A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity

OBJECTIVE: In both humans and rodents, males have lower levels of leptin th an females at any level of adiposity. Experimental data support the idea th at testosterone exerts a negative influence on leptin levels. There are, ho wever, major inconsistencies in available data concerning the possible asso ciation between androgenicity and leptin in humans. Reasons could be the in fluence of androgenicity on leptin production being dependent on body compo sition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biolog ically active testosterone and leptin after careful stratification for gend er and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n = 158; 85 men and 73 pre- and post menopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cro ss-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-bind ing globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concent rations of free testosterone and non-SHBG-bound testosterone were calculate d. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inv ersely correlated to testosterone levels in non-obese men (r = -0.56, P < 0 .01) and obese women (r = -0.48, P < 0.05). In contrast, leptin and testost erone correlated in a positive manner in non-obese women (r = 0.59, P < 0.0 1). Levels of SHBG were negatively associated with leptin in men with low w aist circumference (r = -0.59, P < 0.01). The following factors were associ ated with leptin in a multivariate model: low revels of biologically active testosterone and SHBG in men with low and medium waist circumference, insu lin in men with high waist circumference, high levels of testosterone and i nsulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgen icity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results w e suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels.