a-t 2017; 48: 15

Diethylstilbestrol (DES; in the past e.g. CYREN) - harmful effects over three generations: Despite lack of evidence for its efficacy, up to the late 1970s, millions of pregnant women world-wide were treated with the synthetic oestrogen, diethylstilbestrol, (DES; in the past e.g. CYREN) to prevent miscarriage (1). This drug has since then been considered teratogenic and carcinogenic (a-t 1977; No. 12: 102). Approximately one of 1,000 young women whose mothers were treated with this oestrogen during pregnancy (referred to as the "DES daughters"), developed vaginal or cervical adenocarcinoma and, as for their mothers, they have an increased risk of breast cancer. Benign changes or malformed sex organs were reported for more than 50% of the DES daughters and also for DES sons in case reports (a-t 1986; No. 8: 75) (1-3). Uterine malformations led to complications during pregnancies such as ectopic pregnancies, miscarriages and premature births (1). According to a current French study, approximately one-quarter of the children of DES daughters were born prematurely. This is probably also one reason why the risk of cerebral palsy is increased ten-fold compared to the control group without a family history of DES exposure (4). In another study with a similarly high preterm birth rate, the risk of early infant deaths in the first four weeks after birth increased eight-fold (1,5). An increase in the number of malformations has also been recorded in this DES grandchildren generation, who were never directly exposed to the synthetic oestrogen: compared to sons of mothers with no prenatal DES exposure, the rate of hypospadias is five times more prevalent in DES grandchildren (1). This missing urethral closure, which varies in severity from one patient to another, and the incorrect positioning of the urethral opening are already treated surgically during childhood and have also been observed in DES sons (2). Hormonal disorders due to endogenous factors and substances or hormones with endocrine activity during urethral and penile development, amongst other things, have been discussed as potential causes (1,2). Experimental results indicate that DES could trigger epigenetic changes that are passed on to the next generation (1,6). Other assumed DES-induced malformations in the grandchildren generation are primarily oesophageal atresias, which are associated with tracheoesophageal fistulas (1,4). The evaluation of the consequences of treatment with DES is far from complete with the pregnancies of DES daughters possibly continuing up until 2020 (1,4).

  1 Prescrire International 2016; 25: 294-98
  2 KLIP, H. et al.: Lancet 2002; 359: 1102-07
  3 Réseau, D.E.S. France: press release, 1 Dec. 2014; http://www.bretagne.mutualite.fr/content/download/38657/258585/version/1/file/2014+12+01+DP+R%C3%A9sultats+Distilb%C3%A8ne.pdf
  4 TOURNAIRE, M. et al.: Therapie 2016; 71: 395-404
  5 HOOVER, R.N. et al.: N. Engl. J. Med. 2011; 365: 1304-14
  6 SCHAEFER, C. et al. (Hrsg.): "Arzneimittel in Schwangerschaft und Stillzeit" (Drugs during pregnancy and breastfeeding), 8. ed, Urban & Fischer, Munich 2012, page 407

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