This project, which has been active on the MGH GCRC since the early 1980's, now focuses on detailed characterization of the growth, final height, and pubertal outcomes of children with central precocious puberty (CPP) who have undergone long-term pituitary-gonadal suppression induced by chronic administration of a GnRH agonist (GnRHa). Evaluations continue to be performed at 6-12 month intervals in children with CPP who have undergone long-term pituitary-gonadal suppression induced by GnRHa administration and who have not yet completed their linear growth and pubertal development. Results in the initial cohort of children with CPP who completed their growth defined a statistically significant increase in adult stature of 4-6 cm compared to pretherapy predictions. However, recent analyses which have included more patients who initiated GnRHa treatment at younger ages and earlier stages of puberty demonstrate a more substantial effect on final height. In the cohort of patients enrolled before CA 6 years, final HTs exceed pretherapy predictions by 8-10 cm. As our final group of young patients complete their therapy with GnRHa and complete their growth post-GnRHa, the impact of long-term gonadal sex steroid suppression on growth and final height may be viewed across the full developmental spectrum of our patient population. The investigators continue to monitor the return of pubertal pituitary function following the discontinuation of GnRHa administration and the eventual development of mature reproductive endocrine function. Follow-up is underway to characterize reproductive function (including fertility) in patients in whom therapy has been discontinued for several years. Most recently, we have utilized the ability of GnRHa administration to reversibly suppress pituitary-gonadal function to probe further the physiology of the non-steroidal FSH regulators, inhibin A & B and follistatin, and leptin, the product of the ob gene.
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