This study employed the MR research method to investigate the causal relationship between digestive system diseases and ED. Leveraging genetic data for analysis allowed us to circumvent common pitfalls such as confounding bias, selection bias, and reverse causality often encountered in observational studies. Our investigation revealed notable findings regarding the relationship between specific digestive system diseases and ED. Specifically, celiac disease, Crohn's disease, colorectal cancer, and primary sclerosing cholangitis were associated with an increased risk of ED, while gastric cancer exhibited a mitigating effect on ED risk (Fig 8). Particularly, Crohn's disease and colorectal cancer have a direct causal effect on ED.
Few studies have investigated the risk of upper gastrointestinal diseases and ED, leading to an unclear understanding of the relationship between upper gastrointestinal diseases and ED. Within the existing literature, two studies have investigated the correlation between gastric ulcers and ED risk[17,18]. Both studies employed a case-control design to explore the link between gastric ulcer and the likelihood of developing ED, with findings suggesting a positive correlation. However, in our study, there was no obvious causal relationship between gastric ulcer and ED. Moreover, our investigation uncovered a protective effect of gastric cancer against ED, a phenomenon not previously documented in extant research. To date, there is a dearth of studies examining the potential correlation between gastric cancer and ED. Notably, Junke Chang et al.'s research identified a certain correlation between gastric cancer and testosterone levels[19], while testosterone is closely linked to ED[20-22]. Hence, we speculate that the observed protective effect of gastric cancer against ED may be mediated by testosterone levels. Nevertheless, direct evidence supporting this conjecture is lacking, and the underlying mechanism remains elusive, necessitating further validation through empirical experimentation. Overall, in our study, we found that upper digestive tract diseases were not harmful to erectile dysfunction.
The relationship between lower digestive tract diseases and ED is not clear, and the results of relevant studies are different. Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by the absence of organic lesions, often associated with the patient's mental state[23]. Research conducted by C-Y Hsu et al. suggests that IBS is closely related to both organic and psychogenic ED[24]. Furthermore, another study indicates that patients with IBS are at a higher risk of developing ED compared to those without IBS[25]. However, in our study, we didn't find a significant causal effect between IBS and ED. Celiac disease is a chronic autoimmune enteropathy with an unclear etiology. Our research indicates that celiac disease can increase the risk of developing ED. Lorenzo Romano et al.’s survey found that a significant portion of celiac disease patients experience sexual dysfunction, including ED[26]. This aligns with our study findings. Additionally, research by M.J.G. Farthing et al. suggests that ED in celiac disease patients may be associated with sex hormones imbalance[27]. Inflammatory bowel disease (IBD) is a specific type of chronic inflammatory condition affecting the intestines, primarily comprising Crohn's disease and ulcerative colitis. The relationship between IBD and ED remains enigmatic in existing literature. Some studies suggest no significant correlation between IBD and ED[28,29], while others indicate a positive correlation between IBD and the risk of ED[30,31]. Nonetheless, our research findings show a clear causal relationship between Crohn's disease and ED, while ulcerative colitis doesn't exhibit a significant causal relationship with ED. Research by Jinzhi Zhang et al. proposes that ED stemming from Crohn's disease and ulcerative colitis may be attributed to active perianal disease and psychological factors[32]. Most studies on the relationship between colorectal cancer and ED primarily focus on post-treatment erectile function in patients, but there are also studies exploring the relationship between colorectal cancer itself and ED. Marjan Johanna Traa et al. investigated the sexual function and quality of sexual life in colorectal cancer patients before treatment, finding a decrease in erectile function and a decline in sexual quality of life compared to normal individuals[33]. Similarly, Amirmohammad Dahouri et al.'s research also suggests a positive correlation between colorectal cancer and the risk of ED[34], a viewpoint supported by our own study. In conclusion, it can be seen in our study that lower digestive tract diseases are more harmful to ED.
The liver is the largest digestive gland in the human body and an essential metabolic organ, closely involved in both hormone regulation and sugar metabolism. Liver dysfunction can precipitate various metabolic disruptions, potentially impacting erectile function. Several studies posit that most liver diseases, including non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, and hepatic cancer, may heighten the risk of ED[35-38]. However, our study did not find a significant causal relationship between liver diseases and ED. Research attention regarding the interplay between gallbladder and bile duct diseases and ED has been limited. Nonetheless, one study found that gallstones may increase the risk of organic ED[39], a conclusion not corroborated in our study. Instead, our research discovered a positive correlation between primary sclerosing cholangitis and the risk of ED, although the underlying mechanism remains unexplored. The pancreas is a vital digestive gland and plays a crucial role in regulating blood sugar levels. Despite its significance, scant research has delved into the relationship between pancreatic diseases and ed. And in our study, we did not find a significant correlation between pancreatic diseases and ED. Further research is needed to explore the relationship between hepatobiliary and pancreatic diseases and ED.
In this study, we utilized MR analysis to provide new insights into the potential causal relationship between digestive system diseases and ED. In the absence of direct experimental evidence, we employed large-scale GWAS data to validate the causal effect of digestive system diseases on ED, thereby furnishing valuable literature support for continued exploration in this domain. Furthermore, our findings not only contribute to advancing scientific understanding but also underscore the theoretical significance of monitoring the erectile function status among individuals afflicted with digestive system diseases. Such insights hold potential implications for clinical practice, emphasizing the importance of holistic healthcare approaches that encompass both gastrointestinal and sexual health considerations.
Our study also has certain limitations. The inherent limitations of the MR method, coupled with its reliance on specific assumptions, preclude us from definitively elucidating the underlying mechanism of its causal relationship. Therefore, further studies, including randomized controlled trials and comprehensive mechanistic studies, are necessary to validate and elucidate the connection between digestive system diseases and ED. Additionally, this study only selected 23 types of digestive system diseases and did not encompass all digestive system diseases, thus the research results may not be comprehensive. Furthermore, the primary reliance on genome-wide association study (GWAS) data derived from European populations presents a notable limitation. As such, the generalizability of our analysis to non-European populations may be constrained. Therefore, it is imperative that forthcoming research endeavors address this gap by exploring the relationship between digestive system diseases and ED within non-European populations. In summation, while our study contributes valuable insights, it is imperative to recognize these limitations and pave the way for future investigations aimed at elucidating the intricate relationship between digestive system diseases and ED across diverse populations.