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Postnatal Dysregulation of Androgens in Extremely Preterm Male Infants
Anders K Nilsson1, Ulrika Sjöbom1,2, Andreas Landin3
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-405 30, Sweden.
Insights
Extremely preterm infant males show early and elevated androgen levels post-birth, suggesting hypothalamic-pituitary-gonadal axis activation. This early hormonal surge may impact neurodevelopment, requiring further investigation.
Area of Science:
- Neonatal endocrinology
- Neurodevelopmental research
- Pediatric endocrinology
Background:
- Neurodevelopmental impairments are common in extremely preterm infants, especially males.
- Hyperactivation of the hypothalamic-pituitary-gonadal (HPG) axis is a suspected, yet understudied, cause.
Purpose of the Study:
- To determine androgen levels and their changes over time in extremely preterm infant males.
- To investigate the early activation of the HPG axis in this population.
Main Methods:
- An observational cohort study of infant males born between 22.8-27.9 weeks gestational age.
- Analysis of cord blood and postnatal plasma (up to 11 weeks) for testosterone, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).
- Hormone quantification using gas chromatography mass spectrometry, enzyme-linked immunosorbent assay, and Luminex xMAP multiplex assay.
Main Results:
- Postnatal androgen (testosterone and DHT) levels on day 0 were significantly higher than cord blood levels and peaked early.
- Androgen levels declined rapidly by day 5 and remained relatively constant, but were approximately 6-fold higher than in utero levels.
- Follicle-stimulating hormone and luteinizing hormone exhibited similar postnatal patterns to androgens, while sex hormone-binding globulin increased, reducing bioavailable testosterone.
Conclusions:
- The hypothalamic-pituitary-gonadal axis is activated immediately after birth in extremely preterm males, leading to an early androgen pulse.
- This premature, elevated androgen exposure during a critical neurodevelopmental window warrants further research into its long-term implications.
Context:
Neurodevelopmental impairments are common among survivors of extremely preterm birth, particularly in males. Hyperactivation of the hypothalamic-pituitary-gonadal (HPG) axis has been suggested as an underlying cause, but this has been poorly investigated.
Objective:
Establish levels and temporal changes in circulating androgens in extremely preterm infant males.
Methods:
Observational cohort study analyzing cord blood serum (n = 25) and postnatal plasma (n = 13) collected from day 0 until week 11 from infant males born at 22.8-27.9 weeks gestational age. Testosterone and dihydrotestosterone (DHT) were determined using gas chromatography mass spectrometry, sex hormone-binding globulin (SHBG) with an enzyme-linked immunosorbent assay, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with the Luminex xMAP multiplex assay.
Results:
Testosterone and DHT levels were higher on day 0 (median 4.27 and 0.30 ng/mL) than in cord blood (0.15 and 0.01 ng/mL) (P < .001 for both). Levels of the hormones then declined rapidly until day 5 (median 0.16 and 0.12 ng/mL), then remained relatively constant throughout the study period. Median levels of testosterone and DHT across the whole study period were approximately 6-fold higher than reported in utero levels. FSH and LH showed similar postnatal patterns as the androgens. SHBG steadily increased over time, and, as a result, the fraction of bioavailable testosterone declined with infant postnatal age.
Conclusion:
The HPG axis is activated immediately after birth in extremely preterm infant males, resulting in an androgen pulse occurring several months earlier than during a normal pregnancy. The long-term implications of high androgen exposure during a sensitive neurodevelopmental period warrant further studies.
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