Background: Methods: Results: Interpretation:

Background & Aims: Female sex hormones have been suggested to increase the risk of gastroesophageal reflux symptoms via a relaxing effect on the lower esophageal sphincter. We investigated the relationship of oral contraceptives and postmenopausal hormone therapy (HT) to risk of reflux symptoms, controlling for genetic factors and body mass. Methods: Information on exposures and reflux symptoms was obtained by telephone interviews conducted in 1998–2002 among women in the Swedish Twin Registry. Use of oral contraceptives was also assessed in 1973 by questionnaires. Both cross-sectional and prospective nested case-control designs were used, each with external control analysis. The cross-sectional design was further submitted to monozygotic co-twin control analysis. Results: The cross-sectional study design comprised 4365 twins with reflux and 17,321 without. In ever users of estrogen HT, the risk of reflux symptoms was increased by 32% (odds ratio, 1.32; 95% confidence interval, 1.18–1.47). This association remained in the nested case-control analyses and increased slightly with higher body mass index. A similar pattern was observed for the use of progestin in the cross-sectional design, but no association remained in the nested case-control analysis. Use of oral contraceptives was not associated with an increased risk of reflux symptoms. Generally, the risk estimates remained virtually unchanged after adjustments for potential confounding factors, including genetic factors. Conclusions: This population-based twin study indicates that estrogen HT is an independent risk factor for reflux symptoms, while the influence of progestin HT and oral contraceptives is less consistent.

There is a striking male predominance in esophageal cancer patients. Sex hormones have been suggested as a contributing factor and these are influenced by age and race. In this study, we examined the male-to-female incidence rate ratios of esophageal cancer in the United States. We used data from 13 registries in the Surveillance, Epidemiology, and End Results (SEER) database to calculate male-to-female incidence rate ratios of esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) diagnosed during 1992-2006 in different age and race groups. For EA, all races had similar sex and age-specific incidence patterns showing a peak in the male-to-female incidence rate ratio in the age group 50-59, and an age-related decline thereafter. The highest male-to-female ratio was seen in Hispanics (20.5) and the lowest in Blacks (7.0) compared with 10.8 in Whites. By contrast, the male-to-female incidence rate ratios were low and fairly stable throughout the different age groups in ESCC. The male-to-female incidence rate ratios in esophageal cancer vary considerably according to histology, age, and race. The highest sex ratios were seen in EA in the age group 50-59, rendering plausibility to the hypothesis that female sex hormone exposure may play a protective role in the development of this cancer.