The Effect of Long-Acting GnRHa Therapy on Central Precocious Puberty

Long-acting gonodotropin-releasing hormone agonist (GnRHa) therapy for central precocious puberty (CPP) has similar efficacy to shorter acting variants. Infrequent dosing of long-acting GnRHa therapy for precocious puberty may lead to improved compliance and quality of life, according to results published in the Journal of Endocrine Society.

Researchers aimed to evaluate long-acting GnRHa formulations and assess their ability to suppress leutenizing hormone (LH), physical changes, and bone age (BA) advancement in patients with CPP.

A retrospective study (ClinicalTrials.gov Identifier: NCT03695237) was conducted using the first part of a phase 3, open-label, multicenter study. The first part of the study was a 48-week treatment period consisting of 2 scheduled doses of leuprolide acetate (LA) depot 45 mg that was given at baseline and again at week 24. 

Children with a diagnosis of CPP (defined as the appearance of prepubertal changes before the chronological age [CA] of 8 years in girls or 9 years in boys and a BA advanced ≥1 year over CA) who were GnRHa therapy naive or had been previously treated with a standard GnRHa were included in the study. Individuals with a diagnosis of peripheral precocious puberty or short stature, or with endocrine abnormalities were excluded from the study.

The primary endpoint was the proportion of patients with stimulated LH suppression of less than 4 mIU/mL at week 24. Stimulated LH suppression at weeks 12, 20, 44, and 48 were assessed as secondary endpoints.

Physical pubertal signs were evaluated by breast palpation in girls and genitalia examination in boys. Suppression was defined as regression or no progression in breast development and testicular volume for girls and boys, respectively. X-rays of the left hand and wrist were evaluated for BA using a BoneXpert automated system, and BA/CA ratio was calculated and compared at baseline and throughout the study.

A total of 45 participants (41 girls and 4 boys) were included in the final evaluation, of which 18 were previously treated and 27 were GnRHa-naïve. Overall, 86.7% (95% CI, 73.3%-95.0%) of patients had peak-stimulated LH suppressed to less than 4 mIU/mL at week 24, with suppression maintained at week 4 through to week 48 for 86.7% to 91.1% of the study cohort. Compared with previously treated patients, treatment-naive patients had a lower mean LH concentration below baseline value post-week 4 through week 48 (<1.6 mIU/mL vs <2.1 mIU/mL).

At 24 and 48 weeks, breast development in girls overall was suppressed in 92.7% and 90.2% of patients, respectively. Boys had similar results, with 50% and 75% having physical signs suppressed at week 24 and 48, respectively.

Of note, mean BA/CA ratio declined by 0.1 in both the treatment naive and previously treated groups. The mean change in BA/CA at weeks 24 and 48 was 0.2 to 0.7, indicative of a slower advancement of BA compared to CA.

The inclusion of a small number of boys in the study and no direct comparison of other GnRHa treatments for CPP were cited as the major limitations of the study.

The authors wrote, “The LA 6-month IM depot formulation provides an additional option for individualized treatment decisions that may benefit patients by reducing the number of injections required to maintain suppression, which can potentially improve treatment compliance and quality of life.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.