Anogenital distance as a marker of androgen exposure in humans
Journal of Andrology
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Thankamony, A., Pasterski, V., Ong, K., Acerini, C., & Hughes, I. (2016). Anogenital distance as a marker of androgen exposure in humans. Journal of Andrology https://doi.org/10.1111/andr.12156
Abnormal fetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a ‘testicular dysgenesis syndrome’. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during fetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of fetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of fetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD.
anogenital distance, endocrine disrupters, prental androgen exposure, masculanising programming window, testis development, testicular dysgenesis syndrome, TDS
The CBGS studies referred to in this review were supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation, the Mothercare Foundation, the Evelyn Trust and the NIHR Cambridge Biomedical Research Centre.
Medical Research Council (MC_U106179472)
External DOI: https://doi.org/10.1111/andr.12156
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253050