Tremellen K, McPhee N, Pearce K, Bedson S, Schedlowski M, Engler H. Endotoxin initiated inflammation reduces testosterone production in men of reproductive age. American Journal of Physiology - Endocrinology and Metabolism 2017. Endotoxin initiated inflammation reduces testosterone production in men of reproductive age
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 analysed the relationship between serum levels of lipopolysaccharide binding protein (LBP), an indirect measure of endotoxin exposure, against male reproductive hormones, inflammatory markers (CRP, IL-1β, IL-6, TNF-α) and adiposity in 75 men.
Adiposity was positively correlated with endotoxin exposure (LBP) and inflammation (CRP, IL-6), while 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 results in impaired Leydig cell function.
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 analysed the relationship between serum levels of lipopolysaccharide binding protein (LBP), an indirect measure of endotoxin exposure, against male reproductive hormones, inflammatory markers (CRP, IL-1β, IL-6, TNF-α) and adiposity in 75 men.
Adiposity was positively correlated with endotoxin exposure (LBP) and inflammation (CRP, IL-6), while 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 results in impaired Leydig cell function.
