Global Variation in Female Pubertal Onset, Progression, and Duration, and Biochemical Thresholds for Diagnosis: A Comparative Review across Continents and Gonadotropin–estradiol Cutoffs

Abstract

Background: Female pubertal onset is a complex, multifactorial biological event with substantial global variation. Secular trends show progressive earlier thelarche and menarche across continents, yet biochemical thresholds for diagnosing pubertal onset and central precocious puberty remain inconsistently defined worldwide. Aim: This study summarizes the biochemical thresholds of gonadotropins and estradiol used to define pubertal onset in girls, highlighting regional variations and diagnostic cutoffs. Objectives: (1) To comprehensively characterize continental and ethnic variation in the timing, progression, and duration of female puberty over the past 25 years; (2) to synthesize published gonadotropin and estradiol cutoff values that define pubertal onset across different assay platforms and global populations; and (3) to propose an evidence-based diagnostic algorithm for evaluating girls with precocious or early puberty in diverse clinical settings. Methods: This is a narrative-analytical comparative review of literature published between January 2000 and April 2026. No quantitative pooling of effect estimates was performed; all findings are presented as descriptive syntheses and ranges from the most relevant or highest-quality studies identified. Studies reporting age at thelarche, pubarche, menarche, or pubertal duration in female populations, as well as those reporting biochemical gonadotropin or estradiol cutoffs for pubertal onset, were included. Quality assessment tools (Newcastle-Ottawa Scale for observational studies; AMSTAR-2 for systematic reviews) were applied as post hoc interpretive frameworks to contextualize evidence quality, not as gatekeeping criteria for inclusion. PRISMA guidelines were not applied. Results: Globally, mean age at thelarche ranges from 8.8 years (African American girls, USA) to 11.0 years (rural sub-Saharan Africa), and mean age at menarche from 11.9 years (urban East Asia/USA) to 14.5 years (rural sub-Saharan Africa). Secular trends show a decline of approximately 0.24 years per decade in age at thelarche from 1977 to 2013. Precocious puberty prevalence is highest in South America (21.5%) and lowest in Europe (3.2%). Biochemical thresholds for CPP diagnosis vary: basal LH cutoffs range from 0.1 to 1.1 IU/L, stimulated peak LH from 5.0 to 15.0 IU/L, and estradiol from 10 to 20 pg/mL, depending on the assay platform. A five-step evidence-informed diagnostic algorithm is proposed, incorporating Tanner staging, first-line basal LH screening (≤0.1 IU/L effectively excludes CPP), pelvic ultrasonography, GnRH agonist stimulation testing (peak LH ≥5 IU/L confirms CPP), and brain MRI for confirmed cases, with a simplified two-step pathway for limited-resource settings. Conclusion: Pubertal timing in girls is profoundly influenced by ethnicity, geography, nutrition, socioeconomic status, and endocrine-disrupting chemical exposure. Current biochemical cutoffs require regional and assay-specific standardization. The proposed evidence-informed diagnostic algorithm integrates clinical, biochemical, and radiological parameters to guide clinicians across varied resource settings.