Visceral Adipose Tissue and Leptin Hyperproduction Are Associated With Hypogonadism in Men With Chronic Kidney Disease.

ABSTRACT

OBJECTIVE: Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population. DESIGN: Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5. SUBJECTS: A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m2). In them, serum levels of total testosterone, estrogen, sex hormone binding globulin, and leptin were quantified, together with visceral adipose tissue (VAT) by thoracic and abdominal CT scan. INTERVENTION None, observational study. MAIN OUTCOME MEASURE: Total testosterone, hypogonadism. RESULTS: The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction, was strongly and independently associated with the prevalence of hypogonadism in multivariable regression analyses. CONCLUSION: Visceral adiposity independently associated with lower testosterone levels among men with CKD stage 3-5 nondialysis. The observed link between hyperleptinemia and hypogonadism is in line with previous evidence on direct effects of leptin on testosterone production.