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Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty
Martina Weise1, Armando Flor, Kevin M Barnes
1Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA.
Insights
Children with precocious puberty (PP) treated with GnRH analogs (GnRHa) experience reduced height velocity. This impaired growth is linked to estrogen-induced growth plate senescence, with bone age being the strongest predictor.
Area of Science:
- Pediatric Endocrinology
- Growth and Development
- Reproductive Endocrinology
Background:
- Precocious puberty (PP) treatment with Gonadotropin-releasing hormone analogs (GnRHa) can lead to decreased height velocity in children.
- Previous animal studies suggest impaired growth may result from accelerated growth plate senescence due to estrogen exposure.
Purpose of the Study:
- To test the hypothesis that impaired growth during GnRHa therapy in central PP is caused by excessive growth plate senescence from prior estrogen exposure.
- To determine the relationship between height velocity during GnRHa treatment and markers of prior estrogen exposure.
Main Methods:
- Analysis of data from 100 girls with central PP treated with GnRHa.
- Correlation of height velocity during treatment with bone age (BA) as a marker of growth plate senescence.
- Assessment of the relationship between growth abnormality severity and markers of estrogen exposure (PP duration, Tanner stage, BA advancement).
Main Results:
- Height velocity during GnRHa therapy was significantly low for age.
- Absolute height velocity strongly correlated with bone age (r = -0.727, P < 0.001).
- Growth abnormality severity inversely correlated with PP duration, Tanner breast stage, and BA advancement.
- Bone age was the best independent predictor of growth during GnRHa therapy.
Conclusions:
- Impaired growth during GnRHa therapy in central PP is likely partly due to premature growth plate senescence induced by prior estrogen exposure.
- Bone age serves as a crucial indicator for predicting growth response during GnRHa treatment.
Abstract:
In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure.
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