Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.
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.
Quigley
Charmian A
CA
Eli Lilly & Co., Indianapolis, Indiana 46285, USA. qac@lilly.com
Crowe
Brenda J
BJ
Anglin
D Greg
DG
Chipman
John J
JJ
D001827:Body Height / Q000187:drug effects*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D045166:Estradiol Congeners / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D010919:Placebos; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome; D014424:Turner Syndrome / Q000188:drug therapy* / Q000473:pathology*
D045166:Estradiol Congeners; D010919:Placebos; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D004997:Ethinyl Estradiol