Can Colorectal Cancer Cause Low Testosterone?

by Benjamin Bunting BA(Hons) PGCert

ben bunting BA(Hons) PgCert Sport & Exercise Nutriton  Written by Ben Bunting: BA(Hons), PGCert. Sport & Exercise Nutrition. L2 Strength & Conditioning Coach.

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The clinical presentation of colorectal cancer (CRC) varies, depending on its location and stage. Patients may experience anything from weight loss and altered bowel habits to anorexia. Right-sided CRC typically has a poor prognosis. Testosterone levels and colorectal neoplasia are often associated, and the findings are important for predicting the likelihood of developing colorectal cancer.

High-affinity SHBG regulates sex hormone bioactivity

Sex hormone binding globulin (SHBG) is a molecule synthesized in the liver that binds sex hormones with a high affinity. This molecule prevents the release of these hormones in the body, making them unavailable to their target tissues. This molecule has many functions and may be involved in the earliest stages of colorectal carcinogenesis. Here, we show that SHBG regulates the bioactivity of sex hormones.

The results show that the expression of SHBG levels can help determine the severity of hyperandrogenism in women with polycystic ovary syndrome (PCOS). Serum levels of SHBG may be an important factor in determining treatment efficacy. Furthermore, serum SHBG levels may also be involved in the development of PCOS complications. This hormone is a key regulator in the pathogenesis of PCOS. Patients with PCOS have low levels of SHBG while having elevated androgen levels. High levels of androgens and insulin inhibit the secretion of SHBG. Hence, their serum testosterone levels are significantly elevated.

In this study, researchers found that the concentration of SHBG was associated with 12 genomic regions, including the UGT2B7 gene. Interestingly, UGT2B7 was upregulated in the tumor tissues of Chinese women with colon cancer. Moreover, the study identified a genetic variant associated with a risk of developing non-small cell lung cancer (NSCLC). These results support previous reports that have linked the high-affinity SHBG gene to colon cancer.

Whats the link between CRC and androgens?

A 2010 paper explains that prostate cancer is dependant on androgenic hormones. 

As such, therapies include reducing testosterone synthesis to reduce plasma testosterone levels in the prostate. However, over time, tumour cells can become resistant to the treatment. 

A closer look at CRC?

Furthermore, research has found that there is a growing body of evidence linking increased female hormones such as estrogen and progestin with a reduced risk of CRC.

This evidence triggered a study comparing the effects of estrogen and progestin against a placebo group which saw a 40% lower risk of CRC when being treated with the female hormones.

That said, not all of the studies had the same results, and these clinical trials only involved females. 

On the other hand, males with lower levels of testosterone seem to be at a higher risk of CRC. 

Rodent studies have found that androgens such as testosterone prevent tumour growth. 

In addition, obese men are linked to an increased risk of CRC. It is thought there is a link between hyperinsulinemia and insulin resistance and obesity which is often associated with lower levels of testosterone. 

When obese men are treated for their low testosterone this also reduces insulin resistance in men. Therefore, the theory is that androgens can affect the risk of CRC, particularly in men. 

However, to muddy the waters even more, a 2016 study (admittedly it did suggest more research was required) drew associations between a higher risk of CRC amongst males because of their higher levels of testosterone. 

A 2012 meta-analysis looking at the relationship between testosterone and cancers, specifically lung, prostate and CRC saw associations with the former forms of cancer, but couldn't draw a significant link between CRC and testosterone.

There's more...

In 2021 a submission to the journal of American Association for Cancer Research evaluated the link between testosterone and CRC. 

The analysis looked at over 350,000 participants in the United Kingdom and concluded that there was little association between sex hormones and CRC. 

The authors of the study did suggest further analysis was required to dig deeper for a greater understanding. 

Taking a view of these studies does place us in a situation whereby there's not a definite conclusion whether testosterone or estrogen levels increase the risk of CRC.

What happens to testosterone when a person has CRC? 

While researchers cannot certainly conclude how sex hormones can influence the risk or development of CRC, can CRC influence sex hormones?

Yang et al., published a study in 2019 that looked at sex hormones amongst CRC survivors. 

They found that there was a lower risk of mortality for those which had higher levels of circulating testosterone for males, but this was the opposite for females. 

The study suggested that sex hormones did have an influence on the risk of developing CRC, but there didn't appear to be an alteration of sex hormone levels among CRC survivors.   

SHBG is associated with lower risk of conventional adenomas

Although there have been many studies linking low serum concentrations of SHBG with a reduced risk of conventional adenomas, few have investigated the link between low SHBG and the risk of stroke. The Women's Health Initiative study, for example, was not designed to analyze the link between low SHBG and stroke, and it was limited to data collected from only a fraction of the participants. Still, the researchers were able to draw conclusions based on the findings, including the fact that SHBG is associated with lower risks of conventional adenomas and the development of insulin resistance.

While there is no definitive mechanism, it may be related to the interaction between estrogen and SHBG in estrogen-sensitive breast cancer cells. Although SHBG has no membrane receptor, it may interact with extracellular matrix associated proteins. Fibulins are known to interact with SHBG, and their phosphorylation may affect the behavior of estrogen-sensitive breast cancer cells. As a result, studies are currently underway to determine whether low levels of SHBG are associated with decreased risks of conventional adenomas.

Serrated polyps are difficult to remove by endoscopy

The most common type of serrated polyps is a small, flat, and indistinct lesion that is difficult to remove by endoscopy. Fortunately, there are ways to remove serrated polyps without compromising your health. Serrated polyps are characterized by their indistinct borders and architectural features that distinguish them from traditional adenomatous polyps.

Serrated polyps are classified as hyperplastic and sessile. Sessile refers to the shape and morphology of the polyp. In addition, it refers to the fact that they are flat or nonpedunculated. In addition, they are more likely to contain nodular components and can be more difficult to remove by endoscopy. These polyps are difficult to remove through endoscopy because of their hardness and irregular borders.

While the risk of bleeding is low with endoscopic mucosal resection, serrated polyps can be difficult to remove. In the endoscopy study, clipping was associated with a lower risk of major bleeding than adenomas. While it is not completely effective, clipping may be an option for large adenomatous polyps. However, the risks associated with this procedure are not worth risking.

Serrated polyps are associated with fatigue

Serrated polyps (SSPs) are benign, growth-promoting adenomas of the spleen, or adenomas with a serrated component. These tumors often cause fatigue and may be associated with symptoms of depression and irritability. However, their true prevalence is unknown. Detection rates and pathologic classification play a vital role in the accurate diagnosis of SSPs.

Women and men are equally at risk for this condition. It usually starts in the 50s and 60s, and the disease has no cure. Genetic testing is necessary to diagnose SPS. It may be hereditary, but there is no definitive genetic test that can identify the disease. Many patients do not exhibit any symptoms, so a physician should be consulted for a diagnosis. However, patients should seek medical attention if they develop any of the following symptoms:

In one study, fatigue did not affect the detection rates of SSPs. Serrated polyp detection rates varied by sex, age, and colonic segment. Interestingly, endoscopists' specialty did not influence their detection rates. These findings are in accordance with other studies. In addition to the findings of Kahi et al., the New Hampshire colonoscopy registry has also reported that SSP detection rates differ significantly among patients and endoscopists.

Conclusion

There's no definite answer whether CRC can cause a reduction in testosterone levels. One study didn't record any significant differences in hormone levels for those pre and post diagnosis of CRC. 

There are also mixed views regarding levels of sex hormones and their influence on the risk of developing CRC.

Some studies suggest there is a link between higher testosterone levels and a reduced risk of developing CRC and a reduced risk of mortality for men.

Whereas lower levels of testosterone in women were more beneficial to reduce a risk of developing CRC. 

Therefore, while testosterone levels may influence the risk of developing and the outcome of CRC, it doesn't appear to be affected by CRC.

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