Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis

Abstract

Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of ‘microgenderome’ and ‘sex hormone–gut microbiome axis.’ Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone–gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment. Graphical Abstract: (Figure presented.)