Can testosterone therapy cause elevated creatinine levels (hypercreatininemia)?

Can Testosterone Cause Elevated Creatinine?

Yes, testosterone therapy can cause elevated serum creatinine levels due to its effect on increasing muscle mass, which may not reflect true kidney dysfunction. 1

Mechanism of Testosterone's Effect on Creatinine

Testosterone replacement therapy (TRT) affects creatinine levels through several mechanisms:

1. Increased Muscle Mass: Testosterone promotes muscle hypertrophy, leading to higher creatinine production as a byproduct of muscle metabolism 1

2. Altered Body Composition: TRT can decrease fat mass while increasing lean body mass, changing the overall creatinine production and distribution 2

3. Physiological Changes: Men naturally have higher creatinine levels than women due to greater muscle mass, and testosterone therapy enhances this effect 3

Clinical Significance and Monitoring

Impact on Kidney Function Assessment

• Creatinine elevation from testosterone may represent a laboratory artifact rather than true kidney dysfunction
• In a study of men with testosterone-induced muscle hypertrophy, correlation between creatinine and cystatin C (another marker of kidney function) varied based on body composition 1
• For patients on TRT, creatinine-based estimated glomerular filtration rate (eGFR) calculations may falsely suggest kidney impairment

Recommendations for Monitoring

• Use alternative markers: Consider cystatin C for kidney function assessment in patients on TRT, as it's less affected by muscle mass 4
• Regular monitoring: Check renal function according to CKD stage (e.g., every 3 months for CKD stages 3-4) 4
• Baseline assessment: Obtain baseline kidney function before starting testosterone therapy 4
• Consider body composition: Interpretation of creatinine should account for BMI and percent body fat 1

Special Populations and Considerations

Transgender Patients

• In transgender patients on hormone therapy, creatinine levels may shift toward the reference range of their affirmed gender 4
• Female-to-male transgender patients on testosterone therapy may show increased creatinine levels that reflect physiological changes rather than kidney disease 3

Patients with Existing Kidney Disease

• For patients with chronic kidney disease, testosterone deficiency is common and may contribute to muscle wasting 2
• Testosterone therapy in men with cirrhosis (including decompensated disease) has shown benefits for muscle and bone mass 4
• Careful monitoring is needed when using testosterone in patients with kidney disease

Potential Pitfalls and Caveats

• Misdiagnosis risk: Elevated creatinine from testosterone use may lead to unnecessary nephrology referrals or interventions 5
• Medication adjustments: Dosing of renally-cleared medications might be inappropriately modified based on falsely low eGFR calculations
• Anabolic steroids: Non-prescribed anabolic steroids (like boldenone) can cause more dramatic elevations in creatinine than prescribed testosterone 5
• Fluid retention: Testosterone can cause mild fluid retention, which should be considered in patients with heart failure or renal insufficiency 4

Clinical Approach

1. Before starting testosterone:

   • Obtain baseline creatinine, eGFR, and consider cystatin C
   • Document baseline muscle mass/body composition

2. During testosterone therapy:

   • Monitor creatinine and kidney function at 1-2 months, then every 3-6 months for the first year
   • Consider cystatin C-based eGFR for more accurate assessment
   • Evaluate for other signs of kidney dysfunction (proteinuria, electrolyte abnormalities)

3. If creatinine rises:

   • Assess for changes in muscle mass
   • Consider cystatin C measurement
   • Evaluate for other causes of kidney dysfunction
   • Don't automatically attribute elevated creatinine to kidney disease

By understanding the relationship between testosterone and creatinine, clinicians can avoid unnecessary concern about kidney function while still appropriately monitoring patients on testosterone therapy.