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Chen et al,1 using a nationally representative sample of the US population from the National Health and Nutrition Examination Survey III (NHANES III), intriguingly suggest infection with Helicobacter (H) pylori may have positive health effects in addition to a causal role in gastric cancer. H pylori has a long history of coexistence with humans. Research on the human microbiome has also highlighted the symbiotic relation of gut microorganisms with their hosts. Animal biology suggests immune defence trades-off against reproductive success such that infections suppresses androgens.2 Correspondingly, changing the gut microbial environment in mice changes mice testosterone levels.3 The same mechanisms may also apply to humans, particularly at older ages when the immune system is less effective. H pylori could modulate androgen production and thereby affect health because androgens, and similarly endocrine disruptors, may play a role in chronic diseases.
Two androgen biomarkers (serum testosterone and androstanediol glucuronide (3-α-diol-G) (AAG)) were assayed for a male subsample (12+ years) from NHANES III who attended a morning examination session (n=2205) in phase I (1988–91) and had surplus sera available,4 using a competitive electrochemiluminescence immunoassay for serum testosterone and an enzyme immunoassay for AAG.4 H pylori antibodies, assayed using an ELISA, and antigens to cagA positive H pylori strains were also obtained from surplus sera.1 NHANES III was approved by the Institutional Review Board of the US Centers for Disease Control and Prevention and all participants provided written informed consent.
Of 1445 men (18+ years) with an androgen and clearly negative or positive H pylori status, 50.9% were H pylori positive. H pylori was associated with older age, less education, other than non-Hispanic white ethnicity and higher body mass index (BMI).1 H pylori was negatively associated with AAG, adjusted for age, race/ethnicity, education, BMI and smoking (model 2) using linear regression adjusted for the complex sample and weighted back to the US population (table 1). Somewhat similar associations occurred for joint H pylori/cagA status among men aged 20+ years, where the associations did not appear to differ for cagA+ (table 1). The association of H pylori with AAG, but not with testosterone, varied with age, such that H pylori was more strongly associated with lower AAG among older men (figure 1).
H pylori was most clearly associated with lower AAG, although testosterone had non-significant associations in the same direction. AAG was weakly positively correlated with testosterone (0.13), which may not capture all androgen activity,5 consistent with anti-androgens treating prostate cancer effectively at castrate levels of serum testosterone.5 ,6 AAG also had the biologically expected positive association of an androgen with higher haemoglobin (0.06 g/l per nmol/l AAG, 95% confidence interval (CI) 0.002 to 0.12 in model 2) whereas testosterone did not (0.22 g/l per nmol/l testosterone, 95% CI −0.17 to 0.62 in model 2).
These findings are consistent with some ecological observations. Some populations with high levels of stomach cancer, such as in China,7 also have lower androgen related parameters, such as testicular weight,8 than Caucasians, and lower rates of prostate cancer.7 The association of H pylori with lower androgens may also shed light on other observations. H pylori is positively associated with type 2 diabetes;9 lower androgens is a possible mechanism, as androgen deprivation increases vulnerability to diabetes. Antibiotic use is associated with prostate cancer10 for which raising androgens by eliminating H pylori is a speculative mechanism. Clearly, these findings need to be confirmed or refuted in other study designs capable of establishing causality. H pylori is currently very common; ongoing eradication could have widespread health consequences, particularly for older men, via altered androgens, such as increasing hormonally modulated cancers or affecting other chronic diseases.
Correction notice This article has been corrected since it was published Online First. The units in figure 1 and table 1 have been amended to ng/ml.
Contributors CMS originated the idea, analysed the data and wrote the first draft. JBD and HJ made suggestions about the analysis and reviewed the manuscript for important intellectual content. All authors read and approved the final version.
Funding This project was supported in part (for HJ and CMS) by funds from the Clinical Translational Science Center (CTSC), National Center for Advancing Translational Sciences (NCATS) grant # UL1-RR024996.
Competing interests None.
Ethics approval CDC Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement This is an analysis of publicly available data.
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