Is hormone replacement therapy in post-menopausal women associated with a reduced risk of oesophageal cancer?

Purpose: The rise in oesophageal adenocarcinoma incidence in women with age is delayed compared with men until the post-menopausal period. A matched cohort study was therefore undertaken of post-menopausal women on hormone replacement therapy (HRT) to examine the association between HRT, oesophageal cancer and the potentially associated conditions, reflux oesophagitis and Barrett's oesophagus. Methods: Women aged over 50 years within the UK General Practice Research Database with a history of HRT exposure were matched by age and general practice with controls without HRT exposure (1: 1). Matched Cox-regression analysis was performed to estimate adjusted hazard ratios. Results: 51,851 HRT users and controls were studied. Prolonged HRT use for 5-10 years (hazard ratio 0.25 (95% CI 0.07-0.95)) and time-dependent covariates for increasing duration of HRT use (0.06 (0.01-0.43)) were associated with a reduced oesophageal cancer risk. HRT use was associated with reflux oesophagitis (1.27 (1.12-1.43)), but when analysis was confined to women with codes for both reflux oesophagitis and endoscopy there was no association (1.1 (0.81-1.44)), suggesting increased reporting of reflux symptoms among HRT users rather than an association with endoscopic reflux oesophagitis. Conclusion: Long-term post-menopausal HRT may be associated with a reduced risk of oesophageal cancer.