DENVER – A subdermal implant that was approved to treat central precocious puberty for 1 year may in fact last twice as long, according to an ongoing, prospective, observational study.
The histrelin implant suppresses early activation of the hypothalamic-pituitary-gonadal (HPG) axis in children experiencing central precocious puberty, Dr. Katherine A. Lewis said at the meeting Endo Pharmaceuticals' 50-mg Supprelin LA implant accomplishes this through the daily release of 65-mcg histrelin, a potent gonadotropin-releasing hormone analogue (GnRHa).
“If you calculate this out, theoretically it could maintain [HPG axis] suppression for 2 years,” Dr. Lewis said.
The researchers enrolled 32 children with a clinical or biochemical diagnosis of central precocious puberty. They then assessed the 7 boys and 25 girls at baseline and every 6 months for growth and pubertal stage.
So far, 29 children have completed 1 year of the study and 18 have completed the full 24 months. Bone age x-rays were taken at baseline and at 12 and 24 months.
Ultrasensitive luteinizing hormone (LH) testing was performed at 6 and 18 months. Any patient with an ultrasensitive LH value greater than 1 IU/L also underwent a GnRHa stimulation test. Otherwise, participants had GnRHa stimulation testing at 12 and 24 months.
Peak LH was 0.9 IU/L at 1 year (range, 0.2-2.2), well within the definition of HPG suppression used in the study (peak LH less than 4.0 IU/L). The researchers found that peak LH was 1.0 IU/L at 24 months. “So clearly all patients had HPG axis suppression on their stimulation tests,” said Dr. Lewis, a pediatric endocrinology fellow at Riley Hospital for Children, Indianapolis.
“The histrelin implant maintains continued HPG axis suppression when left in place for 2 years,” Dr. Lewis said. “Obviously, this has some implications for clinical care and could potentially lead to reduced cost and reduced number of procedures for patients undergoing treatment for central precocious puberty.”
Implants were removed before the end of the study in two patients who demonstrated progression of puberty, Dr. Lewis said. For example, one patient had the implant removed at 18 months because of increasing breast development and advancing bone age. The other patient had the implant removed at 22 months because of increasing breast development. However, both patients still demonstrated complete biochemical HPG axis suppression according to GnRHa stimulation testing just prior to implant removal (peak LH values of 0.04 IU/L and 0.06 IU/L, respectively).
“We are looking at [those data] for additional information that will give us any idea why” these two patients progressed despite the biochemical suppression, Dr. Lewis said. An initial theory about androgen excess was not supported. Both patients did have significant weight gain during the study, she added.
In all, 19 children were naive to treatment and 13 were previously treated with depot leuprolide, Dr. Lewis said. Mean age at implantation time was 7.2 years (range, 2.5-10.8 years). Median weight was 30 kg. Two girls had a history of menarche, but no patient achieved menarche during the study.
The bone age to chronological age ratio at 12 months was 1.25 vs. 1.22 at 24 months. “This was a mild difference and not statically significant,” Dr. Lewis said.