Body Mass and Reflux Oesophagitis: an Oestrogen-dependent Association?

Nilsson, Magnus; Lundegårdh, Göran; Carling, L; Ye, W; Lagergren, Jesper

doi:10.1080/00365520212502

Cited by 126 publications

(96 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, given the recognised multistep progression from gastro-oesophageal reflux, erosive oesophagitis, Barrett's oesophagus with and without dysplasia, to OAC, it would be valuable also to investigate if oestrogens influence these earlier steps in the carcinogenic pathway. Paradoxically, the risk of gastro-oesophageal reflux disease has been found to be increased among women using HRT, [41][42][43] despite the fact that such reflux is a main risk factor for OAC. 5 However, it is possible that the increased risk of reflux and the decreased risk of OAC among HRT users are explained by different timing of HRT exposure.…”

Section: Discussionmentioning

confidence: 99%

Hormone Replacement Therapy and Oral Contraceptives and Risk of Oesophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

Lagergren

Brusselaers

2015

International Journal of Epidemiology

Self Cite

View full text Add to dashboard Cite

There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results. We conducted a systematic literature search and meta-analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel-Haenszel random-effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR 5 0.75; 95% CI: 0.58-0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR 5 0.76; 95% CI: 0.57-1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted.Oesophageal adenocarcinoma (OAC) is up to nine times more common in men than women, yet the reasons behind this pattern remain unclear. 1,2 Gastro-oesophageal reflux and high body mass index (BMI), the two main risk factors for OAC, seem to influence the risk of developing OAC similarly in both genders, and might not explain the male predominance. [3][4][5][6] The typical male fat distribution, with mainly abdominal adiposity, is a stronger risk factor for OAC than BMI alone, 7 but it is uncertain if this exposure contributes the sex ratio of OAC. 8 It has also been hypothesised that female sex hormones, mainly oestrogen, are protective. This oestrogen hypothesis is supported by a 20-year delay in the onset of OAC in women compared to men, 9 and a particularly high male-to-female ratio during women's reproductive years. 10 Individual investigations of the potential role of exogenous hormonal therapy in women, including hormone replacement therapy (HRT) and oral contraceptives (OC), in the aetiology of OAC have failed to provide conclusive results. 11-15 The low incidence of OAC in women has hampered the statistical precision in the available studies. HRT is used to mitigate discomfort caused by decreased levels of circulating oestrogen and progesterone after menopause. Combined HRT includes both oestrogens and progesterone, and is recommended to women with an intact uterus, as it counteracts endometrial hyperplasia associated with oestrogen therapy. Oestrogen only HRT is recommended to women who have undergone hysterectomy. 16,17 The most commonly used OCs contain both oestrogen and progesterone. The often called 'mini pill' contains progesterone only, 18 and is recommended during breastfeeding as oestrogen reduces the amount of breast milk. 19 With the purpose of improving the knowledge of the relationship between HRT and OC exposure and risk of OAC, we conducted a systematic review and meta-analysis. Material a...

show abstract

Section: Discussionmentioning

confidence: 99%

Hormone Replacement Therapy and Oral Contraceptives and Risk of Oesophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

Lagergren

Brusselaers

2015

International Journal of Epidemiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…[13][14][15][16][17][18][19] Based on twin studies, the heritability of GERD has been estimated to be 31 -43%, 13, 20 implying that potential confounding by genetic factors should be taken into account when investigating other risk factors for GERD. Some data suggest, including two studies by our group, that the association between obesity and reflux symptoms is stronger among women than among men 14,21 and that the association is strengthened by the use of postmenopausal hormone therapy (HT). We therefore hypothesized that estrogen and possibly progestin therapy might be causally linked to reflux symptoms, by having a direct effect on the lower esophageal sphincter (LES) possibly via nitric oxide.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

View full text Add to dashboard Cite

show abstract

“…9,[26][27][28][29][30][31][32][33][34][35][36][37][38] A meta-analysis has described that the men/women ratio in the prevalence of reflux esophagitis was 1.57 (95% CI, 1.40-1.76) and the mean age of men with reflux esophagitis was lower than that of women. 7 In a systematic review based on data of 67 056 patients using the PubMed database between 1997 and 2011 (including 12 unbiased population-based studies, 8 studies from Asian countries, 2 studies from Europe, and 1 study from the US), the prevalence of reflux esophagitis was lower in women compared to that men (women: 6.1 ± 1.6%, range: 2.1-16.8%; men: 15.9 ± 2.5%, range: 7.0-28.1%; P < 0.01).…”

Section: Endoscopy-based Studymentioning

confidence: 99%

Sex and Gender Differences in Gastroesophageal Reflux Disease

Kim

2016

J Neurogastroenterol Motil

117

View full text Add to dashboard Cite

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.

show abstract

Body Mass and Reflux Oesophagitis: an Oestrogen-dependent Association?

Abstract: The study discloses a strong and dose-dependent association between body mass and reflux oesophagitis in women as opposed to no association among men. This association might be caused by increased oestrogen activity in overweight and obese females.

Cited by 126 publications

References 24 publications

Hormone Replacement Therapy and Oral Contraceptives and Risk of Oesophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

Hormone Replacement Therapy and Oral Contraceptives and Risk of Oesophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

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

Sex and Gender Differences in Gastroesophageal Reflux Disease

Contact Info

Product

Resources

About