Precautions for Patients with Low Testosterone Levels
When treating a patient with low testosterone levels, clinicians should implement comprehensive diagnostic confirmation, careful monitoring, and awareness of potential adverse effects to minimize morbidity and mortality risks. 1
Diagnostic Confirmation
- Confirm the diagnosis with two separate morning total testosterone measurements below 300 ng/dL before initiating treatment 1, 2
- Ensure symptoms of testosterone deficiency are present in addition to low laboratory values (reduced energy, reduced endurance, diminished performance, fatigue, depression, poor concentration, infertility, reduced sex drive, erectile dysfunction) 1
- Measure serum luteinizing hormone (LH) levels to establish the etiology of testosterone deficiency 1
- Measure serum prolactin in patients with low testosterone and low/normal LH levels to screen for hyperprolactinemia 1
- Consider pituitary MRI for patients with total testosterone <150 ng/dL and low/normal LH regardless of prolactin levels 1
- Measure serum estradiol in patients presenting with breast symptoms or gynecomastia prior to starting therapy 1
Pre-Treatment Assessment
- Assess all patients for cardiovascular disease risk factors (both fixed and modifiable) 1
- Measure hemoglobin/hematocrit at baseline to monitor for polycythemia 1
- Perform digital rectal examination and measure PSA before initiating treatment 1
- Conduct a reproductive health evaluation in men interested in fertility before treatment 1
- Evaluate for sleep apnea by history taking 1
Monitoring During Treatment
- Schedule first follow-up visit at 1-2 months to assess efficacy and consider dose adjustments 1
- Monitor at 3-6 month intervals for the first year and yearly thereafter 1
- At each visit, assess:
Potential Adverse Effects to Monitor
- Polycythemia (elevated hematocrit) - may require temporary discontinuation, dose reduction, or phlebotomy 1, 2
- Gynecomastia - may develop and occasionally persist 2
- Fluid retention - particularly concerning in patients with cardiac, renal, or hepatic disease 2
- Venous thromboembolic events (DVT, PE) - evaluate patients with symptoms of leg pain, edema, warmth 2
- Cardiovascular events - some studies report increased risk of major adverse cardiovascular events 2
- Hypercalcemia - particularly in patients with breast cancer or immobilized patients 2
- Liver abnormalities - monitor for jaundice or abnormal liver function tests 2
- Testicular size and consistency diminishment 1
- Skin reactions - more common with patches (66%) than with gels (5%) 1
- Local injection site reactions with intramuscular formulations 1
Special Considerations
- Use testosterone cautiously in men with congestive heart failure or renal insufficiency due to potential fluid retention 1
- Be aware that testosterone therapy will greatly compromise fertility due to gonadotropin down-regulation 1
- Consider the potential for testosterone abuse and monitor for signs of misuse 2
- Avoid treating based on symptoms alone without laboratory confirmation 3
- Target testosterone levels in the mid to upper-normal range for optimal response, but avoid supraphysiologic levels 1, 4
- Consider the pharmacokinetic profiles of different formulations - subcutaneous formulations may have fewer side effects than intramuscular injections 4
Treatment Selection Considerations
- Injectable testosterone enanthate or cypionate: Effective but causes significant fluctuations in testosterone levels 5, 4
- Subcutaneous testosterone: Associated with lower post-therapy estradiol and hematocrit levels compared to intramuscular formulations 4
- Transdermal testosterone gel: Provides more stable serum levels with fewer side effects than patches 5, 6
- Long-acting testosterone undecanoate: Requires fewer injections with more stable serum testosterone levels 5, 7
By following these precautions, clinicians can safely manage patients with testosterone deficiency while minimizing risks and optimizing outcomes.