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

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 1; pp. 103 - 107
• Main Authors: Weise, Martina, Flor, Armando, Barnes, Kevin M, Cutler, Gordon B, Baron, Jeffrey
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.01.2004; Copyright by The Endocrine Society
• Subjects: Age Determination by Skeleton; Biological and medical sciences; Body Height; Child; Child, Preschool; Estrogens - physiology; Female; Gonadotropin-Releasing Hormone - adverse effects; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - therapeutic use; Growth Disorders - chemically induced; Growth Plate - physiopathology; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Puberal and climacteric disorders (male and female); Puberty; Puberty, Precocious - drug therapy; Puberty, Precocious - physiopathology; Regression Analysis; Time Factors; Triptorelin Pamoate - adverse effects; Triptorelin Pamoate - analogs & derivatives; Triptorelin Pamoate - therapeutic use; Endocrinopathy; Hypothalamic hormone; Human; Growth; Analog; Peptide hormone; Gonadotropin RH; Hormone replacement therapy; Hormone releasing factor; Precocious puberty
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-021999

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.