ESPE Abstracts (2018) 89 RFC8.4

Establishing Age, Sex, and Method Related Reference Ranges for Anogenital Distance - a Marker of In Utero Androgen Action

Marie Lindhardt Ljubicica,b, Ajay Thankamonyc, Carlo Acerinic, Tina Kold Jensena,b,d, Katharina M Maina,b, Jørgen Holm Petersena,b, Alexander S Buscha,b, Emmie Upnersa,b, Casper P Hagena,b, Shanna H Swane & Anders Juula,b

aDepartment of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark; bInternational Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; cDepartment of Paediatrics, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK; dDepartment of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odensen, Denmark; eDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Background: Anogenital distance (AGD) is an indicator of androgen action in utero. Reduced AGD has been found in males with hypospadias, cryptorchidism, low semen quality and infertility. Its usefulness as a clinical marker in patients with Disorders of Sex Development (DSD) is currently being investigated. However, detailed age, sex and method related reference ranges do not exist. Whether individual (body-size-adjusted) AGD is stable postnatally also remains to be elucidated.

Objective: i) To create age, sex and method-related reference ranges for both ‘short’ (anus-scrotum/fourchette (AGDas/f) and ‘long’ (anus-penis/clitoris (AGDap/c) measurement techniques for AGD. ii) To evaluate individual longitudinal changes of AGD in young children.

Method: The International AGD Database contains a total of 7703 AGD examinations performed on 3623 healthy children aged 0–26 months. Reference ranges for AGDas/f (TIDES and Cambridge method) and AGDap/c (Cambridge) were generated using the Lambda-Mu-Sigma (LMS) method. Individual dynamics of AGD was evaluated by longitudinal observations (146 individuals, 488 observations) of AGD and adjusting for body size (length, weight, BMI and BSA).

Results: We present age-, sex- and method related reference ranges for AGD. E.g. the short AGD in boys (AGDas, TIDES method) increased from birth (24.3±3.9 mm (mean ±2 S.D.)) to 4 months of age (36.3±5.8 mm) after which it was relatively stable until 20 months. In boys, individual short AGD (AGDas, TIDES method) was stable when adjusting AGD (mm) per body length (cm), BMI (kg/m2) or body surface area (m2) from birth to 14 months of age (mean coefficients of variation (CV) of 7.9, 8.2 and 9.6%, respectively). Similarly, in girls, short AGD (AGDas, TIDES method) was stable from birth to 14 months when adjusting AGD (mm) per body length (cm) and BMI (kg/m2) (mean CVs of 8.3% for both).

Conclusion: We provide age, sex and method related reference ranges for AGD. Intra-individual AGD adjusted for body size remained stable during infancy which supports AGD as a prenatally determined marker. Reference ranges could be used for future epidemiological research and may have a clinical application when evaluating prenatal androgen action in DSD patients.