Reductions in fertility in DES sons and daughters

Diethylstilbestrol Revisited: A Review of the Long-Term Health Effects

1995 Research Abstract

DES Sons

Some investigators have reported abnormalities of the urogenital system in DES sons, whereas others have found no increase in such abnormalities compared with men who were not exposed to DES. Gill and coworkers examined 308 men exposed to DES and 307 men receiving placebo who were traced from Dieckmann and colleagues’ cohort and found that the prevalence of epididymal cysts and hypotrophic testes was four times greater among exposed men. In men with testicular hypoplasia, cryptorchidism was observed in 65% (17 of 26) of men exposed to DES compared with 17% (1 of 6) of controls. No significant differences were found in mean circulating follicle-stimulating hormone, luteinizing hormone, or testosterone levels in the two groups. Spermatozoa were analyzed in 134 men (44%) exposed to DES and in 84 men (27%) who received placebo. The average sperm density of the group exposed to DES was lower than that of the placebo group (91 sperm cells X 106 /mL compared with 115 sperm cells X 106 /mL; P = 0.05). Semen quality was compared using the average Eliasson score, a scoring system that assesses sperm concentration, percentage of motile sperm, motility, and morphology. A score of 1 is classified as normal; a score of 5 to 10 is classified as pathologic; and a score of greater than 10 is classified as severely pathologic. The average Eliasson score was higher in the group exposed to DES than in the group exposed to placebo (4.9 compared with 2.5; P = 0.01); more men exposed to DES than controls had severe semen pathologic disorders (an Eliasson score > 10) (24 of 134 men exposed to DES [18%] compared with 7 of 87 controls [8%]; P = 0.05). In contrast, a study done by the Mayo Clinic found no significant differences between men who were and were not exposed to DES in the proportion of testicular or penile anomalies, sperm density or Eliasson score, or the number of pregnancies attained by their wives. These conflicting results may be related to differences in the maternal DES dose levels, heterogeneous hormone (non-DES) exposures, or different methods of recruiting study participants in the reported studies.

DES Daughters

Developmental abnormalities in the female reproductive tract frequently occur after DES exposure. Among DESAD participants at the Baylor College of Medicine who were exposed to DES, 50 of 282 (18%) were found to have gross anatomical changes of the cervix (absent pars vaginalis, coxcomb, hypoplastic cervix collar, or pseudopolyp). Among a subgroup of DESAD participants recruited for a fertility study, 154 of 293 (53%) were found to have abnormal hysterosalpingograms. These abnormalities included T-shaped and hypoplastic uteri; constriction of the upper, middle, or cornual regions; and irregular uterine margins. Data from the Dieckmann and colleagues’ cohort have consistently shown reductions in fertility in DES daughters. On the basis of data analyzed until 1986, 33% of the exposed women compared with 14% of the unexposed women reported primary infertility. Secondary infertility was also reported significantly more often among the exposed women. Vaginal epithelial changes and cervicovaginal ridges were found more often among the exposed women with primary infertility. In contrast, an early analysis of data from the DESAD cohort found that exposed and unexposed daughters were similar in the number achieving pregnancy, the total number of pregnancies, and age at first pregnancy. However, these women may have been studied too early in their reproductive life span to detect major differences in fertility. Kaufman and associates found no difference in the proportion of women with normal and abnormal hysterosalpingograms who had difficulty with conception, suggesting that structural abnormalities of the uterus alone did not account for failure to conceive. Some clinical studies and case reports have suggested that hormonal changes in DES daughters occur, including elevated testosterone and prolactin levels. However, a prospective cohort study suggested that although in utero DES exposure was related to a reduction in the duration and amount of menstrual bleeding, exposure did not affect cycle length and variability of cycle length. This suggests that gross endocrine function was not disturbed. Failure of implantation and alterations in ovarian steroidogenesis have also been postulated as possible causes of infertility in these women. Once pregnancy is achieved, DES daughters are at high risk for an unfavorable pregnancy outcome. In a review of English-language articles, Swan estimated that, overall, DES daughters are 8.6 times more likely to have an ectopic pregnancy, 1.8 times more likely to have a miscarriage, and 4.7 times more likely to have a premature birth than unexposed women. Among women with an abnormality of the cervix, vagina, or uterus, the relative risks for ectopic pregnancy, miscarriage, and premature birth are even higher (13.5, 2.6, and 9.6, respectively).



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