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Histrelin Halts Precocious Puberty

January 13, 2006

Premature puberty - or "precocious puberty" - is caused by hormonal imbalance. It can cause girls to go through puberty as early as age seven or eight years, well before they are ready to begin sexual maturation.

Now, Israeli researchers have developed a method to stop the process of precocious puberty using an implant of the drug histrelin.

The study was published in Pediatrics in December and reported by Reuters Health on December 26, 2005.

Histrelin strongly inhibits gonadotropin-releasing hormone (also called luteinizing hormone-releasing hormone, or LHRH). LHRH is produced by the hypothalamus; it signals the anterior pituitary gland to secrete luteinizing hormone and follicle-stimulating hormone.

According to researchers Hirsch et al, the histrelin implant effectively treats central precocious puberty.

"The histrelin implant consistently suppresses clinical and laboratory parameters of puberty for one year and is a promising new technique for treating central precocious puberty without the pain and inconvenience of monthly injections," write authors Dr Irving M Spitz, from Shaare Zedek Medical Centre, Jerusalem, and colleagues.

Precocious puberty is usually treated by administering intramuscular or subcutaneous gonadotropin-releasing hormone agonist every 3-4 weeks. Although the method is usually effective in suppressing clinical and laboratory parameters of puberty, the injections are painful and require monthly clinic visits that may decrease treatment compliance.

The researchers set out to determine whether a subcutaneous histrelin implant would suppress release of estradiol and gonadotropin. Release of these two hormones brings on puberty and menstruation.

The study was small, consisting of 11 girls of average age six years (age range 2-9 years) who had central precocious puberty. The trial duration was 12 months, after which time Hirsch et al compared results of the histrelin suppression with the effects of standard treatment.

The researchers followed six girls for 15 months after implant insertion; in the remaining five girls, researchers removed the implant after nine months and inserted a new implant at the same incision site.

Results showed that none of the girls had menstrual bleeding whiel receiving the implant treatment, and mean breast-development regressed somewhat, growth velocity decreased and bone-age advancement was slowed during treatment.

Acceleration of bone maturation and growth velocity both normally signal the end of growth in height.

At nine months after commencement of treatment, puberty hormones remained suppressed in all 11 girls, and at 15 months the hormones remained suppressed in the six girls who returned to have the implant removed.

The results showed that all of the participants reported decreased pain, discomfort and interference with school activity and work, compared with standard monthly injections.

"A multicenter clinical trial is currently underway in the United States," Dr Spitz told Reuters Health. "We are continuing to follow our Israeli patients, and we plan to study (normal hormone) recovery following implant removal at the completion of the course of treatment."

Hormone-blocking implant halts too-early puberty, Will Boggs, MD, Reuters Health on Yahoo! News, December 26, 2005.
The Histrelin Implant: A Novel Treatment for Central Precocious Puberty. Harry J Hirsch, MD, et al. Pediatrics, volume 116(6), pages e798-e802, December 2005.

Posted: January 2006