Does testosterone supplementation cause elevated creatinine levels, indicating impaired renal function?

Testosterone Supplementation and Creatinine Levels

Testosterone supplementation can cause elevated creatinine levels, but this typically reflects increased muscle mass rather than impaired renal function. 1

Mechanism of Creatinine Elevation with Testosterone

Testosterone therapy affects creatinine levels through several mechanisms:

• Increased muscle mass: Testosterone therapy leads to approximately 4 kg increase in lean body mass after 1 year, resulting in higher creatinine production 1, 2
• Altered laboratory values: Creatinine shifts toward the reference range of the affirmed gender in transgender individuals on testosterone for at least 1 year 2
• False impression of renal dysfunction: The elevated creatinine can create a misleading impression of decreased estimated glomerular filtration rate (eGFR) when using creatinine-based equations 1

Clinical Implications

Effect on Renal Function Assessment

• Creatinine-based eGFR limitations: May falsely suggest reduced kidney function due to increased muscle-derived creatinine 1
• Alternative assessment: Cystatin C-based GFR estimation is recommended as it's less dependent on muscle mass 1, 2
• Actual renal function: Studies suggest testosterone may actually improve glomerular filtration rate in hypogonadal men through:
  • Vasodilatory effects on renal vasculature
  • Reduction in inflammatory markers affecting kidney function 1

Sex Differences in Testosterone-Kidney Function Association

• In men: Higher free testosterone is associated with higher eGFR when measured by cystatin C, suggesting a potential protective effect 3
• In women: Higher free testosterone is associated with lower eGFR, indicating possible sex-specific effects 3

Monitoring Recommendations

For patients on testosterone therapy:

• Establish baseline: Measure renal function before starting testosterone therapy 1
• Regular monitoring: Check renal function every 3-6 months during therapy 1
• Interpretation context: Interpret creatinine values in the context of testosterone therapy and increased muscle mass 2, 1
• Watch for warning signs: Monitor for unexplained decreases in eGFR not attributable to muscle mass changes 1

Special Considerations

• Use with caution: In patients with pre-existing renal insufficiency or congestive heart failure due to potential fluid retention 1
• Fluid retention: Although uncommon, testosterone can cause fluid retention which may impact patients with compromised renal or cardiac function 2, 1
• Discontinuation criteria: Consider stopping therapy if there is an unexplained decrease in eGFR that cannot be attributed to increased muscle mass 1

Pitfalls to Avoid

• Misdiagnosis of kidney disease: Don't mistake testosterone-induced creatinine elevation for kidney dysfunction 1, 4
• Inappropriate dose adjustments: Don't unnecessarily adjust doses of renally-cleared medications based solely on creatinine-based eGFR in patients on testosterone 2
• Overlooking other causes: Always evaluate for other potential causes of renal dysfunction in patients with significantly elevated creatinine 2

By understanding these relationships, clinicians can more accurately assess renal function in patients receiving testosterone supplementation and avoid unnecessary diagnostic procedures or treatment modifications.