Puberty is the developmental stage where sexual maturity and reproductive capacity are acquired, leading to the adult phenotype. The biological process of puberty involves a complex orchestration of hormonal signaling regulated by the hypothalamic-pituitary-gonadal (HPG) axis. In both sexes, this system is activated by gonadotropin-releasing hormone (GnRH) from the hypothalamus, which stimulates the release of  luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. These in turn drive gonadal production of sex steroids such as estrogen and testosterone (Argente et al., 2023).

Expected pubertal timing in humans has a wide variation. In females, puberty typically begins with adrenarche, followed by thelarche (breast development), pubarche (hair growth), and menarche (onset of menstruation). In males, the sequence includes adrenarche, gonadarche (testicular growth and testosterone production), pubarche, and spermarche (onset of sperm production). These physical changes reflect deeper neuroendocrine dynamics that differ by sex. Trends indicate an advancement in the typical age range of puberty onset in girls, although the underlying biological reason for this sex difference remains unclear (Argente et al., 2023). This review focuses on the biological and environmental evidence that may explain why females generally enter puberty earlier than males. 

Sex differences in puberty onset are primarily influenced by variations in kisspeptin expression , neurokinin b (NKB) signaling, and insulin-like growth factor-binding protein-5 (IGFBP-5) regulation. These molecular pathways help determine how early the hypothalamic-pituitary-gonadal (HPG) axis is reactivated in each sex (Argente et al., 2023).

Kisspeptin and NKB Signaling

Kisspeptin, encoded by the KISS1 gene, is a neuropeptide that directly stimulates GnRH neurons and plays a key role in triggering pubertal onset (Semaan et al., 2022). Females show higher levels of Kiss1 mRNA in the arcuate nucleus (ARC), which leads to earlier and more robust GnRH release (Semaan et al., 2022). NKB, a neuropeptide co-expressed with kisspeptin in the ARC, enhances this stimulatory effect and is also regulated differently between sexes (Yao et al., 2022). These patterns of kisspeptin and NKB expression contribute to earlier reproductive axis activation in females (Yao et al., 2022). 

IGFBP-5 and Growth Factor Regulation

IGFBP-5 modulates the availability of insulin-like growth factor-1 (IGF-1), a hormone that supports GnRH neuron activity (Kauffman et al., 2009). In males, elevated IGFBP-5 expression reduces IGF-1 bioavailability, which dampens GnRH stimulation and delays the onset of puberty (Kauffman et al., 2009). This mechanism may help explain why males typically begin puberty later than females (Argente et al., 2023; Kauffman et al., 2009).

Conclusion

Females tend to begin puberty earlier than males due to sex-specific differences in hypothalamic signaling and growth factor regulation. Higher kisspeptin and NKB expression in the female brain leads to earlier activation of GnRH neurons, while greater IGFBP-5 expression in males reduces IGF-1 activity, delaying puberty onset (Semaan et al., 2022; Yao et al., 2022; Kauffman et al., 2009). 

In simpler terms, females begin puberty earlier because their brains activate the hormonal systems responsible for sexual development sooner and more strongly than in males. Environmental and nutritional factors such as body mass index, rapid early growth, and exposure to endocrine-disrupting chemicals may further influence these pathways and reinforce the sex difference in timing (Yao et al., 2022). Together, these findings highlight the multifactorial nature of puberty and the interplay between internal and external drivers of its onset. 

References

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2. Semaan, S. J., & Kauffman, A. S. (2022). Developmental sex differences in the peri-pubertal pattern of hypothalamic reproductive gene expression, including Kiss1 and Tac2, may contribute to sex differences in puberty onset. Molecular and cellular endocrinology, 551, 111654. https://doi.org/10.1016/j.mce.2022.111654

3. Yao, Z., Lin, M., Lin, T., Gong, X., Qin, P., Li, H., Kang, T., Ye, J., Zhu, Y., Hong, Q., Liu, Y., Li, Y., Wang, J., & Fang, F. (2022). The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats. Reproductive biology and endocrinology: RB&E, 20(1), 100. https://doi.org/10.1186/s12958-022-00966-7

4. Kauffman, A. S., Navarro, V. M., Kim, J., Clifton, D. K., & Steiner, R. A. (2009). Sex differences in the regulation of Kiss1/NKB neurons in juvenile mice: implications for the timing of puberty. American journal of physiology. Endocrinology and metabolism, 297(5), E1212–E1221. https://doi.org/10.1152/ajpendo.00461.2009