Summary
Foetal diethylstilbestrol syndrome is characterized by a group of symptoms likely to occur in children and grandchildren of a woman who was treated while pregnant with diethylstilbestrol (DES). The drug is a synthetic nonsteroidal oestrogen, used in the US until 1971 and in Europe until 1978 to try and prevent miscarriage, premature delivery, and other pregnancy complications. DES is still available in several developing countries but was withdrawn from the market in Western countries after it was shown that its use during pregnancy was associated with a number of reproductive tract abnormalities in the offspring. It has been estimated that 25% of female foetuses exposed to DES in utero during the first trimester have subsequently developed genital tract anomalies including vaginal adenosis, cervical malformations, vaginal septae, uterine cavity anomalies, or fallopian tube anomalies causing subsequent fertility problems. DES was so largely prescribed in the sixties (to approximately 4 million women in the United States) that as many as 10 million (or 1 out of every 20 people) in the US and Europe are currently estimated to be DES-exposed mothers, daughters, or sons. Women with in utero DES exposure have been estimated to be at a 0.014 to 0.14% risk of developing clear cell adenocarcinoma of the vagina, a condition very specific to DES. This cancer may therefore affect between 1 in 1 500 and 1 in 15 000 exposed women. The age of onset is very variable, occurring between 7 and 48 years of age, although this lesion is most commonly diagnosed in women around the age of 19. Pregnancy outcome in women with in utero DES exposure is poorer than in controls with an increase in premature delivery, spontaneous abortion and ectopic pregnancy. In utero exposure to DES during pregnancy has also been associated with a slight but significantly higher risk of developing breast cancer and depressive disorders. Male urogenital tract anomalies have also been reported in association with in utero DES exposure at the end of pregnancy, and they mainly included urinary difficulties and decreased fertility. A possible transgenerational effect of DES is suggested by the increased risk of hypospadias uncovered by a cohort study investigating the incidence of this defect among sons of women who were exposed to DES in utero. Although the absolute risk of hypospadias in DES grandsons remains low, the prevalence ratio of this defect was apparently increased 20-fold. This transgenerational effect might result from an impaired uteroplacental function in women with in utero DES exposure. Studies have also suggested that psychological or psychiatric pathologies were more prevalent in prenatally DES-exposed individuals, but these findings are still under debate. *Author: Dr E. Robert-Gnansia (February 2006)*.
