Associations between hypospadias, cryptorchidism and anogenital distance: Systematic review and meta-analysis

Hypospadias and cryptorchidism are potential manifestations of testicular dysgenesis syndrome (TDS) at birth. Anogenital distance (AGD) has been presumed as an indicator related to endocrine disruptors proposed as one of the pathogenetic mechanisms underlying male reproductive disorders. In humans, recent studies have correlated AGD in boys to testicular anomalies. However, the associations between hypospadias, cryptorchidism and AGD remain inconsistent and have not been combined. Hence, we conducted a meta-analysis to assess gradations in the severity of the endocrine disruption in cryptorchidism or hypospadias by using AGD. A total of 2,119 boys from five birth cohort studies and two cross-sectional studies were subjected to meta-analysis. Random-effect model was used to calculate the standardised mean difference (SMD) of AGD. Our results reveal that boys with hypospadias or cryptorchidism have shorter AGD ([SMD, -2.63; 95% CI, -4.65 to -0.62] and [SMD, -0.69; 95% CI, -1.36 to -0.02]) respectively. There was no indication of a publication bias either from the result of Egger's test or Begg's test for hypospadias and cryptorchidism.