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Determinants of Growth during Gonadotropin-Releasing Hormone Analog Therapy for Precocious Puberty

Developmental Endocrinology Branch (M.W., A.F., K.M.B., J.B.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862; and Lilly Research Laboratories (G.B.C.), Eli Lilly & Co., Indianapolis, Indiana 46285

Address all correspondence and requests for reprints to: Jeffrey Baron, M.D., National Institutes of Health, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, Maryland 20892-1862. E-mail: jbaron{at}mail.nih.gov.

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.

Abbreviations: BA, Bone age; CA, chronological age; E2, estradiol; GnRHa, GnRH analogs; PP, precocious puberty; SDS, SD score.

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