Insulin-like factor 3 as a marker of testicular function in obese men

Objectives: Testicular function declines with obesity as a result of central and peripheral mechanisms, including a primary dysfunction of the Leydig cells. The levels of insulin-like factor 3 (INSL3), a sensitive marker of Leydig cell impairment, have never been evaluated in obese men. To better evaluate the hormonal function of the testis in obese men, we analysed their INSL3 plasma levels and compared them with the obesity status and the other reproductive hormones. DESIGN: Cross-sectional study. PATIENTS: Thirty-one obese men [body mass index (BMI) >30 kg/m(2)) aged 22-49 years and 64 age-matched nonobese men. MEASUREMENTS: Plasma concentrations of INSL3, testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E(2)), LH, FSH. Free testosterone (FT) levels were calculated. RESULTS: Obese men had significantly lower plasma concentrations of total T, SHBG, FT and INSL3, and higher levels of E(2) with respect to nonobese men. LH and FSH values were not different from controls. In obese men, we found a significant negative correlation between BMI and INSL3, and a positive correlation between INSL3 and T. Only one (1/31, 3.2%) obese man had subnormal T levels. On the contrary, 10/31 (32.3%) obese men had low INSL3 values. CONCLUSIONS: This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment, whereas T mainly reflects the steroidogenic activity of these cells.