There are a few reports of side-effects of LHRHa treatment in childhood, the mechanisms of which remain little understood. Such effects can be local reactions: erythema, induration, wheal and sterile abscess formation, which can be possible causes of therapy failure. There are negative effects on growth velocity and final height requiring rhGH therapy or a suppressive treatment when bone age >13 years. Excessive weight gain can occur by various mechanisms: menopausal-like phenomena, or LHRHa influence on hypothalamic and/or leptin-mediated control of body weight. Other possible adverse effects involve increased ovarian volume with possible POS development; however, there is no evidence correlating LHRHa, hyperandrogenism and POS. The latter appears related to CPP onset with pre-existing hyperandrogenism, although lengthier follow-up is necessary to confirm this. Bone density decreases during therapy, but final peak bone mass is in the normal range. Frequent transitory side-effects include headaches, hot flushes, depression and irregular menses.