Testosterone Supplementation and Proteinuria
Based on the available evidence, testosterone supplementation can cause proteinuria through direct effects on the kidney. 1
Mechanisms and Evidence
Prenatal testosterone administration in animal studies has been shown to increase proteinuria in male rats by 256%, an effect that was prevented when an androgen receptor blocker was co-administered, indicating that this effect is mediated through androgen receptors 1
Testosterone administration eliminated the protective effect of castration on progressive glomerular injury in hypercholesterolemic male rats, significantly increasing proteinuria in a dose-dependent manner 2
Research has demonstrated that testosterone levels are associated with albuminuria, with higher testosterone levels correlating with increased albumin leakage through the glomerular filtration barrier 3
Risk Factors and Considerations
While the comprehensive guidelines on testosterone replacement therapy from the New England Journal of Medicine list numerous potential risks including cardiovascular effects, erythrocytosis, and prostate concerns, they do not specifically mention proteinuria as a recognized side effect 4
The risk of fluid retention is noted as a potential side effect of testosterone therapy, though it is described as "rarely of clinical significance" 4
Erythrocytosis is a common side effect of testosterone therapy (occurring in 3-18% with transdermal formulations and up to 44% with injections), which could potentially impact kidney function indirectly 4
Clinical Implications
Dietary patterns may interact with testosterone levels and kidney function, with "fried-processed" dietary patterns being associated with both decreased testosterone levels and increased risk of impaired kidney function and proteinuria 5
The relationship between testosterone and kidney function appears to be complex, as some research suggests that estrogen may play a protective role against glomerular injury independent of testosterone levels 6
Monitoring Recommendations
Although current guidelines for testosterone therapy monitoring focus primarily on prostate-specific antigen (PSA), hematocrit/hemoglobin levels, and cardiovascular parameters 7, the animal research suggests that monitoring for proteinuria may be warranted
Given the evidence from animal studies showing a direct relationship between testosterone administration and proteinuria 1, 2, clinicians should consider baseline and follow-up urinalysis to detect protein excretion in patients receiving testosterone supplementation
Common Pitfalls and Caveats
The effects of testosterone on kidney function may be sex-specific, with males potentially being more susceptible to testosterone-induced proteinuria than females 1
The relationship between testosterone and kidney function may be influenced by other hormones and factors, including growth hormone levels 6
Most of the direct evidence for testosterone-induced proteinuria comes from animal studies, and human data specifically addressing this relationship is limited 1, 2, 3