Although laboratory animal studies have reported third-generation (offspring of DES Daughters and Sons) health effects of DES exposure, little is known about human health effects in the children of the women exposed to DES before birth. The goal of this study was to examine the risk of hypospadias (abnormality of the penis) in the sons of women exposed to DES before birth.

This Dutch cohort study consisted of a questionnaire of 16,284 women with diagnosed fertility problems. The researchers compared the prevalence of the rate of hypospadias between the sons of mothers who had been exposed to DES before birth with sons whose mothers had not been exposed to DES. The mothers of 205 sons reported DES exposure, and four of these sons had confirmed hypospadias; eight sons of the remaining 8,729 sons in the study had hypospadias. Risk of hypospadias was not affected by maternal age, fertility treatment, or use of assisted reproductive techniques.

Results suggested that although absolute risk was small, the third-generation health effects of DES exposure warrant additional studies.

Citation: Klip H, Verloop J, van Gool JD, Koster META, Burger CW, van Leeuwen FE. Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study. Lancet 2002; 359:1102-7.