Can improperly administered testosterone injections cause congestive heart failure (CHF) or acute kidney injury (AKI)?

Can Improperly Administered Testosterone Injections Cause CHF or AKI?

Testosterone injections themselves—regardless of administration technique—carry an increased risk of acute kidney injury (AKI), but the evidence does not support a direct causal relationship with congestive heart failure (CHF), though fluid retention can worsen pre-existing CHF. The risks stem from the formulation and pharmacokinetics of injectable testosterone rather than improper injection technique per se.

Acute Kidney Injury Risk with Testosterone Injections

• The TRAVERSE trial demonstrated a significantly increased risk of AKI in men receiving testosterone replacement therapy (hazard ratio not specified but statistically significant), which was validated in a large retrospective cohort study showing a 53% increased risk (RR 1.53,95% CI 1.07-2.18) within 3 years of starting therapy 1, 2.

• This AKI risk appears related to the testosterone therapy itself rather than injection technique, as it was observed with transdermal gel in TRAVERSE and with topical formulations in the validation study 1, 2.

• The mechanism of testosterone-associated AKI remains unclear, but may relate to erythrocytosis-induced hyperviscosity, direct renal effects, or hemodynamic changes 2.

Congestive Heart Failure Considerations

• The FDA drug label explicitly warns that "edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease" 3.

• However, fluid retention from testosterone is "rarely of clinical significance" in patients without pre-existing cardiac disease 4.

• Testosterone does not cause CHF de novo, but can precipitate decompensation in patients with pre-existing heart failure through fluid retention 3, 4.

• The cardiovascular safety profile of testosterone is actually neutral to potentially beneficial—the TRAVERSE trial showed non-inferiority for major adverse cardiac events (hazard ratio 0.96,95% CI 0.78-1.17) 1.

Injection-Specific Cardiovascular Risks (Not Related to Technique)

Injectable testosterone carries substantially higher cardiovascular risk than transdermal formulations due to pharmacokinetic properties, not administration errors:

• Injections are associated with 43.8% incidence of erythrocytosis (hematocrit >52%) compared to 3-18% with transdermal preparations, which increases blood viscosity and could aggravate vascular disease 5, 6.

• A case-crossover study found injection testosterone was associated with increased acute cardiovascular events in older men (OR 1.45,95% CI 1.07-1.98) in the immediate post-injection period, likely due to supraphysiologic testosterone spikes 7.

• Fluctuating testosterone levels from injections lead to increased time in both supratherapeutic and subtherapeutic ranges between doses, unlike stable transdermal levels 5.

Clinical Management Algorithm

Patient Selection and Contraindications

• Avoid testosterone therapy entirely in men with:
  • Hematocrit >50% at baseline 6
  • Decompensated CHF or severe renal insufficiency 3
  • Recent cardiovascular events (though TRAVERSE showed safety in stable disease) 1

Formulation Selection

• Strongly prefer transdermal testosterone gel over injections for all patients, especially those with cardiovascular disease or risk factors, due to lower erythrocytosis risk and more stable hormone levels 5, 6.

• If injections must be used, target mid-normal testosterone levels (500-600 ng/dL measured midway between doses) to minimize supraphysiologic peaks 5.

Mandatory Monitoring Protocol

• Baseline assessment:

  • Hematocrit/hemoglobin 4
  • Creatinine/eGFR (given AKI risk) 2
  • Assess for pre-existing cardiac or renal disease 3

• Follow-up monitoring:

  • Hematocrit at 2-3 months, then every 6-12 months (more frequently with injections) 5, 6
  • Renal function monitoring at similar intervals given demonstrated AKI risk 2
  • Assess for fluid retention, worsening dyspnea, or edema at each visit 3

Management of Complications

• If erythrocytosis develops (hematocrit >54%): Temporarily withhold testosterone, consider therapeutic phlebotomy, or switch to transdermal formulation 6.

• If AKI develops: Discontinue testosterone and evaluate for other causes; consider permanent discontinuation if recurrent 2.

• If fluid retention worsens pre-existing CHF: Discontinue testosterone immediately 3.

Common Pitfalls to Avoid

• Don't attribute all cardiovascular or renal complications to "improper injection technique"—the risks are inherent to injectable testosterone's pharmacokinetics and should prompt formulation change rather than technique correction 5, 7.

• Don't overlook the AKI risk, which is a newly recognized complication that requires proactive renal function monitoring 1, 2.

• Don't use testosterone in men with uncontrolled CHF or significant renal impairment, as these are high-risk populations where risks clearly outweigh benefits 3.

• The FDA mandated labeling changes in 2015 warning of possible cardiovascular risks, though the 2023 TRAVERSE trial has provided reassuring data for appropriately selected patients using transdermal formulations 5, 1.