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Cited by 216Growth Hormone and Insulin-like Growth FactorsGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and Disorders

The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.

Growth Hormone plus Childhood Low-Dose Estrogen in Turner's Syndrome

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Ross, Judith L., Quigley, Charmian A., Cao, Dachuang, Feuillan, Penelope, Kowal, Karen, Chipman, John J., Cutler, Gordon B.·2011·New England Journal of Medicine
DOI 10.1056/nejmoa1005669PMC PMC3083123
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Abstract

BACKGROUND: Short stature and ovarian failure are characteristic features of Turner's syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner's syndrome. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 149 girls, 5.0 to 12.5 years of age, to four groups: double placebo (placebo injection plus childhood oral placebo, 39 patients), estrogen alone (placebo injection plus childhood oral low-dose estrogen, 40), growth hormone alone (growth hormone injection plus childhood oral placebo, 35), and growth hormone-estrogen (growth hormone injection plus childhood oral low-dose estrogen, 35). The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week. The doses of ethinyl estradiol (or placebo) were adjusted for chronologic age and pubertal status. At the first visit after the age of 12.0 years, patients in all treatment groups received escalating doses of ethinyl estradiol. Growth hormone injections were terminated when adult height was reached. RESULTS: The mean standard-deviation scores for adult height, attained at an average age of 17.0±1.0 years, after an average study period of 7.2±2.5 years were -2.81±0.85, -3.39±0.74, -2.29±1.10, and -2.10±1.02 for the double-placebo, estrogen-alone, growth hormone-alone, and growth hormone-estrogen groups, respectively (P<0.001). The overall effect of growth hormone treatment (vs. placebo) on adult height was a 0.78±0.13 increase in the height standard-deviation score (5.0 cm) (P<0.001); adult height was greater in the growth hormone-estrogen group than in the growth hormone-alone group, by 0.32±0.17 standard-deviation score (2.1 cm) (P=0.059), suggesting a modest synergy between childhood low-dose ethinyl estradiol and growth hormone. CONCLUSIONS: Our study shows that growth hormone treatment increases adult height in patients with Turner's syndrome. In addition, the data suggest that combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement. (Funded by the National Institute of Child Health and Human Development and Eli Lilly; ClinicalTrials.gov number, NCT00001221.).

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  1. 10.1210/jc.83.5.1462 · DOI
  2. 10.1210/jc.87.5.2033 · DOI · Paper page
  3. Baxter L, 2007, Cochrane Database Syst Rev, 1, CD003887

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Metadata

Authors
Ross, J. L., Quigley, C. A., Cao, D., Feuillan, P., Kowal, K., Chipman, J. J., & Cutler, G. B.
Affiliations
  • Alfred I. duPont Hospital for Children (US)
  • Eli Lilly (United States) (US)
  • National Institutes of Health (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2011-03-31
Volume
364
Issue
13
Pages
1230-1242
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1005669
PMC
PMC3083123
OpenAlex
W2050210944
Cited by
212
References
45
Citations by year
2026: 5 · 2025: 5 · 2024: 15 · 2023: 12 · 2022: 14 · 2021: 13 · 2020: 10 · 2019: 18 · 2018: 12 · 2017: 16 · 2016: 14 · 2015: 18 · 2014: 14 · 2013: 13 · 2012: 18
FWCI
15.72
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS029857)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Keywords
recombinant human growth hormone, ethinyl estradiol, adult height, short stature, ovarian failure, pubertal stage, girls, puberty timing, growth rate, insulin-like growth factor I, bone mineral density
MeSH terms
Adolescent, Adult, Analysis of Variance, Body Height, Child, Child, Preschool, Double-Blind Method, Drug Therapy, Combination, Ethinyl Estradiol, Female, Growth, Growth Disorders, Humans, Turner Syndrome, Estrogen Replacement Therapy, Human Growth Hormone, Intention to Treat Analysis

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