Biphasic Pattern of Circulating Reproductive Hormones in Female Infants – The Longitudinal Copenhagen Minipuberty Study
Background: Minipuberty denotes a transient activation of the hypothalamic-pituitary-gonadal (HPG) hormone axis in infancy. This activation provides an opportunity to examine the gonadal function in infants suspected of hypogonadism before the axis is silenced during childhood. However, female minipuberty remains poorly elucidated.
Objective: The study aimed to evaluate dynamic changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, anti-Müllerian hormone (AMH), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) in infant girls during first year of life and to establish sex- and age-related reference ranges for these hormones.
Method: The COPENHAGEN Minipuberty Study (ClinicalTrials.gov #NTC02784184) is a prospective, longitudinal cohort study of 233 healthy infants (98 girls) born AGA to healthy mothers between 2016 and 2019. Each child was examined 6 times including repeated blood sampling during the first years of life. Random-coefficient spline models were fitted to each hormone using maximum-likelihood estimation procedures for linear mixed models, which allowed for prediction of the individual hormone level trajectories as well as estimation of population-level local peak times of hormones. Generalized Additive Model for Location, Scale and Shape was used to establish reference ranges.
Results: In total, data from 98 infant girls with 266 available serum samples were included in this study. A biphasic hormone pattern with two peaks was observed in raw data as well as normalized mean curves for all hormones. The first peak for all hormones was timed around postnatal days 16-27, while the second peaks occurred day 107-125 for inhibin B, AMH, E1, E2, and SHBG. For LH and FSH, the second peaks occurred slightly later (day 165 and 171, respectively). For all hormones, nadir between peaks was observed between postnatal days 58 to 78. In addition, reference curves were established for LH, FSH, inhibin B, AMH, E1, E2, and SHBG. The average within-child variation was up to ±1.2 standard deviation scores for all hormones, except for E1 (±1.4).
Conclusion: In this study of minipuberty in healthy, infant girls with repeated blood sampling during the first year of life, we found a hitherto undescribed biphasic secretory pattern of reproductive hormones, which appeared more prolonged than previously anticipated. Thus, the window of opportunity for endocrine diagnostics in female infants may be wider than previously assumed.
22 Sep 2021 - 26 Sep 2021