Oestrogen

Oestrogen helps protect the oesophagus against acid erosion. The purpose of this is probably protection during pregnancy when acid reflux is more likely to occur as the growing foetus pushes the stomach up to the diaphragm.

It is probably the reason Women are less likely than men to develop Barrett's Oesophagus or Oesophageal Adenocarcinoma.

According to a recent poll amongst the members of the Barrett's Esophagus Awareness Facebook group, 30% of 130 respondents  developing Barrett's say they never experienced acid reflux symptoms, the majority are women.

Women are more likely to experience acid reflux following the menopause. This may mean they are more likely to start taking acid suppressant medication then. Since osteoporosis is also likely at that age, an obvious correlation has been noticed between the use of PPIs and loss of bone mass; it is false to assume, as many have previously, that PPIs cause loss of calcium.

These are links found in the Research archive from Barrett's Patient Support. 

May 2014 Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum. "in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. ... The role of estrogen in attenuating the esophageal tissue damage in NO-related esophageal damage could explain the well-recognized male predominance" (Journal of Gastroenterology and Hepatology)

25 September 2015 Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium. "The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute." "Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC" (PLoS One)

27 December 2017 Estrogen-DependentNrf2 Expression Protects Against Reflux-Induced Esophagitis. "In the presence of nitric oxide, reflux-induced esophageal damage was less evident, whereas esophageal expression of Nrf2 and its target genes such as Nqo1 was more evident in female or male rats supplemented with 17β-estradiol than in male rats. 17β-Estradiol increased nuclear Nrf2 expression in KYSE30 cells. tert-Butylhydroquinone increased tissue Nqo1 mRNA expression, leading to a reduction in reflux-induced esophageal damage.
CONCLUSIONS: Estrogen-dependent Nrf2 expression might contribute to protection against the development of gastroesophageal reflux disease in females. (Digestive Diseases & Sciences)

4 May 2018 Estradiol mediates relaxation of porcine lower esophageal sphincter. "This finding suggests that GPER [G protein-coupled estrogen receptor] mediates the relaxation of the porcine LES. Estradiol may play a role in LES motility." (Steroids)

December 2019 The roles of estrogen and estrogen receptors in gastrointestinal disease "In recent years, researchers have demonstrated that estrogen and its receptors serve an important role in the gastrointestinal (GI) tract and contribute to the progression of a number of GI diseases, including gastroesophageal reflux, esophageal cancer, peptic ulcers, gastric cancer, inflammatory bowel disease, irritable bowel syndrome and colon cancer." (Oncology Letters)

26 October 2020 Is Estrogen a Curse or a Blessing in Disguise? Role of Estrogen in Gastroesophageal Reflux Disease (full text) " Estrogen can cause GERD as an adverse effect and, at the same time, can be used to protect the mucosa from GERD induced injury and its complications like metaplasia and cancer. The mechanism is complex and requires further studies and trials. We recommend future researchers to look for possible estrogen use to treat erosive GERD and complication prevention." (Cureus)

This paper from Hospital Pharmacy Europe, 7 May 2020, "Is oestrogen protective against COVID-19?" advising that "Prior to the COVID-19 pandemic, studies have shown that the intensity and prevalence of viral infections are generally higher in males than females and animal work has demonstrated that males are more susceptible to severe acute respiratory syndrome coronavirus (SARS-CoV) infection."... " preliminary findings would appear to be consistent with other work indicating that oestrogens have a protective role against COVID-19. ... Clearly more data are required to confirm these findings but perhaps there is a grain of truth in the notion of “man flu” and that women really are protected by their hormones."

This February 2022 paper is from Clinical Gastroenterology & Hepatology: "Effect of Hormonal Replacement Therapy on Gastroesophageal Reflux Disease and its Complications in Postmenopausal Women"

"It has been suggested that estrogen and progesterone confer their effect on the gastrointestinal tract by increasing nitric oxide synthesis, a muscle relaxant which decreases smooth muscle tone of the lower esophageal sphincter and esophageal body predisposing patients to gastroesophageal reflux.6-8 However, the exact mechanism that these hormones play in GERD remains to be elucidated because menopause, which is a risk factor for GERD, is associated with a decrease in estrogen and progesterone levels.“

This report was printed in Gastroenterology and Endoscopy News in April 2022, Study Supports Link Between HRT and GERD, Barrett’s suggesting, "In a multivariate analysis, estrogen-only HRT remained an independent risk factor for both GERD and Barrett’s esophagus. Progesterone-only HRT in this analysis no longer remained a significant risk factor. The relative association of estrogen-only HRT with GERD and its complications proved to be stronger than any other risk factor examined."

Page updated 23 June 2023