Fifty‐ two—Week Treatment With Diet and Exercise Plus Transdermal Testosterone Reverses the Metabolic Syndrome and Improves Glycemic Control in Men With Newly Diagnosed Type 2 Diabetes and Subnormal Plasma Testosterone

Abstract

Men with the metabolic syndrome (MetS) and type 2 diabetes (T2D) often have low testosterone levels. Elevating low testosterone levels may improve features of the MetS and glycemic control. In a single blind, 52-week randomized clinical trial, the effects of supervised diet and exercise (D&E) with or without transdermal testosterone administration on components of the MetS in hypogonadal men with the MetS and newly diagnosed T2D were assessed. A total of 32 hypogonadal men (total testosterone ,12.0 nmol/L) with newly diagnosed T2D and with the MetS as defined by the Adult Treatment Panel III and the International Diabetes Federation received supervised D&E, but 16 received it in combination with testosterone gel (50 mg) once daily (n 5 16). No glucose-lowering agents were administered prior to or during the study period. Outcome measures were components of the MetS as defined by the Adult Treatment Panel III and the International Diabetes Federation. Serum testosterone, glycosylated hemoglobin (HbA 1c ), fasting plasma glucose, high-density lipoprotein cholesterol, triglyceride concentrations, and the waist circumference improved in both treatment groups after 52 weeks of treatment. Addition of testosterone significantly further improved these measures compared with D&E alone. All D&E plus testosterone patients reached the HbA 1c goal of less than 7.0%; 87.5% of them reached an HbA 1c of less than 6.5%. Based on Adult Treatment Panel III guidelines, 81.3% of the patients randomized to D&E plus testosterone no longer matched the criteria of the MetS, whereas 31.3% of the D&E alone participants did. Additionally, testosterone treatment improved insulin sensitivity, adiponectin, and high-sensitivity C-reactive protein. Addition of testosterone to supervised D&E results in greater therapeutic improvements of glycemic control and reverses the MetS after 52 weeks of treatment in hypogonadal patients with the MetS and newly diagnosed T2D.

The role of testosterone in type 2 diabetes and metabolic syndrome in men

“…In these men, there is an increase of serum cholesterol, LDL-cholesterol and triglycerides and a decrease in HDL-cholesterol (20). The role of testosterone is further corroborated by the favorable effects of administration of testosterone on lipid profiles in a study of men with newly diagnosed diabetes mellitus and the metabolic syndrome (13 There is evidence from epidemiological studies on metabolic syndrome that there is an inverse relationship between circulating levels of testosterone and blood pressure. Lower levels of testosterone in men are associated with higher blood pressure, left ventricular mass, and left ventricular hypertrophy for review (22).…”

“…The maximum effect was attained after nine months of testosterone administration. A single-blind randomized study of testosterone administration to men with metabolic syndrome and recent onset of diabetes mellitus established also beneficial effects of testosterone on blood pressure over and above the effects of diet and exercise (13). These effects are persistent as demonstrated in a study of men receiving testosterone treatment up to 9.5 years (21).…”

“…By contrast, two studies replacing testosterone in men with type 2 diabetes and hypogonadism found little or no effect on glycemic control (15,16), but a more recent study analyzing the effects of testosterone administration to 24 hypogonadal men (10 treated with insulin) older than 30 years old with type 2 diabetes found that testosterone replacement therapy reduced insulin resistance (as measured by homeostatic model index) and improved glycemic control in hypogonadal men with type 2 diabetes (17). A recent study in newly diagnosed men showed convincingly that addition of testosterone to a regimen of diet and exercise produced significantly better results than diet and exercise on glycemic control and reversal of the metabolic syndrome (13).…”

Erectile dysfunction, diabetes and cardiovascular risk

“…31 In view of the association between hypogonadism and diabetes, researchers have postulated whether TRT can also improve metabolic parameters in diabetes. Studies have shown an association between TRT and reductions in HbA1c, 32 improvement in insulin resistance 33 and a reduction in body mass index. 34 A large Australian study (T4DM) is currently underway to assess whether …”

Androgens and male aging: current evidence of safety and efficacy

“…There is a positive correlation between serum testosterone levels and insulin sensitivity in men across the full spectrum of glucose tolerance [41] and an improvement of insulin sensitivity was noted after testosterone replacement. The effects of testosterone administration on glycemic control of men with diabetes mellitus were until recently much less certain [42] but there are recent reports indicating a favorable effect of testosterone in addition to diet and exercise [43]. By increasing LBM and reducing fat mass, testosterone therapy modulates insulin resistance and risk of metabolic syndrome [42].…”