Postmenopausal Hormone Therapy as a Risk Factor for Gastroesophageal Reflux Symptoms Among Female Twins

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.