Can low testosterone (hypogonadism) affect kidney function (renal function) in males?

Low Testosterone and Kidney Function in Males

Yes, low testosterone (hypogonadism) is directly associated with reduced kidney function in men, and this relationship appears bidirectional—chronic kidney disease causes hypogonadism, while low testosterone independently predicts worse renal outcomes and increased mortality in men with CKD.

The Bidirectional Relationship

Low Testosterone Causes Reduced Kidney Function

• In the general population, low testosterone independently increases the risk of incident chronic kidney disease by 38% compared to normal testosterone levels 1
• Cross-sectional data from 848 adult men demonstrated that lower salivary testosterone levels were associated with decreased estimated glomerular filtration rate (eGFR), with the magnitude comparable to a 6-year increase in age 2
• This association persisted even after adjusting for age, comorbidities, and blood pressure, suggesting testosterone has a direct protective effect on kidney function 2

Chronic Kidney Disease Causes Hypogonadism

• Over half of men with renal failure (56.5% combined) have low or low-normal testosterone levels, even in the pre-dialysis phase 3
• This occurs across all stages: 26.2% had significantly low testosterone (<10 nmol/L) and 30.3% had low-normal levels (10-14 nmol/L) 3
• The mechanism involves dysfunction of the hypothalamic-pituitary-gonadal axis, though gonadotropin levels often remain paradoxically normal 3, 4

Clinical Outcomes in Men with CKD and Low Testosterone

Mortality and Cardiovascular Risk

• Men with CKD and low testosterone face doubled mortality risk: pooled hazard ratio of 1.98 (95% CI: 1.36-2.89) for all-cause mortality 1
• Cardiovascular events increase 2.4-fold: pooled hazard ratio of 2.40 (95% CI: 1.22-4.71) in hypogonadal men with CKD 1
• In observational studies, untreated hypogonadal men with CKD had 100% cardiovascular mortality, compared to 44% in those receiving testosterone therapy 5

Metabolic and Systemic Complications

Low testosterone in CKD contributes to multiple complications beyond sexual dysfunction 4:

• Protein-energy wasting and sarcopenia (reduced muscle mass and strength)
• Disorders in bone mineralization and reduced bone mineral density
• Progression of atherosclerosis and increased visceral adiposity
• Insulin resistance and worsening lipid profiles
• Anemia (testosterone stimulates erythropoiesis)
• Increased inflammatory markers and blood pressure

Testosterone Replacement Therapy Effects on Kidney Function

Evidence for Renal Protection

• Long-term testosterone therapy (8 years) in hypogonadal men improved multiple renal parameters 5:

  • Serum creatinine decreased from 0.90±0.10 to 1.12±0.9 mg/dL
  • GFR increased from 87.0±12.9 to 98.0±8.0 mL/min/1.73 m²
  • Urea decreased from 47.0±11.8 to 34.0±13.9 mg/dL
  • Uric acid decreased from 6.57±1.2 to 5.49±1.5 mg/dL

• Untreated controls showed deterioration: GFR decreased from 92.0±20.1 to 87.0±26.1 mL/min/1.73 m² over the same period 5

Additional Benefits of Testosterone Therapy in CKD

Testosterone supplementation in men with CKD and hypogonadism provides 4:

• Improved sexual function and libido
• Increased muscle mass and strength (combating sarcopenia)
• Enhanced bone mineral density
• Improved insulin sensitivity and lipid profiles
• Reduced inflammatory markers and blood pressure
• Increased hemoglobin concentration
• Improved mood and well-being

Diagnostic Approach in Men with CKD

When to Screen

• All men with CKD presenting with symptoms of hypogonadism should be screened: decreased libido, erectile dysfunction, reduced muscle mass, fatigue, or decreased spontaneous erections 6
• Given the high prevalence (>50% affected), consider screening even asymptomatic men with moderate-to-severe CKD 3

Laboratory Evaluation

• Measure morning total testosterone (between 8-10 AM) using an accurate and reliable assay 6
• If total testosterone is borderline (close to lower limit of 300 ng/dL or 10.41 nmol/L), measure free testosterone by equilibrium dialysis or calculate using total testosterone, sex hormone-binding globulin, and albumin 6
• Repeat abnormal values on a separate occasion to confirm diagnosis 6
• Measure luteinizing hormone and follicle-stimulating hormone if testosterone is low to distinguish primary from secondary hypogonadism 6

Important Caveat for CKD Patients

In men with chronic kidney disease requiring dialysis, creatinine-based calculations may be unreliable for assessing changes in renal function 6. Consider using cystatin C-based eGFR calculations when available, as it is less dependent on muscle mass 6.

Treatment Considerations

Indications for Testosterone Replacement

• Confirmed hypogonadism with morning free testosterone frankly low on at least 2 separate assessments 6
• Symptomatic patients with sexual dysfunction, reduced muscle mass, fatigue, or other hypogonadal symptoms 6
• Complete workup to exclude other causes of hypogonadism unrelated to CKD 6

Cardiovascular Safety Concerns

• Testosterone replacement in older men with hypogonadism has been associated with increased coronary artery plaque volume 6
• However, there is no conclusive evidence that testosterone supplementation increases cardiovascular risk in hypogonadal men 6
• The observational data showing reduced cardiovascular mortality with treatment in CKD patients (44% vs 100%) suggests potential benefit, though this requires confirmation in randomized trials 5

Formulation Options

Transdermal preparations (gels, patches) are preferred for most patients due to stable testosterone levels and convenience 6:

• Provide day-to-day stability
• Avoid injection discomfort
• Allow dose adjustments

Intramuscular injections (testosterone undecanoate 1000 mg every 12 weeks initially, then every 6 weeks) offer 6, 5:

• Less frequent administration
• Benefit for patients with reduced disease-management skills
• Proven efficacy in long-term CKD studies

Monitoring After Initiation

• Check testosterone levels 2-3 months after treatment initiation to ensure normal serum concentrations are achieved 6
• Monitor renal function parameters including serum creatinine, eGFR, urea, and uric acid 5
• Assess cardiovascular risk factors including blood pressure, lipid profile, and hemoglobin 4

Key Clinical Pitfalls

• Don't assume obesity alone explains low testosterone in CKD patients—while obesity is a major confounder, CKD independently causes hypogonadism through HPG axis dysfunction 6, 3
• Don't rely solely on total testosterone in CKD—measure free testosterone, as sex hormone-binding globulin is often low in CKD and diabetes, leading to falsely low total testosterone with normal free levels 6
• Don't overlook the mortality implications—low testosterone in CKD is not just about sexual function; it's associated with doubled all-cause mortality and cardiovascular events 1
• Successful kidney transplantation may improve testosterone levels, but approximately half of men with pre-transplant hypogonadism do not restore hormonal function and may still require supplementation 4