AbstractBackgroundThe very low‐calorie ketogenic diet (VLCKD) represents an opportunity to attain clinically relevant weight loss in obese patients. Functional hypogonadism represents a frequent hormonal disorder associated with obesity and visceral fat accumulation characterised by low testosterone levels and subnormal luteinising hormone (LH) levels.AimTo evaluate the early effects of VLCKD on serum total testosterone (TT) levels in non‐diabetic obese patients.Methods: Twenty‐two obese male patients (mean age 39.3 ± 11.7 years, mean body mass index (BMI) 38.2 ± 6.4 kg/m2) were enrolled and treated for 28 days with VLCKD. Anthropometric and hormonal variables were assessed before, during and after diet intervention.ResultsAfter 7 and 28 days on a VLCKD, a significant and persistent reduction in body weight, BMI, fat mass, blood glucose, insulin and homeostasis model assessment index was observed compared with baseline. TT significantly increased after 7 days (+35 ± 64 ng/dl) and 28 days (+74 ± 97 ng/dl) on a VLCKD. In addition to TT, a significant increase in serum sex hormone‐binding globulin levels was observed after 7 (+2.1 ± 4.1) and 28 days (+7.7 ± 10.0). However, both calculated free testosterone and LH did not change after 7 or 28 days of VLCKD. Following cessation of VLCKD, hypogonadal subjects achieved a higher percentage of total weight loss (8.5% ± 1.5%), a greater reduction in weight (−9.94 ± 1.66 kg), fat mass (−7 ± 2.1 kg) and waist circumference (−6.31 ± 2.65 cm) and a greater improvement in glycaemia (−8.75 ± 10.92 mg/dl) as compared with eugonadal subjects. Furthermore, hypogonadal subjects exhibited a trend of higher TT increase (+98.12 ± 71.51 ng/dl) as compared with eugonadal subjects.ConclusionsVLCKD results in rapid improvements in TT levels associated with weight loss in male obese non‐diabetic subjects, particularly in the presence of obesity‐related hypogonadism.