Urogenital Abnormalities in Men exposed to DiEthylStilbestrol in Utero

Prenatal exposure to DES increases risk of male urogenital abnormalities

DES Follow-up Study Summary

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Prenatal exposure to DES increases risk of male urogenital abnormalities.

One of the most frequently asked questions from DES exposed families is whether the sons have had any adverse health effects. For that reason, our collaborative follow-up has included over 1,000 DES-exposed sons and over 1,000 other men of the same ages who were never exposed to DES. These men have been completing mailed questionnaires on the same schedule as women in the study, in 1994, 1997, 2001, and 2006. Some of the questions are the same and some are different. The men were asked whether they had ever been diagnosed with any of a list of urogenital abnormalities. These abnormalities were studied more than 20 years ago in both the offspring of mothers from the University of Chicago DES clinical trial and in a group of sons born to mothers at the Mayo Clinic. The two studies reported different findings, with the University of Chicago follow-up finding a higher prevalence of abnormalities in the DES-exposed sons and the Mayo Clinic study finding no difference between DES-exposed and unexposed sons. We thought we might be able to clarify this question with data from the entire collaborative cohort – including the Mayo sons, the Chicago sons, and additional sons from women who gave birth in Massachusetts.

We found that urogenital abnormalities were fairly rare among DES-exposed sons, as is true for the general U.S. population. However, DES-exposed sons did have a higher prevalence of both undescended testicle and epididymal cyst. They were two times as likely to have had one of those conditions as were unexposed men. For both of these conditions, the prevalence was highest if son was exposed during the first 10 weeks of gestation. In men born at the Mayo clinic, DES exposure was not significantly associated with these conditions overall, but there was a significant association with undescended testicle and epididymal cyst for sons exposed early in gestation. In the University of Chicago clinical trial, the protocol was to give DES as soon as a pregnancy was identified and for use to continue until the last weeks of pregnancy. This same protocol was typical in Boston and in some other regions of the U.S. It was not the usual protocol at the Mayo Clinic, however, where women usually began DES later in pregnancy and took it for only a few months. Differences in patterns of use may explain the conflicting findings in earlier studies of urogenital abnormalities in sons. Our conclusion is that DES-exposed sons do indeed have a higher risk of certain urogenital abnormalities particularly if they were exposed in the early months of fetal development. Fortunately, we and others have already shown that prenatal DES exposure does not affect fertility in men, even in those men with these urogenital abnormalities.

Because the sons are now adults, they were also asked if they had ever been diagnosed with infection or inflammation of the urogenital organs. Prenatal DES exposure was not associated with occurrence of infection or inflammation of the prostate, urethra, or epididymus, or with benign prostatic hypertrophy (enlarged prostate). DES-exposed sons were approximately two and a half times more likely to have had an infection or inflammation of the testes. We do not know the reasons for such an increase. It is possible that minimal structural abnormalities, such as minor obstructions, could explain the increase in infection and inflammation. We will continue to investigate these conditions, especially benign prostatic hypertrophy, as men in the study grow older.

2009 Study Abstract:

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results.

In data from a collaborative follow-up of three U.S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth.

Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes.

These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years.


  • Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study,NCBI, PMID: 19689815, 2009 Aug 18;8:37. doi: 10.1186/1476-069X-8-37. Full text PMC2739506.
  • NCI, DES Follow-up Study Published Papers.
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