title: Growth hormone plus childhood low-dose estrogen in Turner's syndrome.
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.).
authors: Jefferson University, Jefferson Medical College, Department of Pediatrics, 1025 Walnut St., Philadelphia, PA 19107, USA. judith.ross@jefferson.edu
authors: Judith L
authors: JL
authors: Ross
authors: Charmian A
authors: CA
authors: Quigley
authors: Dachuang
authors: D
authors: Cao
authors: Penelope
authors: P
authors: Feuillan
authors: Karen
authors: K
authors: Kowal
authors: John J
authors: JJ
authors: Chipman
authors: Gordon B
authors: GB
authors: Cutler
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006128:Growth / Q000187:drug effects; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D019382:Human Growth Hormone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D057194:Intention to Treat Analysis; D014424:Turner Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D019382:Human Growth Hormone; D004997:Ethinyl Estradiol