Table 2

Randomized trials of testosterone replacement in hypogonadal men with metabolic syndrome or type 2 diabetes

StudyKapoor et al. (55)Heufelder et al. (56)Kalinchenko et al. (57)Jones et al.* (37)
SubjectsType 2 diabetesNew type 2 diabetes/metabolic syndromeType 2 diabetes/metabolic syndromeType 2 diabetes/metabolic syndrome
Study designRCT-cNRCTRCT-pRCT-p
n2432184220
Duration (months)31266/12*
Medications for diabetesDiet, oral, insulinNaiveDiet, oralDiet, oral
Baseline serum testosterone (nmol/L)≤8.6≤10.5≤6.7≤10.2
Testosterone formulationTES injections (200 mg/2 weeks)Testosterone gel (50 mg/day)TU depot injectionsTestosterone gel (40–80 mg/day)
Treatment effects (changes)
 HOMA-IR−1.7−0.9−1.49−0.54
 Fasting glucose (nmol/L)−1.6−0.3 (AS)−0.42 (AS)
 Fasting insulin (mIU/mL)↓(AS)
 HbA1c−0.37−0.80ND [−0.45]
 Total cholesterol (nmol/L)−0.4ND [−0.13]
 LDL cholesterol (nmol/L)ND
 HDL cholesterol (nmol/L)§−0.049
 Triglycerides
 Lipoprotein aNDNDND
 BMI
 Waist circumference
 % Body fatNDNDND
 Blood pressure↓‖ND
  • ↔, No significant change; ↑, significant increase; ↓, significant decrease; AS, approaching significance (P = 0.05–0.07); ND, not done; NRCT, randomized open label, not placebo-controlled parallel trial; RCT-c, randomized placebo-controlled crossover; RCT-p, randomized placebo-controlled parallel; TES, mixed testosterone esters; TU, testosterone undecanoate depot injections after the first injection followed by another injection at 6 weeks and then injections every 12 weeks. Testosterone gel was dose-adjusted to give total testosterone level >17 nmol/L.

  • *The study by Jones et al. (TIMES2) had no medication changes in the first 6 months unless overriding clinical needs, but medication changes were allowed in the second 6 months for ethical reasons (intention-to-treat group, modified per protocol group where no changes in medications occurred; data not shown).

  • †Significant difference compared with placebo observed after 9 months, but result may be confounded by allowed medication changes.

  • ‡Metabolic syndrome subgroup showed significant changes in total cholesterol (−0.34 mmol/L), LDL cholesterol (−0.21 mmol/L), and HDL cholesterol (−0.058 mmol/L).

  • §No figure quoted.

  • ‖Diastolic blood pressure only.