Is Estrogen a Curse or a Blessing in Disguise? Role of Estrogen in Gastroesophageal Reflux Disease

Abstract

Gastroesophageal reflux disease (GERD), a condition wherein there is reflux of stomach contents into the esophagus, causing heartburn and regurgitation with a sour and bitter taste in the mouth. It may or may not lead to mucosal injury. GERD symptoms can be troublesome and negatively impact the quality of life. Estrogen, the sex hormone in females, may play a role in the gender differences observed in GERD symptoms. This review article analyzes estrogen's mechanism in the causation of GERD symptoms and its complications. A better understanding of pathophysiology will help us guide early detection, treatment, and prevention of repeated reflux complications. We did a comprehensive PubMed database search and analyzed differences in GERD symptoms experienced by males and females and the role of estrogen in erosive and non-erosive GERD. GERD symptoms in association with hormonal replacement therapy (HRT) and pregnancy, the lower esophageal sphincter (LES) relaxant effects, and estrogens' protective effect on the esophagus from mucosal injury due to repeated reflux are discussed. 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.

The association between menopausal hormone therapy and gastroesophageal reflux disease: a systematic review and meta-analysis

“…For example, the use of estrogen plus a progestogen resulted in a significant reduction in LES pressure in women 20 . Previous investigations suggested that nitric oxide acts as a mediator between estrogen and GERD 11,19-21 . The use of estrogens in postmenopausal women is associated with higher plasma nitric oxide levels, and nitric oxide is a key neurotransmitter for relaxation of LES 22 .…”

“…20 Previous investigations suggested that nitric oxide acts as a mediator between estrogen and GERD. 11,[19][20][21] The use of estrogens in postmenopausal women is associated with higher plasma nitric oxide levels, and nitric oxide is a key neurotransmitter for relaxation of LES. 22 In addition, nitric oxide is also associated with temporary relaxation of the LES, one of the key processes behind GERD in patients with reflux esophagitis.…”

“…8 Previous research has associated female sex with symptomatic GERD, attributed to elevated levels of estrogen and progesterone seen during pregnancy and with oral contraceptive use. [9][10][11] However, the association between HT and GERD in postmenopausal women remains unclear. The purpose of this systematic review and meta-analysis is to provide single summary estimate of the HT effect on GERD and to elucidate the combined HT effect on GERD when results from prior studies were mixed.…”

“…Estrogen increases stomach acid production, whereas progesterone relaxes the esophageal muscles and LES, allowing stomach acid to flow back into the esophagus and causing GERD symptoms 8 . Previous research has associated female sex with symptomatic GERD, attributed to elevated levels of estrogen and progesterone seen during pregnancy and with oral contraceptive use 9-11 . However, the association between HT and GERD in postmenopausal women remains unclear.…”

Characteristics of Laryngopharyngeal Reflux: A retrospective descriptive study

“…However, several studies have shown that estrogen could protect the mucosa from GERD injury. This matter still needs further analysis (Kang, Khokale, Awolumate, Fayyaz, & Cancarevic, 2020;Zia & Heitkemper, 2016).…”