Growth Promotion and Turner-Specific Bone Age after Therapy with Growth Hormone and in Combination with Oxandrolone: When Should Therapy Be Started in Turner Syndrome?

Abstract

The aims of this comparative multicenter study of 67 girls with Turner syndrome (TS) on three different therapeutical regimens were, first, to evaluate the effect of either recombinant human growth hormone (GH) alone or in combination with the anabolic steroid oxandrolone (Oxa) on height velocity and on Turner-specific bone age (BA’TS) and, second, to estimate the gain in final height taking the age at the onset of treatment into account. The mean advancement of BA’TS in 2 years of treatment was 2.5 years/2 years in group 1 (low dose GH: 16 IU/m²/week), 2.8 years/2 years in group 2 (high dose GH: 28 IU/m²/week) and 3.3 years/2 years in group 3 (GH: 24 IU/m²/week + Oxa: 0.06 mg/kg/day) instead of the expected 2 years/2 years advancement in untreated girls with TS. On all treatment regimens the advancement of BA’TS was more pronounced in the younger girls. In many girls with a BA’TS below 9 years at the onset of treatment the increase in height did not outweigh the advancement in BA’TS, suggesting that starting growth-promoting treatment before 9 years would not be the best way to improve final height. In our opinion, the optimal age for starting growth-promoting therapy is at 9 years. A start at a younger age might have no advantage in regard of an ultimate gain in final height. On the other hand, therapy should not be delayed much after the age of 9 years giving the girls with TS the possibility to catch up substantially before estrogen treatment is initiated.

Bone Age Progression during the First Year of Growth Hormone Therapy in Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency, Turner Syndrome or Idiopathic Short Stature, and in Short Children Born Small for Gestational Age: Analysis of Data from KIGS (Pfizer International Growth Database)

“…The ratio of the change in BA to the change in CA in girls with TS receiving GH therapy has been reported to be 0.9–1.4 during pre-puberty [24,25,26,27,28,29,30,31,32], which is in agreement with the results of the present KIGS analysis. There was no effect of the dose of GH on BA acceleration [28, 29, 33, 34], which is also consistent with our findings.…”

“…Similar findings have been observed in other studies in TS, where younger children with a more delayed BA showed greater BA advancement and greater height velocity [24,25,26]. This could also be explained by the different natural progression of BA in girls with TS.…”

Estatura final (EF) em síndrome de Turner (ST): experiência de 76 casos acompanhados na Unidade de Endocrinologia Pediátrica do Hospital de Clínicas da Universidade Federal do Paraná

“…Outros grupos de investigadores também relataram ganho de estatura final com o uso isolado de oxandrolona. Urban e cols., em 1979, relataram ganho de 5,9 cm na estatura final (n = 25); Joss e cols., 5,2 cm (n = 67) e Stahnke e cols., 2,4 cm (n = 29) (38,39). Entretanto, Sybert não observou diferença entre pacientes tratadas com oxandrolona comparadas com aquelas que receberam apenas estrogênios e progestágenos (32).…”

“…Esse achado é semelhante ao publicado por Sybert (32), porém diferente dos de outros grupos (38,39).…”

Expectation bias with respect to growth hormone therapy in Turner syndrome

“…In several studies bone age advanced significantly more than chronological age during high-dose growth hormone therapy alone or in combination with oxandrolone or estrogens (7)(8)(9). Bone age accelerates especially at younger ages, so it is suggested that the optimal age of starting growth promoting therapies is 9 years (7).…”