What are the treatment options for hypogonadism (low testosterone)?

Treatment Options for Hypogonadism (Low Testosterone)

Testosterone replacement therapy (TRT) should be considered when morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments, and a complete hypogonadism workup has been performed to rule out etiologies unrelated to the patient's condition. 1

Diagnostic Confirmation Before Treatment

Before initiating treatment, it's essential to:

• Confirm hypogonadism with morning total testosterone concentrations drawn between 8-10 AM on at least two separate days 1, 2
• Measure free testosterone by equilibrium dialysis and sex hormone-binding globulin levels, especially in obese patients 1
• Determine if primary (testicular) or secondary (pituitary-hypothalamic) hypogonadism by measuring LH and FSH levels 1
• For secondary hypogonadism, consider additional testing including serum prolactin, iron saturation, pituitary function tests, and MRI of the sella turcica 1

Treatment Options

1. Transdermal Testosterone Preparations (First-Line)

• Gels (1% or 1.62%): Applied daily to shoulders and upper arms 2, 3

  • Advantages: Stable day-to-day testosterone levels, convenient application 1
  • Dosing: Start with 40.5 mg (2 pump actuations or single 40.5 mg packet) applied once daily 3
  • Dose adjustments based on serum levels:

    • 750 ng/dL: Decrease daily dose by 20.25 mg

    • 350-750 ng/dL: No change
    • <350 ng/dL: Increase daily dose by 20.25 mg 3

• Patches: Applied daily to skin

  • Advantages: Minimize transfer risk compared to gels 1
  • Disadvantages: Skin irritation (up to 66% of users) and adhesion issues 2

2. Injectable Testosterone

• Testosterone Enanthate/Cypionate: Intramuscular injections
  • Advantages: Less frequent administration, lower cost, avoids daily application 1, 2
  • Disadvantages: Fluctuating testosterone levels, injection discomfort 1
  • Peak levels occur 2-5 days post-injection with return to baseline by 10-14 days 2

3. Implantable Testosterone Pellets

• Advantages: Long-term option, avoiding daily administration 1
• Disadvantages: Requires implantation procedure 1

4. Alternative Therapies

• Clomiphene Citrate: For men who wish to preserve fertility
  • Dosing: 50 mg every other day
  • Shown to increase testosterone levels comparable to TRT (573 ng/dL vs 553 ng/dL) 4
  • Lower cost ($83/month vs $265-270/month for gels) 4

Monitoring

• Test testosterone levels 2-3 months after treatment initiation and after any dose changes 2
• Once stable, monitor every 6-12 months 1, 2
• For injectable testosterone, measure levels midway between injections 1
• Monitor hematocrit/hemoglobin and PSA regularly 2
• Target testosterone levels: 450-600 ng/dL (mid-normal range) 2

Benefits of Treatment

• Increased lean muscle mass and reduced body fat 2, 5
• Improved sense of well-being and energy levels 2, 5
• Enhanced sexual function and libido 2, 5
• Improved bone density and reduced fracture risk 2
• Improved mood 5

Safety Considerations and Contraindications

• Contraindications: Prostate cancer, male breast cancer, desire for near-term fertility, severe sleep apnea, uncontrolled heart failure, hematocrit >54% 2

• Potential Adverse Effects:

  • Erythrocytosis (dose-dependent: 2.8-17.9%) 2
  • Fluid retention (caution in heart failure or renal insufficiency) 2, 6
  • Skin reactions with transdermal preparations 2
  • Risk of secondary exposure with gels (risk of virilization in women and children) 3
  • Potential cardiovascular effects (long-term safety uncertain) 2
  • Suppression of spermatogenesis 2

• Special Caution:

  • FDA has not established safety and efficacy for "age-related hypogonadism" 3
  • Risk of venous thromboembolism (DVT/PE) 6
  • Potential for hepatic adverse effects with certain formulations 2, 6

Clinical Pearls

• Transdermal testosterone is safer for patients with liver concerns compared to oral formulations 2
• Application site matters: arms/shoulders > chest/abdomen > legs for absorption 7
• Proper patient education is crucial regarding application technique, risk of transfer, and long-term therapy expectations 2
• Weight loss and lifestyle modifications should be considered as complementary approaches, especially in obese patients 2

The choice of testosterone preparation should consider the patient's preference, cost considerations, and specific clinical factors, with transdermal preparations being the most commonly recommended first-line option due to their favorable pharmacokinetic profile and ease of use.