Sex and Gender Differences in Gastroesophageal Reflux Disease

Abstract

It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area.

Esophageal acid sensitivity in patients with gastroesophageal reflux disease: Does esophageal hypomotility matter?

“…25 Therefore, our finding may support the notion that reflux symptoms such as heartburn, regurgitation, and extra-esophageal symptoms are more frequently reported by women than by men, indicating that sex and gender play a role in symptom perception. 26 The findings in our study are in agreement with prior works that noticed esophageal acid hypersensitivity in patients with GERD. 27 In previous studies on symptomatic patients with and without esophagitis, it has been shown that chronic esophageal acid exposure could result in microscopic mucosal alteration and defects in mucosal function barriers.…”

“…Other studies also found that healthy females have a lower threshold to esophageal noxious stimuli than healthy males . Therefore, our finding may support the notion that reflux symptoms such as heartburn, regurgitation, and extra‐esophageal symptoms are more frequently reported by women than by men, indicating that sex and gender play a role in symptom perception …”

Inducing and Aggravating Factors of Gastroesophageal Reflux Symptoms

“…19 Similar issue has also been demonstrated by other systematic review studies. [20][21] In a study on rats with GERD, Masaka et al have reported that greater damage of esophageal tissue is e perienced by male rats compared to female rats as well as by female rats that have undergone ooverctomy than female rats that still have ovarium. 22 Similar issue has also been addressed by Asanuma et al who have suggested that estrogen hormon may have an effect on GERD symptoms as the estrogen modulates fat meabolism; while obesity so far has been reported as a risk factor of GERD.…”

Bacterial species and total bacterial load in the distal oesophagus in patients with and without clinical gastric reflux

“…There are studies showing that GERD and Barrett's oesophagus trigger the development of oesophageal adenocarcinoma. Microbiota is altered when these diseases develop; however, its etiopathogenesis is not clear (Bor et al 2005;Blackett et al 2013;Kim et al 2016;Okc ßu and C ßiftel 2016).…”