ESPE Abstracts

Background: Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, which leads to an increased release of gonadotropin-releasing hormone (GnRH). GnRH stimulates the development of secondary sexual features, rapid bone maturation and growth. GnRH agonists (GnRHa) represent the gold-standard therapy in CPP children and their use is responsible for pituitary GnRH receptors down-regulation, luteinizing hormone (LH) and follicle stimulating hormone (FSH) suppression up to gonadal sex hormones blockade. Several pharmaceutical formulations of GnRHa, such as buserelin, histrelin, leuprorelin, triptorelin and goserelin, are available and used clinically. The treatment is generally safe and well tolerated. However, several studies reported side effects, including bruising, pain, injection reactions and sterile abscesses. Furthermore, flushes, headaches, and nausea were observed and are classified as minor menopausal-like side effects. Study design: The present study is intended to: a) identify which side effects were featured in CPP patients; b) discover possible correlations between clinical and radiological parameters and side effects. 85 female patients (median age 7.35 ± 0.67) affected by CPP were enrolled in this retrospective study, carried out from 2018 to 2020. The enrolled patients were treated with leuprolide (46 patients) or triptorelin (39 patients) and minor menopausal-like side effects appearance during therapy was investigated. Moreover, clinical parameters and radiological changes were monitored to evaluate the possible relationship between GnRHa treatment and side effects appearance. Results: Overall 40 (47,1%) of the studied patients reported minor menopausal-like symptoms. Although the bone age was significantly lower in symptomatic patients (P = 0,004) than in those asymptomatic, no significant differences were observed between symptomatic and asymptomatic patients in chronological age (P = 0,16), weight (P = 0,20) and height (P = 0,29) before treatment. In addition, symptomatic patients showed a higher ovarian volume and breast growth (BG) than asymptomatic females (P = 0,005), whereas no significant differences were detected in peak-stimulated or basal LH, FSH and somatomedin C levels between the two groups of patients. Concerning the drug used, 23 patients treated with triptorelin and 17 patients with leuprolide reported symptoms (P = 0,043). The patients treated with triptorelin or leuprolide showed headache (33,3% vs 15,2%), mood swings (20,5% vs 17,4%), increased appetite (20,5% vs 17,4%) and nausea (2,6% vs 10,9%). Symptoms were managed with analgesics or over the counter (OTC) medications so that it was possible to keep GnRHa treatment. Conclusion: Our results suggest the need of implementing pharmacovigilance activity in pediatric patients treated with GnRH agonists in order to optimise and personalise the treatment.