This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chernausek, S. D. Articles by Frane, J. Search for Related Content PubMed PubMed Citation Articles by Chernausek, S. D. Articles by Frane, J.

Growth Hormone Therapy of Turner Syndrome: The Impact of Age of Estrogen Replacement on Final Height¹

Genentech, Inc., San Francisco, California 94080

Address all correspondence and requests for reprints to: Dr. Steven D. Chernausek, Children’s Hospital Medical Center, Division of Endocrinology, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.

Clinical trials of recombinant human GH therapy in Turner syndrome that began more than a decade ago show that GH accelerates the linear growth rate. Several studies indicate that final height is also improved, although the magnitude of the increase has been debated. The age at which feminization is induced could be an important factor in determining the patient’s ultimate growth response. To test this, 60 patients from a large (n = 117), previously unreported, clinical trial of GH treatment were randomly assigned to begin conjugated estrogens at either 12 or 15 yr of age. The 60 patients were all less than 11 yr of age at entry (mean, 9.5 yr) and received 0.375 mg/kg·week of GH for nearly 6 yr on a daily or three times weekly regimen. Height gain was calculated by comparing the study patients’ final or near final heights to their pretreatment projected heights as well as to those of a separate set of age-matched, historical control patients. Patients in whom estrogen treatment was delayed until age 15 yr gained an average of 8.4 ± 4.3 cm over their projected height, whereas those starting estrogen at 12 yr gained only 5.1 ± 3.6 cm, on the average (P < 0.01). Analysis of the interval data showed that growth was stimulated for approximately 2 yr after estrogen initiation, but then declined in association with bone age advancement. Patients who were older than 11 yr at entry (n = 57) all initiated estrogen 1 yr after beginning GH and showed a mean gain in adult height of 4.7 cm, similar to those given estrogen at age 12 yr. Multivariate analysis revealed that the number of years of GH therapy before estrogen treatment was a strong factor in predicting height gained, indicating that the timing of estrogen introduction is an important determinant of final height in this cohort of GH-treated patients with Turner syndrome matched for baseline age and other characteristics.

This article has been cited by other articles:

				M. L. Davenport, B. J. Crowe, S. H. Travers, K. Rubin, J. L. Ross, P. Y. Fechner, D. F. Gunther, C. Liu, M. E. Geffner, K. Thrailkill, et al. Growth Hormone Treatment of Early Growth Failure in Toddlers with Turner Syndrome: A Randomized, Controlled, Multicenter Trial J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3406 - 3416. [Abstract] [Full Text] [PDF]

				D. S. Hardin, S. F. Kemp, and D. B. Allen Twenty Years of Recombinant Human Growth Hormone in Children: Relevance to Pediatric Care Providers Clinical Pediatrics, May 1, 2007; 46(4): 279 - 286. [Abstract] [PDF]

				C. A. Bondy and for The Turner Syndrome Consensus Study Group Care of Girls and Women with Turner Syndrome: A Guideline of the Turner Syndrome Study Group J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 10 - 25. [Abstract] [Full Text] [PDF]

				J.-C. Carel, C. Elie, E. Ecosse, M. Tauber, J. Leger, S. Cabrol, M. Nicolino, R. Brauner, J.-L. Chaussain, and J. Coste Self-Esteem and Social Adjustment in Young Women with Turner Syndrome--Influence of Pubertal Management and Sexuality: Population-Based Cohort Study J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2972 - 2979. [Abstract] [Full Text] [PDF]

				C. E. Hamelin, G. Anglin, C. A. Quigley, C. L. Deal, and on behalf of the Canadian Growth Hormone Advisory Genomic Imprinting in Turner Syndrome: Effects on Response to Growth Hormone and on Risk of Sensorineural Hearing Loss J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3002 - 3010. [Abstract] [Full Text] [PDF]

				R. L. Rosenfield, N. Devine, J. J. Hunold, N. Mauras, T. Moshang Jr., and A. W. Root Salutary Effects of Combining Early Very Low-Dose Systemic Estradiol with Growth Hormone Therapy in Girls with Turner Syndrome J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6424 - 6430. [Abstract] [Full Text] [PDF]

				L. Soriano-Guillen, J. Coste, E. Ecosse, J. Leger, M. Tauber, S. Cabrol, M. Nicolino, R. Brauner, the StaTur Study Group, J.-L. Chaussain, et al. Adult Height and Pubertal Growth in Turner Syndrome after Treatment with Recombinant Growth Hormone J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5197 - 5204. [Abstract] [Full Text] [PDF]

				H. G. Doerr, M. Bettendorf, B. P. Hauffa, O. Mehls, C.-J. Partsch, E. Said, S. Sander, H.-P. Schwarz, N. Stahnke, H. Steinkamp, et al. Uterine size in women with Turner syndrome after induction of puberty with estrogens and long-term growth hormone therapy: results of the German IGLU Follow-up Study 2001 Hum. Reprod., May 1, 2005; 20(5): 1418 - 1421. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]

				S. Piippo, H. Lenko, P. Kainulainen, and I. Sipila Use of Percutaneous Estrogen Gel for Induction of Puberty in Girls with Turner Syndrome J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3241 - 3247. [Abstract] [Full Text] [PDF]

				G. Massa, C. Heinrichs, S. Verlinde, M. Thomas, J. P. Bourguignon, M. Craen, I. Francois, M. Du Caju, M. Maes, and J. De Schepper Late or Delayed Induced or Spontaneous Puberty in Girls with Turner Syndrome Treated with Growth Hormone Does Not Affect Final Height J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4168 - 4174. [Abstract] [Full Text] [PDF]

				Y. K. van Pareren, S. M. P. F. de Muinck Keizer-Schrama, T. Stijnen, T. C. J. Sas, M. Jansen, B. J. Otten, J. J. G. Hoorweg-Nijman, T. Vulsma, W. H. Stokvis-Brantsma, C. W. Rouwe, et al. Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1119 - 1125. [Abstract] [Full Text] [PDF]

				M. Bonamico, A. M. Pasquino, P. Mariani, H. M. Danesi, F. Culasso, L. Mazzanti, A. Petri, and G. Bona Prevalence and Clinical Picture of Celiac Disease in Turner Syndrome J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5495 - 5498. [Abstract] [Full Text] [PDF]

				O. Pinhas-Hamiel and A. Achiron Testing the Tests Arch Pediatr Adolesc Med, December 1, 2002; 156(12): 1268 - 1270. [Full Text] [PDF]

				C. Ankarberg-Lindgren, M. Elfving, K. A. Wikland, and E. Norjavaara Nocturnal Application of Transdermal Estradiol Patches Produces Levels of Estradiol That Mimic Those Seen at the Onset of Spontaneous Puberty in Girls J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3039 - 3044. [Abstract] [Full Text] [PDF]

				P. Saenger, K. A. Wikland, G. S. Conway, M. Davenport, C. H. Gravholt, R. Hintz, O. Hovatta, M. Hultcrantz, K. Landin-Wilhelmsen, A. Lin, et al. Recommendations for the Diagnosis and Management of Turner Syndrome J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3061 - 3069. [Abstract] [Full Text] [PDF]

				D A PRICE and M B RANKE Growth hormone in Turner syndrome Arch. Dis. Child., June 1, 2001; 84(6): 525m - 525. [Full Text]

				E. O. Reiter, S. L. Blethen, J. Baptista, and L. Price Early Initiation of Growth Hormone Treatment Allows Age-Appropriate Estrogen Use in Turner's Syndrome J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1936 - 1941. [Abstract] [Full Text]

				D I Johnston, P Betts, D Dunger, N Barnes, P G F Swift, J M H Buckler, and G E Butler A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis Arch. Dis. Child., January 1, 2001; 84(1): 76 - 81. [Abstract] [Full Text]