Sex-Based Differences in Leptin Levels During Puberty in Normal Weight and Obese Youth

Overview

This meta-analysis evaluated sex differences in leptin concentrations across pubertal stages in children and adolescents with normal weight and overweight/obesity. Girls with normal weight consistently exhibited higher leptin levels than boys at all pubertal stages, whereas these sex differences were diminished or absent in children with overweight/obesity. The findings suggest that leptin alone does not fully explain the sex-specific effects of obesity on pubertal timing.

Background

Leptin, an adipocyte-derived hormone, plays a critical role in energy homeostasis and the initiation of puberty by signaling nutritional sufficiency to the hypothalamic-pituitary-gonadal axis. Puberty involves complex hormonal changes, with sex steroids influencing body composition and leptin levels. Obesity in childhood is associated with elevated leptin levels and altered pubertal timing, particularly earlier puberty in girls. However, the extent to which sex differences in leptin levels emerge during puberty and how obesity affects these differences remains unclear.

Data Highlights

Key Findings

• Girls with normal weight have significantly higher leptin levels than boys at all pubertal stages (MD: 3.99; 95% CI, 2.63-5.35).
• In children with overweight/obesity, no significant sex differences in leptin levels were observed during prepubertal and pubertal stages.
• Postpubertal girls with overweight/obesity showed higher leptin levels than boys, but this finding is based on a single study (MD: 14.60; 95% CI, 0.95-28.25).
• Among pubertal children with overweight/obesity, boys had a higher BMI standard deviation score than girls (MD: −0.67; 95% CI, −0.74 to −0.61).
• The typical sex-specific leptin differences seen in normal-weight children are lost in obesity, indicating leptin alone may not explain sex differences in pubertal timing related to obesity.
• Other factors, such as sex dimorphism in kisspeptin signaling, may contribute to the differential effects of obesity on puberty between sexes.

Clinical Implications

Clinicians should recognize that leptin levels differ by sex in normal-weight children but that these differences are attenuated in obesity, which may influence pubertal development. Since leptin alone does not fully explain the earlier pubertal onset observed in obese girls, a multifactorial approach considering other neuroendocrine regulators is warranted when assessing pubertal timing in overweight and obese youth. Monitoring pubertal progression alongside metabolic and hormonal profiles remains essential.

Conclusion

Sex differences in leptin concentrations are evident throughout puberty in normal-weight children but are diminished in those with overweight or obesity. This suggests that leptin is not the sole mediator of obesity-related alterations in pubertal timing, highlighting the need to explore additional mechanisms underlying sex-specific pubertal development.

References

1. Sex-Based Variations in Leptin Concentrations Among Normal Weight and Overweight/Obese Children and Adolescents Throughout Puberty: A Comprehensive Review and Meta-Analysis