Testosterone Supplementation Improves Carbohydrate and Lipid Metabolism in Some Older Men with Abdominal Obesity.

Background/objectives: The effects of testosterone supplementation on carbohydrate and lipid metabolism in obese older men are uncertain. We conducted a single-arm open-label prospective pilot study to investigate the effects of testosterone supplementation on central and peripheral insulin sensitivity in older men with upper body obesity and insulin resistance.

Subjects/methods: Twenty men (62-78 years-old) with morning testosterone levels <13.9 nmol/L (400 ng/dL), waist circumference ≥ 102 cm, and HOMA-IR ≥ 4.0 or HgbA1C 5.7-6.4% applied transdermal testosterone (10 mg) daily for 20 weeks. Insulin sensitivity (Si) was determined by a 2-stage glucose clamp, liver and intramyocellular lipid by ¹H-MR spectroscopy and body composition by DEXA.

Results: Testosterone supplementation significantly reduced total fat (-.9 ± 2.4 kg, p=0.002), trunk fat (-1.3 ± 1.4 kg, p=0.0007) and extremity fat (-0.7 ± 1.1 kg, p=0.01), and increased extremity lean tissue (+1.3 ± 1.4 kg, p=0.0006). Whole body (WB) Si improved by 21% (0.76 ± 1.57 dL/min per µU/mL, p=0.04) and insulin-stimulated glucose uptake (Rd) by 24% (0.91 ± 1.74 dL/min per µU/mL, p=0.03). Improvements in glucose kinetics were limited to men with reductions in trunk and extremity fat greater than median declines for the entire group. Reductions in intramyocellular lipid were associated with improvements in WB Si (p=0.04) and Rd (p=0.03). Change in Rd accounted for 90% of the change in WB Si. Hepatic glucose output and liver lipid/H₂O were unchanged (p>0.05). Multivariable analyses revealed that reductions in extremity fat, trunk fat, and FFA levels during the clamp accounted for 45% (p=0.004), 31% (p=0.002) and 8% (p=0.04) of respective changes in Rd. Triglycerides decreased by -0.40 ± 0.67mmol/L (p=0.02), LDL-C by-0.35 ± 0.57 mmol/L (p=0.02), and HDL-C by -0.14 ± 0.19 mmol/L (p=0.004).

Conclusions: Testosterone supplementation that resulted in greater reductions in regional adiposity was associated with improved insulin sensitivity, lower LDL-C and fasting triglycerides, but lower HDL-C. Placebo controlled trials need to further examine the potential cardiometabolic risks/benefits of androgen supplementation for older men with low testosterone levels, central obesity, and insulin resistance.