Physiology of pubertal development in females Original paper

What was reviewed?

This review article provides a comprehensive overview of the hormonal, physiological, and anatomical changes that occur during female puberty. The authors detail the sequential events, from the activation of neuroendocrine axes to the emergence of secondary sexual characteristics, and discuss the regulatory factors influencing pubertal onset and progression. Special emphasis is placed on the roles of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, the development and maturation of the reproductive system, and the clinical assessment using the Tanner staging system. The review highlights the multifactorial control of puberty, with genetic, hormonal, nutritional, and environmental contributions, and underscores how deviations from normal physiology can manifest as disorders of pubertal timing.

Who was reviewed?

The review synthesizes data from a broad range of studies and clinical observations involving female children and adolescents, primarily in the United States but with recognition of international and ethnic variations. The summary incorporates findings from large population-based cohorts, such as the National Health and Nutrition Examination Survey (NHANES III), and references clinical and laboratory research on hormonal assays and physical development. The populations discussed include females across the entire pediatric age spectrum, from fetal life through adolescence, and stratify findings by ethnicity and body mass index (BMI) to account for known differences in pubertal timing and progression.

Most important findings

The review delineates the orchestrated activation of the HPG axis as the fundamental driver of female puberty, marked by the pulsatile release of gonadotropin-releasing hormone (GnRH), subsequent increases in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and ovarian maturation. Menarche is the culminating event, signifying reproductive maturity but not necessarily full ovulatory cycles initially. The HPA axis independently mediates adrenarche, manifested by increased adrenal androgen production leading to pubic and axillary hair, sweat gland maturation, and acne. The timing of pubertal milestones, such as thelarche, pubarche, growth spurt, and menarche, varies by ethnicity and BMI; higher BMI is associated with earlier puberty onset, and non-Hispanic black and Mexican American females may experience thelarche and menarche earlier than non-Hispanic white females. The review establishes Tanner staging as the clinical standard for assessing secondary sexual development.

Notably, the article summarizes the hormonal interplay: LH stimulates theca cells to produce androgens, FSH stimulates granulosa cells to convert androgens to estrogens, and estrogen is pivotal for breast development, endometrial growth, and bone maturation. The review also addresses the impact of estrogen on epiphyseal closure and bone mineral density, linking delayed menarche to increased fracture risk. The regulatory cascade involves excitatory neuropeptides (like kisspeptin and glutamate) and inhibitory neurotransmitters (such as GABA) that modulate GnRH release. While the review does not focus on the microbiome, it provides a critical physiological background for interpreting how emerging research on the gut and vaginal microbiota might intersect with pubertal development, particularly regarding hormonal regulation and metabolic changes.

Key implications

For clinicians, this review underscores the importance of understanding normative pubertal physiology to accurately identify and manage disorders of puberty, such as precocious or delayed puberty. The nuanced discussion of population differences in pubertal timing and the role of BMI highlights the need for individualized assessment. The physiological framework described herein is essential for integrating future research on microbiome signatures and their impact on pubertal progression, hormone metabolism, and disease risk. Recognizing the hormonal and developmental milestones enables clinicians to better counsel patients and families, promote healthy development, and anticipate complications arising from abnormal pubertal trajectories, including impacts on bone health and psychosocial well-being.