Current Environmental Health Reports

, Volume 5, Issue 4, pp 499–511 | Cite as

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

  • Rajiv Raghavan
  • Megan E. Romano
  • Margaret R. Karagas
  • Frank J. PennaEmail author
Early Life Environmental Health (J Sunyer and P Dadvand, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Early Life Environmental Health


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.


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.


Hypospadias Endocrine disrupting chemicals Pharmaceuticals Phthalates Pesticides In-utero 



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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Rajiv Raghavan
    • 1
  • Megan E. Romano
    • 2
  • Margaret R. Karagas
    • 2
  • Frank J. Penna
    • 1
    Email author
  1. 1.Division of Pediatric Urology, Children’s Hospital at DartmouthDartmouth|Geisel School of MedicineLebanonUSA
  2. 2.Department of EpidemiologyDartmouth|Geisel School of MedicineLebanonUSA

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