GnRH agonists continually stimulate the pituitary gonadotrophs, leading to desensitization and decreases in LH release and, to a lesser extent, FSH release after an initial flare-up. They have transformed the management of precocious puberty since their initial use in early 80s. However, several issues remain unresolved that are pertinent to the indications and use of these medications. Different GnRH agonists are available in various depot forms and their use results in the regression or stabilization of clinical pubertal symptoms. Gonadotropin levels can be monitored but the optimal level of suppression has not been established. The main endpoints considered for GnRH agonist treatments are short term effects on pubertal development (clinical, biological or by ultrasound examination) and long term effects on height. No controlled trial comparing treated and untreated outcome has been performed and the evaluation relies on the comparison between observed and pretreatment predicted outcomes. Height gains of variable magnitude are observed and are associated with several factors. The optimal time to stop treatment has not been established prospectively. Pubertal signs generally reappear a few months after interruption of GnRH agonist treatment. Long-term fertility has not been fully evaluated, but preliminary results are reassuring. Tolerance is considered satisfactory but treatment may be associated with menopause-like symptoms and local tolerance can be a concern. Concerns have been raised about the possible risk of obesity and osteoporosis. Unresolved issues concern the association of GnRH agonists with other medications such as growth hormone and steroids.
03 - 07 May 2008
European Society of Endocrinology