title: Gender difference in gastro-esophageal reflux diseases.
abstract: The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.
authors: Kiyotaka Asanuma, Katsunori Iijima, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi Prefecture 980-8574, Japan.
authors: Kiyotaka
authors: K
authors: Asanuma
authors: Kiyotaka Asanuma, Katsunori Iijima, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi Prefecture 980-8574, Japan.
authors: Katsunori
authors: K
authors: Iijima
authors: Kiyotaka Asanuma, Katsunori Iijima, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi Prefecture 980-8574, Japan.
authors: Tooru
authors: T
authors: Shimosegawa
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D001471:Barrett Esophagus / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D015897:Comorbidity; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D054624:Health Status Disparities; D006801:Humans; D015994:Incidence; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology
chemical_list: D004967:Estrogens
keywords: Barrett’s esophagus; Esophageal adenocarcinoma; Estrogen; Gastro-esophageal reflux disease; Male predominance