Gradually increasing ethinyl estradiol for Turner syndrome may produce good final height but not ideal BMD

Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an...

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Published inEndocrine Journal Vol. 64; no. 2; pp. 221 - 227
Main Authors Igaki-Miyamoto, Junko, Hasegawa, Yukihiro, Hatano, Megumi, Ariyasu, Daisuke, Yagi, Hiroko, Fukuma, Mami, Izawa, Masako, Goto, Masahiro
Format Journal Article
LanguageEnglish
Published Japan The Japan Endocrine Society 01.01.2017
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ISSN0918-8959
1348-4540
1348-4540
DOI10.1507/endocrj.EJ16-0170

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Abstract Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm3) was significantly different from that of group L or E (0.262 or 0.262 g/cm3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.
AbstractList Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week similar to 0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 plus or minus 3.4 cm and the standard deviation (SD) was 2.02 plus or minus 0.62 for Turner syndrome. The final height in group L was 148.5 plus or minus 3.0 cm with a SD of 1.30 plus or minus 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 plus or minus 0.026 g/cm super(3)) was significantly different from that of group L or E (0.262 or 0.262 g/cm super(3) as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.
Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm ) was significantly different from that of group L or E (0.262 or 0.262 g/cm as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.
Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm3) was significantly different from that of group L or E (0.262 or 0.262 g/cm3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.
Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm3) was significantly different from that of group L or E (0.262 or 0.262 g/cm3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm3) was significantly different from that of group L or E (0.262 or 0.262 g/cm3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.
Author Goto, Masahiro
Ariyasu, Daisuke
Igaki-Miyamoto, Junko
Fukuma, Mami
Hatano, Megumi
Hasegawa, Yukihiro
Yagi, Hiroko
Izawa, Masako
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  organization: Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan
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  organization: Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan
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  organization: Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27916781$$D View this record in MEDLINE/PubMed
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6. van Pareren YK, de Muinck Keizer-Schrama SM, Stijnen T, Sas TC, Jansen M, et al. (2003) Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens. J Clin Endocrinol Metab 88: 1119-1125.
25. Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, et al. (2007) Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 115: 840-845.
21. Nanao K, Tsuchiya Y, Kotoh S, Hasegawa Y (2002) Low vertebral cancellous bone density in peripubertal girls with Turner’s syndrome and boys with hypogonadism. J Pediatr Endocrinol Metab 15: 1537-1542.
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2. Gravholt CH (2004) Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol 151: 657-687.
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8. Bettendorf M, Inta IM, Doerr HG, Hauffa BP, Mehls O, et al. (2013) Height gain in Ullrich-Turner syndrome after early and late growth hormone treatment start: results from a large retrospective German study and potential basis for an individualized treatment approach. Horm Res Paediatr 80: 356-362.
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References_xml – reference: 17. Mochizuki T, Fujita K, Yokoya S (2010) A Quetionnaire Survey of the Follow-up in Adults Turner Women in Japan. J of Japanese Society for Pediatrics 114: 43-47 (In Japanese).
– reference: 6. van Pareren YK, de Muinck Keizer-Schrama SM, Stijnen T, Sas TC, Jansen M, et al. (2003) Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens. J Clin Endocrinol Metab 88: 1119-1125.
– reference: 21. Nanao K, Tsuchiya Y, Kotoh S, Hasegawa Y (2002) Low vertebral cancellous bone density in peripubertal girls with Turner’s syndrome and boys with hypogonadism. J Pediatr Endocrinol Metab 15: 1537-1542.
– reference: 19. Bulun SE (2014) Aromatase and Estrogen receptor α deficiency. Fertil Steril 101: 323-329.
– reference: 3. Bondy CA, Turner Syndrome Study Group (2007) Care of girls and women with Turner syndrome: a guideline of the Turner syndrome Study Group. J Clin Endocrinol Metab 92: 10-25.
– reference: 2. Gravholt CH (2004) Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol 151: 657-687.
– reference: 8. Bettendorf M, Inta IM, Doerr HG, Hauffa BP, Mehls O, et al. (2013) Height gain in Ullrich-Turner syndrome after early and late growth hormone treatment start: results from a large retrospective German study and potential basis for an individualized treatment approach. Horm Res Paediatr 80: 356-362.
– reference: 16. Tanaka T, Horikawa R, Tanae A, Hibi I (2000) Final Height in Girls with Turner Syndrome after Growth Hormone Treatment; Experience at National Children’s Hospital. Clin Pediatr Endocrinol 9: 41-46.
– reference: 7. Stephure DK; Canadian Growth Hormone Advisory Committee (2005) Impact of growth hormone supplementation on adult height in turner syndrome: results of the Canadian randomized controlled trial. J Clin Endocrinol Metab 90: 3360-3366.
– reference: 26. Ross JL, Cassorla F, Carpenter G, Long LM, Royster MS, et al. (1988) The effect of short term treatment with growth hormone and ethinyl estradiol on lower leg growth rate in girls with Turner’s syndrome. J Clin Endocrinol Metab 67: 515-518.
– reference: 13. Isojima T, Yokoya S, Ito J, Horikawa R, Tanaka T (2009) New reference growth charts for Japanese girls with Turner syndrome. Pediatr Int 51: 709-714.
– reference: 15. Tanaka T, Igarashi Y, Ozono K, Oyama K, Ogawa M, et al. (2011) Efficacy of high dose growth hormone treatment in Turner syndrome: Seven-year experience of Turner syndrome Research Collaboration. J of Japanese Association for Human Auxology 17: 8-15 (In Japanese).
– reference: 25. Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, et al. (2007) Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 115: 840-845.
– reference: 1. Turner HH (1938) A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology 23: 566-574.
– reference: 12. Aso K, Koto S, Higuchi A, Ariyasu D, Izawa M, et al. (2010) Serum FSH level below 10 mIU/mL at twelve years old is an index of spontaneous and cyclical menstruation in Turner syndrome. Endo J 57: 909-913.
– reference: 18. Rongen-Westerlaken C, Corel L, van den Broeck J, Massa G, Karlberg J, et al. (1997) Reference values for height, height velocity and weight in Turner’s syndrome. Swedish Study Group for GH treatment. Acta Paediatr 86: 937-942.
– reference: 14. Kroeger H, Kotaniemi A, Vainio P, Alhava E (1992) Bone densitometry of the spine and femur in children by dual-energy x-ray absorption. Bone Miner 17: 75-85.
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Snippet Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final...
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SubjectTerms Adolescent
BMD (bone mineral density)
Body Height - drug effects
Bone Density - drug effects
Child
Child, Preschool
Cohort Studies
Dose-Response Relationship, Drug
Estrogen Replacement Therapy - methods
Ethinyl estradiol
Ethinyl Estradiol - administration & dosage
Ethinyl Estradiol - adverse effects
Female
Final height
Follow-Up Studies
Human Growth Hormone - therapeutic use
Humans
Infant
Japan
Menarche - drug effects
Turner syndrome
Turner Syndrome - drug therapy
Title Gradually increasing ethinyl estradiol for Turner syndrome may produce good final height but not ideal BMD
URI https://www.jstage.jst.go.jp/article/endocrj/64/2/64_EJ16-0170/_article/-char/en
https://www.ncbi.nlm.nih.gov/pubmed/27916781
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https://www.proquest.com/docview/1881766497
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