Symptoms of gastro-oesophageal reflux disease are equally common in both sexes and at all ages. However, complications of gastro-oesophageal reflux disease such as reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma, although more common in men, increase sharply in older women, suggestive of a protective effect of female sex hormones in menstruating women. Oestrogen has anti-inflammatory properties, improves healing in oral and skin wounds and may therefore reduce the severity of reflux-induced oesophageal mucosal injury, consequently protecting women from developing severe reflux oesophagitis. Long-term oestrogen treatment with hormone replacement therapy seems to be additionally associated with a reduction in the risk of oesophageal cancer. Moreover, there are gender-specific genotypic differences in the response of oesophageal mucosa to chronic acid reflux suggestive of multiple factors that may play a role in explaining the male predominance of oesophageal adenocarcinoma. Finally, oestrogen has no association with the severity of acid reflux once adjustment is made for the influence of increasing body mass index in women undergoing oesophageal pH monitoring. The gender difference in the prevalence of gastro-oesophageal reflux disease and its complications may thus be related to the effect of female sex hormones, particularly oestrogen and its 'protective' effect in pre-menopausal women.