Longer-Term Histrelin Safe, Effective for Central Precocious Puberty

Long-term treatment with the histrelin implant safely and effectively sustained gonadotropin suppression and improved predicted adult height in central precocious puberty.

Treatment with a once-yearly subcutaneous histrelin implant (Supprelin LA, Endo Pharmaceuticals) was safe and effective for up to 6 years in children with central precocious puberty, new data published in the Journal of Clinical Endocrinology & Metabolism suggest.

“Children with [central precocious puberty] may require extended therapy, often for 3 or more years, to reach an age where the patient, family, and practitioner agree that puberty should resume,” researchers wrote.

Although histrelin has demonstrated continuous suppression of the hypothalamic-pituitary-gonadal (HPG) axis for 1 year and continued suppression through 2 years, “there have been no detailed reports on the suppression of the HPG axis with once-yearly histrelin therapy beyond 2 years,” according to background information in the article. 

In this study, the researchers evaluated 36 children with central precocious puberty (33 girls and three boys) who participated in a phase 3 open-label study and required further treatment with gonadotropin-releasing hormone analogs (GnRHa).

Sixteen children had received GnRHa therapy before and 20 were naïve to treatment. All children received a histrelin 50-mg subcutaneous implant for 12 months. Those who required further GnRHa therapy received a new implant and underwent removal of the old implant after 12 months for up to 6 years.

During the course of therapy, pubertal development was halted, as was demonstrated by measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Physical development of puberty, as assessed through Tanner stage, was also minimal, according to study results.

The researchers also observed a decrease in bone age/chronological age ratio, from 1.417 (n=20) at baseline to 1.18 (n=8) at 48 months, in children who had not received prior GnRHa therapy (P<.01). Additionally, predicted adult height increased from 151.9 cm at baseline to 166.5 cm at 60 months in girls (n=6; P<.05). The height gain was 10.7 cm in children who had no prior GnRHa treatment (n=5).

In terms of safety, data suggested no adverse effect on growth, and LH and FSH levels increased to pubertal levels within 6 months after stopping therapy. The implant was also generally well tolerated during long-term therapy, with the most common treatment-related adverse events being mild to moderate implant site reactions (n=19; 52.8%).

The implant also broke upon removal in 25 of 113 (22.1%) of cases, but complete removal was achieved in all but two cases.

Most patients (92%) who opted not to receive a subsequent year of treatment were deemed age-appropriate for discontinuation of therapy and progression of puberty or had completed the study.

In light of their findings, the researchers concluded: “Sequential therapy with once-yearly histrelin implants is a viable option for patients with [central precocious puberty] who are candidates for continuous long-term GnRHa therapy.”

This study was supported by Endo Pharmaceuticals.


  1. Silverman LA et al. J Clin Endocrinol Metab. 2015;doi:10.1210/jc.2014-3031.