Prenatal Diethylstilbestrol Exposure: A Harbinger for Future Testicular Cancer Incidence?

摘要

Testicular cancer incidence has increased 65% during the course of the last 40 years. In 1975, the age-adjusted rate of testicular cancer was 3.73 × 10 y and in 2016 it rose to 6.17 × 10 y ( ). Possibly this increase could be partially attributable to increased prenatal exposure to estrogen-like compounds. As early as 1979, the disease was believed to have prenatal origins ( ). Numerous studies have since been conducted to support the hypothesis that prenatal exposure to hormone or hormone-like compounds, specifically diethylstilbestrol (DES), influence testicular cancer development. These studies, however, have been hampered by considerable statistical uncertainty because of two factors. Testicular cancer occurs relatively rarely with only a 0.4% likelihood of it developing over the course of a male’s lifetime. Furthermore, testicular cancer accounts for only 0.5% of all incident cancers in a particular year. Contrasted with prostate cancer, which is associated with a 11.6% lifetime risk and attributable to 9.9% of all cancers developing in a year, testicular cancer is a particularly infrequent occurrence ( ). This makes prospective studies of testicular cancer challenging to design as evidenced by the study by Strohsnitter et al. Only seven testicular cancer cases developed during approximately 40 years of follow-up among a cohort of 1787 men exposed to DES before birth. Although the investigators observed an increase in testicular cancer risk among this cohort when compared with the national rates, the estimate of this effect was imprecise (relative risk [RR] = 2.04, 95% confidence interval [CI] = 0.82 to 4.20). The imprecision was more pronounced when testicular cancer rates among this cohort were compared with those among a cohort of unexposed men followed for the same length of time (RR = 3.05, 95% CI = 0.65 to 21.96) ( ). Also, DES was not frequently used. It was administered to between two and four million women for, among other indications, threatened miscarriage between 1940 and 1971 ( ). Its use was then banned on report of women prenatally exposed to the drug having increased risk of clear cell adenoma of the cervix and vagina ( ). Nonetheless, during this time period, it was not frequently used, with an exposure prevalence ranging from 1.5% ( ) to 7% ( ). The infrequency of DES usage also made case-control studies of the effects of DES on testicular cancer prone to imprecision.