Mortality in women given diethylstilbestrol during pregnancy

Abstract

We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI ¼ 0.98 -1.16), and 1.11 (95% CI ¼ 1.02 -1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI ¼ 0.94 -1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI ¼ 0.96 -1.69) for DES and breast cancer, and 1.38 (95% CI ¼ 1.03 -1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES -cohort interaction was not significant (P ¼ 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses. British Journal of Cancer (2006) (Dieckmann et al, 1953;Swyer and Law, 1954), use continued for another two decades. Diethylstilbestrol was withdrawn from use during pregnancy in the early 1970s, after it was shown that in utero exposure was strongly associated with the risk of vaginal adenocarcinoma (Herbst et al, 1971). Until that time, as many as 2 million women in the US (Noller and Fish, 1974), and 4 million women worldwide (Newbold, 1993) were given DES during pregnancy.Most studies, but not all (Vessey et al, 1983), have suggested a positive association between DES taken during pregnancy and breast cancer incidence (Bibbo et al, 1978;Clark and Portier, 1979;Beral and Colwell, 1980;Greenberg et al, 1984;Hadjimichael et al, 1984;Colton et al, 1993;Titus-Ernstoff et al, 2001), although the latter four studies produced findings compatible with chance. Of the studies assessing DES in relation to breast cancer mortality, one observed a significant association (Calle et al, 1996); four produced suggestive findings that were not of statistical significance (Bibbo et al, 1978;Clark and Portier, 1979;Hadjimichael et al, 1984;Colton et al, 1993); and another found no association (Greenberg et al, 1984). To date, only one study formally assessed all-cause or disease-specific mortality outcomes, and found little evidence of an association with DES (Greenberg et al, 1984). In the present paper, we present findings based on the largest study to date of mortality outcomes in women with documented DES exposure. MATERIALS AND METHODSWe assessed exposure to DES during pregnancy in relation to cause-specific and total mortality, with a particular interest in gynaecological cancers, and those known to be influenced by exposure to exogenous oestrogen. The analyses were based on a combined cohort, the design and methods of which have been described pr...

Perinatal Environmental Exposures Affect Mammary Development, Function, and Cancer Risk in Adulthood

“…Administration of DES to pregnant mice causes similar reproductive abnormalities and dysfunction in their offspring (63). An increased incidence of breast cancer has also been noted in prenatally DES-exposed women (64–66) and their mothers (38, 67). Women >40 years of age and exposed in utero to DES have an estimated 1.9 times increased risk of developing breast cancer compared with unexposed women of the same age.…”

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy

“…6 Mothers administered DES during pregnancy have an increased risk of breast cancer incidence 7 and mortality. 8 Sons who were exposed in utero have an increased risk of genitourinary defects 9 and a possible increase in testicular cancer. 10 The possibility of epigenetic transmission with consequent adverse outcomes in the offspring of prenatally exposed women is under investigation.…”

An evaluation of evidence for the carcinogenic activity of bisphenol A

“…One of the clearest examples involves diethylstilbestrol (DES). While adult exposure to diethylstilbestrol (DES) modestly increases the risk of breast cancer and mortality from this disease later in life (RR = 1.27-1.35 for risk of disease and mortality with DES exposure) [19][20][21], fetal exposure to this agent apparently increases the incidence breast cancer in adult women much more dramatically (RR = 3.0 after the age of 50 yr) [22]. Similarly, clear cell adenocarcinomas of the vagina, a very rare cancer, has been observed in patients exposed prenatally to DES, but not after adult exposure [19;23;24].…”