OBJECTIVE:Recently published animal studies indicate that leptin and ghrelin play a role in puberty initiation and progress as well as in reproduction. The aim of our study was to evaluate the relation of these two hormones to the pubertal maturity and fertility status in patients with β-thalassemia. DESIGN: Blood levels of leptin, acylated ghrelin and sex hormones were determined in 97 (59 males and 38 females) beta-thalassemic patients, aged 18-23 years and in 50 healthy subjects (27 males and 23 females) matched for age. Body Mass Index (BMI) was also assessed. RESULTS: Besides lower BMI, all the hormones evaluated were significantly lower in β-thalassemic patients compared to controls (p<0.001). Furthermore, the leptin/ghrelin ratio in female patients was lower than the values obtained in the controls (p<0.001). Finally, significant negative correlations (p=0.050) were detected between circulating levels of acylatedghrelin and LH, FSH and sex hormones in female and male patients. CONCLUSIONS: The lower values of leptin and ghrelin in patients with β-thalassemia possibly constitute another hormonal imbalance which may contribute to the phenotype of impaired growth and sexual maturation encountered in these patients. The findings on the ghrelin levels constitute a novel observation.