What is the treatment approach for hypogonadism (low testosterone)?

Treatment Approach for Hypogonadism (Low Testosterone)

Testosterone replacement therapy (TRT) should be initiated in men with confirmed hypogonadism, defined as low morning testosterone levels on at least two separate assessments, along with symptoms of hypogonadism. 1

Diagnosis and Evaluation

• Morning total testosterone concentration should be drawn between 8 AM and 10 AM, along with free testosterone level by equilibrium dialysis and sex hormone-binding globulin level, especially in patients with obesity 1
• If testosterone levels are subnormal, they should be repeated, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) should be measured to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1
• For secondary hypogonadism (low testosterone with low LH/FSH), further evaluation should include measurements of serum prolactin and iron saturation, pituitary function testing, and potentially MRI of the sella turcica 1

Indications for Treatment

• Treatment should be considered when symptoms of hypogonadism are present, including:
  • Decreased libido and erectile dysfunction 1
  • Fatigue and decreased energy 1
  • Decreased muscle mass and strength 1
  • Mood changes and depressive symptoms 1
  • Hot flashes, gynecomastia, and infertility 1
  • Increased abdominal fat mass 1

Treatment Options

Transdermal Preparations (First-line option)

• Testosterone gels and patches are recommended as first-line therapy for most hypogonadal men 1
• Advantages:
  • Produce stable day-to-day testosterone levels 1
  • Avoid discomfort of injections 1
  • Patients typically find them most convenient 1
• Disadvantages:
  • Higher cost than injectable options 1
  • Potential for skin irritation with patches 1
  • Risk of transfer to others through skin contact with gels 1
  • Variable absorption with gels 1
• Annual cost (2016): approximately $2,135 per Medicare beneficiary 1

Injectable Preparations

• Intramuscular testosterone is an effective alternative 1
• Advantages:
  • Lower cost (approximately $156 annually per Medicare beneficiary) 1
  • Avoids daily administration 1
  • Beneficial for patients with reduced personal disease-management skills 1
• Disadvantages:
  • Discomfort from injections 1
  • Fluctuating testosterone levels 1

Other Formulations

• Implantable testosterone pellets offer longer-term treatment but require a procedure for implantation 1
• Buccal and nasal formulations are also available 2
• Oral testosterone formulations are emerging but not yet first-line therapy 3

Monitoring and Follow-up

• Testosterone levels should be tested 2-3 months after treatment initiation or dose change 1
• Once stable levels are achieved, monitoring every 6-12 months is typically sufficient 1
• Timing of measurements depends on the preparation:
  • For injections: measure midway between injections, targeting mid-normal values (500-600 ng/dL) 1
  • For transdermal preparations: can be measured at any time, understanding that peak values occur 6-8 hours after patch application 1
• Monitor for adverse effects:
  • PSA levels (most common adverse reaction in clinical trials) 4
  • Hematocrit/hemoglobin increases 4
  • Cardiovascular events 1
  • Emotional lability 4
  • Sleep apnea, especially in patients with obesity or chronic lung disease 4

Benefits of Treatment

• Small improvement in sexual function and erectile function 1
• Small improvements in vitality and fatigue 1
• Less-than-small improvement in depressive symptoms 1
• Improvements in metabolic parameters:
  • Weight loss 1
  • Improved fasting plasma glucose and insulin resistance 1
  • Improved lipid profile 1
  • Increased lean body mass and reduced fat mass 1

Contraindications and Cautions

• Not indicated for use in women 4
• Use with caution in patients with:
  • Cardiovascular disease 1
  • Prostate cancer risk 4
  • Benign prostatic hypertrophy 5
  • Sleep apnea 4
  • Edema or congestive heart failure 4

Common Pitfalls and Caveats

• Avoid treating men with low total testosterone but normal free testosterone levels, especially in obesity 1
• Ensure diagnosis is based on at least two separate morning testosterone measurements 1
• Be aware that TRT may suppress spermatogenesis and affect fertility 4
• Long-term safety data is limited, particularly regarding cardiovascular outcomes 1
• Consider patient preferences and cost when selecting a formulation, as these factors significantly impact adherence 1