What is the treatment for hypogonadism due to low testosterone levels?

Treatment of Hypogonadism Due to Low Testosterone Levels

Testosterone replacement therapy (TRT) is the first-line treatment for men with confirmed hypogonadism, with transdermal preparations recommended as the preferred method for most patients due to their convenience and ability to produce stable testosterone levels. 1

Diagnostic Confirmation Before Treatment

Before initiating treatment, proper diagnosis is essential:

• Measure morning total testosterone levels between 8-10 AM on at least two separate occasions 1
• If total testosterone is low, measure free testosterone by equilibrium dialysis, particularly in obese patients 1
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish between:
  • Primary hypogonadism (testicular failure): low testosterone with elevated LH/FSH
  • Secondary hypogonadism (pituitary-hypothalamic dysfunction): low testosterone with low/normal LH/FSH 1

For secondary hypogonadism, further evaluation may include:

• Serum prolactin
• Iron saturation
• Pituitary function testing
• MRI of sella turcica 1

Treatment Options

Testosterone Replacement Therapy

1. Transdermal preparations (first-line for most patients):

   • Gels or patches applied daily
   • Advantages: stable day-to-day testosterone levels, avoid injection discomfort
   • Disadvantages: potential skin irritation, transfer risk to others (gels), variable absorption 1

2. Injectable testosterone:

   • Advantages: less frequent administration, lower cost, good for patients with limited self-management skills
   • Disadvantages: fluctuating testosterone levels, injection discomfort 1

3. Implantable testosterone pellets:

   • Advantages: long-term option
   • Disadvantages: requires implantation procedure 1

Dosing and Monitoring

• Starting dose for testosterone gel 1.62%: 40.5 mg applied topically once daily to shoulders and upper arms 2
• Target testosterone levels: mid-normal range (500-600 ng/dL) 1
• Monitor testosterone levels:
  • 2-3 months after treatment initiation or dose change
  • Every 6-12 months once stable 1
  • For injectable testosterone: measure midway between injections 1

Special Considerations

Fertility Concerns

• Important: Testosterone monotherapy should NOT be prescribed for men interested in current or future fertility 1
• Alternative options for men wishing to preserve fertility:
  • Aromatase inhibitors (AIs)
  • Human chorionic gonadotropin (hCG)
  • Selective estrogen receptor modulators (SERMs) 1, 3

Contraindications and Precautions

• Absolute contraindications:

  • Known or suspected prostate or breast cancer 4, 5
  • Desire for fertility in the near future 1

• Use with caution in:

  • Severe cardiovascular disease
  • Thrombophilia
  • Polycythemia 5, 3
  • Severe LUTS/BPH symptoms 1

Benefits Beyond Sexual Function

Testosterone replacement in hypogonadal men has been associated with:

• Weight loss
• Improved glucose control and insulin sensitivity
• Better lipid profile
• Increased lean body mass
• Decreased waist circumference 1

Monitoring for Adverse Effects

• Cardiovascular risk assessment
• Prostate monitoring (PSA)
• Complete blood count (risk of polycythemia)
• Liver function tests
• Observe for edema, gynecomastia 5

Algorithm for Treatment Decision

1. Confirm diagnosis: Two morning testosterone measurements <300 ng/dL with symptoms
2. Determine type: Primary vs. secondary hypogonadism
3. Assess fertility desires:
   • If fertility desired: Consider SERMs, AIs, or hCG
   • If fertility not a concern: Proceed with TRT
4. Select delivery method based on patient factors:
   • For most patients: Transdermal preparations
   • For patients with limited self-management: Injectable testosterone
   • For convenience with long-term therapy: Consider implantable pellets
5. Monitor response and adjust dose to achieve mid-normal testosterone levels

Remember that testosterone therapy should only be initiated after confirming hypogonadism with frankly low testosterone levels on at least two separate assessments and completing appropriate workup to rule out other etiologies of hypogonadism.