Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome

Massa, Guy; Maes, Marc; Heinrichs, Claudine; Vandeweghe, Mark; Craen, Margarita; Vanderschueren-Lodeweyckx, M

doi:10.1111/j.1365-2265.1993.tb01003.x

Cited by 20 publications

(16 citation statements)

References 15 publications

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“…Other studies, in contrast, found a decrease in HV and an increase in bone maturation leading to a decrease in height gain (25,30). The reason why our results are in conflict with these studies, however, might be that a higher dose of estrogen was used compared with that in our study.…”

Section: Discussioncontrasting

confidence: 96%

Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens

Pareren

Keizer‐Schrama

Stijnen

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

215

147

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Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age.Girls were randomly assigned to group A (4 IU/m 2 ⅐d; ϳ0.045 mg/kg/d), group B (first year, 4 IU/m 2 ⅐d; thereafter 6 IU/m 2 ⅐d), or group C (first year, 4 IU/m 2 ⅐d; second year, 6 IU/m 2 ⅐d; thereafter, 8 IU/m 2 ⅐d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 ؎ 0.7 yr, low dose micronized 17␤-estradiol was given orally. After a mean duration of GH treatment of 8.6 ؎ 1.9 yr, FH was reached at a mean age of 15.8 ؎ 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 ؎ 6.5 or ؊1.6 ؎ 1.0 in group A, 162.9 ؎ 6.1 or ؊0.7 ؎ 1.0 in group B, and 163.6 ؎ 6.0 or -0.6 ؎ 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, ؊1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than ؊2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated.In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV. (2), subnormal levels of GH and IGF-I have been reported (3, 4). It has been postulated that a diminished sensitivity for growth factors might explain their growth retardation (5, 6). Nevertheless, GH treatment in a supraphysiological dosage has been shown to accelerate growth (4, 7). Another clinical feature in most girls with TS is the absence of spontaneous pubertal development, for which estrogen substitution is necessary. Although GH treatment for short stature in TS is now an accepted treatment in many countries, reports on final height are inconsistent (8,9), and which dosage to use and which age to start puberty induction are issues of debate.Previously, we have demonstrated that long-term GH treatment in TS leads to normalization of height (4, 10). This study shows final height (FH) results in 60 girls with TS treated in a randomized dose-response trial comparing 3 dosage schedules. In addition, we show the effect of low dose estrogen treatment begun at a relatively ...

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Section: Discussioncontrasting

confidence: 96%

Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens

Pareren

Keizer‐Schrama

Stijnen

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

215

147

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“…On the one hand, this is in accordance with reports com paring advancement of BA conventionally assessed in treated and untreated girls with TS [7,8,11,13,15,24,26]: but on the other hand, it is in contrast to the state ment that growth-promoting therapy leads to 'no undue advancement of BA' [2,9,10,14,16], This latter state ment, however, docs not take into account that in un treated girls with TS the BA assessed by conventional methods will advance far less than 1 year/ycar, especially in older girls ( fig. I).…”

Section: Discussionsupporting

confidence: 78%

“…Other investigators having been aware of this method ological problem have plotted the BA advancement on therapy on a graph including the norms of untreated TS [11,15,26] or mentioned for each age group which advancement of BA would have been expected in un treated TS [7], Since the use of Turner-specific charts for height and height velocity is generally accepted, we suggest the same procedure for BA. Consequently, in untreated girls with TS the Turner-specific BA (BATS) will advance by defi nition 1 year/year at any age.…”

Section: Introductionmentioning

confidence: 99%

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?

et al. 1997

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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.

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“…The optimal age at which estrogens should be introduced, and the optimal dosage, are still a matter of debate. However, the results of all studies indicate that the early introduction of estrogens has a deleterious effect on height [17,18]. The general per ception is that there is a trade-off between the achieve ment of puberty within the normal physiological timeframe and improvement of FH, but no consensus on the optimal age for introduction of estrogen therapy has been reached.…”

Section: Karg F Rmentioning

confidence: 92%

Growth Hormone Therapy for Turner Syndrome: Evidence for Benefit

Carel¹,

Mathivon²,

Gendrel³

et al. 1997

Horm Res

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Growth hormone (GH) is registered for children with Turner syndrome (TS) in several countries. Improving the final heights (FH) is certainly the most worthy goal of therapy, but evaluation of treatment effect is complicated by methodological difficulties. Several series of FH results have now been published, with estimated benefits ranging from 0-9.3 cm, as compared to predicted height before treatment. The majority of studies report height gains of less than 5 cm, but in these studies, GH was started at a relatively late age and used at low doses. Several approaches can be utilized to improve FH results in TS, including early initiation of GH therapy, increased or optimized GH dose regimens, or optimization of sexual steroid utilization.

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Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome

Cited by 20 publications

References 15 publications

Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens

Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens

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?

Growth Hormone Therapy for Turner Syndrome: Evidence for Benefit

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