Timing of onset of menses after GnRH agonist treatment for central precocious puberty

Karen O Klein; Marcela Vargas Trujillo; Sanja Dragnic; Stephen Van Komen; Moming Li; Peter A Lee

doi:10.1515/jpem-2023-0543

Timing of onset of menses after GnRH agonist treatment for central precocious puberty

J Pediatr Endocrinol Metab. 2024 Apr 15. doi: 10.1515/jpem-2023-0543. Online ahead of print.

Authors

Karen O Klein^{1

2}, Marcela Vargas Trujillo^{1

2}, Sanja Dragnic³, Stephen Van Komen³, Moming Li³, Peter A Lee⁴

Affiliations

¹ Rady Children's Hospital, San Diego, CA, USA.
² Department of Pediatrics, University of California, San Diego, CA, USA.
³ AbbVie, North Chicago, IL, USA.
⁴ Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Penn State Hershey Medical Center, Hershey, PA, USA.

PMID: 38618862
DOI: 10.1515/jpem-2023-0543

Abstract

Objectives: To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP).

Methods: This exploratory post hoc analysis of a phase 3 and 4 trial of girls with CPP treated with once-monthly intramuscular leuprolide acetate examined onset of menses after treatment completion using a time-to-event analysis. Pretreatment and end-of-treatment chronologic age (CA), bone age (BA)/CA ratio, and Tanner breast stage; pretreatment menses status; and end-of-treatment BA and body mass index (BMI) were studied as potential factors influencing the onset of menses.

Results: Median time to first menses after stopping treatment was 18.3 months among 35 girls (mean age at onset of treatment, 6.8 years) examined. Of 26 girls experiencing menses, 11 (42 %) menstruated at 16-21 months after stopping treatment. Most girls with pretreatment BA/CA≥1.4 started menstruating very close to 18 months after stopping treatment; those with less advanced BA/CA experienced menses at 9-18 months. End-of-treatment BA/CA≥1.2 was associated with a quicker onset of menses (14.5 vs. 18.5 months for BA/CA<1.2, p=0.006). End-of-treatment BA≥12 years predicted longer time to menses. No relationship with time to menses was observed for pretreatment menarche status, pretreatment or end-of-treatment Tanner breast stage (<3/≥3) or CA (<6/≥6 or ≤11/>11), or end-of-treatment BMI percentiles (<85.6/≥85.6 and <92.6/≥92.6).

Conclusions: Pretreatment menarche status or CA do not appear to predict onset of menses, but pre- and end-of-treatment BA/CA may be helpful in anticipating time to first menses after stopping treatment.

Keywords: bone age; central precocious puberty; leuprolide; menstruation; posttreatment; pubertal maturation.