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 in | Endocrine Journal Vol. 64; no. 2; pp. 221 - 227 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Japan
The Japan Endocrine Society
01.01.2017
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Online Access | Get full text |
ISSN | 0918-8959 1348-4540 1348-4540 |
DOI | 10.1507/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. |
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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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References | 5. Rosenfeld RG, Attie KM, Frane J, Brasel JA, Burstein S, et al. (1998) Growth hormone therapy of Turner’s sundrome: Beneificial effect on adult height. J Pediatr 132: 319-324. 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). 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. 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. 22. Soucek O, Lebl J, Snajderova M, Kolouskova S, Rocek M, et al. (2011) Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages. Clin Endocrinol (Oxf) 74: 445-452. 4. Sybert VP, McCauley E (2004) Turner’s syndrome. N Engl J Med 351: 1227-1238. 24. Scarabin PY, Oger E, Plu-Bureau G, Estrogen, THromboEmbolism Risk Study Group (2003) Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet 362: 428-432. 20. Klein KO, Baron J, Colli MJ, McDonnell DP, Cutler GB Jr (1994) Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. J Clin Invest 94: 2475-2480. 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). 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. 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. 10. Quigley CA, Wan X, Garg S, Kowal K, Cutler GB Jr, et al. (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: E1754-1764. 9. Wasniewska M, Aversa T, Mazzanti L, Guarneri MP, Matarazzo P, et al. (2013) Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose. Eur J Endocrinol 169: 439-443. 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. 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. 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. 19. Bulun SE (2014) Aromatase and Estrogen receptor α deficiency. Fertil Steril 101: 323-329. 2. Gravholt CH (2004) Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol 151: 657-687. 1. Turner HH (1938) A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology 23: 566-574. 11. Ross JL, Quigley CA, Cao D, Feuillan P, Kowal K, et al. (2011) Growth hormone plus childhood low-dose estrogen in Turner’s syndrome. N Engl J Med 364: 1230-1242. 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. 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. 23. Aycan Z, Cetinkaya E, Darendeliler F, Vidinlisan S, Bas F, et al. (2008) The effect of growth hormone treatment on bone mineral density in prepubertal girls with Turner syndrome: a multicentre prospective clinical trial. Clin Endocrinol (Oxf) 68: 769-772. 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. 22 23 24 25 26 10 11 12 13 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 21 |
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. – reference: 4. Sybert VP, McCauley E (2004) Turner’s syndrome. N Engl J Med 351: 1227-1238. – reference: 22. Soucek O, Lebl J, Snajderova M, Kolouskova S, Rocek M, et al. (2011) Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages. Clin Endocrinol (Oxf) 74: 445-452. – reference: 10. Quigley CA, Wan X, Garg S, Kowal K, Cutler GB Jr, et al. (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: E1754-1764. – reference: 23. Aycan Z, Cetinkaya E, Darendeliler F, Vidinlisan S, Bas F, et al. (2008) The effect of growth hormone treatment on bone mineral density in prepubertal girls with Turner syndrome: a multicentre prospective clinical trial. Clin Endocrinol (Oxf) 68: 769-772. – reference: 24. Scarabin PY, Oger E, Plu-Bureau G, Estrogen, THromboEmbolism Risk Study Group (2003) Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. 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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 |
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