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Testosterone deficiency has a high prevalence in men with T2DM, and it is also associated with impaired insulin sensitivity, increased percentage body fat, central obesity, dyslipidemia, hypertension and cardiovascular diseases (CVD)

A meta-analysis of four randomized controlled trials (RCTs) showed that TRT seemed to improve glycemic control as well as fat mass in T2DM subjects with low testosterone levels and sexual dysfunction.

testosterone administration could increase muscle mass and strength

Insulin stimulates glucose uptake into muscle and adipose tissue via the Glut4 glucose transporter isoform. When insulin activates signaling via the insulin receptor, Glut4 interacts with insulin receptor substrate 1 to initialize intracellular signaling and facilitate glucose transportation into the cell

The benefits of TRT on glucose metabolism can mainly be explained by its influence on the insulin signaling pathway

Insulin resistance as assessed by, which is calculated from the equation (If*Gf/22.5, where If is fasting insulin and Gf is fasting glucose), was definitely improved by TRT after testosterone administration in three studies

Testosterone was observed to elevate the expression levels and stimulate translocation of Glut4 in cultured skeletal muscle cells and to upregulate Glut4 by activating insulin receptor signaling pathways in neonatal rats

These effects were inhibited by a dihydrotestosterone (DHT) blocker, indicating that glucose uptake may correlate with conversion of testosterone to DHT and activation of the androgen receptor.

TRT reduced triglyceride levels

TRT has been reported to have a positive effect in the decrease of total and LDL cholesterol levels and triglycerides in hypogonadal men

a recent meta-analysis showed that statins could significantly lower testosterone concentrations.

Epidemiological studies have found a negative relationship between testosterone levels and typical cardiovascular risk markers, such as body mass index, waist circumference, visceral adiposity and carotid intima-media thickness.

Testosterone treatment was shown to raise hemoglobin, hematocrit and thromboxane, all of which might give rise to CVD

The RRs were 0.95 (0.54, 1.67) under 55 years

1.35 (0.77, 2.38) at 55–59

1.29 (0.71, 2.35) at 60–64,

1.35 (0.44, 4.18) at 65–69, 1.62

3.43 (1.54, 7.66) at 75 years and older

The adjusted post/pre RR for PDE5I across all ages was 1.08

For TT prescription, in men under age 65 years, the RR was 2.90 (1.49, 5.62) for those with a history of heart disease and 0.90 (0.61, 1.34) for those without

In men aged 65 year and older, the RR was 2.16 (0.92, 5.10) for those with a history of heart disease and 2.21 (1.09, 4.45) for those without.

Among men aged 65 years and older, we observed a two-fold increase in the risk of MI in the 90 days after filling an initial TT prescription

Among younger men with a history of heart disease, we observed a two to three-fold increased risk of MI in the 90 days following an initial TT prescription and no excess risk in younger men without such a history

Among older men, the two-fold increased risk was associated with TT prescription regardless of cardiovascular disease history

our own findings appear consistent with a higher frequency of thrombotic events following TT prescription among men with more extensive coronary vascular disease.

Our findings are consistent with a recent meta-analysis of placebo-controlled randomized trials of testosterone therapy lasting 12 or more weeks among mainly older men, which reported that testosterone therapy increased the risk of adverse cardiovascular-related events (OR = 1.54, 95%CI:1.09, 2.18), as well as serious adverse cardiovascular-related events (OR = 1.61, 95%CI:1.01, 2.56) which included myocardial infarction along with other conditions

This association appeared unrelated to average baseline testosterone level (p = 0.70) but varied by source of funding (p = 0.03), with a stronger summary effect in a meta-analysis of studies not funded by the pharmaceutical industry (OR = 2.06, 95%CI:1.34, 3.17) compared with studies funded by the pharmaceutical industry

the evidence supports an association between testosterone therapy and risk of serious, adverse cardiovascular-related events–including non-fatal myocardial infarction–in men

there is some evidence that low endogenous testosterone levels may also be positively associated with cardiovascular events

effects of endogenous and exogenous testosterone may differ. Exogenous testosterone (TT) is associated with physiologic changes that predispose to clotting and thrombotic disorders including increased blood pressure [18], polycythemia [19], reductions in HDL cholesterol [18], [20], and hyperviscosity of the blood and platelet aggregation. [20]–[23]; TT also increases circulating estrogens [24], [25] which may play a role in the observed excess of adverse cardiovascular-related events, given that estrogen therapy has been associated with this excess in both men and women

did not include information on the serologic or diagnostic indications for treatment.

no association between PDE5I prescriptions and the risk of MI

Recently TT has been increasing extraordinarily rapidly, including among younger men and among those without hormone measurement