Does testosterone replacement therapy affect glomerular filtration rate (GFR) in men?

Testosterone Replacement Therapy and Glomerular Filtration Rate in Men

Testosterone replacement therapy (TRT) appears to improve glomerular filtration rate (GFR) in hypogonadal men, with studies showing increases in GFR over long-term treatment. 1

Effects of TRT on Renal Function

Testosterone therapy has been shown to have several effects on renal function:

• Improved GFR: Long-term testosterone therapy has been demonstrated to increase GFR from 87.0 ± 12.9 to 98.0 ± 8.0 mL/min/1.73 m² over an 8-year period in hypogonadal men 2

• Changes in renal biomarkers: TRT has been associated with:

  • Decreased urea (47.0 ± 11.8 to 34.0 ± 13.9 mg/dL)
  • Decreased uric acid (6.57 ± 1.2 to 5.49 ± 1.5 mg/dL)
  • Increased serum creatinine (0.90 ± 0.10 to 1.12 ± 0.9 mg/dL) 2

• Mechanism of action: Testosterone may improve renal function through:

  • Changes in body composition (increased lean muscle mass)
  • Potential vasodilatory effects on renal vasculature
  • Reduction in inflammatory markers that affect kidney function 1

Relationship Between Testosterone Levels and GFR

The relationship between testosterone and GFR is supported by several observations:

• Hypogonadism and hyperfiltration: Patients with idiopathic hypogonadotropic hypogonadism demonstrate glomerular hyperfiltration (GFR 163.1 ± 46.9 mL/min vs 117.9 ± 30.5 mL/min in controls) 3

• Testosterone as a permissive factor: In animal studies, testosterone administration after gonadal ablation amplifies compensatory glomerular growth, suggesting testosterone acts as a permissive factor for glomerular growth 4

Monitoring Considerations

When initiating TRT, the following monitoring protocol should be implemented:

• Baseline assessment: Establish baseline renal function before starting TRT 1

• Regular monitoring: Check renal function parameters at 3-6 month intervals during testosterone therapy 1

• Interpretation challenges: Be aware that increased muscle mass due to TRT can lead to higher creatinine production, potentially resulting in falsely lower estimated GFR when using creatinine-based equations 1

• Alternative measurement: Consider cystatin C-based GFR estimation for more accurate assessment of renal function in men on TRT, as it is less dependent on muscle mass 1

Special Considerations

• Use with caution in men with congestive heart failure or renal insufficiency due to potential fluid retention 1

• Discontinue TRT if there is an unexplained decrease in eGFR, as this may indicate adverse effects on renal function 1

• Mortality benefit: Long-term TRT may reduce cardiovascular mortality in hypogonadal men compared to untreated controls (7.8% vs 15.2% mortality, with 44% vs 100% of deaths due to cardiovascular causes) 2

Practical Approach

1. Measure baseline renal function before initiating TRT
2. Start TRT in men with testosterone levels <230 ng/dL with symptoms
3. Consider TRT in men with levels 231-346 ng/dL with symptoms after discussing risks/benefits
4. Target testosterone levels in the mid-range (350-600 ng/dL), especially in men with heart failure
5. Monitor renal function every 3-6 months
6. Consider cystatin C-based GFR measurement if available
7. Interpret creatinine-based GFR with caution due to increased muscle mass

In conclusion, TRT appears to have a beneficial effect on GFR in hypogonadal men, but careful monitoring is essential to ensure safety and optimize outcomes.