Hormonal Risk Factors for Testicular Cancer

Environmental endocrine modulators and human health: an assessment of the biological evidence, 1998

Abstract

Prenatal exposure of mice to DES (100 µg/kg on days 9 to 16 of gestation) results in numerous statistically significant adverse effects on the testes and related structures, including a high percentage of cryptorchidism (91%), inflammation (29%), hyperplasia (56%), and adenocarcinoma (5%). Even though the testicular neoplasms were expressed later in life, interference with normal testicular development in utero may be necessary for their development. The adenoma carcinomas observed occurred in the rete testis, a structure connecting the testis and epididymis. Tumors of the rete testis appear to be similar in mice and humans.

Despite the animal experimental data demonstrating an association between in utero exposure to DES and subsequent testicular cancer, the human data with DES are less compelling. A number of studies have investigated the relationship between in utero exposure to DES and subsequent testicular cancer in offspring. Using the Connecticut Tumor Registry data, a case-control study of 79 males exposed to DES in utero demonstrated that such exposure did not increase the risk for testicular cancer compared with controls. Another case-control study on 273 cases of testicular cancer in northern California found no association between testicular cancer risk and in utero exposure to exogenous hormones during pregnancy (OR = 0.9).378 A case-control study of 108 cases of testicular cancer in the Los Angeles area reached a different conclusion reporting that exposure of the mother to exogenous estrogen (i.e., DES, estrogen, progestin, or estrogen in a pregnancy test) during pregnancy was a significant risk factor (RR = 8.0) for testicular cancer in the offspring. The extent of estrogen exposure in this group is somewhat uncertain because the mothers of five of the nine cases took only a single hormonal preparation as a pregnancy test. A recent review of the available data by the National Cancer Institute concluded that in utero DES exposure has not been linked to testicular cancer. However, a problem that plagues these comparisons is that, in all likelihood, most women who were exposed to DES are unaware of their exposure. Resulting exposure misclassification would tend to obscure effects.

There are several case reports of testicular seminoma in men in their late 20s who were exposed to DES in utero.  However, it is difficult to ascertain the significance of isolated cases in light of the overall lack of increased incidence of testicular cancer in DES-exposed cohorts. Because testicular cancer reaches a peak incidence rate between the ages of 30 to 35, with substantial increases starting at ages 20 to 24, one might expect that if in utero exposure to DES were a significant risk factor that more than a few isolated cases would have been reported by this time. Unlike most cancers that occur later in life, the peak incidence ages for testicular cancer suggests that sufficient time has elapsed so significant numbers of DES-exposed men are in this age range. To date, there is no significant association between in utero exposure to DES and increased incidence of testicular cancer; however, ongoing studies of the DES sons cohort may provide additonal data. On the other hand, if in utero exposure to DES were associated with increased incidence of testicular cancer after the age of 60, it would be premature to expect to see such in increase in the DES-exposed cohort. This issue can only be resolved by additional follow-up of DES-exposed cohorts as they age.

References

  • Environmental endocrine modulators and human health: an assessment of the biological evidence, Critical reviews in toxicology, NCBI PubMed, PMID: 9557209, 1998.
  • Featured image Jack Patrick.
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