Pharmacotherapy for children with central precocious puberty or early puberty: A systematic review and meta-analysis

The intervention of gonadotropin-releasing hormone agonist or in combination with recombinant human growth hormone (rhGH) is still controversial for children with central precocious puberty (CPP) or early puberty (EP). This study aimed to systematically review and compare the efficacy and safety of current therapeutic regimens for CPP or EP based on different timings of intervention.

We searched 7 databases and 2 registers for available studies from inception until December 2023. Two independent reviewers screened literature, extracted data, and assessed the risk of bias. Eligible data from randomized controlled trials and non-randomized studies of interventions were synthesized with meta-analysis and further performed subgroup analysis.

A total of 55 studies were included in this review, including 11 randomized controlled trials and 44 non-randomized studies of interventions. The pharmacotherapy was beneficial to final height (FH) for the girls with CPP or EP (for combination therapy: mean difference [MD] 1.58, 95% confidence interval [CI] 0.66-2.51; for monotherapy: MD 2.51, 95% CI 1.26-3.76), and subgroup analysis showed that CPP with puberty onset aged before 8 years (for combination therapy: MD 3.69, 95% CI 1.59-5.79; for monotherapy: MD 4.83, 95% CI 3.29-6.17), early intervention before 8 years of age (for combination therapy: MD 3.50, 95% CI 1.75-5.25; for monotherapy: MD 6.50, 95% CI 4.99-8.01), and the course of combination with rhGH for more than 2 years (MD 3.31, 95% CI 2.14-4.47) improved higher FH. The pharmacologic intervention had less impact on the body mass index at FH (MD -0.06, 95% CI -0.50 to 0.38), but probably increase the risk of the incidence of polycystic ovary syndrome (risk ratio 1.93, 95% CI 1.26-2.98) in the long term.

The gonadotropin-releasing hormone agonist improved the FH of children with CPP, and in combination with rhGH appeared to further increase the effectiveness of pharmacotherapy. The increasing risk of polycystic ovary syndrome should be considered before treatment and further confirmed through high-quality comparative studies in the future.