Abstract

BackgroundAnogenital distance (AGD), a sexually dimorphic measure of genital development, is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies. Given the correlation between anogenital distance and genital development, we sought to determine if anogenital distance varied in fertile compared to infertile adult men.MethodsA cross sectional study of consecutive men being evaluated for infertility and men with proven fertility was recruited from an andrology clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. ANOVA and linear regression were used to determine correlations between AGD, fatherhood status, and semen analysis parameters (sperm density, motility, and total motile sperm count).FindingsA total of 117 infertile men (mean age: 35.3±17.4) and 56 fertile men (mean age: 44.8±9.7) were recruited. The infertile men possessed significantly shorter mean AGD and PL compared to the fertile controls (AGD: 31.8 vs 44.6 mm, PL: 107.1 vs 119.5 mm, p<0.01). The difference in AGD persisted even after accounting for ethnic and anthropomorphic differences. In addition to fatherhood, on both unadjusted and adjusted linear regression, AGD was significantly correlated with sperm density and total motile sperm count. After adjusting for demographic and reproductive variables, for each 1 cm increase in a man's AGD, the sperm density increases by 4.3 million sperm per mL (95% CI 0.53, 8.09, p = 0.03) and the total motile sperm count increases by 6.0 million sperm (95% CI 1.34, 10.58, p = 0.01). On adjusted analyses, no correlation was seen between penile length and semen parameters.ConclusionA longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men.

Highlights

  • Over the past half century there has been a reported decline in semen quality and male births with an increased rate in male genital abnormalities and testis cancers [1,2,3]

  • A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential

  • While the phenomenon and etiology is uncertain, several groups postulate an environmental factor which disrupts normal endocrine signaling leading to abnormal androgen action and altered testicular development [3,4]

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Summary

Introduction

Over the past half century there has been a reported decline in semen quality and male births with an increased rate in male genital abnormalities and testis cancers [1,2,3]. Human studies have validated such findings in infants and toddlers demonstrating that boys have longer perineal lengths than girls [8,9,10,11]. Investigators have used such a gender discrepancy to show that agents which disrupt androgen signaling can lead to abnormal genital lengths in animal models [12,13]. Anogenital distance (AGD), a sexually dimorphic measure of genital development, is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies. Given the correlation between anogenital distance and genital development, we sought to determine if anogenital distance varied in fertile compared to infertile adult men

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