Various complications of pregnancy, notably threatened abortion, were commonly treated with diethylstilboestrol (DES) during the 1940’s through the 1960’s. Prenatal exposure to DES became a cause for concern in 1971 when accumulated evidence linked clear-cell adenocarcinoma of the vagina and vaginal adenosis with the administration of DES during pregnancy to the mothers of the affected young women.
Later, concern arose regarding hazards of transplacental DES on the developing male fetus. Follow-up comparison 25 years or later on subjects involved in a double-blind study of the efficacy of DES in preventing untoward effects of pregnancy showed DES-exposed males to have a greater prevalence of epididymal cysts, hypoplastic testes or both. Of 308 males exposed to DES, 31.5 percent had epididymal cysts, hypoplastic testes or both, as compared with 7.8 percent of 307 placebo-exposed controls. Of 26 DES-exposed males with testicular hypoplasia, 17 had a history of cryptorchidism, while only 1 of 6 placebo-exposed males with testicular hypoplasia had a history of testicular maldescent. Analysis of semen of 134 males exposed to DES showed severe pathologic changes in 18 percent compared with 8 percent of 87 male controls. This finding suggests that DES exposure in utero may have an effect on male fertility.
Although there is no control study showing an increased incidence of malignant tumors among DES-exposed men,one must keep in mind the increased risk of testicular carcinoma in testes that are or were cryptorchid. Testicular carcinoma has been reported in three men who had a history of exposure to DES in utero and of cryptorchidism. There has as yet been no report of carcinoma of the prostatic utricle in men exposed to DES in utero. The prostatic utricle, the miillerian duct remnant that is homologous to the female vagina, has been found to be the site of carcinoma in older men.
In summary, administration of DES during pregnancy appears to be followed by male genital tract abnormalities that are both structural (epididymal cysts, hypoplastic testes and cryptorchidism) and functional (abnormal semen). Due to prolonged latency in expression of DES effects, it will probably be another decade or more before the question of potential malignancy in men exposed to DES in utero is answered. Additional follow-up will also give insight into the probability of sub-normal fertility in males exposed to DES in utero.
THE WESTERN JOURNAL OF MEDICINE, EPITOMES-PEDIATRICS, ROBERT PENNY MD, APRIL 1982
- Pediatrics-epitomes of progress: the effect of des on male offspring, NCBI, PMID 18749074 PMCID: PMC1273720,
West J Med. 1982 Apr;136(4):329-30.
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