-Tendera E, Hochberg Z (2007) Clinical significance of the parental origin of the X chromosome in Turner syndrome. J Clin Endocrinol Metab 92(3):846–852CrossRefPubMed Sagi L, Zuckerman-Levin N, Gawlik A, Ghizzoni L, Buyukgebiz A, Rakover Y, Bistritzer T, Admoni O, Vottero A, Baruch O, Fares F, Malecka-Tendera E, Hochberg Z (2007) Clinical significance of the parental origin of the X chromosome in Turner syndrome. J Clin Endocrinol Metab 92(3):846–852CrossRefPubMed
22.
go back to reference Wojcik M, Janus D, Zygmunt-Gorska A, Starzyk JB (2015) Insulin resistance in adolescents with Turner syndrome is comparable to obese peers, but the overall metabolic risk is lower due to unknown mechanism. J Endocrinol Invest 38:345–334CrossRefPubMed Wojcik M, Janus D, Zygmunt-Gorska A, Starzyk JB (2015) Insulin resistance in adolescents with Turner syndrome is comparable to obese peers, but the overall metabolic risk is lower due to unknown mechanism. J Endocrinol Invest 38:345–334CrossRefPubMed
23.
go back to reference Salgin B, Amin R, Yuen K, Williams RM, Murgatroyd P, Dunger DB (2006) Insulin resistance is an intrinsic defect independent of fat mass in women with Turner’s syndrome. Horm Res 65:69–75PubMed Salgin B, Amin R, Yuen K, Williams RM, Murgatroyd P, Dunger DB (2006) Insulin resistance is an intrinsic defect independent of fat mass in women with Turner’s syndrome. Horm Res 65:69–75PubMed
24.
go back to reference Giordano R, Forno D, Lanfranco F, Manieri C, Ghizzoni L, Ghigo E (2011) Metabolic and cardiovascular outcomes in a group of adult patients with Turner’s syndrome under hormonal replacement therapy. Eur J Endocrinol 164:819–826CrossRefPubMed Giordano R, Forno D, Lanfranco F, Manieri C, Ghizzoni L, Ghigo E (2011) Metabolic and cardiovascular outcomes in a group of adult patients with Turner’s syndrome under hormonal replacement therapy. Eur J Endocrinol 164:819–826CrossRefPubMed
25.
go back to reference Casanova G, Bossardi Ramos R, Ziegelmann P, Spritzer P (2015) Effects of low-dose versus placebo or conventional dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials. J Clin Endocrinol Metab 100(3):1028–1037CrossRefPubMed Casanova G, Bossardi Ramos R, Ziegelmann P, Spritzer P (2015) Effects of low-dose versus placebo or conventional dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials. J Clin Endocrinol Metab 100(3):1028–1037CrossRefPubMed
Metadata
Title
Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results
Authors
Anna Ruszala
Malgorzata Wojcik
Agata Zygmunt-Gorska
Dominika Janus
Joanna Wojtys
Jerzy B. Starzyk
Publication date
01-08-2017
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 8/2017
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-017-0665-3

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