Expert citations
- CPP is closely related to overweight and obesity, and increased BMI may be one of the important factors promoting the initiation and progression of puberty, so it is of great significance to pay attention to the effect of GnRHa treatment on BMI in children with CPP.
- Treatment with GnRHa may increase BMI in children with CPP in the short term, but it is possible that BMI will return to normal when the child reaches adult height.
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As a worldwide public health problem, overweight and obesity seriously affect the healthy growth of children. Most children with obesity have manifestations of early puberty, and children with central precocious puberty (CPP) also have a clear trend of obesity. Maintaining a healthy weight is important for children with CPP. Whether gonadotropin-releasing hormone analogues (GnRHa) as the standard therapy for CPP affect the weight of children with CPP remains controversial.
In this issue, Professor Hou Ling from Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology is invited to discuss the topic of "The Effect of GnRHa Treatment on the Weight of Children with CPP".
Expert Profile
Prof. Ling Hou
- Professor, Chief Physician, Doctor of Medicine, Doctoral Supervisor, Deputy Director of the Department of Pediatric Genetics, Endocrinology and Respiration
- Member of the Pediatric Clinical Pharmacology Group of the Chinese Medical Association
- Member of the Adolescent Medicine Committee of the Pediatric Branch of the Chinese Medical Association
- He is a member of the Pediatric Genetic Diseases Committee of the Chinese Medical Doctor Association
- He is a member of the Standing Committee of the Children's Drug Evaluation Branch of the China Medical Education Association
- He is a member of the Standing Committee of the Children's Medicine and Food Homologous Metabolic Intervention Committee of the China Maternal and Child Health Association
- Member of the Genetic, Metabolic and Endocrinology Group of the Pediatric Branch of Hubei Medical Association
- He has presided over a number of sub-projects of major national science and technology projects and provincial scientific research projects, mainly participated in the key projects of international (regional) cooperation and exchange of the National Natural Science Foundation of China, and was specifically responsible for the World Diabetes Foundation projects and a number of national multi-center drug clinical studies as a secondary leader.
CPP is closely related to overweight and obesity
- Increased BMI may be one of the important factors in promoting the initiation and progression of puberty
Several studies have shown that overweight and obesity in children are closely related to precocious puberty, with most children with precocious puberty having a tendency to be obese, and obese children also have early development of secondary sexual characteristics compared with children of normal weight [1].
Body mass index (BMI) is the most commonly used evaluation index in the evaluation system of obesity [1], which can be used to evaluate the relationship between obesity and other diseases [2]. A multicenter study in mainland China found that BMI was positively correlated with sexual development in Chinese children and higher in girls [2]. Increased BMI may be one of the important factors contributing to the initiation and progression of puberty [3].
A study investigating the relationship between body fat percentage and precocious puberty in girls in mainland China also showed that the whole body fat percentage of CPP children was significantly higher than that of healthy control children (P<0.05), and in precocious puberty girls, the basal values of luteinizing hormone (LH) in the high body fat percentage group and the peak LH and LH/follicle-stimulating hormone under the provocation test were significantly higher than those in the low body fat percentage group (P<0.05) [1]. It can be seen that overweight and obesity interact with CPP. Therefore, it is particularly important to pay attention to the effect of GnRHa treatment on the body weight of children with CPP in the treatment of CPP.
Treatment with GnRHa does not increase the risk of overweight and obesity in children with CPP
GnRHa has been the first-line treatment for CPP [4], and there is substantial evidence-based evidence confirming the efficacy and safety of GnRHa therapy. However, the effect of GnRHa treatment on BMI or standard deviation score of BMI (BMI-SDS) has been controversial. A recent systematic review and meta-analysis, published in January 2024, included a total of 28 studies designed to evaluate the short- and long-term effects of GnRHa therapy on BMI in patients with CPP [4].
Short-term results showed that at the end of GnRHa treatment, the BMI-SDS of girls with CPP and children with normal body weight was higher than that of baseline BMI-SDS
At the end of GnRHa treatment (duration of treatment 0.5 to 5 years), the BMI-standard deviation score (BMI-SDS) was greater than the baseline BMI-SDS (WMD = 0.14, 95% CI: 0.04 to 0.23; p = 0.004）。 Sex-based subgroup analysis showed that at the end of GnRHa treatment, the BMI-SDS of girls with CPP was higher than that of baseline BMI-SDS, with a statistically significant difference (WMD = 0.15, 95% CI: 0.05-0.25; P = 0.005)； No difference was found in BMI-SDS compared to baseline in boys with CPP (WMD = 0.04, 95% CI: -0.15-0.23; p = 0.698) (Figure 1).
Figure 1. Forest plot of the short-term effect of GnRHa treatment on BMI
In normal-weight boys and girls, BMI-SDS at the end of GnRHa treatment was higher than baseline BMI-SDS (WMD = 0.34; 95% CI: 0.19-0.48; p < 0.001); there was no significant difference between BMI-SDS at the end of GnRHa treatment and baseline BMI-SDS in overweight or obese children (WMD = - 3.65, 95% CI: - 9.96-2.67; p = 0.258) (Figure 2).
Figure 2. Forest plot of the short-term effect of GnRHa treatment on BMI in children with different body weights
Long-term results show that BMI-SDS returns to baseline after reaching adult height in children with CPP
BMI-SDS returned to baseline after reaching adult height (AH) in children with CPP (WMD = - 0.03, 95% CI: - 0.39 to 0.32; P = 0.815), suggesting that the effect of GnRHa treatment on BMI would disappear as the child grows.
Sex-based subgroup analysis showed that all girls (WMD = - 0.08, 95% CI: - 0.50 to 0.34; p = 0.716) and boys (WMD = 0.16, 95% CI: - 0.07 - 0.39; P = 0.174) was not significantly different from baseline in BMI-SDS (Figure 3).
Figure 3. Forest plot of the long-term effect of GnRHa treatment on BMI
Weight-based subgroup analysis showed that at AH, normal-weight children (WMD = - 0.18, 95% CI: - 0.67 to 0.31; P = 0.467) and BMI-SDS (WMD = - 0.27, 95% CI: - 1.12-0.58; p = 0.536) (Figure 4).
Figure 4. Forest plot of the long-term effects of GnRHa treatment on BMI in children with different body weights
The above data suggest that GnRHa treatment may increase BMI in patients with CPP in the short term, but it is possible that BMI may return to normal when patients reach adult height. The results of this study are consistent with the view expressed in the Chinese Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2022) that "GnRHa treatment does not aggravate the trend of obesity, and body mass index (BMI) returns to normal levels after stopping GnRHa treatment [3]".
【Experts' Conclusion】
Overweight and obesity are closely related to CPP, and both of them can damage the physical health of children to varying degrees. Therefore, there is an urgent need for effective treatments to treat CPP without increasing the risk of overweight and obesity in children. GnRHa is the basic treatment for CPP, and it is generally believed that GnRHa does not cause obesity. In patients with CPP treated with GnRHa, BMI should be monitored longitudinally to determine the long-term effect of treatment. For the long-term effects of GnRHa treatment, the study found no significant effect of GnRHa on BMI, and although GnRHa treatment may increase BMI in the short term, it is possible that BMI will return to normal when patients reach adult height. Based on the current findings, GnRHa treatment has no long-term effect on BMI in children with CPP, nor does it increase the risk of obesity.
References 1.Wang Lingxiao, Cheng Ruoqian, Zhang Miaoying, et al.Relationship between whole body fat ratio and precocious puberty in girls[J].CJCP,2020,22(07):762-767.
2. Xu Xiaoqin, Zhang Jianwei, Chen Ruimin, et al.Relationship between body mass index and sexual development level in Chinese children[J] .Chinese Journal of Pediatrics,2022,60(4): 311-316.
3. Endocrinology, Genetics and Metabolism Group, Chinese Society of Pediatrics, Chinese Journal of Pediatrics, Editorial Committee.Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2022)[J].Chinese Journal of Pediatrics,2023,61(01):16-22.
4.Hou L, Ying Y, Wu W, Zhang C, Luo X. The effect of GnRHa treatment on BMI in central precocious puberty: A systematic review and meta-analysis. Horm Res Paediatr. 2024 Jan 5.
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