The efficacy and safety of pharmacotherapy for girls with central precocious puberty or early puberty: a retrospective cohort study

Abstract

Purpose: The use of recombinant human growth hormone (rhGH) for central precocious puberty (CPP) and early puberty (EP) is off-label and lacks reliable evidence for clinical practice. This study aimed to compare the long-term efficacy and safety of gonadotrophin releasing hormone analogue (GnRHa) in combination with or without rhGH for the treatment of CPP and EP, and to explore the differences in the efficacy of different intervention timing. Methods: The medical information of girls with CPP or EP at a women’s and children’s hospital from January 2013 to December 2018 was retrospectively collected. The primary outcome of efficacy was final height, and the secondary outcome included height gain, genetic height gain, standard deviation score of final height (FHSDS), and standard deviation score of height (HSDS) gain. The safety outcomes were the rate of composite adverse event and the rate of each adverse event. The generalized linear model (GLM) including confounders as covariates was applied to compare the difference between the groups, and subgroup analysis was further performed to explore the efficacy with different timing of intervention. Results: A total of 182 girls with CPP or EP were finally included in this study. The adjusted results of GLM showed that the final height in the combination therapy group (162.58 ± 0.46 cm) was significantly higher than that in the monotherapy group (160.25 ± 0.35 cm) and the no treatment group (158.39 ± 0.47 cm) (P < 0.001), and the height gain, genetic height gain, FHSDS, and HSDS gain were all significantly different among the three groups (P < 0.001). Besides, the incidence of composite adverse events was greatly increasing in the combination therapy group (P < 0.001), among which the incidence of fasting insulin elevation and hypothyroidism was significantly higher than the other two groups (P < 0.001). Subgroup analysis showed that the girls who entered puberty after the age of 8 years (P = 0.051), initiated pharmacotherapy at the age of 10-12 years (P = 0.204, P = 0.178), treated with GnRHa for less than one year (P = 0.718), and combined with rhGH for less than one year (P = 0.064) may not improve the final height. Conclusions: The combination of GnRHa and rhGH can improve the final height of girls with CPP and EP to a certain extent, especially for those who began pharmacotherapy before 10 years of age and continued treatment for more than one year, but meanwhile increased the incidence of adverse events. The benefits, risks, and affordability of medication should still be comprehensively considered before the decisions on pharmacotherapy.