Anogenital distance in patients with Klinefelter syndrome

Anogenital distance (AGD) is a sexually dimorphic marker of genital development and fetal androgen activity. Shortened AGD has been linked to impaired male fertility. The distinct phenotypic and reproductive characteristics associated with Klinefelter syndrome (KS) may influence AGD. This study aimed to investigate AGD measurements in men with KS and evaluate their clinical significance.

A case-control study was conducted involving 87 male participants categorized into three groups: normospermic (n=51), KS (n=18), and idiopathic non-obstructive azoospermia (iNOA; n=21). AGD was measured as the anoscrotal distance (AGDAS) using a digital caliper. Physical and hormonal evaluations, semen analyses, and karyotyping were performed. Group differences were analyzed using analysis of variance with post hoc testing, and Pearson correlations were calculated between AGD and clinical variables.

AGD measurements differed significantly between groups (F(2,87)=15.2, p<0.0005). AGD was longer in the normospermic group compared to the iNOA group (p<0.0005) and longer in the KS group than in the iNOA group (p=0.015). No significant difference was observed between normospermic and KS groups (p=0.153). Hormonal analyses showed lower testosterone and estradiol levels in KS patients compared to iNOA. Correlation analyses did not identify significant associations between AGD and clinical or hormonal parameters.

AGD in men with KS is comparable to normospermic individuals and longer than in iNOA patients. In clinical assessments, the presence of small testes in individuals with AGD measurements similar to normospermic men may raise suspicion for KS.