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Growth Hormone and Low Dose Estrogen in Turner Syndrome: Results of a United States Multi-Center Trial to Near-Final Height
Abstract
A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS.
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“Despite numerous studies of GH treatment in TS, only six randomized, controlled trials (RCTs) have compared GH treatment with a concurrent non-treatment or placebo control for at least one year157-162”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [161]
In the citing paper
“a 2007 Cochrane Center review156 concluded that girls treated with GH grew 3 cm year−1 more than untreated girls in the first 12-18 months of therapy”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [161]
In the citing paper
“An additional RCT that used a similar regimen but with higher ethinyl estradiol doses found no long-term growth benefit from prepubertal estrogen treatment.161”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [161]
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Metadata
- Authors
- Quigley, C. A., Crowe, B. J., Anglin, D. G., & Chipman, J. J.
- Affiliations
- Eli Lilly (United States) (US)
- ORCID
- Crowe, Brenda J.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2002-05
- Volume
- 87
- Issue
- 5
- Pages
- 2033-2041
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1997601373
- Cited by
- 159
- References
- 28
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 1 · 2020: 4 · 2019: 9 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 10 · 2012: 5
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- 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
- Turner syndrome, growth hormone therapy, recombinant human growth hormone, low-dose estrogen, ethinyl estradiol, short stature, dose-response relationship, bone age
- MeSH terms
- Body Height, Child, Dose-Response Relationship, Drug, Double-Blind Method, Ethinyl Estradiol, Female, Humans, Longitudinal Studies, Placebos, Recombinant Proteins, Safety, Turner Syndrome, Treatment Outcome, Human Growth Hormone, Estradiol Congeners
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