Hypospadias in DES Sons

Latrogenic legacy from diethylstilbestrol exposure

2002 Study Abstract

Hypospadias, characterised by the emergence of the urethral orifice on the ventral surface of the penis or on the perineum rather than at the tip of the glans, is one of the most common birth defects in boys. Although there is no increased mortality associated with hypospadias, there is substantial morbidity, including surgical operations and the psychosocial consequences of having a genital abnormality.

Little is known about the causes of hypospadias. However, since fusion of the urethral groove is mainly under the control of androgens originating in the fetal testis, it has been suggested that agents with antiandrogenic or oestrogenic activities might increase the risk.

Diethylstilbestrol also seems to affect sons exposed in utero, leading to higher risks of structural urogenital anomalies, including cryptorchidism, testicular hypoplasia, microphallus, abnormalities of the penile urethra, hypospadias, and epididymal cysts. Similar disorders were induced in mice exposed to diethylstilbestrol in utero.

In males, fusion of the urethral folds brings the urogenital meatus from the perineal region to the tip of the phallus between the 8th and 14th week of gestation, and genital malformations were more frequent among males exposed to diethylstilbestrol before the 11th week than among those exposed later.


  • Latrogenic legacy from diethylstilbestrol exposure, NCBI PubMed PMID: 11943252, 2002 Mar.
  • Featured image credit mcgill.ca.

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