Longitudinal evaluation of fetal and infant AGD in healthy children: association with penile size, testosterone and DHT

Margit Bistrup Fischer; Gylli Mola; Lærke Priskorn; Lone Scheel; Hanne Kristine Hegaard; Karin Sundberg; Hanne Frederiksen; Anna-Maria Andersson; Anders Juul; Casper P Hagen

doi:10.1210/clinem/dgae342

Longitudinal evaluation of fetal and infant AGD in healthy children: association with penile size, testosterone and DHT

J Clin Endocrinol Metab. 2024 May 18:dgae342. doi: 10.1210/clinem/dgae342. Online ahead of print.

Authors

Margit Bistrup Fischer^{1

2}, Gylli Mola^{1

2}, Lærke Priskorn^{1

2}, Lone Scheel³, Hanne Kristine Hegaard^{4

5}, Karin Sundberg³, Hanne Frederiksen^{1

2}, Anna-Maria Andersson^{1

2}, Anders Juul^{1

2

6}, Casper P Hagen^{1

2}

Affiliations

¹ Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
² International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Denmark.
³ Center of Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Obstetrics, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁵ Hospital Rigshospitalet, Copenhagen, Denmark.
⁶ Department of Clinical Medicine, University of Copenhagen, Denmark.

PMID: 38761403
DOI: 10.1210/clinem/dgae342

Abstract

Context: The anogenital distance (AGD) is considered a postnatal readout of early fetal androgen action. Little is known of prenatal AGD and how it correlates with AGD postnatally.

Objectives: We present longitudinal measurements of fetal- and infant AGD. We evaluate the impact of testosterone and dihydrotestosterone at minipuberty on AGD and penile size.

Design: Secondary analyses of an observational, prospective pregnancy and birth cohort, COPANA (2020-2022).

Setting: Copenhagen University Hospital - Rigshospitalet.

Participants: 685 healthy, singleton pregnant women enrolled, 657 women attended 3rd trimester ultrasound, 589 infants completed follow-up.

Main outcome measures: 3rd trimester ultrasound (GW29-34): Fetal AGD. Minipuberty clinical examination (app. 3.5 months postpartum): infant AGD, penile width and stretched length (SPL), circulating testosterone and dihydrotestosterone (LC-MS/MS).

Results: AGD was available in 650/657 fetuses (310 boys) and 588/589 infants (287 boys). Boys had longer fetal and infant AGD compared to girls; fetal AGDas: mean (SD) 21.4 mm (±3.5), fetal AGDaf: 12.8 mm (±2.3), p < 0.001, infant AGDas: 32.0 mm (±5.6) and infant AGDaf: 15.8 (±3.3), p < 0.001. Fetal AGD correlated with infant AGD in boys and girls (Spearman's r = 0.275, p < 0.001 and r = 0.189, p = 0.001 respectively), but not with circulating testosterone or dihydrotestosterone at minipuberty. Penile size correlated positively with circulating androgen levels at minipuberty, i.e.: SPL vs testosterone: r = 0.235, p < 0.001.

Conclusions: AGD is sexual dimorphic already in the 3rd trimester. Fetal and infant AGD correlates. AGD is associated with body size but not circulating androgen levels at minipuberty. These findings suggest that fetal and infant AGD, reflect androgen action during early fetal development.

Keywords: androgen action; anogenital distance; fetal anogenital distance; minipuberty.

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