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.)

Application of Analyte Harvesting Nanoparticle Technology to the Measurement of Urinary HGH in Healthy Individuals

“…Firstly, therapeutic administration of hGH has expanded beyond the treatment of short stature to now encompass traumatic brain injury [1], Turner syndrome [2] and aging [3]. Secondly, the abuse of hGH supplementation for enhancement of sport performance is believed to be widely prevalent [4].…”

Turner syndrome caused by rare complex structural abnormalities involving chromosome X

“…Growth hormone (GH) treatment has been demonstrated to be an effective and safe strategy to improve growth in TS patients. Patients treated with GH were ~5.0 cm taller as compared with those who received placebo injections, and a greater effect was achieved when combined with estrogen (7). In the present study, the two subjects were offered GH treatment; however, case 1 refused the treatment, whereas case 2 showed a 1.0-cm increase in height after 1 month of treatment.…”

“…Previously results have indicated that, although estrogen treatment may significantly improve nonverbal processing speed, motor performance and verbal and nonverbal memory in patients with TS, the clinical practice is often postponed to puberty, predominantly because estrogen may reduce adult height by accelerating epiphyseal fusion (5,6). A randomized, double-blind, placebo-controlled study suggested that the combination of ultra-low-dose estrogen replacement and growth hormone in childhood not only ameliorated adult height, but also improved the neurocognitive and behavioral function (7).…”

Endocrine diseases, perspectives and care in Turner syndrome

“…A recently published study compared the effects of rhGH treatment associated with the use of very low doses of estrogen during childhood. Even though the use of ethinyl estradiol alone decreased adult height, when compared with a control group, the use of rhGH alone increased adult height by 5.0 cm, and the association with low doses of estrogen increased adult height by other 2.1 cm (13).…”