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

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. 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.

Keywords: Endocrine disrupting chemicals; Hypospadias; In-utero; Pesticides; Pharmaceuticals; Phthalates.

Conflict of interest statement

Conflict of Interest The authors declare that they have no conflict of interest.

Figures

Fig. 1

Literature review methodology flowchart

Fig. 2

Hypospadias classification schemes and clinical implications. Some common terms found in the literature are described and associated with the terms that we used to consistency in this review. Clinical information regarding complications and epidemiologic data are provided. Incidence of each hypospadias grade is subject to debate due to inconsistent classification schemes [22, 43]