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Pharmacologic and Environmental Endocrine Disruptors in the Pathogenesis of Hypospadias: a Review

  • Early Life Environmental Health (J Sunyer and P Dadvand, Section Editors)
  • Published:
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Abstract

Purpose of Review

Endocrine disrupting chemicals (EDCs) potentially have a role in causing hypospadias malformation through modifiable in-utero exposure. Considering the emerging literature on the role of potential endocrine disrupting substances on the occurrence of hypospadias and the potential to inform public health efforts to prevent the occurrence of these malformations, we have summarized the current literature, identified areas of consensus, and highlighted areas that warrant further investigation.

Recent Findings

Pharmaceuticals, such as diethylstilbestrol, progestin fertility treatments, corticosteroids, and valproic acid, have all been associated with hypospadias risk. Data on exposure to dichlorodiphenyltrichloroethane and hexachlorobenzene pesticides, as well as non-persistent pollutants, particularly phthalates, is less consistent but still compelling.

Summary

Improving exposure assessment, standardizing sample timing to relevant developmental windows, using clear case identification and classification schemes, and elucidating dose-response relationships with EDCs will help to provide clearer evidence. Promising directions for future research include identification of subgroups with genetic hypospadias risk factors, measurement of intermediate outcomes, and study of EDC mixtures that will more accurately represent the total fetal environment.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgements

We wish to thank Dr. Lucas Salas for expert assistance in interpreting Spanish language literature relevant to this review and Leah Hofgesang for her professional illustrative contributions to Fig. 2.

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Authors and Affiliations

  1. Division of Pediatric Urology, Children’s Hospital at Dartmouth, Dartmouth|Geisel School of Medicine, 1 Medical Center Drive, Lebanon, NH, 03756, USA

    Rajiv Raghavan & Frank J. Penna

  2. Department of Epidemiology, Dartmouth|Geisel School of Medicine, Lebanon, NH, USA

    Megan E. Romano & Margaret R. Karagas

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Raghavan, R., Romano, M.E., Karagas, M.R. et al. Pharmacologic and Environmental Endocrine Disruptors in the Pathogenesis of Hypospadias: a Review. Curr Envir Health Rpt 5, 499–511 (2018). https://doi.org/10.1007/s40572-018-0214-z

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