Treatment with a Luteinizing HormoneReleasing Hormone Agonist in Adolescents with Short Stature
Jack A. Yanovski, M.D., Ph.D., Susan R. Rose, M.D., Giovanna Municchi, M.D., Ora H. Pescovitz, M.D., Suvimol C. Hill, M.D., Fernando G. Cassorla, M.D., and Gordon B. Cutler, Jr., M.D.
Background Treatment with a luteinizing hormonereleasinghormone (LHRH) agonist increases adult height in children withLHRH-dependent precocious puberty and is prescribed by somepractitioners to augment height in short adolescents. We performeda randomized clinical trial to determine whether treatment withan LHRH agonist increases adult height in short adolescentswith normally timed puberty.
Methods Fifty short adolescents (18 boys and 32 girls) withlow predicted adult height (mean [±SD], 3.3±1.2SD below the population mean) received either placebo (24 subjects)or an LHRH agonist (26 subjects). The mean (±SD) durationof treatment was 3.5±0.9 years in the LHRH-agonist groupand 2.1±1.2 years in the placebo group (P<0.001).Adult height was measured when bone age exceeded 16 years ingirls and 17 years in boys and when the rate of growth was lessthan 1.5 cm per year.
Results Forty-seven adolescents (94 percent) were followed untilthey attained adult height. At the time adult height was achieved,the subjects who had been treated with an LHRH agonist wereolder than those who had received placebo (20.5±2.1 yearsvs. 18.0±2.5 years, P=0.01) and were taller (standard-deviationscore, 2.2±1.1 vs. 3.0±1.2; P=0.01).Analysis of covariance showed that LHRH-agonist treatment resultedin an increase of 0.6 (95 percent confidence interval, 0.2 to0.9) in the standard-deviation score for height, or an increaseof 4.2 cm (95 percent confidence interval, 1.7 to 6.7), overthe initially predicted adult height (P=0.01). Treatment withan LHRH agonist resulted in significantly greater adult heightthan did placebo in boys and girls, in adolescents with idiopathicshort stature, and in those who had a growth-limiting syndrome.The principal adverse event in the LHRH-agonist group was decreasedaccretion of bone mineral density (mean lumbar vertebral bonemineral density at the time adult height was achieved, 1.6±1.2SD below the population mean, vs. 0.3±1.2 SD below thepopulation mean in the placebo group; P<0.001).
Conclusions Treatment with an LHRH agonist for 3.5 years increasesadult height by 0.6 SD in adolescents with very short staturebut substantially decreases bone mineral density. Such treatmentcannot be routinely recommended to augment height in adolescentswith normally timed puberty.
Source Information
From the Unit on Growth and Obesity (J.A.Y.) and the Section on Developmental Endocrinology (J.A.Y., S.R.R., G.M., O.H.P., F.G.C., G.B.C.), Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and the Diagnostic Radiology Division, Warren Grant Magnuson Clinical Center (S.C.H.), National Institutes of Health, Bethesda, Md.
Address reprint requests to Dr. Yanovski at the National Institutes of Health, 10 Center Dr., Bldg. 10, Rm. 10N262, MSC 1862, Bethesda, MD 20892-1862, or at yanovskj{at}mail.nih.gov.
Carel, J.-C., Eugster, E. A., Rogol, A., Ghizzoni, L., Palmert, M. R., on behalf of the members of the ESPE-LWPES GnRH An,
(2009). Consensus Statement on the Use of Gonadotropin-Releasing Hormone Analogs in Children. Pediatrics
123: e752-e762
[Abstract][Full Text]
Cohen, P., Rogol, A. D., Deal, C. L., Saenger, P., Reiter, E. O., Ross, J. L., Chernausek, S. D., Savage, M. O., Wit, J. M., on behalf of the 2007 ISS Consensus Workshop parti,
(2008). Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J. Clin. Endocrinol. Metab.
93: 4210-4217
[Abstract][Full Text]
Shulman, D. I., Francis, G. L., Palmert, M. R., Eugster, E. A., for the Lawson Wilkins Pediatric Endocrine Society,
(2008). Use of Aromatase Inhibitors in Children and Adolescents With Disorders of Growth and Adolescent Development. Pediatrics
121: e975-e983
[Abstract][Full Text]
van Gool, S. A., Kamp, G. A., Visser-van Balen, H., Mul, D., Waelkens, J. J. J., Jansen, M., Verhoeven-Wind, L., Delemarre-van de Waal, H. A., de Muinck Keizer-Schrama, S. M. P. F., Leusink, G., Roos, J. C., Wit, J. M.
(2007). Final Height Outcome after Three Years of Growth Hormone and Gonadotropin-Releasing Hormone Agonist Treatment in Short Adolescents with Relatively Early Puberty. J. Clin. Endocrinol. Metab.
92: 1402-1408
[Abstract][Full Text]
Bonjour, J.-P., Chevalley, T.
(2007). Pubertal Timing, Peak Bone Mass and Fragility Fracture Risk. IBMS BoneKEy
4: 30-48
[Abstract][Full Text]
Maghnie, M., Ambrosini, L., Cappa, M., Pozzobon, G., Ghizzoni, L., Ubertini, M. G., di Iorgi, N., Tinelli, C., Pilia, S., Chiumello, G., Lorini, R., Loche, S.
(2006). Adult Height in Patients with Permanent Growth Hormone Deficiency with and without Multiple Pituitary Hormone Deficiencies. J. Clin. Endocrinol. Metab.
91: 2900-2905
[Abstract][Full Text]
Carel, J.-C., Elie, C., Ecosse, E., Tauber, M., Leger, J., Cabrol, S., Nicolino, M., Brauner, R., Chaussain, J.-L., Coste, J.
(2006). 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.
91: 2972-2979
[Abstract][Full Text]
Foster, C. M.
(2006). Does lupron dosage make a difference in outcome when treating children with precocious puberty?. J. Clin. Endocrinol. Metab.
91: 1667-1668
[Full Text]
Zhou, P., Shah, B., Prasad, K., David, R.
(2005). Letrozole Significantly Improves Growth Potential in a Pubertal Boy With Growth Hormone Deficiency. Pediatrics
115: e245-e248
[Abstract][Full Text]
Brownstein, C. M., Mertens, A. C., Mitby, P. A., Stovall, M., Qin, J., Heller, G., Robison, L. L., Sklar, C. A.
(2004). Factors That Affect Final Height and Change in Height Standard Deviation Scores in Survivors of Childhood Cancer Treated with Growth Hormone: A Report from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab.
89: 4422-4427
[Abstract][Full Text]
Carel, J.-C., Lahlou, N., Roger, M., Chaussain, J. L.
(2004). Precocious puberty and statural growth. Hum Reprod Update
10: 135-147
[Abstract][Full Text]
Faustini-Fustini, M., Balestrieri, A., Rochira, V., Carani, C.
(2003). The Apparent Paradox of Tall Stature with Hypopituitarism: New Insights from an Old Story. J. Clin. Endocrinol. Metab.
88: 4002-4003
[Full Text]
Taback, S. P., Sellers, E. A.C., Dean, H. J., Lee, M. M.
(2003). Is Luteinizing Hormone-Releasing Hormone Agonist Justified in Short Adolescents?. NEJM
349: 192-193
[Full Text]
Lee, M. M.
(2003). Is Treatment with a Luteinizing Hormone-Releasing Hormone Agonist Justified in Short Adolescents?. NEJM
348: 942-945
[Full Text]