The negative association between serum free testosterone and leptin is dependent on insulin-like growth factor-binding protein 1 in healthy young and middle-aged men

OBJECTIVE: Previous studies have shown that serum levels of testosterone correlate negatively with leptin and positively with insulin-like growth factor binding protein 1 (IGFBP-1). The present study examined whether these associations are linked.

DESIGN AND PATIENTS: The association between serum levels of IGFBP-1, free testosterone and insulin on one hand and leptin on the other hand were investigated in 38 healthy men with a median age of 48 years (range 23-62 years).

RESULTS: Univariate analyses revealed that serum levels of leptin correlated negatively with serum free testosterone (r = - 0.42, P = 0.008) and with serum IGFBP-1 (r = - 0. 45, P = 0.005) and positively with body mass index (BMI; r = 0.46, P = 0.003) and serum insulin (r = 0.45, P = 0.004). Serum free testosterone correlated with IGFBP-1 (r = 0.42, P = 0.008) but not with serum insulin (r = - 0.08, ns). The correlations between leptin and free testosterone and between leptin and IGFBP-1 remained significant after adjustement for the influences of BMI and insulin. Forward stepwise multiple regression when BMI, insulin, testosterone and IGFBP-1 were entered in a model as independent variables and leptin as the dependent variable showed that BMI and IGFBP-1 were independent predictors of circulating leptin. These two parameters yielded an r 2 of 0.38, thereby together explaining approximately 40% of serum leptin.

CONCLUSION: Serum levels of free testosterone and IGFBP-1 correlate negatively with serum leptin in healthy nonobese men but this influence is dependent on the influence of IGFBP-1. The study therefore suggests an important impact of IGFBP-1 on the regulation of circulating leptin in young and middle-aged men.