In 1971, the New England Journal of Medicine published a report showing that seven of eight girls and young women (ages 14 to 22) who had been diagnosed with vaginal clear cell adenocarcinoma had been exposed prenatally to DES.
The most recent published research on DES daughters' adverse health outcomes documented by the U.S. National Cancer Institute (NCI) appears in the October 6, 2011 issue of the New England Journal of Medicine under the authorship of RN Hoover et al., and lists these adverse effects and risk factors: Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5%; spontaneous abortion, 50.3% vs. 38.6%; preterm delivery, 53.3% vs. 17.8%; loss of second-trimester pregnancy, 16.4% vs. 1.7%; ectopic pregnancy, 14.6% vs. 2.9%; preeclampsia, 26.4% vs. 13.7%; stillbirth, 8.9% vs. 2.6%; early menopause, 5.1% vs. 1.7%; grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4%; and breast cancer at 40 years of age or older, 3.9% vs.
In the 1970s and early 1980s, studies published on prenatally DES-exposed males investigated increased risk of testicular cancer, infertility and urogenital abnormalities in development, such as cryptorchidism and hypospadias.
[19] There is some evidence linking prenatal hormonal influences on sexual orientation, gender identity and transgender development, but this is an area of behavioral research that remains controversial.
[20][21][22][23] Several published studies in the medical literature have examined the hypothesis that prenatal exposure to estrogens (including DES) may cause significant developmental impact on sexual differentiation of the brain, and on subsequent behavioral and gender identity development in exposed males and females.
[citation needed] An Internet survey reported a high rate of transgender and intersex identity in people assigned male at birth participating in an online support forum for DES sons.
[25][27][26] The first real study on transgender identity in people assigned male at birth who were prenatally exposed to DES was published in 2020 and found a very low incidence of transgenderism (2 in about 930 or around 0.2%).
If epigenetic changes occur and are heritable, studies of the DES-exposed third generation have implications for the influence of environmental endocrine disruptors on human health and evolution.
Recent studies from the US National Cancer Institute (NCI) show that the daughters of women who were exposed in utero to DES may be less likely than the unexposed to have regular menstrual periods.
An increased risk of ovarian cancer in the daughters of women exposed in utero was observed, but it was based on three cases of almost 800, so the finding is considered preliminary and requires further study.