Endogenous Sex Hormones and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis


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Emmanouil Bouras, Christopher Papandreou, Ioanna Tzoulaki, Konstantinos Tsilidis

Abstract

Background

Epidemiological evidence suggests that sex hormones may be implicated in colorectal cancer (CRC) development, however, findings are often conflicting. The aim of this systematic review and meta-analysis (MA) was to investigate the associations between endogenous concentrations of sex hormones and CRC risk.

Method

MEDLINE-PubMed and Elsevier’s Scopus databases were searched up to June 17th 2020 for studies evaluating the association between pre-diagnostic levels of endogenous sex hormones, namely plasma testosterone, estradiol, and sex-hormone binding globulin (SHBG), and CRC risk. Two researchers, working independently, screened all titles, abstracts and full texts to identify studies that met the inclusion criteria, namely prospective cohort studies published in English. Generalized least-square regression, as proposed by Greenland & Longnecker, was used to estimate the linear trends and express the study-specific estimates on a continuous scale. Inverse variance random effects DerSimonian-Laird MA was applied to pool study-specific estimates, separately in men and port-menopausal women. Heterogeneity was evaluated using the I2 metric.

Results

Initial search yielded 3,859 non-duplicate records and after further screening, eight studies were deemed eligible for inclusion, three of which were from USA, two from Australia, and one each from the UK, Denmark and Japan. Half of the studies had a nested case-control design, one was a case-cohort and the rest followed a cohort style analysis. Studies included on average 295 cases (range:48-732) and 2,105 controls. No significant association was observed for testosterone, estradiol and SHBG in neither men nor women, with evidence for heterogeneity observed only among women (Table 1).

Table 1. Meta-analysis estimates of the association between endogenous sex hormones and colorectal cancer.


 

Men

 

 

Women

 


RR (95%CI)

I2

Studies (n)

RR (95%CI)

I2

Studies (n)

Testosterone,

per 100 ng/dL

0.97(0.92-1.03)

31%

4

1.85(0.55-6.28)

62%

3

Estradiol,

per 10 pg/ml

1.05(0.95-1.16)

0%

3

1.06(0.88-1.28)

53%

5

SHBG,

per 10 nmol/L

0.94(0.85-1.05)

43%

3

1.02(0.96-1.09)

76%

4


Conclusion

Findings from this MA do not support significant associations of pre-diagnostic concentrations of testosterone, estradiol and SHBG with incident CRC in men or post-menopausal women.

Impact statement

Evidence from prospective studies do not support a role of endogenous testosterone, estradiol and SHBG concentrations in colorectal cancer risk.