Functional Dyspepsia: A Narrative Review With a Focus on Sex-Gender Differences

Abstract

Functional dyspepsia (FD) is among the most common gastrointestinal disorders affecting quality of life (QoL). As it frequently occurs in women than in men the comparison of various aspects including prevalence, clinical manifestations, and QoL in FD between women and men is very important for understanding the disease distribution and burden, evaluating treatment options, developing new drugs, and allocating medical resources. However, little is known about sex or gender differences among patients with FD. In spite of limited studies, consistent points are that FD occurs more often in women than in men and there are several symptom differences between men and women with FD. In addition, women with FD tend to have lower QoL than men with FD. Similarly, the pathophysiology of FD likely to vary depending on gender. Furthermore, a sex-gender-oriented approach in healthcare system could enhance understanding heterogeneous patients suffering from FD. Due to the sex-gender differences in physiological and psychological factors, treatment strategies should differ between women and men with FD. In conclusion, an individualized and multicomponent approach that considers sex and gender issues might improve FD treatment and improve patient Qol, especially for women.

Keywords: Dyspepsia; Gender; Sex.

Figure 1

Odds ratio (OR) for uninvestigated dyspepsia in women versus men according to geographical location. The Overall OR for dyspepsia in women compared with men was 1.24 (95% confidence interval [CI], 1.13 to 1.36), with significant heterogeneity between studies (I2 = 91.9%, P < 0.001), but no evidence of funnel plot asymmetry (Egger test, P = 0.860). Data were pooled using a random effects model to give a more conservative estimate of the prevalence of dyspepsia and the odds of dyspepsia in these various groups. Evidence of publication bias was assessed for, by applying Egger’s test to funnel plots of ORs, where a sufficient number of studies were available. Reprinted from Ford et al with permission.

Figure 2

Prevalence of functional dyspepsia (FD) according to sex and age group. The prevalence of FD was significantly higher between the ages of 18 years and 34 years than in the age groups 35-49 years and 50-64 years, with the lowest prevalence of FD seen in individuals older than 65 years. This pattern was seen across both sexes. Women had a significantly greater prevalence of FD than their men counterparts across all age groups, except for in those older than 65 years. Reprinted from Aziz et al with permission.

Figure 3

Sex and gender related differences in pathophysiology of functional dyspepsia (FD). Although the detailed investigation is lacking, the underlying pathophysiology of FD likely to vary depending on women and men. That is, although the pathophysiology of FD is complex and heterogeneous, accumulating knowledge indicates that sex and gender difference in sex hormone, psychological distress, central signaling via corticotropin-releasing factor (CRF), altered functional connectivity of amygdala, ghrelin, genetic factor, gut microbiome, and luminal factor such as food might affect enteric nerve system, duodenal immune activation, mucosal barrier function, duodenal low-grade inflammation, or alteration of gut motility and sensitivity, resulting in the difference outcome of FD between women and men.