KEY POINTS

• In a prospective, observational, long-term study, 181 obese (BMI ≥30kg/m²) hypogonadal men, with and without type 2 diabetes mellitus (T2DM), were treated with testosterone undecanoate (TU) over 5 years. 40% (72 patients) also had T2DM
  1. Patients were aged between 33–67 years (mean 59.11±6.06 years) with serum testosterone <12.1 nmol/L
• After 5 years treatment with TU, there were significant anthropometric improvements, with all patients having lost weight (mean reduction 18.86±0.36 kg), mean waist circumference decreased by 8.87% and BMI reduced by 16.44%
  1. All patients lost weight, 99% of patients lost ≥5 kg, 90% lost ≥10 kg, 70% lost ≥15 kg, and 40% lost ≥20 kg. Mean weight significantly decreased from 114.71±11.59 kg at baseline to 93.2±8.49 kg over the 5 year study period (p<0.0001). Reduction in body weight was continual and sustained over the 5 year treatment period (Figure 1)
  2. Waist circumference decreased significantly (p<0.0001 vs baseline and previous year) from 111.20±7.54 cm at baseline to 100.46±7.10 cm after 5 years (Figure 1)
  3. A significant decrease (p<0.0001) in BMI occurred over the 5 year study period from 36.72±3.72 to 30.2±2.59 kg/m²
• There were similar reductions in anthropometric parameters in the diabetic subgroup. Mean body weight and BMI decreased by 15.97%, weight circumference decreased by 10.31 cm
  1. Mean body weight decreased from 116.94±11.62 to 94.42±9.42 kg over 5 years (p<0.0001 vs baseline and previous year)
  2. Waist circumference significantly decreased by 10.31±0.29 cm from 112.93±7.16 to 101.48±7.24 cm (p<0.0001 compared with baseline and previous year)
  3. In addition, a significant decrease in BMI was observed (p<0.0001) over the 5 year treatment period. BMI decreased by 6.02±0.18 kg/m² from 37.71±3.50 to 30.95±2.96 kg/m²
• In the total study population there was an improvement in all cardiovascular risk factors and metabolic state. Significant improvements were seen in lipid profile, blood pressure, fasting glucose, HbA_1c and liver function
  1. Fasting blood glucose significantly decreased from 5.84±0.84 to 5.41±0.12 mmol/L (p<0.0001) and HbA_1c decreased from 7.4±1.47 to 6.02±0.61% (p<0.0001)
  2. Significant improvement were seen in the lipid profile of patients (p<0.0001 vs baseline for all). Reductions were seen in total cholesterol from 7.63±0.95 to 4.9±0.28 mmol/L, LDL cholesterol from 4.47±1.02 to 2.93±0.93 mmol/L, and triglycerides from 3.32±0.56 to 2.17±0.13 mmol/L. HDL cholesterol increased from 1.58±0.44 to 1.61±0.44 mmol/L
  3. Both systolic (SBP) and diastolic blood pressure (DBP) improved over 5 years. SBP decreased from 159.17±15.9 to 139.04±10.96 mmHg and DBP from 96.5±11.01 to 80.36±7.52 mmHg
  4. A reduction was seen in serum levels of C-reactive protein from 4.03±4.80 to 0.77±1.53 mg/dL
• In the diabetic subgroup there were significant improvements in fasting glucose and HbA_1c with comparatively greater decreases seen in the diabetic subgroup than in the general population. Fasting glucose decreased by 1.35 mmol/L and HbA_1c decreased by 2.01%
  1. HbA_1c declined steadily over 5 years from 8.35±0.70% to 6.21±0.6% (p<0.0001). Fasting glucose declined from 6.58±0.79 to 5.42±0.16 mmol/L
• Treatment with TU was well tolerated. Increases in both haemoglobin (3.37%) and haematocrit (5.32%) remained within the normal range. Both parameters reached a plateau after 3 years of treatment with minor fluctuations thereafter
  1. Haemoglobin increased from 14.54±0.62 to 15.03±.04 g/dL over 2 years and then remained stable. Haematocrit increased from 43.71±2.51 to 49.03±1.65%
• Prostate volume increased slightly (<10%) over three years then stabilised, and mean prostate specific antigen increased over the 5 years by 0.18 ng/dL⁶