Growth Hormone and Low Dose Estrogen in Turner Syndrome: Results of a United States Multi-Center Trial to Near-Final Height

• Published in: The journal of clinical endocrinology and metabolism Vol. 87; no. 5; pp. 2033 - 2041
• Main Authors: Quigley, Charmian A., Crowe, Brenda J., Anglin, D. Greg, Chipman, John J.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.05.2002; Endocrine Society
• Subjects: Age; Biological and medical sciences; Body height; Body Height - drug effects; Body weight; Child; Dose-Response Relationship, Drug; Double-Blind Method; Estradiol Congeners - administration & dosage; Estradiol Congeners - adverse effects; Estradiol Congeners - therapeutic use; Estrogens; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - adverse effects; Ethinyl Estradiol - therapeutic use; Female; Genetic disorders; Growth hormones; Gynecology. Andrology. Obstetrics; Hormones. Endocrine system; Human Growth Hormone - adverse effects; Human Growth Hormone - therapeutic use; Humans; Longitudinal Studies; Male and female genital diseases. Gonadal dysgenesis. Hermaphroditism. Sex hormones resistance; Medical sciences; Pharmacology. Drug treatments; Placebos; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Safety; Treatment Outcome; Turner Syndrome - drug therapy; Turner Syndrome - pathology; Turner's syndrome; United States; North America; America; United States > US; Chromosomal aberration; Human; Dysgenesia; Low dose; Estrogen; Somatotropin hormone; Oral administration; Sexual differentiation disorder; Turner syndrome; Long term; Female genital diseases; Randomization; Malformation; Gonad; Bone age; Adult; Female; Failure; Comparative study
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.87.5.8477

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.