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Epidemiological study of hypospadias induced by diethylstil- bestrol (DES): an exponential trans-generation effect

N. Kalfa¹ ², F. Paris ¹ ³, MO. Soyer-Gobillard avec l’association Hhorages*, RB. Galifer², JP. Daures**, C. Sultan¹ ³

¹Department of Hormonology (Development and Reproduction), Lapeyronie Hospital, CHU Montpellier

²Pediatric Surgery Department, Lapeyronie Hospital, CHU Montpellier

³Pediatric Endocrinology – Gynecology Department, 1st Department of Pediatrics, Arnaud de Villeneuve Hospital, CHU Montpellier

*Hhorages Association, BP 32, Drancy

**Department of Biostatistics, Research Institute, Montpellier University, France



Introduction: Prenatal exposure to DES, treatment formally used for hypofertility, is a known risk factor for genital malformations in the male fetus, particularly hypospadias. More of a surprise, animal experiments (mice exposed to DES) raise the suspicion of a trans-generation effect: the DES could have a deletion effect transmitted to future generations. The aim of this work is to evaluate the impact of a prenatal exposure to DES in the small children of women treated with DES during the course of their pregnancy.

Material and methods: A national epidemiologic study, in collaboration with an association of women exposed to DES involved 529 families. The study included 1180 children of the first generation (180 first born with no exposure to DES, 448 boys and 552 girls exposed in utero) and 465 boys of the second generation. The 180 first born with no exposure to DES and their offspring make up an ideal control group (same family and therefore same genetic background).

Results: Among the non exposed boys, the incidence of hypospadias was 0% at the first (n=180) and second (n=260) generations. Among the 448 boys exposed in utero, the incidence was 3.57% (16/448). In the second generation, the incidence of hypospadias among boys born to women exposed in utero to DES was 8.2% (8/97). On the contrary, none of the grandsons of men exposed in utero to DES presented hypospadias.

Conclusion: Besides confirming the impact of prenatal exposure to synthetic estrogens on the development of male external genitalia, these results make us fear a trans-generation effect in boys of the second generation. A boy exposed prenatally to DES has little chance of “transmitting” a hypospadias to his own son, but the genital anomalies of DES exposed girls seem to interfere with the genital development of the male fetus.


Key words: diethylstilbestrol, prenatal exposure, incidence of hypospadias