SynthesisEuropean journal of pediatrics2026
Association between anogenital distance and hypospadias: a systematic review and meta-analysis.
Synthesis in European journal of pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The association between hypospadias, its severity, and anogenital distance remains inconsistent. This study aims to investigate the association between anogenital distance and hypospadias through a meta-analysis. We conducted a comprehensive search in international databases (PubMed, Web of Science, Cochrane Library, Embase, Medline) and Chinese databases (China National Knowledge Infrastructure, Wanfang Data, VIP database). We searched for studies on the association between anogenital distance and hypospadias. The search period extended until November 1, 2025. Thirteen studies involving 6905 male infants were included in the meta-analysis. We calculated the standardized mean difference and 95% confidence interval for anogenital distance using a random-effects model. The results indicated that children with hypospadias had a shorter anogenital distance (standardized mean difference, - 1.24; 95% confidence interval, - 1.74 to - 0.74). A negative correlation was observed between anogenital distance and hypospadias severity. Children with more severe hypospadias had a shorter anogenital distance. The standardized mean differences were - 1.05 (95% confidence interval, - 2.23 to 0.13) for distal hypospadias, - 1.66 (- 3.14 to - 0.18) for middle hypospadias, and - 3.00 (- 4.70 to - 1.31) for proximal hypospadias.
conclusionOur study suggests that shortened anogenital distance is associated with hypospadias and may correlate with disease severity, consistent with the hypothesis of fetal androgen disruption. However, due to the observational nature of the included studies and significant heterogeneity, causal inference is limited. Anogenital distance may serve as a research endpoint, but prospective studies are needed to validate its etiological and clinical utility.
trial registrationThe study protocol has been registered in PROSPERO ( https://www.crd.york.ac.uk/prospero ) under the registration number CRD42023407183. WHAT IS KNOWN: • In animal studies, anogenital distance is negatively correlated with hypospadias severity. • The association between anogenital distance and hypospadias has yielded inconsistent results in human studies. WHAT IS NEW: • Anogenital distance is negatively correlated with the severity of hypospadias in human studies, which supports the role of impaired fetal androgen production/action in the pathogenesis of hypospadias. • Anogenital distance may serve as an indicator for reproductive health assessment endpoints.
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