Endocrine Abstracts

Low levels of testosterone and SHBG levels are often present in subjects with overweight and obesity; functional hypogonadism further alters the metabolic balance and may drag subjects in a sort of vicious cycle, reducing exercise and energy expenditure. The very low-calorie ketogenic diet (VLCKD) has been reported to rapidly reduce body weight, glycaemia and insulinemia, but its effects on total testosterone (TT) and SHBG levels are less clear. We thus aimed to evaluate the response of TT and SHBG circulating levels to a VLCKD in a cohort of overweight or obese nondiabetic male subjects. All subjects underwent a VLCKD for 4 weeks. Anthropometric parameters, oral glucose tolerance test (OGTT), bioelectrical impedance analysis, and blood testing for the measurement of glycaemia, insulin, TT, SHBG, LH, were performed before and after 1 and 4 weeks of VLCKD. Seventeen patients [mean age 41.3 (12.2) years, mean BMI 36.4 (5.2) kg/m², mean TT 2.5 (1.0) ng/ml, mean SHBG (24.2) nmol/l] were enrolled. After VLCKD treatment, body weight (-9.3 kg (1.8)), fat mass [-6.5 kg (2.1)] and BMI [-3.1 (0.7)] significantly decreased, and a mean 14.9 ± 3.9% loss of the initial body weight was achieved. A significant increase of 0.49 (0.59) ng/ml and of 0.89 (0.91) ng/ml in serum TT levels was achieved after 1 and 4 weeks after VLCKD, respectively; similarly, a mean increase of 3.47 (4.73) and of 10.94 (12.87) in serum SHBG levels was achieved after 1 and 4 weeks, respectively. A stratification was further performed in high vs low responders in regard to TT variations after 1 week of VLCKD (>+0.44 vs <+0.44 ng/ml). While showing comparable variation of all variables analyzed, high responders differed only by the level of insulin sensitivity. Indeed, low responders, despite a comparable level of glycemia during OGTT, displayed a significantly higher level of insulinemia [area under curve: 25858 (11821) vs 13924 (11592)], indicating that they were more insulin-resistant vs high responders. This is the first study that evaluated the early response of androgen levels to institution of a VLCKD. VLCKD promotes a rapid effect on TT levels, especially in insulin-sensitive subjects with overweight or obesity. This highlights the tight relation between insulin action, energy balance, and testicular function. Further, VLCKD could be safely used to improve hypoandrogenemia, and possibly rescue obese patients from functional hypogonadism.