Gastroesophageal Reflux Disease Presents Differently in Women and Men
STEVEN SANDBERG-LEWIS
N.D., DHANP
Gastroesophageal reflux disease (GERD) is the overarching term for a constellation of symptoms caused by the upward flow (reflux) of stomach contents into the esophagus and/or throat leading to symptoms of heartburn and regurgitation. In some cases, there is no typical heartburn, but instead there is some combination of hoarseness, chronic sore throat, shortness of breath, chronic dry cough and enlarged tonsils. GERD is very common, occurring in 15-20% of the North American population. It is still more common in Argentina, Iceland, Pakistan, Turkey and the UK, with the highest incidence found in India, Greece, Poland and Romania. GERD can take many physical forms, which are diagnosed through an upper endoscopy (EGD) by a gastroenterologist (digestive disease specialist). An upper endoscopy is a procedure that allows the doctor to directly see the inner lining of the esophagus, stomach and the beginning of the small intestine. In addition, biopsy specimens can be taken during the procedure to microscopically examine the cells and tissues for more detailed diagnosis of GERD. In patients with reflux, the most common finding on an EGD is that all looks normal. The term non-erosive reflux disease (NERD) is the diagnostic term used for this situation, where everything appears normal, yet reflux is believed to be occurring. When the lower esophagus appears red and raw in places, the patient is considered to have erosive esophagitis. The diagnosis of Barrett’s esophagus (Barrett’s metaplasia) is determined when, under the microscope, the type of cell that lines the inner esophagus has changed from the normal flattened type (squamous) to a more cube shape (cuboidal). Barrett’s can progress further into dysplasia (containing precancerous cells) or esophageal cancer, but only in a very small percentage of cases. Barrett’s metaplasia may actually be the body's best attempt to adapt to the irritation of chronic unrelenting reflux.
Sex and GERD
A meta-analysis (combining the data from multiple research studies) found that the male subjects had significantly more erosive esophagitis and about twice the incidence of Barrett's esophagus compared to females (Kang A, 2020). The patient’s sex is a major factor determining the progression, or lack of progression in GERD.
Significant risk factors for erosive esophagitis in women include age over 70 years, obesity, elevated blood triglycerides, central obesity (waist circumference > 33.5 inches), current smoking status, and sliding hiatal hernia. Women often experience more heartburn, regurgitation and extra-esophageal symptoms (i.e., cough, hoarseness). They also have a higher incidence of non-erosive disease (NERD). The incidence of erosive esophagitis is significantly less common in women than men up to the age of 70, however, after 70 this condition increases significantly in women.
Significant risk factors for reflux esophagitis in men include being overweight or obese, high blood pressure, elevated blood triglycerides, central obesity (waist circumference >40 inches), current or past tobacco smoking, excessive alcohol consumption, and sliding hiatal hernia. For men, age does not appear to be a significant risk factor. Men are more likely than women to develop Barrett’s esophagus, Barrett’s with dysplasia and esophageal cancer.
A British study found that men and women have the same risk of developing Barrett’s but it starts much later in life for women. This may explain why the risk of Barrett’s progressing to more serious disease is low in women. For men this increase starts at age 20, but in women it is delayed until almost age 40. This 17-year age difference gave men over three times the risk of having Barrett’s (van Blankenstein M, 2005). Large Dutch and Irish studies found similar results (van Soest EM, 2005 and Coleman HG, 2011). It appears that women experience more symptoms of GERD, but develop Barrett’s later in life and likely will die from other causes before developing esophageal cancer. This correlation may, in part, be due to the protective, anti-inflammatory effects of estrogen. Some studies suggest that other factors may include gender differences in alcohol and tobacco use.
Protective Effect of Estrogen
As noted above, research suggests that estrogen may improve esophageal resistance to refluxed stomach fluids. The mechanism appears to be strengthening of esophageal tight junctions – “preventing leaky esophagus”. The higher levels of estrogen in women prior to menopause may explain the decreased prevalence of reflux esophagitis in women, and the increase after age 50. Estrogen may also delay the onset of Barrett’s esophagus and esophageal cancer. A Swedish population-based study of over 200,000 women suggested that hormone replacement therapy for women had a protective effect against esophageal cancer. Both estrogen-only hormone replacement and combination estrogen and progestin therapy were significantly protective in all age groups. (Brusselaers N, 2017).
Options for Reversing or Halting the Progression of Barrett’s
The Best Practice Advice from the American College of Gastroenterology (Freedberg DE, 2017) includes the statements :
1) Patients with GERD and acid related complications (ie. Erosive esophagitis or peptic stricture) should take a proton pump inhibitor (PPI) for short-term healing, maintenance of healing and long-term symptom control.
2) Patients with Barrett’s esophagus and symptomatic GERD should take a long-term PPI
3) Asymptomatic patients with Barrett’s esophagus should consider a long-term PPI
Research on acid suppression and Barrett’s Esophagus is mixed. A meta-analysis found a 71% reduction in the risk dysplasia and cancer of the esophagus, while a Danish population-based study with over a decade of follow-up found that patients with the best compliance in taking PPIs had the highest risk of esophageal adenocarcinoma (Hvid-Jensen F, 2014). A 2017 meta-analysis concluded that “no dysplasia or cancer-protective effects of PPI usage in patients with Barrett’s esophagus were identified by our analysis. Therefore, we conclude that clinicians who discuss potential chemopreventive effects of PPIs with their patients, should be aware that such an effect, if it exists, has not been proven with statistical significance” (Hu Q, 2017).
My Key Objectives:
In addressing GERD, my primary methods are to treat diabetes, reduce excessive waist circumference when possible, support smoking cessation, and reduce or eliminate alcohol consumption. I also treat other underlying causes of reflux, (for details see Getting Real About Reflux, which I am currently writing, and expect to publish in 2022).
-control or correct reflux (by treating the cause when possible)
-prevent dysplasia in areas of Barrett’s metaplasia
-promote healing of the esophageal mucous membrane
-maintain antioxidant nutrients such as superoxide dismutase, catalase, glutathione and vitamin E. (Schiffman SC, 2012)
Additional Nutritional Supports for Healing Barrett’s Esophagus:
Increased intakes of vegetables and fruits are associated with a lower risk of Barrett’s in men and women (Thompson OM, 2009). Berry extracts enhance superoxide dismutase, an antioxidant produced in human body cells that protect against the formation of mutations and DNA damage. Superoxide dismutase reduces cell damage from free radicals produced during various responses in the body, (Schiffman SC, 2012).
Green tea catechins – polyphenon E (in green tea extract) inhibits the growth of transformed epithelial cells. (Song S, 2009).
Selenium slows growth of cancer cells and protects healthy cells from DNA damage. In Barrett’s patients, higher selenium levels were associated with a decreased risk of later stages of progression such as high-grade dysplasia and may protect anti-cancer genes. (Rudolph RE, 2003)
Turmeric (curcumin) – in a rat model, curcumin effectively prevented reflux esophagitis and was more effective than lansoprazole (PPI) in inhibiting a mix of acid and bile reflux. (Mahattanadul S, 2006)
Vitamin E and overall antioxidant nutrient intake– higher intake of vitamin E from food and supplements combined was associated with decreased risk of esophageal cancer. A combination of multiple antioxidants reduces the risk of developing esophageal cancer. (Ibiebele TI, 2013).
Steven Sandberg-Lewis, ND, has been in clinical practice for 43 years, with a focus on functional gastroenterology. He has been a professor since 1985, teaching a variety of courses but primarily focusing on gastroenterology and GI physical medicine. In 2019, Dr. Sandberg-Lewis co-founded Hive Mind Medicine, continuing his specialization in gastroenterology with a focus on reflux, SIBO, inflammatory bowel disease and functional GI disorders. He is currently working on his new book, Getting Real About Reflux, written to help non-medical and medical professionals alike develop a better understanding of diseases affecting the gastrointestinal tract.
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