Endocrine Abstracts

Context: Obesity, diabetes and cardiovascular disease in men are associated with low testosterone levels. Leptin is produced in adipose tissue in proportion to obesity and is known to be negatively associated with testosterone in men. The shared association of testosterone and leptin with obesity is in line with the proposed adipocytokine–hypogonadal–obesity cycle which aims to explain the relationships between these variables.

Methods: We investigated the associations of leptin with testosterone and oestrogen levels in 112 men with type 2 diabetes. Androgen receptor CAG repeat polymorphism (AR CAG) was measured by sequence analysis. Total testosterone (TT), sex-hormone binding globulin (SHBG), oestradiol (E2) and leptin were measured by ELISA. Bioavailable testosterone (BioT) was measured following ammonium sulphate precipitation. Free testosterone (FT) was also derived using Vermuelen’s formula. Waist circumference and body mass index (BMI) were also assessed.

Results: After adjustment for age leptin correlated negatively with TT (r=−0.188, P=0.048), BioT (r=−0.194, P=0.042) and TT:E2 ratio (r=−0.291, P=0.002) and positively with AR CAG (r=0.203, P=0.033). There was a trend towards a positive correlation with E2 (r=0.164, P=0.053). Leptin was strongly correlated with waist circumference (r=0.699, P<0.001) and BMI (r=0.691, P<0.001). TT was negatively associated with waist (r=−0.300, P=0.001) and BMI (r=−0.215, P=0.024). After adjustment for waist and BMI all significant associations with leptin were lost apart from a correlation with AR CAG (r=0.228, P=0.017).

Discussion: Our data confirms that low testosterone is associated with obesity and serum leptin levels in men and can be seen as supportive towards the adipocytokine–hypogonadal obesity cycle hypothesis. Correlations of testosterone with leptin were abolished by statistical adjustment obesity suggesting that this relationship explicable by adiposity. By contrast AR CAG remained associated with leptin after adjustment for obesity. Testosterone and the androgen receptor may have actions which are independent of each other in affecting leptin and other variables.