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

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.