Do sex hormones play a role in the etiology of esophageal adenocarcinoma? A new hypothesis tested in a population-based cohort of prostate cancer patients.

The striking male predominance in patients with adenocarcinoma of the esophagus (male:female ratio = 6:1) is not explained by known risk factors. We hypothesized that sex hormones could be responsible for this sex imbalance. If the hypothesis is correct, treatment that increases the estrogen level and/or decreases the testosterone level in males might reduce the risk of developing esophageal adenocarcinoma. To test our hypothesis, we performed a population-based, retrospective cohort study among all patients given a diagnosis of prostate cancer in Sweden between 1958 and 1992. The vast majority had received prolonged antiandrogenic treatment, typically with estrogens. A total of 100,215 patients were followed up for an average of 4 years. The standardized incidence ratio, the ratio of the observed to the expected number of incident cancers, was used as a measure of relative risk, with the expected number derived from the entire Swedish population. We observed 14 adenocarcinomas of the esophagus during follow-up in the cohort, compared to the 16 expected, yielding a relative risk close to unity (standardized incidence ratio = 0.9; 95% confidence interval = 0.5-1.5). Analysis by latency intervals after prostate cancer diagnosis revealed no clear trend toward increasing or decreasing risk over time. In conclusion, our Swedish data did not provide any support for our hypothesis of a role of sex hormones in the etiology of esophageal adenocarcinoma.