Average HbA1c Reduction with Testosterone Therapy
Testosterone replacement therapy (TRT) reduces HbA1c by approximately 0.4-0.9% in hypogonadal men with type 2 diabetes or prediabetes.
Evidence for HbA1c Reduction
Testosterone therapy has been shown to have beneficial effects on glycemic control in hypogonadal men, particularly those with type 2 diabetes or prediabetes. The magnitude of this effect varies across studies:
A double-blind placebo-controlled crossover study in hypogonadal men with type 2 diabetes showed that testosterone therapy reduced HbA1c by 0.37% (±0.17%) compared to placebo 1
A more recent double-blind, randomized, placebo-controlled clinical study in obese hypogonadal diabetic males demonstrated a reduction in HbA1c by 0.94% (±0.88%) after one year of testosterone undecanoate treatment 2
A meta-analysis of 18 randomized controlled trials involving 1415 patients found that testosterone replacement therapy reduced HbA1c by an average of 0.67% (95% CI -1.35, -0.19) 3
An 8-year registry study showed that testosterone therapy in men with hypogonadism and prediabetes decreased HbA1c by 0.39% (±0.03%), while HbA1c increased by 0.63% (±0.1%) in the untreated group 4
Mechanisms of Action
The improvement in glycemic control with testosterone therapy appears to be mediated through several mechanisms:
Improved insulin sensitivity: Testosterone therapy reduces insulin resistance as measured by HOMA-IR index 1, 3
Reduced visceral adiposity: Treatment results in decreased waist circumference and waist/hip ratio 1, 3
Effects on erythropoiesis: Testosterone stimulates red blood cell production, which may affect HbA1c measurements 5
Important Considerations
Effect on Erythropoiesis and HbA1c Interpretation
It's crucial to note that testosterone stimulates erythropoiesis, which can affect HbA1c interpretation. Research has shown:
Serum bioavailable testosterone concentration correlates positively with hemoglobin concentration and negatively with the ratio of glycated albumin to HbA1c 5
This effect may lead to underestimation of HbA1c in hypogonadal men with type 2 diabetes 5
Clinicians should be aware that testosterone therapy commonly causes erythrocytosis, with higher rates seen with injectable formulations (43.8%) compared to transdermal preparations (15.4%) 6
Monitoring Requirements
When initiating testosterone therapy, regular monitoring is essential:
Hemoglobin and hematocrit should be monitored due to the risk of erythrocytosis 6
If erythrocytosis develops, appropriate measures such as dosage reduction, withholding testosterone, therapeutic phlebotomy, or blood donation may be necessary 6
Clinical Context
For patients with diabetes, it's important to remember that:
The American College of Physicians recommends an HbA1c target between 7% and 8% for most patients with type 2 diabetes 6
An HbA1c of 6.9% corresponds to an estimated average glucose of approximately 150 mg/dL 7
The modest reduction in HbA1c with testosterone therapy (0.4-0.9%) may be clinically significant for patients near their glycemic targets
Conclusion
Testosterone replacement therapy provides a modest but significant reduction in HbA1c levels (approximately 0.4-0.9%) in hypogonadal men with type 2 diabetes or prediabetes. However, clinicians should be aware that testosterone's effect on erythropoiesis may lead to underestimation of actual glycemic control when using HbA1c as a marker.