Risks and Considerations for Patients Undergoing Testosterone Therapy
Patients undergoing testosterone replacement therapy (TRT) must be monitored regularly for multiple potential adverse effects including erythrocytosis, cardiovascular events, prostate issues, and fertility concerns, as these complications can significantly impact morbidity and mortality. 1
Key Risks of Testosterone Therapy
Hematologic Risks
- Erythrocytosis: A common and potentially serious complication
- Higher risk with injectable forms (43.8% with IM injections vs 15.4% with transdermal patches) 2
- Direct relationship between testosterone dosage and erythrocytosis risk 2
- Can lead to increased blood viscosity that may aggravate vascular disease in coronary, cerebrovascular, or peripheral circulation 2
- Monitoring recommendation: Maintain hematocrit <54%; discontinue therapy if exceeded 1
- Management options: Dose reduction, withholding testosterone, therapeutic phlebotomy, or blood donation 2
Cardiovascular Risks
- Venous thromboembolism: Reports of DVT and pulmonary embolism with testosterone products 3
- Fluid retention: May cause edema with or without congestive heart failure, especially in patients with pre-existing cardiac, renal, or hepatic disease 3
- Major adverse cardiovascular events (MACE): Inconclusive evidence regarding risk of non-fatal MI, non-fatal stroke, and cardiovascular death 3
Prostate Concerns
- Benign prostatic hyperplasia: Rare but possible exacerbation of symptoms 2
- Prostate cancer: Theoretical concern, though unproven direct causation 2
- Monitoring recommendation: Regular PSA monitoring; consider biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year 1
Other Significant Risks
- Fertility impairment: Suppresses spermatogenesis; contraindicated in men desiring current or future fertility 1
- Sleep apnea: May exacerbate existing condition 1
- Gynecomastia: Frequently develops and occasionally persists 3
- Liver toxicity: Potential for peliosis hepatis and hepatic neoplasms with prolonged high-dose use 3
- Hypercalcemia: Particularly in patients with breast cancer or immobilized patients 3
Monitoring Requirements
Initial Evaluation
- Baseline assessment of:
Follow-up Schedule
- First follow-up: 1-2 months after starting treatment 1
- Subsequent monitoring: Every 6-12 months once stable levels are confirmed 1
- Morning testosterone level (pre-dose) for accurate monitoring 1
- Recheck levels 14-28 days after dose adjustment 1
Formulation Considerations
- Injectable testosterone: Associated with higher risk of erythrocytosis (43.8%) and greater fluctuations in testosterone levels 2, 1
- Transdermal gel: Provides more stable testosterone levels with lower risk of erythrocytosis (11.3-17.9% depending on dose) 2, 1
- Transdermal patches: Lowest risk of erythrocytosis (2.8-5.5%) 2
Contraindications
- Active prostate or breast cancer
- Hematocrit >50%
- Severe untreated sleep apnea
- Severe lower urinary tract symptoms
- Uncontrolled heart failure
- Desire for current or future fertility 1
Risk Mitigation Strategies
- Use physiologic dosing within target range (450-600 ng/dL) 1
- Consider transdermal formulations for patients at higher risk of erythrocytosis 2, 1
- Regular monitoring of hematocrit, PSA, and cardiovascular parameters 1
- Implement lifestyle modifications: weight management, regular exercise, Mediterranean diet, limiting alcohol consumption 1
- Discontinue therapy if serious adverse effects occur 3
TRT offers benefits for appropriate patients with hypogonadism, but the potential risks require careful patient selection, appropriate formulation choice, and vigilant monitoring to minimize morbidity and mortality risks.