International AGD Database; Determinants of AGD and Establishment of Normative Data

Introduction Increasing incidence of cryptorchidism, hypospadias, and testicular cancer has paralleled the concomitant decline in male fertility in several countries(1). Exposures of environmental agents, which act as endocrine disruptors resulting in abnormalities in the development and function of fetal tests, have been hypothesised to underlie these trends. However, these outcomes are relatively rare, and in some cases occur a long period after exposure. Development of a sensitive biomarker of fetal androgen action during infancy is critical to evaluate the effects of potential endocrine disrupting environmental agents on the reproductive system.

Anogenital distance (AGD) defined as the distance from the anus to genital tubercle is a sensitive marker for prenatal exposure to endocrine-disrupting chemicals in animals (1,2). However, unlike in animals, the external genitalia are well differentiated in humans and the anatomical landmarks to measure AGD have been a matter of debate. This has resulted in several proxy measurements of AGD using multiple anterior landmarks such as anterior insertion of the penis, posterior insertion of penis or perineoscrotal junction (3).

Nevertheless, several human studies have reported an association between exposure to a variety of commonly used environmental chemicals and reduction in AGD in humans (1,2,4). AGD remains the single biomarker, which has showed consistent alterations related to prenatal exposure to environmental agents with established endocrine-disrupting activity in animals. Furthermore, a reduced AGD has been shown in common disorders of male reproductive health such as hypospadias, cryptorchidism, reduced semen quality and infertility (1,2,5).

Rationale for the study The use of AGD in epidemiological studies has several limitations. Varying methods used for measurement is believed to result in considerable variations in the AGD values (6). A few small studies have also suggested the possibility of ethnic variation. Normative data is vital particularly in cross-sectional studies. Normative data for some types of AGD has been published, however, population data using more standardised methods for measurement and on other types of AGD are vital in understanding the potential effect of endocrine disruptors on reproductive health (7,8). Large datasets from international collaboration are important to study variations related to types of measurement techniques and ethnicity, and explore the relationship between AGD, environmental exposures and male reproductive disorders.

The aim of the project is to set up an international AGD database to promote and facilitate research in the area related to AGD and, therefore, provide the researchers access to a large dataset derived from multiple studies.