Leuprolide Acetate 1-Month Depot for Central Precocious Puberty: Hormonal Suppression and Recovery

Children with central precocious puberty (CPP) prematurely develop pubertal pulsatile release of gonadotropin-releasing hormone (GnRH), leading to an increase in gonadotropin and sex steroid levels, development of secondary sexual characteristics, advancement of bone age (BA), and consequent reduction in adult height (AH) [1]. Treatment goals include hormonal suppression, cessation of development of secondary sex characteristics, halting or preventing menarche, and preservation of AH. If left untreated, children with CPP can also face psychological challenges resulting from premature physical maturation that contrasts with their immature emotional development [2].GnRH analogs (GnRHa) have been the standard of care for CPP for over 15 years [1]. Continuous exposure to GnRHa desensitizes pituitary gonadotroph receptors and suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion. Efficacy of various GnRHa in CPP has been established [3–14], but truly long-term studies are limited, particularly for leuprolide. Furthermore, most GnRHa studies have not utilized sensitive gonadotropin assays that can accurately assess the extent of hormonal suppression. The objectives of this open-label treatment study of leuprolide acetate 1-month depot and long-term observational extension study were to evaluate the suppression of the pituitary-gonadal axis and the clinical sexual characteristics during treatment and to examine the long-term impact on the growth pattern, AH, and reproductive function of children treated for CPP. Initial results from the treatment period led to FDA approval of leuprolide acetate 1-month depot for the treatment of CPP. Here we report hormonal suppression during the treatment period, safety, recovery of hormone secretion, and long-term reproductive outcomes. A separate paper reports the auxological outcomes [15].All patients were na？ve to GnRHa therapy. Females with Tanner breast stage ≥2 before 8.0 years old and chronological a