Free Testosterone and IGF-I Mediate Sex-Specific Linear Growth During Minipuberty

Pridik, Charlotte; Juul, Anders; Busch, Alexander S

Zusammenfassung

Objective: Postnatal growth velocity peaks in early infancy with transient sex differences, and about 15% of adult height is gained in the first year. This period overlaps with minipuberty, the temporary activation of the hypothalamic-pituitary-gonadal axis. Although minipuberty is critical for reproductive development, its role in somatic growth and its interaction with IGF-I remain unclear. We investigated 1) the relationship between free testosterone (free T) and growth velocity in early infancy, 2) sex differences in these associations, and 3) whether IGF-I mediates these effects. Design: Prospective, longitudinal, population-based birth cohort study (Copenhagen Minipuberty Study, 2016-2018; one-year follow-up). Methods: 189 healthy, full-term, appropriate-for-gestational-age infants (88 girls, 101 boys) followed from birth with repeated anthropometric and hormonal assessments up to 12 months of age. Results: After birth, growth velocity declined in both sexes, with boys growing faster during the first three months before trajectories converged. Free T was positively associated with growth velocity, most strongly in boys. In boys, shifting free T from the 25th to 75th percentile corresponded to an 8.3 cm/year higher growth velocity (95%CI: 3.5-15.3), of which 32.6% (95%CI: 15.3-85.3) was mediated via IGF-I. In girls, indirect effects via IGF-I were modest (0.8 cm/year, 95%CI: 0.05-1.8), while direct effects were not significant. Conclusions: Free testosterone contributes to early postnatal growth both directly and indirectly via IGF-I, with stronger effects in boys. These findings underscore sex-specific endocrine regulation of infant growth and suggest that androgen activity during minipuberty may influence long-term growth trajectories.