Women whose mothers took a synthetic estrogen called DES before it was discontinued in 1971 have been found to suffer from a variety of fertility problems and cancers, according to a major new study.
The study appearing in Thursday's New England Journal of Medicine examines the daughters of females exposed in the womb to diethylstilbestrol (DES), which was prescribed in the mistaken belief it could reduce certain complications of pregnancy.
Researchers at the National Cancer Institute and several other medical centers followed some 6,500 women, including 4,600 exposed to DES.
They concluded that the daughters with exposure to DES in the womb had an increased risk of 12 medical conditions, including a twofold higher risk of infertility and a fivefold increased risk of having a preterm delivery.
The women also had 40 times the risk of developing a rare cancer of the vagina among young women, called clear cell adenocarcinoma - although the number of cases remains around one in 1,000, the researchers said.
The follow-up of a 1992 study aimed to get better information on the health risks of DES, which was first prescribed in 1940 in the United States. Between five million and 10 million pregnant women and babies had been exposed to the drug in various forms, including pills, creams and vaginal suppositories.
"Our study carefully documents elevated risk for DES-exposed daughters for a host of medical problems -- many of them also quite common in the general population," said study author Robert Hoover at the cancer institute, part of the National Institutes of Health.
"Without the sentinel finding of a very rare cancer in young women, and without the sustained follow-up of those who were exposed, we would not know the full extent of harm caused by DES exposure in the womb."
The study is the first to estimate the cumulative proportion of all DES-exposed women who developed these conditions because of their exposure, the scientists said.
The study concluded that one of five DES-exposed daughters will experience some level of infertility because of their exposure.
While the first women diagnosed with the rare cancer in the late 1960s were adolescents and young adults at the time of their diagnosis, the research now shows that the risk for DES-exposed daughters continues through at least age 40.
In addition, these women are more than twice as likely to develop pre-cancerous cells in the cervix or vagina and have an 80 per cent higher chance of developing breast cancer after age 40.
By age 55, according to the researchers one in 25 DES-exposed daughters will develop abnormal cellular changes in the cervix or vagina, and one in 50 will develop breast cancer due to their DES exposure.
This study did not evaluate sons with DES exposure in the womb, but previous reports have indicated an increased risk for certain testicular abnormalities, including undescended testicles. So far, research has shown no decreased fertility for these men, even with testicular abnormalities.
The other research centers involved in this work are Boston University Slone Epidemiology Center; Cedars-Sinai Medical Center DES Project; University of Chicago Department of Obstetrics and Gynecology; Dartmouth-Hitchcock Medical Center; The Mayo Clinic DES Project; The Methodist Hospital-Research Institute Department of Obstetrics and Gynecology; and Tufts Medical Center.