Are there proven cardiovascular risks associated with testosterone therapy in older adults with Type 2 Diabetes Mellitus (T2DM)?

Cardiovascular Risks of Testosterone Therapy in Older Type 2 Diabetic Adults

Testosterone replacement therapy in older adults with Type 2 diabetes has been associated with increased coronary artery plaque volume, though there is no conclusive evidence that it increases overall cardiovascular risk in hypogonadal men. 1

Testosterone and Cardiovascular Risk Assessment

Testosterone levels are frequently lower in men with diabetes compared to age-matched men without diabetes, though obesity is a significant confounder of this relationship 1. When considering testosterone therapy in older diabetic men, several cardiovascular considerations must be addressed:

Established Cardiovascular Effects:

• Coronary Artery Plaque: Testosterone replacement in older men with hypogonadism has been associated with increased coronary artery plaque volume 1
• Venous Thromboembolism (VTE): FDA labeling warns that VTE, including deep vein thrombosis and pulmonary embolism, have been reported in patients using testosterone products 2
• Myocardial Infarction and Stroke: Some postmarketing studies have shown increased risk of myocardial infarction and stroke with testosterone replacement therapy 2

Cardiovascular Risk Factors:

• Fluid Retention: Edema with or without congestive heart failure may occur in patients with preexisting cardiac, renal, or hepatic disease 2
• Sleep Apnea: May be exacerbated in those with risk factors 2
• Lipid Profile: Effects on lipid profiles are inconsistent, with most studies showing neutral effects or minimal reduction in HDL cholesterol 1

Monitoring and Risk Management

When considering testosterone therapy in older diabetic men:

1. Baseline Assessment:

   • Morning total testosterone level using an accurate and reliable assay 1
   • Free testosterone determination for borderline cases 1
   • Cardiovascular risk assessment 1
   • Prostate-specific antigen (PSA) testing 2
   • Complete blood count with hematocrit 2
   • Liver function tests and lipid profile 2

2. Ongoing Monitoring:

   • Regular monitoring of testosterone levels, PSA, hemoglobin, hematocrit, liver function tests, and lipid concentrations 2
   • Vigilance for signs of VTE, including deep vein thrombosis and pulmonary embolism 2
   • Monitoring for fluid retention, especially in patients with cardiac, renal, or hepatic disease 2

Potential Benefits vs. Risks

Potential Benefits:

• Improved sexual function, well-being, muscle mass and strength, and bone density 1
• Some studies suggest improvements in insulin sensitivity and glycemic control 3
• Potential reduction in visceral adiposity and improvements in lipid profiles 3

Cardiovascular Risks:

• Increased coronary artery plaque volume 1
• Potential increased risk of VTE 4, 2
• Possible increased risk of myocardial infarction and stroke in some populations 2

Clinical Decision-Making Algorithm

1. Confirm Hypogonadism:

   • Measure morning total testosterone level
   • If borderline, determine free testosterone concentrations
   • Rule out other causes of symptoms

2. Risk Stratification:

   • Assess baseline cardiovascular risk factors
   • Consider age, duration of diabetes, existing cardiovascular disease
   • Evaluate for sleep apnea risk

3. Treatment Decision:

   • For men with testosterone levels <230 ng/dL with symptoms: Consider treatment 1
   • For men with testosterone levels between 231-346 ng/dL with symptoms: Consider a 4-6 month trial 1
   • For men with testosterone levels >350 ng/dL: Replacement not usually required 1

4. Treatment Approach:

   • For older patients (>70 years) and those with chronic illness: Use easily titratable formulations (gel, spray, patch) rather than long-acting injectables 1
   • Target mid-range testosterone levels (350-600 ng/dL), especially in men with heart failure history 1
   • Monitor closely for adverse cardiovascular effects

Important Caveats

• The relationship between testosterone therapy and cardiovascular outcomes remains controversial with conflicting results across studies 5
• Long-term, large-scale studies on cardiovascular outcomes are still needed 1
• Benefits may be more pronounced in certain subgroups, such as older (>64.6 years) and less overweight (≤93.8 kg) men 6
• Consider concurrent weight reduction programs, as the benefits of testosterone therapy appear greater in men with lower weight 6

Testosterone therapy should be approached cautiously in older men with Type 2 diabetes, with careful consideration of individual cardiovascular risk factors and close monitoring for adverse effects.