What is the best treatment for testosterone deficiency?

Best Treatment for Testosterone Deficiency

For men with testosterone deficiency, testosterone replacement therapy (TRT) adjusted to achieve total testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL) is the recommended treatment, combined with lifestyle modifications. 1, 2

Diagnosis Confirmation

Before initiating treatment:

• Confirm diagnosis with morning total testosterone measurements below normal range on at least two separate days 3
• Measure between 8-10 AM to account for diurnal variation 2
• Consider free testosterone by equilibrium dialysis and SHBG levels, especially in obese patients 2
• Total testosterone levels <300 ng/dL are generally considered low 2

Treatment Algorithm

First-Line Approach:

1. Lifestyle Modifications (Grade B evidence) 1

   • Weight loss for overweight/obese patients
   • Regular physical activity
   • Adequate sleep
   • Stress reduction
   • Healthy diet
   • Moderate alcohol consumption
   • Smoking cessation

2. Testosterone Replacement Therapy 1, 3

   • Starting dose: 40.5 mg testosterone gel applied topically once daily
   • Target: Total testosterone level of 450-600 ng/dL
   • Available formulations:
     • Transdermal gels/patches
     • Injectable testosterone
     • Testosterone pellets

Special Considerations:

• Men seeking fertility: TRT should NOT be prescribed as it suppresses spermatogenesis 1, 4

  • Alternative options include:
    • Human chorionic gonadotropin (hCG)
    • Selective estrogen receptor modulators
    • Aromatase inhibitors

• Medication-induced hypogonadism: Consider medication adjustment when possible 2

  • Common culprits:
    • Opioids/opiates
    • Glucocorticoids
    • Antipsychotics (especially second-generation)

• Recent cardiovascular events: Delay TRT for 3-6 months 1

Monitoring and Follow-up

• Check total testosterone levels at approximately 14 and 28 days after starting treatment 3
• Adjust dose based on pre-dose morning serum testosterone concentration 3
• Regular monitoring of:
  • Total testosterone
  • Hematocrit (discontinue if exceeds 54%)
  • PSA (baseline, then 3-6 months after starting therapy, then annually)
  • Digital rectal examination

Important Caveats

• Cardiovascular risk: Counsel patients that current evidence cannot definitively state whether TRT increases or decreases cardiovascular events 1
• Prostate cancer: Use TRT with caution in men with in-situ prostate cancer on active surveillance or previously treated prostate cancer 1
• Venous thromboembolism: Observational studies have not shown increased risk with TRT, despite FDA warning 1
• Secondary exposure: Warn patients about risk of virilization in children who contact unwashed application sites 3

Nutraceutical Supplements

While some supplements show modest effects, they should be considered adjunctive rather than primary treatment 5:

• Zinc
• Vitamin D (in cases of deficiency)
• L-arginine
• Ashwagandha

The effects of these supplements on testosterone levels are modest and may not translate directly into clinical benefits 5.