Abstract
BackgroundDiethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s-70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results.MethodsIn 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.ResultsPrenatal 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 1.1-3.4) for cryptorchidism, 2.5 (1.5-4.3) for epididymal cyst, and 2.4 (1.5-4.4) for testicular inflammation/infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.6-5.2) for cryptorchidism, 3.5 (2.0-6.0) for epididymal cyst, and 3.0 (1.7-5.4) for inflammation/infection of testes.ConclusionThese 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.
Highlights
Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters
The present results indicate that DES exposed sons have a higher occurrence of cryptorchidism and epididymal cysts than unexposed sons, and that the increased risk is related to timing and dose
It has already been shown that prenatal DES exposure in men does not materially affect fertility, even in men with urogenital anomalies [5,19,20]
Summary
Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Diethylstilbestrol (DES), a synthetic estrogen that was widely prescribed to pregnant women during the 1940s to 1970s, has been associated with an increased prevalence of abnormalities of the reproductive tract in women who were exposed in utero [1]. Two studies found a higher prevalence of genital tract abnormalities among exposed men [2,3,4,5]. A third study, reported no association between prenatal DES exposure and genital tract abnormalities [6]. In a continuation of follow-up of U.S prospective cohorts of DES-exposed and unexposed sons, we combined data from both of the previous prospective studies discussed above and a third, previously unexplored, cohort of exposed and unexposed men to reexamine this question and investigate modifying effects of the timing and dose of DES exposure
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