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Am J Physiol Endocrinol Metab. 2018 Mar 1;314(3):E206-E213. doi: 10.1152/ajpendo.00279.2017. Epub 2017 Nov 28.

Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age.

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Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University , Bedford Park, South Australia , Australia.
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia , Adelaide, South Australia , Australia.
Repromed, Dulwich, South Australia, Australia.
Institute of Medical Psychology and Behavioural Immunobiology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany.


Inflammation, both acute and chronic, is associated with testosterone deficiency, raising the possibility of a direct causal link. One potential trigger for inflammation in obese men is the passage of intestinal bacteria into the circulation due to a breakdown in mucosal barrier integrity. Recently, we hypothesized that this endotoxin exposure may cause androgen deficiency in obese men. To test this hypothesis, we analyzed the relationship between serum levels of lipopolysaccharide-binding protein (LBP), an indirect measure of endotoxin exposure, against male reproductive hormones, inflammatory markers (C-reactive protein, IL-1β, IL-6, TNF-α), and adiposity in 75 men. Adiposity was positively correlated with endotoxin exposure (LBP) and inflammation (C-reactive protein, IL-6) and negatively correlated with testosterone. Furthermore, endotoxemia (LBP) was negatively correlated with serum testosterone but positively correlated with IL-6. Multivariate analysis revealed a significant, negative correlation between serum IL-6 and free testosterone. In a second interventional study, low-dose endotoxin challenge in lean men produced a transient inflammatory response that was followed by a decline in serum testosterone, without changes in LH or FSH, providing further evidence that endotoxin-driven inflammation may result in impaired Leydig cell function.


endotoxin; inflammation; interleukin-6; lipopolysaccharide; obesity; testosterone

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