What is the recommended treatment for testosterone replacement therapy (TRT) in patients with hypogonadism?

Testosterone Replacement Therapy for Hypogonadism

The recommended treatment for testosterone replacement therapy (TRT) in patients with hypogonadism is to start with 40.5 mg of testosterone gel 1.62% applied topically once daily in the morning to the shoulders and upper arms, with dose adjustments based on serum testosterone levels measured at 14 and 28 days after initiation. 1

Diagnosis Confirmation

Before initiating TRT:

• Confirm hypogonadism diagnosis with two morning testosterone measurements (between 8-10 AM) on separate days showing levels below normal range 2
• Determine whether primary (testicular) or secondary (pituitary-hypothalamic) hypogonadism by measuring LH and FSH levels 2

Treatment Options and Dosing

Topical Gel (First-line option)

• Starting dose: 40.5 mg testosterone gel 1.62% applied once daily to clean, dry shoulders and upper arms 1
• Dose adjustment based on pre-dose morning testosterone levels:

  • 750 ng/dL: Decrease dose by 20.25 mg

  • 350-750 ng/dL: No change
  • <350 ng/dL: Increase dose by 20.25 mg 2, 1
• Target testosterone level: 450-600 ng/dL (mid-normal range) 2

Intramuscular Injections

• Testosterone enanthate or cypionate: 100-200 mg every 2 weeks or 50 mg weekly 2
• Testosterone undecanoate: One injection every 3 months (provides more stable levels) 3

Monitoring Protocol

Initial Follow-up

• First follow-up: 1-2 months after starting treatment 2
• Check testosterone levels 2-3 months after initiation and after any dose changes 2

Regular Monitoring

• Testosterone levels: Every 6-12 months once stable 2
• Hemoglobin/hematocrit: Regular monitoring to detect polycythemia 2
• PSA and digital rectal examination: Regular monitoring for prostate health 2
• Symptom assessment: Evaluate for improvement in symptoms of hypogonadism 2

Side Effects and Management

Common Side Effects

• Erythrocytosis (dose-dependent: 2.8-17.9%) 2
• Suppression of spermatogenesis and reduced testicular size 2
• Acne, oily skin, increased body hair, and flushing 2
• Fluid retention (uncommon but caution in men with heart failure) 2

Serious Concerns

• Secondary exposure risk with gel formulations (children and women should avoid contact with application sites) 1
• Potential exacerbation of sleep apnea, particularly with higher doses 2
• Fertility suppression due to gonadotropin suppression 2

Contraindications

TRT is absolutely contraindicated in patients with:

• Prostate cancer
• Breast cancer
• Desire for near-term fertility
• Severe sleep apnea
• Uncontrolled heart failure
• Recent cardiovascular events 2

Special Considerations

• For elderly patients: Higher risk of deep vein thrombosis, fluid retention, and cardiovascular complications 2
• For obese patients: Consider weight loss through diet and physical activity as first-line approach, as this can reverse obesity-associated secondary hypogonadism 2
• For patients with cardiovascular risk factors: Recent high-quality evidence suggests TRT does not increase stroke or heart attack risk in men 45-80 years old 2

Clinical Pitfalls to Avoid

1. Initiating TRT without confirming diagnosis with two separate morning testosterone measurements
2. Failing to identify the cause of hypogonadism (primary vs. secondary)
3. Not monitoring for erythrocytosis, which is a common dose-dependent side effect
4. Prescribing TRT to men with contraindications such as prostate cancer or uncontrolled heart failure
5. Not providing proper instructions about gel application and the risk of secondary exposure
6. Overlooking the impact of TRT on fertility in men who may want children in the future

By following these evidence-based guidelines for TRT in hypogonadal men, clinicians can effectively manage symptoms while minimizing potential risks and complications.