Mapping Normal and Abnormal Gonadotropins and Sex Steroids Across Puberty and When to Use Testosterone in CDGP: A 20-Year Mini-Review

Background: Pubertal development is regulated by the activation of the hypothalamic–pituitary–gonadal (HPG) axis, resulting in progressive increases in gonadotropins and sex steroids. Accurate mapping of normal and abnormal hormone trajectories across puberty is essential for differentiating physiological from pathological pubertal patterns.

Objectives: To review normative data for gonadotropins and sex steroids across pubertal stages in boys and girls, define cut-off values for early pubertal onset (Tanner stage 2), and summarize their diagnostic applications.

Methods: We reviewed tabulated normative data from longitudinal and cross-sectional studies included in the provided manuscript. Hormone values were presented according to Tanner staging, and where available, cut-offs for Tanner stage 2 were identified.

Results: Across puberty, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol progressively increased with Tanner stage, with distinct male–female patterns.

·         Girls: Tanner stage 2 was defined by estradiol values ≥20 pg/mL, basal LH >0.3–0.6 IU/L, and peak LH >5–8 IU/L following GnRH stimulation.

·         Boys: Tanner stage 2 corresponded to testosterone 25–75 ng/dL, basal LH >0.3–0.6 IU/L, peak LH >5–8 IU/L after GnRH stimulation, and testicular volume 4–6 mL (measured by Prader orchidometer or ultrasound).

·         LH and FSH showed low baseline values in Tanner stage 1, with rapid increments at stage 2 and beyond. In boys, testosterone rose sharply from stage 2 onward, while in girls, estradiol increased more gradually, peaking at later stages.

·         Reference intervals for nine steroid hormones demonstrated sex-specific and age-related variations, with marked overlap between late prepuberty and early puberty for some markers.

·         The review confirmed that uterine length >35 mm and ovarian volume >2 mL in girls were supportive of pubertal onset, while testicular volume ≥4 mL in boys was a reliable marker of central puberty initiation.

Conclusion: Normative pubertal hormone reference ranges allow precise differentiation between normal and abnormal timing of puberty. Tanner stage 2 cut-off values—estradiol ≥20 pg/mL in girls, testosterone 25–75 ng/dL and testicular volume 4–6 mL in boys—provide clinically useful thresholds for identifying pubertal onset. Integration of hormonal stimulation and ultrasound parameters enhances diagnostic accuracy in distinguishing central precocious puberty, delayed puberty, and variants of normal development.