Proximal hypospadias correlates with a higher 2D:4D ratio, and urogenital abnormalities in pre-pubertal boys
Fardod O'Kelly, MD MA FRCS(UROL)1, Michael Leonard, MD FRCSC2, Martin A. Koyle, MD FRCSC3, Walid Farhat, MD FRCSC3, Feargal J. Quinn, MD FRCS(Paed)1, Salvatore Cascio, MD FEBPS FRCS(Paed)1.
1Our Lady's Childrens Hospital, Dublin, Ireland, 2Childrens Hospital of Eastern Ontario (CHEO), Ottawa, ON, Canada, 3The Hospital for Sick Children (Sick Kids), Toronto, ON, Canada.
Hypospadias is an epidemiologically common congenital disorder in males, affecting approximately 1/400 live male births. Among the myriad of associations, much research has focused on the role of prenatal androgen exposure as a putative causative factor, especially during the male programming window (8-14weeks gestation). Whilst finger length differences were apparent in sexual dimorphism since the late nineteenth century, its role in hypospadias severity remains unknown. The objective of our study was to determine if pre-pubertal boys classified into distal or proximal hypospadias have a normal or abnormal 2D:4D ratio, and what correlation exists, if any, with ano-scrotal distance and penile width
Pre-pubertal patients (<5 years old) seen in the outpatient clinic for hypospadias between July 2016 and March 2017 were prospectively enrolled. Anthropomorphic measurements of finger length ratios, penile width and anogenital distance were measured using digital calipers. Birth weight calculations were adjusted for gestational age at birth. Cases and controls were age-matched. Normality of data was assessed using the Anderson-Darling test. Bivariate logistic regression analysis was used to determine the association between glans width and finger length ratios and anogenital distance. Differences were analysed using the Mann-Whitney test for non-normally distributed data. Spearman's rank correlation was calculated for non-continuous data. A p-value of less than 0.05 was considered statistically significant.
Data and measurements were collected for 90 boys with hypospadias (55 distal hypospadias and 35 proximal hypospadias) and 55 controls. There were statistically significant differences in 2D:4D ratios in each hand (p<0.001), as well as individual analysed digits (p<0.001), as well as reduced anogenital distance (p<0.001), when comparing the proximal hypospadias group with either the distal or control groups. There were no significant differences between the distal hypospadias and control groups alone. There were no significant differences in glandular width between any of the three groups with an overall median width of 15mm. There were no significant differences in measurements between term and pre-term births
This study is the first to demonstrate increased 2D:4D ratios with proximal hypospadias, which also correlates with a shortened anogenital distance. This may provide a non-invasive anthropomorphic measurement, which can also be measured in utero, to offer an indirect indicator of aberrant androgen exposure during the MPW, and a useful marker for urogenital development
Anogenital Distance (AGD)
Male programming Window (MPW)
Testicular Dysgenesis Syndrome (TDS)
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