Histrelin

Abstract: Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 μg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n = 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4–8 μg/kg·day, sc) or histrelin (10μ g/kg·day, sc) for 3.1–10.3 yr and were observed at 1, 2, 3, and 4–5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that wher...

Abstract: Context: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin. Objective: The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children. Design: This was a phase III, open-label, prospective study of 1-yr duration. Setting: The study was conducted at nine U.S. medical centers. Patients: Girls ages 2–8 yr (naive) or 2–10 yr (previously treated) and boys 2–9 yr (naive) or 2–11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible. Intervention: A 50-mg histrelin implant was inserted sc in the inner upper arm. Main Outcome Measures: Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures. Results: Thirty-six ...

Abstract: Chronic GmRH agonist (GnRHa) administration has been shown to suppress pituitary-gonadal function in children with central precocious puberty (CPP), but long term data after the reactivation of gonadarche posttherapy are not yet available. This study evaluated the menstrual function of 46 girls with CPP who had been treated for at least 2 yr with GnRHa (deslorelin or histrelin, sc, daily) and were up to 7 yr posttreatment, including 21 postmenarcheal girls who collected weekly overnight urine samples for 12 consecutive weeks to assess rates of ovulation by urinary pregnanediol-3 beta-glucuronide measurements. Menarche occurred at age 12.1 +/- 1.0 yr (mean +/- SD), on the average 1.2 +/- 0.8 yr posttherapy (range, 0.1-4.3 yr). Menstrual cycle lengths became increasingly regular, with cycles of 25- to 35-day duration reported by 41% of the girls in the first year postmenarche and 65% of the girls studied 3 or more years postmenarche. Ovulation was demonstrated in 50% of the girls studied within 1 yr of menarche and in 90% of the girls studied 2 yr or more postmenarche, including 5 girls who reported pregnancies. The development of regular ovulatory menstrual function in these girls with CPP is in accord with previously documented patterns in normal adolescents. While these data provide further evidence supporting the safety of long term GnRHa therapy, continued studies will be necessary to characterize fully the reproductive function in CPP patients through adolescence and adulthood.

Abstract: Objective. Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releas- ing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa histrelin at an average rate of 65 g/day. The aims of this study were to determine if a histrelin im- plant would suppress gonadotropin and estradiol (E2 )i n girls with CPP for 1 year and to compare the suppression to standard treatment. Methods. We studied 11 girls with CPP to determine if the histrelin implant can maintain long-term gonado- tropin suppression. Mean age at diagnosis was 6 1 ⁄2 years (range: 2-9 years). GnRH (100 g intravenously) stimu- lation tests (GnRH-STs) showed peak luteinizing hor- mone and follicle-stimulating hormone responses of 23 28 (mean SD) and 20 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were fol- lowed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed be- fore depot GnRHa treatment, immediately before im- plant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months. Results. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak lutein- izing hormone and follicle-stimulating hormone re- sponses to GnRH-STs at preinsertion versus 9 months were 1.30 1.34 vs 0.25 0.08 and 1.68 1.08 vs 1.13 0.55 mIU/mL, respectively. Basal and stimulated gonad- otropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections. Conclusions. The histrelin implant consistently sup- presses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections. Pediatrics 2005;116:e798-e802. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2005-0538; precocious puberty, gonadotropins, estradiol, GnRH agonists, histre- lin.