Postnatal Ovarian Activation Has Effects in Estrogen Target Tissues in Infant Girls

Context: Shortly after birth, pituitary gonadotropin secretion transiently activates in both sexes, and this surge is more robust in preterm (PT) than in full-term (FT) infants. In boys, the gonadotropin surge is associated with testicular activity and is considered an important part of normal reproductive development. In contrast, gonadal activation and its consequences in infant girls are poorly understood. Objective: Our objective was to evaluate the association of postnatal ovarian activity with simultaneous changes in estrogen target tissues in FT and PT girls. Patients and Methods: We measured urinary estradiol (E-2) levels in 29 FT and 34 PT girls using a mass spectrometric method from 1 week (D7) to 6 months of age (M1-M6). To assess the contribution of ovarian E-2 on urinary E-2 levels, the levels in girls were compared with the levels of boys of similar cohorts (29 FT and 33 PT boys). E-2 levels were compared with simultaneous changes in estrogenic target tissues including mammary glands in both sexes and uterus and vulvar epithelium in girls. Results: Median urinary E-2 levels increased after D7 in girls, but not in boys. Mammary gland diameter was larger in girls than in boys from M4 in FT (P < .001) and M2 in PT infants (P < .0001). In PT girls, E-2 levels increased at term and were then higher than those in FT girls (P < .0001). Urinary E-2 levels in PT girls were positively associated with mammary gland and uterine growth. Conclusions: These findings indicate that gonadal steroidogenesis activates during the postnatal gonadotropin surge in girls. In addition, the resulting elevated E-2 levels affect target tissues, suggesting that postnatal pituitary-ovarian activation plays a role in normal female reproductive development.