Using change in predicted adult height during GnRH agonist treatment for individualized treatment decisions in girls with central precocious puberty

J Pediatr Endocrinol Metab. 2022 Dec 5;36(3):299-308. doi: 10.1515/jpem-2022-0476. Print 2023 Mar 28.

Abstract

Objectives: It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care.

Methods: Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models.

Results: BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months).

Conclusions: These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH.

Keywords: bone age; central precocious puberty; duration of therapy; height velocity; leuprolide; predicted adult height.

MeSH terms

  • Adult
  • Age Determination by Skeleton
  • Age Factors
  • Body Height* / drug effects
  • Duration of Therapy
  • Female
  • Gonadotropin-Releasing Hormone* / agonists
  • Humans
  • Leuprolide* / therapeutic use
  • Precision Medicine
  • Puberty, Precocious* / drug therapy

Substances

  • Gonadotropin-Releasing Hormone
  • Leuprolide